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Incidence of herpes zoster and its complications in ≥50-year-old Spanish adults: A prospective cohort study
Incidencia del herpes zoster y sus complicaciones en adultos españoles ≥50 años: estudio de cohorte prospectivo
Luis García Comasa, Teresa Cerdánb, Maria Del Rosario Cambroneroc,
Corresponding author
charo.m.cambronero-martinez@gsk.com

Corresponding authors.
, Juan Antonio García Martínezc,
Corresponding author
juan-antonio.garcia-martinez@gsk.com

Corresponding authors.
, Marta López Sanromàc, Kusuma Gopalad, Benedetto Simonee, Javier Díez-Domingob
a Health Department of the Community of Madrid, Subdirectorate of Epidemiology, C/ San Martín de Porres 6, Madrid 28035, Spain
b Vaccine Research, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, FISABIO-Public Health, Avda. de Catalunya 21, Valencia 46020, Spain
c GSK, Parque Tecnológico de Madrid, C/ Severo Ochoa, 2, 28760 Tres Cantos, Madrid, Spain
d GSK, GSK Asia Private Limited, Level 4,5 & 6 Prestige Trade Tower, 46 Palace Road, Sampangi Rama Nagar, Bangalore 560001, India
e GSK, Stockley park, Iron Bridge Rd N, Uxbridge UB11 1BT, United Kingdom
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a painful neuropathic complication&#46;<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a> HZ risk is greater in females&#44;<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a> and in the immunocompromised&#46;<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a> Although most cases resolve within one month of rash onset without sequelae&#44; about 25&#37; of patients experience various HZ complications during the acute phase&#44; including ophthalmic&#44; neurological or dermatological complications&#59;<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a> while others will develop more prolonged complications&#44; including PHN which may last for months or years&#46;<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">Globally&#44; HZ incidence estimates in the overall population range from 3&#8211;5 per 1&#44;000 person-years &#40;PY&#41;&#44; with little geographical variation&#46;<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a> In Europe&#44; a recent systematic review reported a mean HZ incidence rate &#40;IR&#41; of 3&#46;4&#47;1&#44;000 PY in the general population&#44; increasing with age&#59; 7&#8211;8&#47;1&#44;000 PY in individuals aged &#8805;<span class="elsevierStyleHsp" style=""></span>50 years and 10&#47;1&#44;000 PY for those aged &#8805;<span class="elsevierStyleHsp" style=""></span>80 years&#46;<a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a> The proportion of patients with HZ developing PHN also shows some variation&#44; ranging from 5&#8211;30&#37;&#44; in part due to differences in terminology and PHN definitions&#46;<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">In Spain&#44; epidemiologic data on the incidence and burden of HZ &#40;and PHN&#41; are&#44; until recently&#44; quite limited&#46; Existing data includes retrospective analyses of databases and case records from regional or municipal health systems&#46;<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bb0050"><span class="elsevierStyleSup">10&#8211;16</span></a> A comprehensive retrospective analysis of primary care records for the period 2009&#8211;2014 in the Valencia region&#44; evaluating the risk of HZ in patients with&#47;without chronic obstructive pulmonary disease &#40;COPD&#41; reported an IR of 7&#46;2&#47;1&#44;000 PY in patients aged &#8805;<span class="elsevierStyleHsp" style=""></span>50 years &#40;without COPD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> A related study across this same period evaluating PHN reported that 15&#46;7&#37; of patients with HZ aged &#8805;<span class="elsevierStyleHsp" style=""></span>50 years developed PHN&#46;<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a> However&#44; prospective studies are less common&#46;<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a></p><p id="p0020" class="elsevierStylePara elsevierViewall">At present there are two vaccines against HZ licensed in subjects &#8805;<span class="elsevierStyleHsp" style=""></span>50 years of age and available for use in Spain&#59; a live-attenuated vaccine &#40;ZVL&#44; <span class="elsevierStyleItalic">Zostavax</span>&#44; Merck and Co&#46;&#44; Inc&#46;&#41; and&#44; since 2018&#44; an adjuvanted recombinant zoster vaccine &#40;RZV&#44; <span class="elsevierStyleItalic">Shingrix&#44;</span> GSK&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a> Understanding local HZ epidemiology is important&#44; in particular as prevention strategies via protective vaccination are available&#46;<a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a> At the time of the present study only the live-attenuated vaccine was available &#40;although uptake in Spain was low&#41;&#46; We wished to assess HZ epidemiology prior to wider implementation of HZ preventive strategies&#46;</p><p id="p0025" class="elsevierStylePara elsevierViewall">The primary objective of the present study was to prospectively estimate the incidence of HZ in Spanish adults aged &#8805;<span class="elsevierStyleHsp" style=""></span>50 years in the primary care setting&#46; Secondary objectives were to estimate the proportion of HZ patients developing PHN&#46; The impact of HZ and PHN on patients&#8217; quality of life&#44; healthcare resource utilization and associated economic costs in the study population has already been reported&#46;<a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a></p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Methods</span><p id="p0030" class="elsevierStylePara elsevierViewall">This was a prospective observational study evaluating the incidence of HZ in older adults &#8805;<span class="elsevierStyleHsp" style=""></span>50 years of age in a primary care cohort&#46; Secondary objectives included pain assessment and PHN development &#40;NCT01521286&#41;&#46; Participating physicians were general practitioners &#40;GPs&#41; belonging to one of the four GP networks operating within three regions&#59; Madrid&#44; Catalonia &#40;in Barcelona&#44; the regional capital&#41; and Valencia &#40;two networks&#58; Centro Superior de Investigacion en Salud P&#250;blica &#40;CSISP&#41; and Centro de Salud Salvador Pau&#41;&#44; caring for an estimated 94&#44;000 persons aged &#8805;<span class="elsevierStyleHsp" style=""></span>50 years&#46;</p><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Study eligibility</span><p id="p0035" class="elsevierStylePara elsevierViewall">Eligible participants were adults aged &#8805;<span class="elsevierStyleHsp" style=""></span>50&#8239;years presenting with an episode of acute HZ within the four participating GP networks&#46; Subjects attending for a secondary GP consultation within 7 days following a HZ diagnosis in an alternative setting &#40;e&#46;g&#46;&#44; emergency room or community-care center&#41; were also eligible&#46; Acute HZ was defined as new unilateral pain &#40;broadly defined to include allodynia and pruritus&#41; accompanied by unilateral rash and no alternative diagnosis&#46;</p><p id="p0040" class="elsevierStylePara elsevierViewall">The study and analyses were conducted from two perspectives&#46; We prospectively estimated the incidence of HZ over a one-year period &#40;in three of the GP networks&#41;&#46; We also prospectively followed up an according to protocol &#40;ATP&#41; study cohort of HZ patients in a broader patient population from all four GP networks &#40;which included some patients participating in the incidence estimations&#41; and evaluated demographic aspects&#44; clinical features and development of complications &#40;and in particular PHN&#41;&#46;</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">HZ incidence estimation</span><p id="p0045" class="elsevierStylePara elsevierViewall">Incidence estimates were based on the number of eligible attending three of the four participating GP networks &#40;Madrid&#44; Barcelona and CSISP Valencia&#41; over a 12-month period&#59; from July 1&#44; 2013 to June 30&#44; 2014&#46; While the initial study aim was to include data from the Pau Valencia network&#44; during data collection it was apparent that a significant proportion &#40;approximately 1&#47;3&#41; of the GPs from the Pau Valencia Network consistently reported fewer cases than would be expected&#44; based on literature<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> and our own preliminary estimations&#46; The reasons for this were unclear&#44; but we believed that inclusion may have added uncertainty to the overall incidence data&#46; As such&#44; as an amendment to the planned analyses&#44; the data from the Pau Valencia network were excluded from the HZ incidence analyses&#46; However&#44; as described below&#44; HZ cases within this network were included in the prospective cohort assessing complications&#46;</p><p id="p0050" class="elsevierStylePara elsevierViewall">Participating GPs provided monthly logbooks detailing the number of eligible patients with HZ presenting each week in the respective month&#59; this included those weeks with zero cases&#46; Relevant regional population denominators and regional aggregates for the number of individuals aged &#8805;<span class="elsevierStyleHsp" style=""></span>50 years &#40;and for all relevant age-strata&#41; were calculated using official registered patient numbers for each participating GP&#44; with adjustment based upon the actual number of patients under their active care during this 12-month period&#46; In this approach&#44; for those weeks where no weekly report was received from a GP&#44; this was considered as a break&#47; disruption in surveillance&#59; and the population denominator adjusted to account for this corresponding period&#46; From these data HZ incidence was estimated per 1&#44;000 PY &#40;with exact Poisson 95&#37; confidence intervals &#91;CIs&#93;&#41;&#44; for all patients and also stratified by gender and age&#46;</p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">Eligibility and data collection in the prospective ATP Study cohort evaluating HZ complications</span><p id="p0055" class="elsevierStylePara elsevierViewall">This ATP patient cohort recruited all patients aged &#8805;<span class="elsevierStyleHsp" style=""></span>50 years with an HZ episode attending any of the four GP networks&#44; with study entry and follow-up between March 2012 and May 2015&#46; Inclusion was based on GP assessment of patient ability to complete study questionnaires and allied study documents&#46; Following enrollment&#44; each GP completed a case report form with demographic data&#44; medical history&#44; and clinical HZ information&#44; including HZ-related complications &#40;also recorded at any subsequent physician consultation during the study period&#41;&#46;</p><p id="p0060" class="elsevierStylePara elsevierViewall">Patients rated HZ pain severity using the Zoster Brief Pain Inventory &#40;ZBPI&#41; questionnaire&#46; Participants were asked to complete the ZBPI at Day 0 &#40;defined as the day of HZ onset&#41; and at Days 15&#44; 30&#44; 60 and 90&#46; The ZBPI questionnaire includes 4 pain severity items &#40;&#8216;worst&#8217;&#44; &#8216;least&#8217;&#44; &#8216;average&#8217; over the last 24 hours and &#8216;now&#8217;&#41;&#44; each of which is rated on an 11-point Likert scale with 0 &#61; &#8216;no pain&#8217; and 10 &#61; &#8216;pain as bad as you can imagine&#8217;&#46; The ZBPI is a well-established method for assessing HZ pain and development of PHN&#44;<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a> used in similar previous studies in HZ patients in Germany and Italy&#46;<a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a> The ZBPI questionnaire was supplied in booklet format and assistance in understanding how to complete each questionnaire provided by the GP at the initial visit if necessary&#46; Additional sets of questionnaires were subsequently self-administered and completed by the patient at the days assigned &#40;Days 15&#44; 30&#44; 60 and 90&#41; and returned to the study centers &#40;in person or by mail&#41;&#46;</p><p id="p0065" class="elsevierStylePara elsevierViewall">PHN was defined as the presence of HZ-associated &#8216;worst&#8217; pain rated &#8805;<span class="elsevierStyleHsp" style=""></span>3 on the ZBPI scale persisting or appearing 90 days or more after HZ onset&#46; Those HZ patients without PHN at Day 90 were considered as having completed the study and not followed up further&#46; Patients with PHN at Day 90 were asked to continue and complete the ZBPI questionnaire for a further 90 days&#44; at Days 120&#44; 150 and 180&#46; At Day 180&#44; those patients with continued PHN remained in the study and asked to complete the ZBPI questionnaire for a final 90-day period&#44; at Days 210&#44; 240 and 270&#46; No patient was followed beyond Day 270&#46;</p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060">Data analyses in the prospective ATP study cohort evaluating HZ complications</span><p id="p0070" class="elsevierStylePara elsevierViewall">Descriptive statistics &#40;mean values&#44; standard deviation &#91;SD&#93; and percentages&#41; are presented for patient demographics&#44; ZBPI pain severity scores and for HZ complications&#46; The proportions of patients with PHN at Days 90&#44; 180 and 270 were calculated with exact 95&#37; CIs&#59; for the overall study cohort &#8805;<span class="elsevierStyleHsp" style=""></span>50 years &#40;and stratified by gender&#44; age group and severity of HZ at the initial visit&#41;&#46; The proportion with PHN at Day 90 was also calculated for those patients that completed the ZBPI at this time point&#46; All statistical analyses were performed using the Statistical Analysis Systems &#40;SAS&#41; version 9&#46;2&#46;</p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Ethics</span><p id="p0075" class="elsevierStylePara elsevierViewall">This study was conducted in accordance with the ethical principles originating in the Declaration of Helsinki&#44; the principles of &#34;good clinical practice&#34; and all applicable regulatory requirements&#46; Written informed consent was obtained from each enrolled participant prior to study data collection&#46; The study protocol&#44; the informed consent form&#44; and other information that required pre-approval were reviewed and approved by the independent ethics committees for each of the participating networks&#46;</p></span></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Results</span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Overall incidence of HZ &#40;incidence cohort&#41;</span><p id="p0080" class="elsevierStylePara elsevierViewall">Between July 1&#44; 2013 and June 30&#44; 2014&#44; a total of 459 HZ cases in patients aged &#8805;<span class="elsevierStyleHsp" style=""></span>50 years attended one of the three GP networks &#40;Madrid&#44; Barcelona and CSISP Valencia&#41; participating in the incidence estimation part of the study&#46; Of these&#44; 257 &#40;56&#37;&#41; were female&#46; The overall HZ incidence in subjects &#8805;<span class="elsevierStyleHsp" style=""></span>50 years was estimated at 4&#46;88&#47;1&#44;000 PY &#40;95&#37; CI&#58; 4&#46;44&#8211;5&#46;35&#41;&#59; increasing with age from 2&#46;54&#47;1&#44;000 PY &#40;95&#37; CI&#58; 1&#46;84&#8211;3&#46;41&#41; in those aged 50&#8211;54 years to a peak of 6&#46;40&#47;1&#44;000 PY &#40;95&#37; CI&#58; 4&#46;86&#8211;8&#46;28&#41; in those aged 75&#8211;79 years&#46; Overall HZ incidence was similar in women &#40;4&#46;90&#47;1&#44;000 PY &#91;95&#37; CI&#58; 4&#46;32&#8211;5&#46;53&#93;&#41; and men &#40;4&#46;85&#47;1&#44;000 PY &#91;95&#37; CI&#58; 4&#46;21&#8211;5&#46;57&#41; with similar trends of greater incidence with increasing age in both genders &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#41;&#46; Some regional variation in the overall incidence was observed across the different GP networks&#59; Barcelona &#40;3&#46;67&#47;1&#44;000 PY&#59; 95&#37; CI&#58; 3&#46;10&#8211;4&#46;31&#41;&#59; Madrid &#40;5&#46;37&#47;1&#44;000 PY&#59; 95&#37; CI&#58; 4&#46;71&#8211;6&#46;10&#41;&#59; and CSISP Valencia &#40;7&#46;52&#47;1&#44;000 PY&#59; 95&#37; CI&#58; 5&#46;94&#8211;9&#46;40&#41;&#46; In all 3 regions a similar pattern of lower incidence in patients aged 50&#8211;54 years and higher incidence in older age strata was also observed &#40;Supplementary Table 1&#41;&#46;</p><elsevierMultimedia ident="t0005"></elsevierMultimedia></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">Patient demographics in the prospective ATP study cohort evaluating HZ complications</span><p id="p0085" class="elsevierStylePara elsevierViewall">A total of 545 HZ patients with an acute HZ episode presenting across the four participating GP networks were included in the prospective study ATP cohort&#59; Madrid &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>229&#41;&#44; Barcelona &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>146&#41;&#44; CSISP Valencia &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>93&#41; and Centro de Salud Salvador Pau&#44; Valencia &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>77&#41;&#46; The mean &#40;SD&#41; age at rash onset was 66&#46;9 &#40;9&#46;7&#41; years &#40;range 50&#8211;91 years&#41;&#59; 312 patients &#40;57&#46;2&#37;&#41; were female&#46;</p></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">Clinical features at the initial visit in the prospective ATP study cohort</span><p id="p0090" class="elsevierStylePara elsevierViewall">The mean &#40;SD&#41; delay between rash onset and the initial GP visit was 6&#46;4 days &#40;18&#46;7&#41;&#46; Of the 403&#47;545 &#40;73&#46;9&#37;&#41; patients who reported having experienced one or more symptoms before rash onset&#44; 276&#47;403 &#40;68&#46;5&#37;&#41; reported prodromal pain&#44; 146&#47;403 &#40;36&#46;2&#37;&#41; reported malaise&#44; and 18&#47;403 &#40;4&#46;5&#37;&#41; reported fever &#40;<a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>&#41;&#46; Pre-existing co-morbidities were reported in 332&#47;545 patients &#40;60&#46;9&#37;&#41; at the initial visit&#46; Twenty-nine patients &#40;5&#46;3&#37; of the overall ATP cohort&#41; reported receiving immunosuppressive therapy within the previous 30 days&#44; the majority of whom &#40;58&#46;6&#37;&#41; received corticosteroids &#40;<a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><p id="p0095" class="elsevierStylePara elsevierViewall">ZBPI &#8216;worst pain&#8217; scores at the initial visit were recorded in 284&#47;545 patients &#40;52&#46;1&#37;&#41;&#46; Of these&#44; 132&#47;284 &#40;46&#46;5&#37;&#41; indicated severe pain &#40;7&#8211;10 score on the ZBPI &#8216;worst pain&#8217; score&#41;&#59; 19&#46;4&#37; of patients with available scores &#40;55&#47;284&#41; indicated having no or mild pain &#40;ZBPI score &#8804;<span class="elsevierStyleHsp" style=""></span>3&#41; &#40;<a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>&#41;&#46; Systemic antivirals were prescribed for 462&#47;545 patients with HZ &#40;84&#46;8&#37;&#41;&#44; either prior to the initial patient GP visit &#40;given during their previous medical care before initial GP assessment&#41; or prescribed by their GP&#59; most frequently valaciclovir &#40;28&#46;4&#37;&#41;&#44; brivudine &#40;27&#46;0&#37;&#41; and acyclovir &#40;24&#46;4&#37;&#41;&#46; A total of 56&#47;545 patients &#40;10&#46;3&#37;&#41; had one or more HZ-related complications &#40;excluding PHN&#41; across the study period&#59; including bacterial superinfection &#40;2&#46;8&#37;&#41;&#44; disseminated VZV &#40;2&#46;4&#37;&#41;&#44; with 5 patients having ocular&#47;ophthalmic complications&#46;</p></span><span id="s0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0090">The proportion of HZ patients in the prospective ATP study cohort developing PHN and their characteristics</span><p id="p0100" class="elsevierStylePara elsevierViewall">HZ-related pain&#44; based on ZBPI worst pain scores was assessed throughout the study period&#46; The proportion of patients completing the ZBPI questionnaire ranged across the study from 53&#46;4&#37; &#40;291&#47;545&#41; at Day 0 to 38&#46;9&#37; &#40;212&#47;545&#41; at Day 90&#59; the time point for PHN assessment&#46; Questionnaire completion compliance was greatest in patients aged &#8805;<span class="elsevierStyleHsp" style=""></span>80 years &#40;Supplementary Fig&#46; 1&#41;&#46; At Day 0&#44; the overall mean ZBPI &#8216;worst pain&#8217; score in the entire cohort was 5&#46;5 at Day 0 and decreased to 2&#46;0 by Day 30&#46; The worst pain score reduced more slowly in the oldest group &#40;<a class="elsevierStyleCrossRef" href="#f0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><p id="p0105" class="elsevierStylePara elsevierViewall">In the overall ATP cohort&#44; a ZBPI &#8216;worst pain&#8217; score &#8805;<span class="elsevierStyleHsp" style=""></span>3 at Day 90 was reported by 25&#47;545 patients&#59; the proportion of all patients &#8805;<span class="elsevierStyleHsp" style=""></span>50 years of age developing PHN was 4&#46;59&#37; &#40;95&#37; CI&#58; 2&#46;99&#8211;6&#46;70&#41;&#46; The PHN proportion was greater in older patients&#44; reaching 10&#46;0&#37; &#40;95&#37; CI&#58; 3&#46;76&#8211;20&#46;51&#41; in patients aged &#8805;<span class="elsevierStyleHsp" style=""></span>80 years&#44; and was higher in men &#40;6&#46;01&#37;&#59; 95&#37; CI&#58; 3&#46;32&#8211;9&#46;88&#41; than in women &#40;3&#46;53&#37;&#59; 95&#37; CI&#58; 1&#46;77&#8211;6&#46;22&#41; &#40;<a class="elsevierStyleCrossRef" href="#t0015">Table 3</a>&#41;&#46; Minor regional differences in the proportion of patients who developed PHN were observed&#59; occurring in 4&#46;8&#37; of patients in the Madrid and Barcelona GP networks and 3&#46;9&#37; and 4&#46;3&#37; in the two Valencia networks&#46;</p><elsevierMultimedia ident="t0015"></elsevierMultimedia><p id="p0110" class="elsevierStylePara elsevierViewall">When considering only those subjects &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>212&#41; with available ZBPI &#8216;worst pain&#8217; scores at Day 90&#44; then the proportion of patients with PHN was higher across all strata&#59; the overall proportion of patients &#8805;<span class="elsevierStyleHsp" style=""></span>50 years with PHN was 11&#46;79&#37; &#40;95&#37; CI&#58; 7&#46;78&#8211;16&#46;91&#41; and 22&#46;22&#37; &#40;95&#37; CI&#58; 8&#46;62&#8211;42&#46;26&#41; in patients aged &#8805;<span class="elsevierStyleHsp" style=""></span>80 years&#44; and higher in men &#40;12&#46;84&#37;&#59; 95&#37; CI&#58; 7&#46;20&#8211;20&#46;61&#41; than in women &#40;10&#46;68&#37;&#59; 95&#37; CI&#58; 5&#46;45&#8211;18&#46;31&#41; &#40;<a class="elsevierStyleCrossRef" href="#t0015">Table 3</a>&#41;&#46; For these subjects with available ZBPI &#8216;worst pain&#8217; scores at Day 90&#44; regional differences in the proportion of patients with</p><p id="p0115" class="elsevierStylePara elsevierViewall">PHN were apparent&#59; higher in GP networks in Centro de Salud Salvador Pau&#44; Valencia &#40;18&#46;7&#37;&#41; and Madrid &#40;15&#46;7&#37;&#41; and lower in the Barcelona &#40;9&#46;2&#37;&#41; and CSISP Valencia &#40;8&#46;0&#37;&#41; networks &#40;<a class="elsevierStyleCrossRef" href="#t0015">Table 3</a>&#41;&#46;</p><p id="p0120" class="elsevierStylePara elsevierViewall">The mean &#40;SD&#41; age of the 25 HZ patients with PHN was 69&#46;5 &#40;10&#46;3&#41; years &#40;range 50&#8211;91 years&#41;&#59; 44&#37; were women&#46; Most HZ characteristics at the initial visit&#44; and the prevalence of patient comorbidities were broadly comparable in patients with and without PHN&#46; However&#44; differences in pain severity at the initial visit were observed between those patients who developed PHN and those who did not&#59; no&#47;mild pain &#40;0&#37; and 26&#46;9&#37; respectively&#41;&#44; moderate pain &#40;42&#46;9&#37; and 31&#46;3&#37;&#41; and severe pain &#40;57&#46;1&#37; and 41&#46;9&#37;&#41;&#46; Subsequently&#44; in patients with PHN&#44; the mean &#8216;worst pain&#8217; score remained above 5 up to and including Day 150&#46; In contrast&#44; those patients not developing PHN showed a marked decline in mean &#8216;worst pain&#8217; score from Day 0 to Day 30&#44; falling from 5&#46;4 to 1&#46;6 &#40;<a class="elsevierStyleCrossRef" href="#f0010">Fig&#46; 2</a>&#41;&#46; Of the 25 patients with PHN&#44; 5 patients had PHN persisting until Day 180&#59; one patient had PHN persisting 270 days after rash onset&#46;</p><elsevierMultimedia ident="f0010"></elsevierMultimedia></span></span><span id="s0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0095">Discussion</span><p id="p0125" class="elsevierStylePara elsevierViewall">We found an overall HZ IR of 4&#46;88&#47;1&#44;000 PY in Spanish adults aged &#8805;<span class="elsevierStyleHsp" style=""></span>50 years presenting in primary care over a 12-month period across 3 different regional GP networks&#46; The incidence increased with age&#44; peaking in the 75&#8211;79 years age group&#46; We found that HZ incidence was similar in both genders&#44; although some differences were seen in different age-strata&#46;</p><p id="p0130" class="elsevierStylePara elsevierViewall">The HZ incidences we observed are somewhat lower than those reported in other European countries&#46; In the United Kingdom &#40;UK&#41;&#44; a retrospective primary care study found an incidence of 5&#46;2&#47;1&#44;000 PY in subjects aged &#8805;<span class="elsevierStyleHsp" style=""></span>50 years&#44;<a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a> whereas recent prospective studies have reported incidence in &#8805;<span class="elsevierStyleHsp" style=""></span>50 year-olds of 6&#46;7&#47;1&#44;000 PY in Germany<a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a> and 6&#46;5&#47;1&#44;000 PY in Italy&#46;<a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a> Previous studies in Spain also report somewhat higher incidence in subjects &#8805;<span class="elsevierStyleHsp" style=""></span>50 years than we observed&#46;<a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> In a relatively small prospective study from Valencia&#44; the annual incidence of HZ ranged from 6&#46;7 per 1&#44;000 inhabitants in patients 50&#8211;59 years of age to 11&#46;1 per 1&#44;000 in those aged &#8805;<span class="elsevierStyleHsp" style=""></span>70 years&#44;<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> while a large retrospective study from this same region reported an IR of 7&#46;2&#47;1&#44;000 PY in those aged &#8805;<span class="elsevierStyleHsp" style=""></span>50 years&#46;<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> Reported incidence in Catalonia ranges from 5&#46;9 per 1&#44;000 aged between 50&#8211;54 years to 9&#46;6 per 1&#44;000 in those aged 70&#8211;74 years&#46;<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a> Most studies&#44; including several recent prospective studies in the primary care setting have also consistently reported higher incidence for women across all age groups&#44;<a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bb0135"><span class="elsevierStyleSup">27&#8211;29</span></a> with higher incidence in females also reported in previous studies from Spain&#46;<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> We have no specific explanation for the relatively lower HZ incidence observed in the present study&#44; nor for our relatively comparable rates in men and women&#44; or for the differences in incidence observed in different regions&#46; In reality&#44; methodological differences may account for some aspects&#46; Previous data from Spain are primarily drawn from retrospective analyses&#44; and it is possible that in our prospective study&#44; not all eligible cases were included&#46; Possible explanations for such underreporting exist&#59; some patients with milder HZ may not have attended for GP care within the relatively narrow inclusion timeframe &#40;within 7 days of rash onset&#41;&#44; while others may have been managed in alternative medical care facilities out with the GP network&#46;</p><p id="p0135" class="elsevierStylePara elsevierViewall">We also evaluated a broader group of 545 patients presenting with HZ in primary care and prospectively assessed the proportion developing PHN&#46; We found that 25 patients &#40;4&#46;6&#37;&#41; developed PHN&#44; although the proportion was greater in older patients &#40;10&#37; in those aged &#8805;<span class="elsevierStyleHsp" style=""></span>80 years&#41;&#44; and higher in men than in females &#40;6&#37; and 3&#46;5&#37; respectively&#41;&#46; These estimates are lower than those reported in other recent studies &#40;using the same PHN definition we used&#41;&#44; where the overall PHN proportion in patients &#8805;<span class="elsevierStyleHsp" style=""></span>50 years has been reported as 11&#46;9&#37; in Germany&#44;<a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a> 9&#46;1&#37; in the UK&#44;<a class="elsevierStyleCrossRef" href="#bb0145"><span class="elsevierStyleSup">29</span></a> and 10&#46;2&#37; in Italy&#46;<a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a> They are also lower than reported in previous Spanish studies&#46; A retrospective database analysis of HZ patients &#8805;<span class="elsevierStyleHsp" style=""></span>50 years of age conducted in the Valencia region reported that 15&#46;7&#37; developed PHN&#59;<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a> in Catalonia the proportion of HZ patients with PHN has been reported as 12&#46;3&#37; in 50&#8211;59 year-olds and 17&#46;5&#37; in those aged &#8805;<span class="elsevierStyleHsp" style=""></span>70 years&#46;<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a></p><p id="p0140" class="elsevierStylePara elsevierViewall">A limitation of the present study was the need to have ZBPI pain scores at Day 90 to determine PHN occurrence in the overall ATP cohort&#44; with only 212&#47;545 patients &#40;38&#46;9&#37;&#41; providing this information&#46; When evaluating PHN proportions only in those patients with available ZBPI pain scores at Day 90&#44; the proportion of HZ patients &#8805;<span class="elsevierStyleHsp" style=""></span>50 years who developed PHN was 11&#46;8&#37;&#46; The corresponding incidences in different age-strata were also higher&#46; These data are more in line with data reported elsewhere&#46; We recognize that failure to return the ZBPI at Day 90 may indicate absence of pain at this timepoint&#44; and so this analytical perspective may be subject to some bias&#59; however&#44; other reasons may have also been responsible for study drop-out&#46; The true frequency of PHN in our cohort remains subject to some uncertainty&#46; We did observe a higher proportion PHN development in males than females&#44; which is contrary to results from similar prospective studies in Italy and Germany&#44;<a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a> and also contrary to data from retrospective studies in Spain and elsewhere&#46;<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0150"><span class="elsevierStyleSup">30</span></a> This reflect the relatively small number of PHN cases we observed and associated wide and overlapping CIs between the male and female PHN proportions&#46;</p><p id="p0145" class="elsevierStylePara elsevierViewall">Our study has a number of additional limitations&#46; The study population denominators used in incidence estimations were adjusted to account for the proportion of time when GPs were not actively reporting HZ cases during the study period&#44; and the assumptions made in calculating these denominators are subject to some uncertainty&#46; Our study populations &#40;for both the incidence estimations and for the proportion with PHN development&#41; include patients presenting in primary care and also those attending their GP as a secondary consultation after presenting elsewhere &#40;including the emergency department and after hospitalization&#41;&#46; Although the majority of HZ cases presented in primary care&#44; as we have reported elsewhere&#44; a small number were hospitalized or attended the emergency department&#46;<a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a> It is possible that differences exist between such cases and those initially presenting to their GP&#44; and this may have influenced the incidence rates and proportions developing PHN we report&#46; Similarly&#44; patient comorbidities would also have an influence&#46; Evaluation of the relative impact of these aspects on incidence and PHN development values was beyond the scope of the present study&#46; In addition&#44; our population comprised subjects with an episode of acute HZ&#44; not necessarily a first episode &#40;and so could include cases of recurrent HZ&#41;&#59; again&#44; we did not evaluate differences in incidence or PHN development between these groups&#46; Our study findings should be interpreted in the context of all these limitations&#46;</p></span><span id="s0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0100">Conclusions</span><p id="p0150" class="elsevierStylePara elsevierViewall">This is one of the few prospective studies of the epidemiology of HZ in Spain&#44; conducted in several regions of the country&#46; The HZ incidence in Spanish individuals aged &#8805;<span class="elsevierStyleHsp" style=""></span>50 years we observed is lower than that previously described in Spain and elsewhere&#46; However&#44; in line with previous studies&#44; we also observed increasing incidence with increasing age&#46; PHN was the most frequent HZ-related complication&#44; especially in patients aged &#8805;<span class="elsevierStyleHsp" style=""></span>80 years&#46; <a class="elsevierStyleCrossRef" href="#f0015">Fig&#46; 3</a> presents a plain language summary of the context&#44; outcomes&#44; and impact of this study&#46;</p><elsevierMultimedia ident="f0015"></elsevierMultimedia></span><span id="s0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0105">Data statement</span><p id="p0155" class="elsevierStylePara elsevierViewall">Anonymized individual participant data and study documents can be requested for further research from <a href="http://www.clinicalstudydatarequest.com">www&#46;clinicalstudydatarequest&#46;com</a>&#46;</p></span><span id="s0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0110">Statement on prior presentation</span><p id="p0160" class="elsevierStylePara elsevierViewall">Some of the material has been previously presented as an oral presentation at the Asociaci&#243;n Espa&#241;ola de Vacunolog&#237;a &#40;AEV&#41; National congress&#44; Valencia&#44; Spain&#44; 2017&#46;</p></span><span id="s0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0115">Funding source</span><p id="p0165" class="elsevierStylePara elsevierViewall">This study was fully funded by GlaxoSmithKline Biologicals SA &#40;<a href="http://ClinicalTrials.gov">ClinicalTrials&#46;gov</a>&#58; NCT01521286&#41; and all costs related to the development and publication of this manuscript&#46;</p></span><span id="s0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0120">Declaration of interests</span><p id="p0170" class="elsevierStylePara elsevierViewall">The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper&#46;</p><p id="p0175" class="elsevierStylePara elsevierViewall">LGC declares having received funds from the GSK group of companies during the conduct of the study&#46; TC declares no financial and non-financial relationships and activities and no conflicts of interest&#46; MDRC&#44; JAGM and KG are employed by the GSK group of companies&#44; and MDRC holds shares in the GSK group of companies&#46; MLS and BS were employed by the GSK group of companies at the time of the study&#46; JDD reports study grant and personal fees from the GSK group of companies&#46; All authors declare no other financial and non-financial relationships and activities&#46;</p></span></span>"
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              "titulo" => "Overall incidence of HZ &#40;incidence cohort&#41;"
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              "titulo" => "The proportion of HZ patients in the prospective ATP study cohort developing PHN and their characteristics"
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        "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Introduction</span><p id="sp0065" class="elsevierStyleSimplePara elsevierViewall">Herpes zoster &#40;HZ&#41; chiefly affects older individuals and the immunocompromised and may lead to persistent pain&#44; postherpetic neuralgia &#40;PHN&#41;&#44; and other complications&#46;</p></span> <span id="as0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Methods</span><p id="sp0070" class="elsevierStyleSimplePara elsevierViewall">From 2012&#8211;2015&#44; we conducted a prospective observational cohort study of adults &#8805;<span class="elsevierStyleHsp" style=""></span>50 years with HZ presenting in primary care in Spain &#40;NCT01521286&#41;&#46; We estimated HZ incidence rates &#40;IR&#41; per 1&#44;000 person-years &#40;PY&#41; over a 12-month period&#44; and prospectively followed up a broader patient cohort&#59; assessing pain severity using the &#8216;Zoster Brief Pain Inventory &#40;ZBPI&#41; and PHN development &#40;defined as ZBPI &#8216;worst pain&#8217; &#8805;<span class="elsevierStyleHsp" style=""></span>3 at Day 90&#41;&#46;</p></span> <span id="as0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Results</span><p id="sp0075" class="elsevierStyleSimplePara elsevierViewall">HZ IR in adults &#8805;<span class="elsevierStyleHsp" style=""></span>50 years was 4&#46;88&#47;1&#44;000 PY &#40;95&#37; confidence interval &#91;CI&#93;&#58; 4&#46;44&#8211;5&#46;35&#41;&#44; similar for both genders&#46; Incidence increased with age&#44; from 2&#46;54 &#40;95&#37; CI&#58; 1&#46;84&#8211;3&#46;41&#41; in 50&#8211;54-year-olds to 6&#46;40&#47;1&#44;000 PY &#40;95&#37; CI&#58; 4&#46;86&#8211;8&#46;28&#41; in 75&#8211;79-year-olds&#46; In 545 HZ patients followed prospectively&#44; the proportion of HZ patients with PHN was 4&#46;59&#37; &#40;95&#37; CI&#58; 2&#46;99&#8211;6&#46;70&#41;&#59; and 11&#46;79&#37; &#40;95&#37; CI&#58; 7&#46;78&#8211;16&#46;91&#41; in those 212 patients with available ZBPI scores at Day 90&#46; The proportion of patients developing PHN increased with increasing age&#46; Mean ZBPI &#8216;worst pain&#8217; scores in patients not developing PHN showed a marked decline between Day 0&#8211;30 &#40;from 5&#46;4 to 1&#46;6&#41; and none at Day 90&#59; in patients with PHN this score remained high &#40;&#62;<span class="elsevierStyleHsp" style=""></span>5&#46;5&#41; up to Day 150&#46; Other complications were observed in 10&#46;3&#37; of patients&#46;</p></span> <span id="as0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Conclusions</span><p id="sp0080" class="elsevierStyleSimplePara elsevierViewall">HZ presents a considerable burden in adults aged &#8805;<span class="elsevierStyleHsp" style=""></span>50 years in Spain&#44; with an IR of ~<span class="elsevierStyleHsp" style=""></span>5&#47;1&#44;000 PY&#46; HZ and PHN risk increased with age&#46;</p></span>"
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        "resumen" => "<span id="as1025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st1035">Introducci&#243;n</span><p id="sp1085" class="elsevierStyleSimplePara elsevierViewall">El herpes zoster &#40;HZ&#41; afecta principalmente a individuos mayores e inmunocomprometidos&#44; pudiendo originar dolor persistente&#44; neuralgia postherp&#233;tica &#40;PHN&#41;&#44; y otras complicaciones&#46;</p></span> <span id="as2030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st9040">M&#233;todos</span><p id="sp9090" class="elsevierStyleSimplePara elsevierViewall">De 2012 a 2015&#44; realizamos un estudio observacional prospectivo de cohorte de adultos &#8805;50 con HZ&#44; que acudieron a atenci&#243;n primaria en Espa&#241;a &#40;NCT01521286&#41;&#46; Calculamos las tasas de incidencia &#40;TI&#41; del HZ por 1&#46;000 personas&#47;a&#241;o &#40;PA&#41; durante un periodo de 12 meses&#44; y realizamos el seguimiento prospectivo de una cohorte de pacientes m&#225;s amplia&#44; evaluando la severidad del dolor utilizando la escala ZBPI &#40;Zoster Brief Pain Inventory&#41; y el desarrollo de PHN &#40;definida como puntuaci&#243;n &#8805;3 de &#8220;peor dolor&#8221; ZBPI al 90&#186; d&#237;a&#41;&#46;</p></span> <span id="as8035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st8045">Resultados</span><p id="sp8095" class="elsevierStyleSimplePara elsevierViewall">La TI de HZ en adultos &#8805;50 a&#241;os fue de 4&#44;88&#47;1&#46;000 PA &#40;95&#37; de intervalo de confianza &#91;IC&#93;&#58; 4&#44;44 -5&#44;35&#41;&#44; similar para ambos sexos&#46; La incidencia increment&#243; con la edad&#44; de 2&#44;54 &#40;95&#37; IC&#58; 1&#44;84 -3&#44;41&#41; en los individuos de 50 -54 a&#241;os de edad&#44; a 6&#44;40&#47;1&#46;000 PA &#40;95&#37; IC&#58; 4&#44;86 -8&#44;28&#41; en los individuos de 75 -79 a&#241;os&#46; En 545 pacientes de HZ seguidos prospectivamente&#44; la proporci&#243;n de pacientes de HZ con PHN fue del 4&#44;59&#37; &#40;95&#37; IC&#58; 2&#44;99 -6&#44;70&#41;&#44; y del 11&#44;79&#37; &#40;95&#37; IC&#58; 7&#44;78 -16&#44;91&#41; en aquellos 212 pacientes con puntuaciones ZBPI disponibles al 90&#186; d&#237;a&#46; La proporci&#243;n de pacientes que desarrollaron PHN increment&#243; al incrementarse la edad&#46; Las puntaciones ZBPI &#8220;de peor dolor&#8221; medias en los pacientes que no desarrollaron PHN reflejaron una reducci&#243;n notable entre los d&#237;as 0 y 30 &#40;de 5&#44;4 a 1&#44;6&#41;&#44; y ninguna al 90&#186; d&#237;a&#46; En los pacientes con PHN esta puntuaci&#243;n sigui&#243; siendo alta &#40;&#62;5&#44;5&#41; hasta el d&#237;a 150&#186;&#46; Se observaron otras complicaciones en el 10&#44;3&#37; de los pacientes&#46;</p></span> <span id="as9040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st9050">Conclusiones</span><p id="sp9100" class="elsevierStyleSimplePara elsevierViewall">HZ presenta una carga considerable en los adultos &#8805;50 a&#241;os de edad en Espa&#241;a&#44; con una TI de ~5&#47;1&#46;000 PA&#46; HZ y el riesgo de PHN se incrementaron con la edad&#46;</p></span>"
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        "etiqueta" => "Fig&#46; 1"
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        "mostrarFloat" => true
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          0 => array:4 [
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            "Ancho" => 1896
            "Tamanyo" => 121817
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          0 => array:3 [
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          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Mean ZBPI worst pain scores over time by age group &#40;ATP cohort&#41;</p> <p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">ATP &#61; According to protocol&#59; YOA &#61; Years of age&#59; ZBPI &#61; Zoster brief pain inventory&#46;</p>"
        ]
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        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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            "Alto" => 908
            "Ancho" => 1896
            "Tamanyo" => 89226
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0010"
            "detalle" => "Fig&#46; "
            "rol" => "short"
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        "descripcion" => array:1 [
          "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Mean ZBPI Worst pain score over time for all HZ cases and PHN cases &#40;ATP cohort&#41;</p> <p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">ATP &#61; According to protocol&#59; HZ &#61; Herpes zoster&#59; PHN &#61; Postherpetic neuralgia&#59; ZBPI &#61; Zoster brief pain inventory&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "f0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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            "Alto" => 884
            "Ancho" => 1021
            "Tamanyo" => 139873
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            "detalle" => "Fig&#46; "
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          "en" => "<p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">Plain Language summary&#46;</p>"
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          "leyenda" => "<p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">CI &#61; Exact Poisson confidence interval&#59; N &#61; number of patients&#59; PY &#61; person-years</p>"
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            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age group &#40;years&#41;</th><th class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_colgroup " colspan="3" align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Female</th><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="3" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Male</th><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="3" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Overall</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Incidence per 1&#44;000 PY&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95&#37; CI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Incidence per 1&#44;000 PY&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95&#37; CI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Incidence per 1&#44;000 PY&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95&#37; CI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">2&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">1&#46;53&#8211;3&#46;70&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">2&#46;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&#46;65&#8211;3&#46;99&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">44&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">2&#46;54&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&#46;84&#8211;3&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">55&#8211;59&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">38&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">4&#46;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">3&#46;37&#8211;6&#46;54&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">3&#46;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">2&#46;29&#8211;5&#46;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">4&#46;19&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">3&#46;22&#8211;5&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">60&#8211;64&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">4&#46;92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">3&#46;43&#8211;6&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">3&#46;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">2&#46;36&#8211;5&#46;58&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">58&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">3&#46;31&#8211;5&#46;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">65&#8211;69&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">43&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6&#46;15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&#46;45&#8211;8&#46;28&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">34&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">5&#46;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">3&#46;94&#8211;7&#46;95&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">5&#46;94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">4&#46;69&#8211;7&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">70&#8211;74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">3&#46;88&#8211;7&#46;92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">6&#46;96&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  """
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          "leyenda" => "<p id="sp0045" class="elsevierStyleSimplePara elsevierViewall">ATP &#61; According to protocol&#59; HZ &#61; Herpes zoster&#59; n &#61; Number of patients concerned&#59; N<span class="elsevierStyleSup">1</span> &#61; The number of patients with initial pain assessment &#40;for 261 patients&#44; the initial pain assessment was missing&#41;&#59; N<span class="elsevierStyleSup">2</span> &#61; The number of patients with symptoms before rash onsets&#59; N<span class="elsevierStyleSup">3</span> &#61; The number of patients with comorbidities&#59; N<span class="elsevierStyleSup">4</span> &#61;<span class="elsevierStyleHsp" style=""></span>The number of patients receiving immunosuppressive&#47;immunomodulatory treatment at initial visit</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n
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                  \t\t\t\t">N<span class="elsevierStyleSup">1</span> &#61; 284</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">No or mild&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">55&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">19&#46;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">Moderate&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">46&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with symptoms before rash onset&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N<span class="elsevierStyleSup">2</span> &#61; 403</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prodromal pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">68&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Malaise&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">146&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">36&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Other symptoms - non-painful&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">82&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Other symptoms &#8211; painful&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with comorbidities at initial visit<a class="elsevierStyleCrossRef" href="#tf0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N<span class="elsevierStyleSup">3</span> &#61; 332</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">137&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Current emotional problems&#44; stress or depression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diabetes mellitus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chronic respiratory disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Neoplasm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal failure&#44; dialysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients under immunological treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N<span class="elsevierStyleSup">4</span> &#61; 29</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral or parenteral corticosteroids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "identificador" => "tf0005"
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              "nota" => "<p class="elsevierStyleNotepara" id="np0005">Most frequent pre-existing conditions &#40;occurring in &#62;<span class="elsevierStyleHsp" style=""></span>5&#37; of patients with comorbidities&#41;&#46;</p>"
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          "en" => "<p id="sp0040" class="elsevierStyleSimplePara elsevierViewall">Pain severity and clinical characteristics of the herpes zoster patients in the ATP cohort at initial visit&#46;</p>"
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      5 => array:8 [
        "identificador" => "t0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="sp0055" class="elsevierStyleSimplePara elsevierViewall">ATP &#61; According to protocol&#59; CI &#61; Confidence interval&#59; CSISP &#61; Centro Superior de Investigacion en Salud P&#250;blica&#59; GP &#61; General practitioner&#59; HZ &#61; Herpes zoster&#59; PHN &#61; Postherpetic neuralgia&#59; ZBPI &#61; Zoster Brief Pain Inventory</p><p id="sp0060" class="elsevierStyleSimplePara elsevierViewall">N<span class="elsevierStyleSup">1</span> &#61; number of HZ patients in the overall ATP cohort&#59; N<span class="elsevierStyleSup">2</span> &#61; number of HZ patients completing the ZBPI questionnaire at Day 90&#59; n &#61; number of HZ patients with PHN &#40;defined as ZBPI &#8216;worst pain score &#8805;<span class="elsevierStyleHsp" style=""></span>3 at Day 90&#41;&#59; &#37; &#61; percentage of patients with PHN</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="4" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Overall ATP cohort&#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>545&#41;</th><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="4" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients with completed ZBPI questionnaire at Day 90&#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>212&#41;</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N<span class="elsevierStyleSup">1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95&#37; CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95&#37; CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age groups&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>50&#8211;54 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;37&#8211;10&#46;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;07&#8211;28&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>55&#8211;59 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;04&#8211;7&#46;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;10&#8211;19&#46;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>60&#8211;64 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6&#46;67&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;49&#8211;13&#46;95&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">39&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">15&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">5&#46;86&#8211;30&#46;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>65&#8211;69 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">4&#46;00&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">1&#46;10&#8211;9&#46;93&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">38&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">10&#46;53&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">2&#46;94&#8211;24&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>70&#8211;74 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">6&#46;98&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">2&#46;60&#8211;14&#46;57&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">34&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">17&#46;65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">6&#46;76&#8211;34&#46;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>75&#8211;79 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;00&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;00&#8211;4&#46;99&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;00&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;00&#8211;13&#46;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>80 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">60&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">10&#46;00&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&#46;76&#8211;20&#46;51&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">22&#46;22&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8&#46;62&#8211;42&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>All &#8805;<span class="elsevierStyleHsp" style=""></span>50 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">545&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7&#46;78&#8211;16&#46;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gender&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">312&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">3&#46;53&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;77&#8211;6&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">103&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">10&#46;68&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">5&#46;45&#8211;18&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">233&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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        "texto" => "<p id="p0185" class="elsevierStylePara elsevierViewall">The authors would like to thank all study participants&#46; They would also like to thank Beatriz Becerro de Bengoa for coordination of data collection&#44; as well as Amit Bhavsar &#40;GSK&#41; for his contributions during manuscript development&#46; The authors would also wish to thank Business &#38; Decision Life Sciences platform for editorial assistance and publications coordination&#44; on behalf of GSK&#59; Matthieu Depuydt&#44; Aur&#233;lie Roth&#44; Elena Chaves Rodriguez and Diego Collin coordinated publication development and editorial support&#46; The authors also thank Niels Neymark &#40;of Neymark Scientific Writing SCS&#41; and Iain O&#8217;Neill &#40;freelance on behalf of GSK&#41; for providing medical writing support&#46;</p>"
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Article information
ISSN: 15769887
Original language: English
DOI:10.1016/j.vacun.2022.01.006
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