Real-world effectiveness of recombinant zoster vaccine in self-identified Chinese individuals aged ≥50 years in the United States.

We evaluated the vaccine effectiveness (VE) of two doses of recombinant zoster vaccine (RZV) against herpes zoster (HZ) and postherpetic neuralgia (PHN) in Chinese adults at Kaiser Permanente Southern California (KPSC). Chinese KPSC members were identified based on self-reported ethnicity or self-reported preferred spoken/written language. Those aged ≥50 years who received two doses of RZV 4 weeks to ≤ 6 months apart were matched 1:4 to RZV unvaccinated Chinese members and followed through June 2022; second doses were accrued 6/1/2018-12/31/2020. We estimated incidence and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) comparing outcomes (HZ and PHN). Adjusted VE (%) was calculated as (1-aHR)×100. 3978 RZV vaccinated Chinese members were matched to 15,912 RZV unvaccinated Chinese members. The incidence per 1000 person-years (95% CI) of HZ in the vaccinated group was 1.5 (0.9-2.5) and 10.9 (9.8-12.1) in the unvaccinated group; aHR (95% CI) was 0.12 (0.07-0.21). Adjusted VE (95% CI) was 87.6% (78.9-92.7) against HZ. We identified 0 PHN cases in the vaccinated group and 19 in the unvaccinated group. Among Chinese adults aged ≥50 years, two doses of RZV provided substantial protection against HZ and PHN supporting the real-world effectiveness of the vaccine in this population.

Herpes Zoster Recurrence: A Narrative Review of the Literature.

INTRODUCTION: Herpes zoster (HZ; shingles) is a painful, cutaneous disease caused by reactivation of the varicella zoster virus, which causes varicella (chickenpox) typically during childhood. The considerable healthcare burden of HZ is relatively well documented, with approximately one in three individuals experiencing at least one episode during their lifetime, debilitating symptoms including neuropathic pain, and complications such as post-herpetic neuralgia, vision loss, and rarely, stroke, and increased severity in immunocompromised individuals. However, we are not aware of a comprehensive review of literature specifically examining the burden of HZ recurrence. METHODS: We conducted a PubMed search (1 January 2003-2 February 2023) to assess available literature on the incidence, risk factors, and clinical features of HZ recurrence. RESULTS: The incidence of HZ recurrence reported by the studies identified was wide ranging. Studies in general populations of immunocompetent or immunocompetent/immunosuppressed (mixed) populations with an initial HZ episode estimate that approximately 1.2-9.6% of individuals may experience HZ recurrence, with an incidence rate of 1.7-16.6 cases per 1000 person-years. HZ recurrence was reported in 0.0-18.2% of immunocompromised individuals with HZ, with an incidence rate of 17.0-55 cases per 1000 person-years. Incidence rates varied according to study design, follow-up, and study populations. Recognized risk factors for HZ recurrence include immunocompromised status, female sex, family history, and comorbidities such as diabetes. Other factors that may predispose individuals to recurrence include long-lasting pain after the initial HZ episode and the presence of herpes zoster ophthalmicus. DISCUSSION: Our review underlines that following an initial HZ episode, individuals remain at risk of HZ recurrence, adding to the disease burden in a population. As HZ is preventable by vaccination, national HZ vaccination recommendations should include the need for and timing of vaccination in both immunocompetent and immunocompromised individuals who have a history of HZ.

Herpes zoster (HZ), also known as shingles, results from the same virus that causes chickenpox in childhood. In shingles, the chickenpox virus is reactivated, most commonly causing a painful skin rash. About one in three people have shingles at least once in their lifetime. Neuralgia (a burning, stabbing, and sometimes severe pain along a nerve pathway) may continue for months after the initial rash. Shingles may lead to loss of vision and rarely stroke. Shingles is more severe in people with weakened immunity. We reviewed published information on shingles recurrence (i.e., a second, third, or later episode of shingles), as we were not aware of a broad review of information specifically on recurrence. We focused on the rate of recurrence and factors that increase the risk of recurrence. Overall, in around one-tenth of individuals who experience shingles, the disease may reoccur after complete resolution. The rate of recurrence varied on the basis of how the studies were carried out and the type of patients included in the studies. Well-known factors that increase the risk of shingles recurrence are reduced immunity, female sex, family history, and other conditions (e.g., diabetes). Other factors that may increase the risk of shingles recurrence include pain that lasts for a long time after the first episode of shingles and having herpes zoster ophthalmicus, which leads to eye complications. Our review summarizes available data. As shingles is preventable by vaccination, strategies to prevent this disease should include those who have a history of shingles.

Geographic Trends in Pediatric Psychotropic Medication Dispensing Before and After the Start of the COVID-19 Pandemic.

OBJECTIVE: This study examined trends and geographic variability in dispensing of prescription psychotropic medications to U.S. youths before and after the start of the COVID-19 pandemic. METHODS: Using national data on prescription medication dispensing, the authors performed a cross-sectional study examining the monthly percent change in psychotropic medications dispensed (total N=95,639,975) to youths (ages 5-18 years) in 2020 versus 2019, across medication classes and geographic regions. RESULTS: For many medications, more were dispensed in March 2020 than in March 2019 and fewer in April-May 2020 versus April-May 2019. Stimulants had the largest decline: -26.4% in May 2020 versus May 2019. The magnitude of the monthly percent change varied by region. CONCLUSIONS: Fewer psychotropic medications were dispensed to U.S. youths after the start of the COVID-19 pandemic compared with 2019. Although some medication classes rebounded to prepandemic dispensing levels by September 2020, dispensing varied by class and region.

Trends in antipsychotic use for youth with attention-deficit/hyperactivity disorder and disruptive behavior disorders.

PURPOSE: To examine trends in off-label antipsychotic use for youth with attention-deficit/hyperactivity disorder with and without a comorbid disruptive behavior disorder. METHOD: This cross-sectional study of annual trends from 2007 through 2015 used the IQVIA PharMetrics® Plus for Academics data. We identified 165 794 commercially-insured youth 3-18-year-old who had a diagnosis of attention-deficit/hyperactivity disorder and classified them into subgroups with and without disruptive behavior disorders comorbidities. Antipsychotic use, with or without a stimulant, was the primary dependent outcome. Logistic regression estimated the odds of antipsychotic use associated with comorbid attention-deficit/hyperactivity disorder and disruptive behavior disorders, adjusting for age, sex, study year, and other psychotropic use. RESULTS: Over 70% of the 165 794 youth with attention-deficit/hyperactivity disorder were 5-14-year-old and male, and 12% had disruptive behavior disorders. Antipsychotic prevalence, with or without a stimulant, was 4.4% in 2007 and 3.4% in 2015. Stimulants with antipsychotics increased significantly from 2007 to 2015 for females (19.5%-28.7%) and youth 15-18-year-old (25.9%-32.7%). Adjusting for age, sex, study year, and other psychotropic use, youth with a comorbid disruptive behavior had a 2.5 (95% CI: 2.3, 2.7) higher likelihood of receiving an antipsychotic than youth with attention-deficit/hyperactivity disorder and no comorbidities. CONCLUSIONS: Antipsychotic use was associated with comorbid disruptive behaviors in youth with attention-deficit/hyperactivity disorder. Off-label antipsychotic use has increased for females and older adolescents.

Evaluating the association between antidepressant dose trajectories and treatment augmentation in pediatric depression.

PURPOSE: To identify antidepressant dose trajectories in the first 6-months of antidepressant initiation and to evaluate the association between antidepressant dose trajectories and augmentation with another psychotropic medication. METHODS: Using the IQVIA PharMetrics® Plus database, we identified 5655 commercially insured youth (3-18 years) with depression who newly initiated an antidepressant anytime from January 2007 to June 2015. No antidepressant use within 1 year prior to the index prescription defined new use. Latent class growth analysis of antidepressant dosing in the 6 months after initiation defined the exposure groups. The outcome was any regimen change, that is, antidepressant augmentation with another psychotropic or discontinuation of the antidepressant, with and without switching to another psychotropic. Baseline covariates measured in the 6 months before antidepressant initiation included demographic factors, psychiatric comorbidities, and health service use. Multinomial logistic regression tested the association between antidepressant dose trajectories and the odds of an antidepressant regimen change. RESULTS: Five dose trajectories were sharp decline (n = 897; 16%), slow decline (n = 1029; 18%), stable minimum dose (n = 1397; 25%), stable maximum dose (n = 1783; 32%), and increasing high dose (n = 549; 10%). Relative to the stable minimum dose group, the sharp and slow decline groups were more likely to discontinue the antidepressant, either switch to another psychotropic (OR [odds ratio]: 5.91; 95%CI: 3.23-10.80 and OR: 1.67; 95%CI: 1.04-2.68, respectively) or stop all psychotropic medication (OR: 6.64; 95%CI: 4.24-10.39 and OR: 1.62; 95%CI: 1.22-2.13, respectively). However, the stable maximum and increasing high-dose groups were less likely to discontinue, either switch (OR: 0.38; 95%CI: 0.24-0.61 and OR: 0.30; 95%CI: 0.16-0.59, respectively) or stop all psychotropic medications (OR: 0.15; 95%CI: 0.12-0.20 and OR: 0.02; 95%CI: 0.01-0.03 respectively) than augment with another psychotropic. CONCLUSIONS: The findings from this cross-sectional study demonstrate an association between antidepressant dose trajectories within 6 months of initiating treatment and the odds of augmenting with another psychotropic.

Cardiovascular Risk of Concomitant Use of Atypical Antipsychotics and Stimulants Among Commercially Insured Youth in the United States.

Objectives: To investigate the risk of cardiovascular events associated with concomitant use of stimulants and atypical antipsychotics (AAPs) among youth and evaluate whether AAP dose and duration of concomitant use modifies the risk. Methods: We used IQVIA PharMetrics® Plus data from 2006 to 2015 to construct a retrospective cohort of commercially-insured youth aged 5-17 years old who initiated a stimulant medication. Time-varying concomitant stimulant/AAP use was defined as current, past and no concomitant use based on person months. The primary time-varying Cox proportional hazard regression analysis evaluated the risk of cardiovascular events comparing current concomitant use with past and no concomitant use, adjusted for baseline cardiovascular risk. A secondary analysis assessed the risk of cardiovascular events comparing AAP daily doses (<1, 1-2, >2 mg) and duration (<3, 3-6, >6 months) of current concomitant use to no concomitant use. Cardiovascular outcomes included severe (i.e., stroke, acute myocardial infarction, ischemic heart disease) and less severe (i.e., angina pectoris, cardiac dysrhythmias, transient cerebral ischemia, hypertensive disease, tachycardia, palpitations, syncope). Results: For this cohort of 61,438 youths, the incidence rate of severe cardiovascular events was 0.18 per 10,000 person-months, and all events occurred in no concomitant use months. The risk of less severe cardiovascular events was significantly higher in current concomitant users compared with no [HR: 2.59 (95%CI: 1.72, 3.90)] and past [HR: 1.89 (95%CI: 1.10, 3.24)] concomitant users. Compared to no concomitant use, the risk of less severe cardiovascular events was significantly higher at all AAP daily doses [HR: <1 mg: 2.82 (95%CI: 1.72, 4.61); 1-2 mg: 2.22 (95%CI: 1.16, 4.25); >2 mg: 2.65 (95%CI: 1.50, 4.71)]. The risk of less severe cardiovascular events significantly elevated for all duration of use and was higher for <3 months of concomitant use [HR: <3 months: 3.45 (95%CI: 2.17, 5.47) relative to 3-6 months: 2.60 (95%CI: 1.29, 5.25) or >6 months: 2.61 (95%CI: 1.59, 4.30)]. Conclusions: Severe cardiovascular events are rare. Concomitant stimulant/AAP use elevates the risk of less severe cardiovascular events. Periodic heart rate or blood pressure monitoring for youth on stimulant/AAP treatment may be warranted.

Evaluation of Switch-to-Brand Rates as a Potential Signal for Therapeutic Equivalency of Generic Antidepressants: A Real-World Retrospective Cohort Study.

Negative clinical outcomes after switching from brand to generic antidepressants have raised concerns regarding therapeutic equivalency. This research aims to estimate the prevalence of switching and to identify predictors for generic to brand switching for various antidepressants. This retrospective cohort study utilized data from a 10% random sample of enrollees in the IQVIA PharMetrics Plus claims database from 2007-2015. The base cohort consisted of commercially insured patients who were prescribed escitalopram, duloxetine, or venlafaxine extended release (ER) anytime from the year prior to the generic launch through December 2014. The primary outcome was defined as a switch from generic to a brand within 14 days of sustained generic use in a 1-year follow-up period. Adjusted logistic regression and generalized estimating equations for repeated measures estimated the drug specific and overall odds of switch-to-brand among brand initiators relative to generic initiators, respectively. A total of 102,831 unique patients across 3 drug products contributed to the final analytic sample. The overall prevalence of switch from generic to brand was 0.74%. Across all three antidepressants, brands initiators were more likely to experience a switch-to-brand: escitalopram (odds ratio (OR): 14.41, 95% confidence interval (CI): 11.14-18.64), duloxetine (OR: 8.08, 95% CI: 4.85-13.41) and venlafaxine ER (OR: 16.46, 95% CI: 11.56-23.46). The pooled odds of a switch-to-brand in brand vs. generic initiators was 13.77 (95% CI: 11.35-16.71). This study suggests a low overall switch-to-brand prevalence and may support therapeutic equivalence between brand and generic antidepressants. Initiating with a brand product was the strongest predictor for switching back to brand and suggests that patient experience may play a role in drug utilization.

Spillover effects of state medicaid antipsychotic prior authorization policies in US commercially insured youth.

PURPOSE: To evaluate spillover effects of Medicaid antipsychotic prior authorization (PA) policies among commercially insured youth. METHODS: Commercially insured youth residing in nine US states that implemented PA exclusively for antipsychotics in 2011 or 2012 were identified using a 10% random sample of enrollees in the IQVIA PharMetrics Plus database spanning 2007 to 2015. Youth were included if they were ≤18 years, met the age criteria of the PA at the time of dispensing, and had at least 1 month of prescription drug coverage from 2007 to 2015. The primary outcome of interest was the monthly prevalence of antipsychotics. We implemented segmented regression of interrupted time series analysis to estimate changes in the monthly prevalence of targeted medications, overall and stratified by age. Trends were compared in the 4-year period before and the 3-year period after implementation of PA policies. RESULTS: Antipsychotics prescribing significantly decreased 6.74/10 000 (95% CI, -9.04 to -4.44) enrollees per month immediately after PA implementation. However, PA was not associated with significant long-term trend changes (-0.06; 95% CI, -0.16 to 0.03). Antipsychotic prescribing in children <12 years-old significantly decreased 0.14/10 000 (95% CI, -0.21 to -0.07) enrollees per month after PA implementation, while prescribing in adolescents 12 to 18 years-old significantly increased 0.32/10 000 (95% CI, 0.16 to 0.47) enrollees per month. CONCLUSION: While Medicaid PA polices for antipsychotic oversight did not affect overall prescribing, there were spillover effects in U.S. commercially insured children <12 years-old. This suggests that state-level Medicaid policies intended to improve the quality of care and safe use of antipsychotics can have broad reach.

Adjuvant-containing control arms in pivotal quadrivalent human papillomavirus vaccine trials: restoration of previously unpublished methodology.

PURPOSE: Trustworthy reporting of quadrivalent human papillomavirus (HPV) vaccine trials is the foundation for assessing the vaccine's risks and benefits. However, several pivotal trial publications incompletely reported important methodological details and inaccurately described the formulation that the control arms received. Under the Restoring Invisible and Abandoned Trials initiative (RIAT), we aim to restore the public record regarding the content and rationale of the controls used in the trials. METHODS: We assembled a cohort (five randomised controlled trials) described as placebo-controlled using clinical study reports (CSRs) obtained from the European Medicines Agency. We extracted the content and rationale for the choice of control used in each trial across six data sources: trial publications, register records, CSR synopses, CSR main bodies, protocols and informed consent forms. RESULTS: Across data sources, the control was inconsistently reported as 'placebo'-containing aluminium adjuvant (sometimes with dose information). Amorphous aluminium hydroxyphosphate sulfate (AAHS) was not mentioned in any trial registry entry, but was mentioned in all publications and CSRs. In three of five trials, consent forms described the control as an 'inactive' substance. No rationale for the selection of the control was reported in any trial publication, register, consent form, CSR synopsis or protocol. Three trials reported the rationale for choice of control in CSRs: to preserve blinding and assess the safety of HPV virus-like particles as the 'safety profile of (AAHS) is well characterised'. CONCLUSIONS: The stated rationale of using AAHS control-to characterise the safety of the HPV virus-like particles-lacks clinical relevance. A non-placebo control may have obscured an accurate assessment of safety and the participant consent process of some trials raises ethical concerns. TRIAL REGISTRATION NUMBERS: NCT00092482, NCT00092521, NCT00092534, NCT00090220, NCT00090285.

Availability of study protocols for randomized trials published in high-impact medical journals: A cross-sectional analysis.

BACKGROUND: To improve reporting transparency and research integrity, some journals have begun publishing study protocols and statistical analysis plans alongside trial publications. We sought to assess the overall availability and characteristics of protocols and statistical analysis plans of randomized clinical trials published in the top five (by impact factor) general medicine journals. METHODS: All randomized clinical trials published in Annals of Internal Medicine, BMJ, JAMA, Lancet, and NEJM in 2016 were identified. For each randomized clinical trial, we searched for protocols and statistical analysis plans on journal websites (including supplementary material) and in the article, for example, a referenced publication or link to trial or institutional website. Characteristics of randomized clinical trials were extracted from the publication and clinical trial registry. A detailed assessment of protocols and statistical analysis plans was conducted in a 20% random sample of randomized clinical trials. RESULTS: Protocols were available for 299 (82%) trials, ranging from 50% in BMJ to >95% in NEJM and JAMA. Statistical analysis plans were available for 182 (50%) trials and varied from <10% for Annals of Internal Medicine, BMJ, and Lancet to 92% for NEJM. Of the 76 randomized clinical trials in the 20% random sample, 63 (83%) had a protocol but less than half (31; 44%) included an a priori (dated prior to patient enrollment) version of the protocol. Statistical analysis plans were available for 35 (46%) trials, and only 5 (7%) included an a priori version. CONCLUSION: Protocols and statistical analysis plans are publicly available for the majority of trials. However, the a priori versions of these documents are only available for a minority of trials. More attention must be paid to ensuring the public availability of a priori versions.

Psychiatric Services Preceding Initiation of Antipsychotic Medication Among Youth in Foster Care.

Objectives: To characterize psychotropic use preceding antipsychotic initiation in a population of youth in foster care and to determine whether the use of intensive psychiatric services before initiating an antipsychotic differs across subgroup of youth defined by past psychotropic use. Methods: We identified youth in foster care in one U.S. State who initiated an antipsychotic from 2010 to 2015 and were aged ≤21 years at initiation. No antipsychotic use 1-year before the index prescription defined new use. Psychotropic class use in the year preceding the index antipsychotic prescription distinguished three subgroups: no psychotropic use, single-class use, and concomitant (>1 class) use. The temporal association of antipsychotic initiation with intensive services (psychiatric hospitalizations or emergency department visits) was estimated through regression models adjusted for psychiatric diagnoses and demographic characteristics. Logistic regression models assessed the interaction between psychotropic class subgroup and psychiatric diagnosis with the odds of hospitalization. Results: Of the 753 youth initiating an antipsychotic, 279 (37%) had no psychotropic use, 304 (40%) had single-class use, and 170 (23%) had concomitant use in the year before. In the year preceding antipsychotic initiation, 183 (24%) were hospitalized and 118 (16%) were hospitalized 1 month before antipsychotic initiation. The number of days between hospital discharge and antipsychotic initiation was 47 (SE = 19) days longer in concomitant users relative to youth with no psychotropic use (p = 0.01). In the year preceding antipsychotic initiation, concomitant users with severe mental illness were less likely to have a hospitalization (OR = 0.24; 95% CI = 0.06-0.93) than youth with no psychotropic use diagnosed with severe mental illness. Conclusions: Variation in psychotropic medication treatment, hospitalizations, and psychiatric diagnosis before antipsychotic initiation distinguished subgroups of youth initiating an antipsychotic. Single-class and concomitant users may have initiated an antipsychotic to augment existing regimen, whereas youth with no psychotropic use may have initiated an antipsychotic following a first episode crisis.

Patient consent to publication and data sharing in industry and NIH-funded clinical trials.

BACKGROUND: Participants are recruited into clinical trials under the assumption that the research will contribute to medical knowledge. Therefore, non-publication trials-and, more recently, lack of data sharing-are widely considered to violate the trust of trial participants. Existing practices regarding patient consent to publication and data sharing have not been evaluated. Analyzing informed consent forms (ICFs), we studied what trial participants were told regarding investigators' intention to contribute to medical knowledge, publish trial results, and share de-identified trial data. METHODS: We obtained 98 ICFs of industry-funded pre-marketing trials for all (17) antibiotics approved by the European Medicines Agency and 46 ICFs of publicly funded trials from the National Heart, Lung and Blood Institute Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) data repository. Three authors independently reviewed ICFs to identify and extract what was stated or implied regarding: (1) publication of results; (2) sharing de-identified data; (3) data ownership; (4) confidentiality of identifiable data; and (5) whether the trial will produce knowledge that offers public benefit. Consensus was obtained from the two reviewers with the greatest overall agreement on all five measures. Disagreements were resolved through discussion among all authors. RESULTS: Four (3%) trials indicated a commitment to publish trial results; 140 (97%) did not commit to publishing trial results; six (4%) indicated a commitment to share de-identified data with third party researchers. Commitments to share were more common in publicly funded trials than industry-funded trials (7% vs 3%). A total of 103 (72%) ICFs indicated the trials will or may produce knowledge that offers public benefits, while 131 (91%) ICFs left unstated who "owned" trial data; of those with statements, the sponsor always claimed ownership. Patient confidentiality was guaranteed in 137 (95%) trials. CONCLUSIONS: Our results suggest that consent forms rarely disclose investigators' intentions regarding the sharing of de-identified data or publication of trial results.