39 research outputs found
Impact of rotavirus vaccination on seizure hospitalizations in children: A systematic review
Background: Previous studies found conflicting results about the effect of rotavirus (RV) vaccination on
seizure hospitalizations in children younger than 5 years old.
Objectives: To evaluate the evidence of the impact of RV vaccination on the prevention of seizure hospitalizations in children.
Methods: A systematic review was conducted in the electronic database MEDLINE of all observational
studies in children younger than 5 years old published since 2006. Two reviewers performed title/abstract, full-text review, and data extraction.
Results: Thirteen studies met eligibility criteria. Nine studies reported a significant reduction in seizure
hospitalizations upon RV vaccine introduction, three studies reported an absence of significant impact,
and one study reported a significant rise in seizure hospitalization after the introduction of RV vaccines.
Limitations: The great variability between study designs, case definitions and potential biases prevent
quantifying the impact of RV vaccination against seizure hospitalizations.
Conclusions: RV vaccination might prevent seizure hospitalizations in children; however, robust, and
well-designed studies are needed to better determine the strength of this associationMedicin
Herpes zoster risk and burden of disease in immunocompromised populations: a population-based study using health system integrated databases, 2009–2014
Background: Estimate the incidence of herpes zoster (HZ), its complications and healthcare utilization rates in
adults (≥ 18-years-old) with a wide range of immunocompromised (IC) conditions compared to IC-free cohort.
Method: A population-based retrospective study using the Valencia healthcare Integrated Databases (VID) (2009–
2014). HZ and IC were defined using ICD-9 codes in primary care (PC) and hospitalization registers. Incidence rates
(IR), risk of HZ, HZ-recurrence, HZ-complications and healthcare utilization rates were estimated in the IC-cohort
compared to IC-free.
Results: The study population consisted of 4,382,590 subjects, of which 578,873 were IC (13%). IR (in 1000
persons-year) of HZ overall, in IC and in IC-free cohort was 5.02, 9.15 and 4.65, respectively. IR of HZ
increased with age in both cohorts and it was higher for all IC conditions studied, reaching up to twelvefold
in subjects with stem cell transplantation. IC subjects had 51% higher risk of developing HZ, 25% higher HZrecurrence and the risk of HZ-complications was 2.37 times higher than in IC-free. HZ-related healthcare
utilization was higher in the IC-cohort than in IC-free (number of hospitalizations 2.93 times greater, hospital
stays 12% longer, 66% more HZ-specialist visits, 2% more PC visits, sick leaves 18% longer and 20% higher
antiviral dispensation).
Conclusions: Patients suffering from all the IC conditions studied are at higher risk of developing HZ, HZrecurrence and post-herpetic complications, which implies a substantial morbidity and a high consumption of
resources. These results should be considered for vaccine policy implementation.Funding for this study was provided by GlaxoSmithKline Biologicals SA (GSK study identifier 207685). GlaxoSmithKline Biologicals SA was provided the opportunity to review a preliminary version of this manuscript for factual accuracy but the authors are solely responsible for final content and interpretation. The Company (GSK) had no role in the analysis or discussion of the results.Medicin
Epidemiology of schizophrenia and its management over 8-years period using real-world data in Spain
Background: Real-World Data (RWD) studies provide important insights in disease epidemiology, in real clinical
populations, with long follow-up periods. The aim of the present study was to describe the epidemiology of
schizophrenia spectrum disorders (SD) during an 8-year period in Spain.
Methods: A retrospective cohort of subjects aged 15 to 64 years was followed-up using electronic healthcare
databases of the Valencia region (2008–2015). SD cases included outpatient and inpatient settings (ICD 9 codes
295.XX). Prevalence of SD was assessed. Incidence rate (IR) in the subpopulation aged between 15 and 34 years was
also provided. Healthcare utilization (HCU) rates, including outpatient, specialists, hospitalizations and antipsychotic
dispensations were estimated.
Results: The cohort included 3,976,071 subjects; 24,749 of them had a prevalent diagnosis of SD. The overall prevalence
for SD was 6.2 per 1000 persons. SD were 76% more prevalent in men than women. IR in the subpopulation aged
between 15 and 34 years was 50.25 per 100,000 persons years and was more than 2 times higher for men than for
women. 83.4% of the overall outpatient visits from the cohort of patients were related to SD. The 21,095 overall
hospitalizations with the SD code resulted in 286,139 days of hospitalization, with a median of 4 days (IQR: 1.6–9.2) per
person-year. 93.2% of subjects diagnosed with SD were ever treated with some antipsychotic drug during the study
period, and 70% of the patients were ever treated with antipsychotic polypharmacy.
Conclusions: This large population-based study using RWD provides novel and recent information SD in a southern
European country. The prevalence and IR of SD showed is greater than previously published and higher in men than in
women. The fact of having used a large arsenal of electronic data (including outpatient and inpatient) for 8 years may
have influenced. SD represents high burden and healthcare utilization. Contrary to guidelines recommendations the
majority of patients were ever treated with antipsychotic polypharmacy.This study was supported by Janssen pharmaceutical. The company had no role in the analysis or discussion of the resultMedicin
Human papillomavirus vaccines effectiveness to prevent genital warts: A population-based study using health system integrated databases, 2009-2017.
Objectives: To assess the effectiveness of the HPV vaccines in preventing genital warts (GW) in women
aged 14–23 years and to estimate the incidence of GW in the whole population aged from 14 to 65.
Design: Population-based retrospective cohort study using real-world data from the Valencia health system Integrated Databases (VID).
Study population: All subjects aged 14–65 years residing in the Valencia Region during 2009–2017
(n = 4,492,724), including a cohort of 563,240 females aged 14–23 years followed-up for the vaccine
effectiveness (VE) estimations.
Main outcome measures: Incident cases of GW defined as the first activation of GW-related codes (ICD-9-
CM 078.11 or ICD-10-CM A63.0) in hospital, primary and specialized care during the study period.
Adjusted VE was estimated as (1-Relative Risk (RR)) 100 by a negative binomial Bayesian model.
Results: There were 23,049 cases of GW in the overall population and 2,565 in the females’ cohort 14–
23 years old. The incidence rate (IR) (in 100,000 persons-year) was 69.1 (95% CI 68.21–69.99) in the population overall, being higher in men (72.73; 95% CI 71.45–74.04). The IR of GW was 104.08 (95% CI
100.79–108.94) in the cohort of young women. The RR of GW increased with age from 14 to 21 years,
reaching a plateau from 21 to 23. The VE of a complete schedule was 74% (95% CrI 68–79) for quadrivalent HPV vaccine (HPV4v). No effectiveness was seen with a full vaccination course with the bivalent HPV
vaccine (HPV2v) in girls up to 21 years old. GW IR tends to be higher in unvaccinated cohorts covered by
HPV4v vaccine than in unvaccinated cohorts not covered by HPV4v vaccine.
Conclusions: A complete HPV4v vaccination schedule was 74% effective in reducing GW in our population. Our results also suggest an indirect protection to unvaccinated and HPV2v vaccinated girlsThis study has been funded by MSD. MSD had no role in the design, collection, analysis, interpretation of the data and writing of the article, and had no access to the data. MSD did not intervene in the decision to submit the manuscript for publication.Medicin
Disposition of d-penicillamine, a promising drug for preventing alcohol-relapse. Influence of dose, chronic alcohol consumption and age: studies in rats
Pharmacokinetic studies concerning D-penicillamine (an acetaldehyde sequestering
agent) are scarce and have not evaluated the influence of chronic ethanol consumption and age on
its disposition. Since recent preclinical studies propose D-penicillamine as a promising treatment
for alcohol relapse, the main aim of the present work was to evaluate the influence of these two factors on D-penicillamine disposition in order to guide future clinical studies on the anti-relapse efficacy
of this drug in alcoholism. Additionally, the effect of the administered dose was also evaluated. To
this end, three studies were carried out. Study 1 assessed the influence of dose on D-penicillamine disposition, whereas studies 2 and 3 evaluated, respectively, the influence of chronic alcohol consumption and age. Rapid intravenous administrations of 2, 10 and 30 mg/kg of D-penicillamine were
performed using young or adult ethanol-naïve rats or adult ethanol-experienced (subjected to a
long-term ethanol self-administration protocol) rats. Pharmacokinetic parameters were derived from
the biexponential model. Statistical analysis of CL, normalized AUC0
∞, V1 and k10 revealed that disposition, in the range plasma concentrations assayed, is non-linear both in young ethanol-naïve and in
adult ethanol-experienced rats. Notably, no significant changes in t1/2 were detected. Chronic ethanol
consumption significantly reduced CL values by 35% without affecting t1/2. D-Penicillamine disposition was equivalent in young and adult animals. In conclusion, although DP pharmacokinetics is
non-linear, the lack of significant alterations of the t1/2 would potentially simplify the clinical use
of this drug. Chronic consumption of ethanol also alters D-penicillamine disposition but, again, does
not modify t1/2. Copyright © 2014 John Wiley & Sons, Ltd.Peer ReviewMedicin
Disposition of d-penicillamine, a promising drug for preventing alcohol-relapse. Influence of dose, chronic alcohol consumption and age: studies in rats
Pharmacokinetic studies concerning d-penicillamine (an acetaldehyde sequestering agent) are scarce and have not evaluated the influence of chronic ethanol consumption and age on its disposition. Since recent preclinical studies propose d-penicillamine as a promising treatment for alcohol relapse, the main aim of the present work was to evaluate the influence of these two factors on d-penicillamine disposition in order to guide future clinical studies on the anti-relapse efficacy of this drug in alcoholism. Additionally, the effect of the administered dose was also evaluated. To this end, three studies were carried out. Study 1 assessed the influence of dose on d-penicillamine disposition, whereas studies 2 and 3 evaluated, respectively, the influence of chronic alcohol consumption and age. Rapid intravenous administrations of 2, 10 and 30 mg/kg of d-penicillamine were performed using young or adult ethanol-naïve rats or adult ethanol-experienced (subjected to a long-term ethanol self-administration protocol) rats. Pharmacokinetic parameters were derived from the biexponential model. Statistical analysis of CL, normalized AUC0∞, V1 and k10 revealed that disposition, in the range plasma concentrations assayed, is non-linear both in young ethanol-naïve and in adult ethanol-experienced rats. Notably, no significant changes in t1/2 were detected. Chronic ethanol consumption significantly reduced CL values by 35% without affecting t1/2. d-Penicillamine disposition was equivalent in young and adult animals. In conclusion, although DP pharmacokinetics is non-linear, the lack of significant alterations of the t1/2 would potentially simplify the clinical use of this drug. Chronic consumption of ethanol also alters d-penicillamine disposition but, again, does not modify t1/2
Data Resource Profile: The Valencia Health System Integrated Database (VID)
The Valencia Health System Integrated Database (VID) is a set of multiple, public, population-wide electronic databases for the Valencia Region, the fourth most populated Spanish region, with ∼5 million inhabitants and an annual birth cohort of 48 000 newborns, representing 10.7% of the Spanish population and around 1% of the European population. The VID provides exhaustive longitudinal information including sociodemographic and administrative data (sex, age, nationality, etc.), clinical (diagnoses, procedures, diagnostic tests, imaging, etc.), pharmaceutical (prescription, dispensation) and healthcare utilization data from hospital care, emergency departments, specialized care (including mental and obstetrics care), primary care and other public health services. It also includes a set of associated population databases and registries of significant care areas such as cancer, rare diseases, vaccines, congenital anomalies, microbiology and others, and also public health databases from the population screening programmes. All the information in the VID databases can be linked at the individual level through a single personal identification code. The databases were initiated at different moments in time (see details in the Data collected section), but all in all the VID provides comprehensive individual-level data fed by all the databases from 2008 to date.Medicin
The impact of childhood RSV infection on children’s and parents’ quality of life: a prospective multicenter study in Spain
Background: Several immunisation candidates against RSV are in late-stage clinical trials. To evaluate the benefts
of a potential vaccination programme, both economic and health benefts will be needed. Health benefts are usually
measured in Health-related Quality of Life (HRQoL) loss using standardised questionnaires. However, there are no
RSV-specifc questionnaires validated for children under 2 years, in whom most RSV episodes occur. Therefore, HRQoL
estimates are taken from literature or inadequate tools. We determined HRQoL loss and direct costs due to an RSV
episode in children younger than 2 years and their caregivers during a month of follow up, using a new questionnaire
administered online.
Methods: An observational prospective multicentre surveillance study was conducted in children aged younger
than two years. Children were recruited from 8 primary care centres and 1 hospital in the Valencia region and Cata‑
lonia (Spain). RSV-positive cases were obtained by immunochromatographic test. HRQoL was assessed using a new
ad-hoc 38 item-questionnaire developed. Parents of infected children completed 4 questionnaires at four timepoints
(day 0, 7, 14 and 30) after diagnosis.
Results: 117 children were enrolled in the study and 86 (73.5%) were RSV+. Median (interquartile range; IQR)
scores were 0.52 (0.42–0.68), 0.65 (0.49–0.79), 0.82 (0.68–0.97) and 0.94 (0.81–1), for days 0, 7, 14 and 30, respectively.
Compared to total recovery (Q30), HRQoL loss was 37.5%, 31.5% and 8.9% on days 0, 7 and 14 since diagnosis of the
disease. The total median cost per patient (including treatments) was €598.8 (IQR: 359.63–2425.85).
Conclusions: RSV had almost 40% impact on HRQoL during the frst week since onset of symptoms and the median
cost per episode and patient was about €600. These results represent a substantial input for health-economic evalua‑
tions of future RSV-related interventions such as vaccination.This study was funded by Conselleria d’Educació, Cultura i Esport of The Valencia Region of Spain.Medicin
Real-world impact of rotavirus vaccination in European healthcare settings: a systematic literature review
Introduction: Rotavirus is one of the most common pathogens causing diarrhea in children <5 years
and has a major impact on childhood morbidity and mortality. Since the implementation of rotavirus
vaccines into childhood immunization programs across Europe, there has been a reduction in rotavirus
burden, including hospitalizations, outpatient cases, costs, and deaths.
Areas covered: A systematic literature review identified publications describing the clinical and
economic impact of rotavirus vaccinations across Europe, from their introduction in 2006 to the end
of 2020. A total of 3,137 articles were identified, of which 46 were included in the review. Included
articles reported the impact of rotavirus vaccination on disease in any age group.
Expert opinion: Rotavirus vaccination has resulted in substantial reductions in hospitalizations and
rotavirus-associated costs across Europe, particularly in children <5 years. There is some evidence of
herd protection afforded to older age groups where vaccine uptake is high among infants, highlighting
the potential for vaccination to confer a greater societal benefit as programs become more established.
Increasing vaccination coverage and continuing investment in widespread rotavirus vaccination programs across countries will likely increase the substantial public health benefits associated with
vaccination and further reduce the clinical and economic burden of disease.This manuscript was funded by Merck & Co., Inc., Kenilworth, NJ, USA. The funder contributed to the design of the study, collection, analysis, and interpretation of data as well as the writing and revision of the manuscript.Medicin
Glutamate and opioid antagonists modulate dopamine levels evoked by innately attractive male chemosignals in the nucleus accumbens of female rats
Sexual chemosignals detected by vomeronasal and olfactory systems mediate intersexual attraction in rodents, and act as a natural reinforcer to them. The mesolimbic pathway processes natural rewards, and the nucleus accumbens receives olfactory information via glutamatergic projections from the amygdala. Thus, the aim of this study was to investigate the involvement of the mesolimbic pathway in the attraction towards sexual chemosignals. Our data show that female rats with no previous experience with males or their chemosignals display an innate preference for male-soiled bedding. Focal administration of the opioid antagonist β-funaltrexamine into the posterior ventral tegmental area does not affect preference for male chemosignals. Nevertheless, exposure to male-soiled bedding elicits an increase in dopamine efflux in the nucleus accumbens shell and core, measured by microdialysis. Infusion of the opioid antagonist naltrexone in the accumbens core does not significantly affect dopamine efflux during exposure to male chemosignals, although it enhances dopamine levels 40 minutes after withdrawal of the stimuli. By contrast, infusion of the glutamate antagonist kynurenic acid in the accumbens shell inhibits the release of dopamine and reduces the time that females spend investigating male-soiled bedding. These data are in agreement with previous reports in male rats showing that exposure to opposite-sex odors elicits dopamine release in the accumbens, and with data in female mice showing that the behavioral preference for male chemosignals is not affected by opioidergic antagonists. We hypothesize that glutamatergic projections from the amygdala into the accumbens might be important to modulate the neurochemical and behavioral responses elicited by sexual chemosignals in rats