Zoster vaccination is associated with a reduction of zoster in elderly patients with chronic kidney disease.

BACKGROUND: Growing epidemiological evidence demonstrates increased zoster risks in people with chronic kidney disease (CKD). Study objectives were to determine zoster vaccine effectiveness in individuals with CKD in pragmatic use. METHODS: A population-based cohort study was undertaken in a 5% random sample of US Medicare from 2007 to 2009 involving 766 330 eligible individuals aged ≥65 years who were (29 785) and were not (736 545) exposed to the zoster vaccine. Incidence rates for zoster in vaccinated and unvaccinated individuals and hazard ratios for zoster comparing vaccinated with unvaccinated were determined for individuals with CKD. Time-updated Cox proportional hazards models were used, adjusting for relevant confounders. RESULTS: CKD was present in 183 762 (24%) of individuals (15% of vaccinees). Adjusted vaccine effectiveness [95% confidence intervals (CIs)] in individuals with CKD was 0.49 (0.36-0.65). The adjusted vaccine effectiveness in participants with both CKD and diabetes mellitus was 0.46 (95% CI 0.09-0.68). Vaccine effectiveness estimates were similar to those previously reported for the general population [vaccine effectiveness 0.48 (95% CI 0.39-0.56)]. CONCLUSIONS: Zoster vaccine is effective against incident zoster in older individuals with CKD. Extra efforts are warranted to increase vaccine uptake in individuals with CKD given the known low uptake in these higher risk individuals

Effectiveness of herpes zoster vaccination in an older United Kingdom population.

BACKGROUND: Vaccination against herpes zoster was introduced in the United Kingdom in 2013 for individuals aged 70 years, with a phased catch-up campaign for 71-79 year olds. Vaccine introduction has resulted in a marked fall in incident herpes zoster and in post-herpetic neuralgia (PHN), but formal evaluation of vaccine effectiveness is needed. METHODS: In a population-based cohort study of older individuals born between 1933 and 1946, we used linked UK anonymised primary care health records for the first three years of the vaccination programme (01/09/2013-31/08/2016) and multivariable Poisson regression to obtain incidence rates and vaccine effectiveness (VE) against zoster and PHN. RESULTS: Among 516,547 individuals, 21% were vaccinated. Incidence of zoster was 3.15/1000 person-years in vaccinees and 8.80/1000 person-years in unvaccinated individuals. After adjustment, VE was 64% (95%CI = 60-68%) against incident zoster and 81% (95%CI = 61-91%) against PHN, with very similar VE estimates in the routine and catch-up cohorts. VE against zoster was lower in those with a previous history of zoster: 47% (95%CI = 31-58%) versus 64% (95%CI = 60-68%) in those without previous zoster. There was evidence of waning VE over time, from 69% (95%CI = 65-74%) in the first year after vaccination to 45% (95%CI = 29-57%) by the third year. CONCLUSION: This first formal assessment of VE in the UK zoster vaccination programme demonstrates good effectiveness of zoster vaccine, and very good protection against PHN. The findings provide evidence that VE is similar across the age groups targeted for vaccination in the UK, and on duration of protection of the vaccine in public health use. The study provides key information for decision-makers about the future direction of UK zoster vaccination programme, indicating that the live zoster vaccine may be more cost-effective than estimated previously. It also supports efforts to communicate the benefits of zoster vaccination to address the declining coverage observed across the UK

A systematic review and meta-analysis of risk factors for postherpetic neuralgia.

Patients with herpes zoster can develop persistent pain after rash healing, a complication known as postherpetic neuralgia. By preventing zoster through vaccination, the risk of this common complication is reduced. We searched MEDLINE and Embase for studies assessing risk factors for postherpetic neuralgia, with a view to informing vaccination policy. Nineteen prospective studies were identified. Meta-analysis showed significant increases in the risk of postherpetic neuralgia with clinical features of acute zoster including prodromal pain (summary rate ratio 2.29, 95% confidence interval: 1.42-3.69), severe acute pain (2.23, 1.71-2.92), severe rash (2.63, 1.89-3.66), and ophthalmic involvement (2.51, 1.29-4.86). Older age was significantly associated with postherpetic neuralgia; for individual studies, relative risk estimates per 10-year increase ranged from 1.22 to 3.11. Evidence for differences by gender was conflicting, with considerable between-study heterogeneity. A proportion of studies reported an increased risk of postherpetic neuralgia with severe immunosuppression (studies, n = 3/5) and diabetes mellitus (n = 1/4). Systemic lupus erythematosus, recent trauma, and personality disorder symptoms were associated with postherpetic neuralgia in single studies. No evidence of higher postherpetic neuralgia risk was found with depression (n = 4) or cancer (n = 5). Our review confirms a number of clinical features of acute zoster are risk factors for postherpetic neuralgia. It has also identified a range of possible vaccine-targetable risk factors for postherpetic neuralgia; yet aside from age-associated risks, evidence regarding risk factors to inform zoster vaccination policy is currently limited

Lansoprazole use and tuberculosis incidence in the United Kingdom Clinical Practice Research Datalink: A population based cohort.

BACKGROUND: Recent in vitro and animal studies have found the proton pump inhibitor (PPI) lansoprazole to be highly active against Mycobacterium tuberculosis. Omeprazole and pantoprazole have no activity. There is no evidence that, in clinical practice, lansoprazole can treat or prevent incident tuberculosis (TB) disease. METHODS AND FINDINGS: We studied a cohort of new users of lansoprazole, omeprazole, or pantoprazole from the United Kingdom Clinical Practice Research Datalink to determine whether lansoprazole users have a lower incidence of TB disease than omeprazole or pantoprazole users. Negative control outcomes of myocardial infarction (MI) and herpes zoster were also studied. Multivariable Cox proportional hazards regression was used to adjust for potential confounding by a wide range of factors. We identified 527,364 lansoprazole initiators and 923,500 omeprazole or pantoprazole initiators. Lansoprazole users had a lower rate of TB disease (n = 86; 10.0 cases per 100,000 person years; 95% confidence interval 8.1-12.4) than omeprazole or pantoprazole users (n = 193; 15.3 cases per 100,000 person years; 95% confidence interval 13.3-17.7), with an adjusted hazard ratio (HR) of 0.68 (0.52-0.89). No association was found with MI (adjusted HR 1.04; 95% confidence interval 1.00-1.08) or herpes zoster (adjusted HR 1.03; 95% confidence interval 1.00-1.06). Limitations of this study are that we could not determine whether TB disease was due to reactivation of latent infection or a result of recent transmission, nor could we determine whether lansoprazole would have a beneficial effect if given to people presenting with TB disease. CONCLUSIONS: In this study, use of the commonly prescribed and cheaply available PPI lansoprazole was associated with reduced incidence of TB disease. Given the serious problem of drug resistance and the adverse side effect profiles of many TB drugs, further investigation of lansoprazole as a potential antituberculosis agent is warranted

Validation of treatment escalation as a definition of atopic eczema flares.

BACKGROUND: Atopic eczema (AE) is a chronic disease with flares and remissions. Long-term control of AE flares has been identified as a core outcome domain for AE trials. However, it is unclear how flares should be defined and measured. OBJECTIVE: To validate two concepts of AE flares based on daily reports of topical medication use: (i) escalation of treatment and (ii) days of topical anti-inflammatory medication use (topical corticosteroids and/or calcineurin inhibitors). METHODS: Data from two published AE studies (studies A (n=336) and B (n=60)) were analysed separately. Validity and feasibility of flare definitions were assessed using daily global bother (scale 0 to 10) as the reference standard. Intra-class correlations were reported for continuous variables, and odds ratios and area under the receiver operator characteristic (ROC) curve for binary outcome measures. RESULTS: Good agreement was found between both AE flare definitions and change in global bother: area under the ROC curve for treatment escalation of 0.70 and 0.73 in studies A and B respectively, and area under the ROC curve of 0.69 for topical anti-inflammatory medication use (Study A only). Significant positive relationships were found between validated severity scales (POEM, SASSAD, TIS) and the duration of AE flares occurring in the previous week - POEM and SASSAD rose by half a point for each unit increase in number of days in flare. Smaller increases were observed on the TIS scale. Completeness of daily diaries was 95% for Study A and 60% for Study B over 16 weeks). CONCLUSION: Both definitions were good proxy indicators of AE flares. We found no evidence that 'escalation of treatment' was a better measure of AE flares than 'use of topical anti-inflammatory medications'. Capturing disease flares in AE trials through daily recording of medication use is feasible and appears to be a good indicator of long-term control. TRIAL REGISTRATION: Current Controlled Trials ISRCTN71423189 (Study A)

Quantification of risk factors for postherpetic neuralgia in herpes zoster patients: A cohort study.

OBJECTIVE: To investigate risk factors for postherpetic neuralgia, the neuropathic pain that commonly follows herpes zoster. METHODS: Using primary care data from the Clinical Practice Research Datalink, we fitted multivariable logistic regression models to investigate potential risk factors for postherpetic neuralgia (defined as pain ≥90 days after zoster, based on diagnostic or prescription codes), including demographic characteristics, comorbidities, and characteristics of the acute zoster episode. We also assessed whether the effects were modified by antiviral use. RESULTS: Of 119,413 zoster patients, 6,956 (5.8%) developed postherpetic neuralgia. Postherpetic neuralgia risk rose steeply with age, most sharply between 50 and 79 years (adjusted odds ratio [OR] for a 10-year increase, 1.70, 99% confidence interval 1.63-1.78). Postherpetic neuralgia risk was higher in women (6.3% vs 5.1% in men: OR 1.19, 1.10-1.27) and those with severely immunosuppressive conditions, including leukemia (13.7%: 2.07, 1.08-3.96) and lymphoma (12.7%: 2.45, 1.53-3.92); autoimmune conditions, including rheumatoid arthritis (9.1%: 1.20, 0.99-1.46); and other comorbidities, including asthma and diabetes. Current and ex-smokers, as well as underweight and obese individuals, were at increased risk of postherpetic neuralgia. Antiviral use was not associated with postherpetic neuralgia (OR 1.04, 0.97-1.11). However, the increased risk associated with severe immunosuppression appeared less pronounced in patients given antivirals. CONCLUSIONS: Postherpetic neuralgia risk was increased for a number of patient characteristics and comorbidities, notably with age and among those with severe immunosuppression. As zoster vaccination is contraindicated for patients with severe immunosuppression, strategies to prevent zoster in these patients, which could include the new subunit zoster vaccine, are an increasing priority

A Roadmap for Potential Improvement of Newborn Screening for Inherited Metabolic Diseases Following Recent Developments and Successful Applications of Bivariate Normal Limits for Pre-Symptomatic Detection of MPS I, Pompe Disease, and Krabbe Disease

The mucopolysaccharidoses (MPS), Pompe Disease (PD), and Krabbe disease (KD) are inherited conditions known as lysosomal storage disorders (LSDs) The resulting enzyme deficiencies give rise to progressive symptoms. The United States Department of Health and Human Services\u27 Recommended Uniform Screening Panel (RUSP) suggests LSDs for inclusion in state universal newborn screening (NBS) programs and has identified screening deficiencies in MPS I, KD, and PD NBS programs. MPS I NBS programs utilize newborn dried blood spots and assay alpha L-iduronidase (IDUA) enzyme to screen for potential cases. Glycosaminoglycans (GAGs) offer potential as a confirmatory test. KD NBS programs utilize galactocerebrosidase (GaLC) as an initial test, with psychosine (PSY) activity increasingly used as a confirmatory test for predicting onset of Krabbe disease, though with an excessive false positive rate. PD is marked by a deficiency in acid α-glucosidase (GAA), causing increased glycogen, creatine (CRE), and other biomarkers. Bivariate normal limit (BVNL) methods have been applied to GaLC and PSY activity to produce a NBS tool for KD, and more recently, to IDUA and GAG activity to develop a NBS tool for MPS I. A BVNL tool based on GAA and CRE is in development for infantile PD diagnosis. Early infantile KD, MPS I, and PD cases were pre-symptomatically identified by BVNL-based NBS tools. This article reviews these developments, discusses how they address screening deficiencies identified by the RUSP and may improve NBS more generally

Seven Key Principles of Program and Project Success: A Best Practices Survey

The National Aeronautics and Space Administration (NASA) Organization Design Team (ODT), consisting of 20 seasoned program and project managers and systems engineers from a broad spectrum of the aerospace industry, academia, and government, was formed to support the Next Generation Launch Technology (NGLT) Program and the Constellation Systems Program. The purpose of the ODT was to investigate organizational factors that can lead to success or failure of complex government programs, and to identify tools and methods for the design, modeling, and analysis of new and more-efficient program and project organizations. The ODT conducted a series of workshops featuring invited lectures from seasoned program and project managers representing 25 significant technical programs spanning 50 years of experience. The result was the identification of seven key principles of program success that can be used to help design and operate future program organizations. This paper presents the success principles and examples of best practices that can significantly improve the design of program, project, and performing technical line organizations, the assessment of workforce needs and organization performance, and the execution of programs and projects

Safety of topical corticosteroids in atopic eczema:an umbrella review

Objective: An umbrella review summarising all safety data from systematic reviews of topical corticosteroids (TCS) in adults and children with atopic eczema .Methods: Embase, MEDLINE, PubMed, Cochrane Database of Systematic Reviews and the Centre of Evidence Based Dermatology map of eczema systematic reviews searched until 7th November 2018 and Epistemonikos until 2nd March 2021. Reviews were included if they assessed safety of TCS in atopic eczema and searched >1 database using a reproducible search strategy. Review quality assessed using AMSTAR-2. PROSPERO registration: CRD42018079409. Results: 38 systematic reviews included, 34 low/critically low quality. Treatment and follow-up usually short (2-4 weeks). Key findings: TCS versus emollient/vehicle: No meta-analyses identified for skin-thinning. Two 2-week randomised controlled trials (RCTs) found no significant increased risk with very potent TCS (0/196 TCS vs 0/33 vehicle in children and 6/109 TCS vs 2/50 vehicle, age unknown). Biochemical adrenal suppression (cortisol) was 3.8% (95% CI 2.4%-5.8%) in a meta-analysis of 11 uncontrolled observational studies (any potency TCS, 522 children). Effects reversed when treatment ceased. TCS versus topical calcineurin inhibitors (TCIs): Meta-analysis showed higher relative risk of skin-thinning with TCS (RR 4.86, 95% CI 1.06-22.28, n=4128, four RCTs, including one 5-year RCT). Eight cases in 2068 participants, 7 using potent TCS. No evidence of growth suppression.Once daily versus more frequent TCS: No meta-analyses identified. No skin-thinning in one RCT (3 weeks potent TCS, n=94) or biochemical adrenal suppression in two RCTs (up to 2 weeks very potent/moderate TCS, n=129).TCS twice/week to prevent flares (‘weekend therapy’) versus vehicle: No meta-analyses identified. No evidence of skin-thinning in five RCTs. One RCT found biochemical adrenal suppression (2/44 children, potent TCS).Conclusions: We found no evidence of harm when TCS used intermittently “as required” to treat flares or “weekend therapy” to prevent flares. However, long-term safety data was limited

Quantification of risk factors for herpes zoster: population based case-control study.

OBJECTIVES: To quantify the effects of possible risk factors for herpes zoster at different ages. DESIGN: Case-control study. SETTING: UK Clinical Practice Research Datalink primary care data. PARTICIPANTS: 144 959 adults diagnosed with zoster between 2000 and 2011; 549,336 age, sex, and practice matched controls. MAIN OUTCOME MEASURES: Conditional logistic regression was used to generate adjusted odds ratios to estimate the strength of association of each potential risk factor with zoster and assess effect modification by age. RESULTS: The median age of the cases and controls was 62 years. Factors associated with increased risk of zoster included rheumatoid arthritis (3111 (2.1%) v 8029 (1.5%); adjusted odds ratio 1.46, 99% confidence interval 1.38 to 1.55), inflammatory bowel disease (1851 (1.3%) v 5118 (0.9%); 1.36, 1.26 to 1.46), chronic obstructive pulmonary disease (6815 (4.7%) v 20 201 (3.7%); 1.32, 1.27 to 1.37), asthma (10 243 (7.1%) v 31 865 (5.8%); 1.21, 1.17 to 1.25), chronic kidney disease (8724 (6.0%) v 29 437 (5.4%); 1.14, 1.09 to 1.18), and depression (6830 (4.7%) v 22 052 (4.0%); 1.15, 1.10 to 1.20). Type 1, but not type 2, diabetes showed some association with zoster (adjusted odds ratio 1.27, 1.07 to 1.50). The relative effects of many assessed risk factors were larger in younger patients. Patients with severely immunosuppressive conditions were at greatest risk of zoster-for example, patients with lymphoma (adjusted odds ratio 3.90, 3.21 to 4.74) and myeloma (2.16, 1.84 to 2.53), who are not eligible for zoster vaccination. CONCLUSIONS: A range of conditions were associated with increased risk of zoster. In general, the increased risk was proportionally greater in younger age groups. Current vaccines are contraindicated in people at the greatest risk of zoster, highlighting the need for alternative risk reduction strategies in these groups