Risk of stroke following herpes zoster: a self-controlled case-series study.

BACKGROUND: Herpes zoster is common and vaccine preventable. Stroke risk may be increased following zoster, but evidence is sparse and could be explained by differences between people with and without zoster. Our objective was to determine if stroke risk is increased following zoster. METHODS: Within-person comparisons were undertaken using the self-controlled case-series method and data from the UK Clinical Practice Research Datalink (1987-2012). Participants had a first-ever diagnosis of zoster and stroke within the study period. Stroke incidence in periods following zoster was compared with incidence in other time periods. Age-adjusted incidence ratios (IRs) and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 6584 individuals were included. Stroke rate was increased following zoster compared with the baseline unexposed period, then gradually reduced over 6 months: weeks 1-4 (age-adjusted IR, 1.63; 95% CI, 1.32-2.02), weeks 5-12 (IR, 1.42; 95% CI, 1.21-1.68), and weeks 13-26 (IR, 1.23; 95% CI, 1.07-1.42), with no increase thereafter. A stronger effect was observed for individuals with zoster ophthalmicus, rising to a >3-fold rate 5-12 weeks after zoster. Oral antivirals were given to 55% of individuals: IRs for stroke were lower among those receiving antivirals compared with those not treated, suggesting a protective effect. CONCLUSIONS: We have established an increased stroke rate within 6 months following zoster. Findings have implications for zoster vaccination programs, which may reduce stroke risk following zoster. The low antiviral prescribing rate needs to be improved; our data suggest that antiviral therapy may lead to a reduced stroke risk following zoster

Angiotensin receptor blockers and risk of dementia: cohort study in UK Clinical Practice Research Datalink.

AIMS: This was a cohort study to evaluate whether individuals exposed to angiotensin receptor blockers have a reduced risk of dementia compared with those exposed to angiotensin-converting enzyme inhibitors. METHODS: The study included new users of angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (from 1995 to 2010) from UK primary care practices contributing to the Clinical Research Practice Datalink. The association between exposure to angiotensin receptor blockers and the risk of incident dementia was analysed using a Cox model, adjusting for age, sex, body mass index, diabetes, hypertension, heart failure, statin use, socioeconomic status, alcohol, smoking, number of consultations and calendar year. RESULTS: A total of 426 089 persons were included in the primary analysis, with 45 541 persons exposed to angiotensin receptor blockers and the remainder to angiotensin-converting enzyme inhibitors. The total number of new diagnoses of dementia was 6517. There was weak evidence of a decreased risk of dementia with exposure to angiotensin receptor blockers, with follow-up beginning at 1 year after the start of treatment (adjusted hazard ratio 0.92, 95% confidence interval 0.85-1.00). An analysis restricted to the first 12 months after the index date showed a larger effect on dementia risk (adjusted hazard ratio 0.60, 95% confidence interval 0.50-0.72). CONCLUSIONS: A small reduction in dementia risk was seen with angiotensin receptor blockers in comparison to angiotensin-converting enzyme inhibitors. However, the strongest association was seen in early follow-up, suggesting that the inverse association is unlikely to be causal, but instead reflects other important but unmeasured differences between angiotensin receptor blocker and angiotensin-converting enzyme inhibitor users

The identification and validity of congenital malformation diagnoses in UK electronic health records: A systematic review

PURPOSE: To describe the methods used to identify and validate congenital malformation diagnoses recorded in UK electronic health records, and the results of validation studies. METHODS: Medline and Embase were searched for publications between 1987 and 2019 that involved identifying congenital malformations from UK electronic health records using diagnostic codes. The methods and code-lists used to identify congenital malformations, and the methods and results of validations, were examined. RESULTS: We retrieved 54 eligible studies; 36 identified congenital malformations from primary care data and 18 from secondary care data alone or in combination with birth and/or death records. Identification in secondary care data relied on codes from the 'Q' chapter for congenital malformations in ICD-10. In contrast, studies using primary care data frequently used additional codes outside of the 'P' chapter for congenital malformation diagnoses in Read, although the exact codes used were not always clear. Eight studies validated diagnoses identified in primary care data. The positive predictive value was highest (80%-100%) for congenital malformations overall, major malformations, and heart defects although the validity of the reference standard used was often uncertain. It was lowest for neural tube defects (71%) and developmental hip dysplasia (56%). CONCLUSIONS: Studies identifying congenital malformations from primary care data provided limited details about the methods used. The few validation studies were limited to diagnoses recorded in primary care. Further assessments of all measures of validity in both data sources and of other malformation subgroups are needed, using robust reference standards and adhering to reporting guidelines

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

Supplementary material for: "Preconception management of hyperthyroidism and thyroid status in subsequent pregnancy: a population-based cohort study"

Supplementary tables produced as part of a study of thyroid control in pregnancy among women with hyperthyroidism using CPRD data

Preconception management of hyperthyroidism and thyroid status in subsequent pregnancy: a population-based cohort study

CONTEXT: Optimal thyroid status in pregnancy is essential in reducing the risk of adverse outcomes. The management of hyperthyroidism in women of reproductive age poses unique challenges and it is unclear how preconception treatment strategies impact on thyroid status in subsequent pregnancy. METHODS: We utilised the Clinical Practice Research Datalink (CPRD) database to evaluate all females aged 15-45 years, with a clinical diagnosis of hyperthyroidism and a subsequent pregnancy (January 2000 to December 2017). We compared thyroid status in pregnancy according to preconception treatment, namely, (1) antithyroid drugs up to or beyond pregnancy onset, (2) definitive treatment with thyroidectomy or radioiodine before pregnancy, and (3) no treatment at pregnancy onset. RESULTS: Our study cohort comprised 4712 pregnancies. TSH was measured in only 53.1% of pregnancies of which 28.1% showed suboptimal thyroid status (TSH >4.0 mU/L or TSH reference range). Pregnancies with prior definitive treatment were more likely to have suboptimal thyroid status compared to pregnancies starting during antithyroid drug treatment (OR = 4.72, 95%CI 3.50-6.36). A steady decline in the use of definitive treatment before pregnancy was observed from 2000-2017. A third (32.6%) of first trimester carbimazole-exposed pregnancies were switched to propylthiouracil while 6.0% of propylthiouracil-exposed pregnancies switched to carbimazole. CONCLUSION: The management of women with hyperthyroidism who become pregnant is suboptimal, particularly in those with preconception definitive treatment, and needs urgent improvement. Better thyroid monitoring and prenatal counselling are needed to optimise thyroid status, reduce teratogenic drug exposure, and ultimately reduce the risk of adverse pregnancy outcomes

Acute Cardiovascular Events after Herpes Zoster: A Self-Controlled Case Series Analysis in Vaccinated and Unvaccinated Older Residents of the United States.

BACKGROUND: Herpes zoster is common and can have serious consequences. Additionally, emerging data suggest an increased risk of acute cardiovascular events following herpes zoster. However, to our knowledge, existing association studies compare outcomes between individuals and are therefore vulnerable to between-person confounding. In this study, we used a within-person study design to quantify any short-term increased risk of acute cardiovascular events (stroke and myocardial infarction [MI]) after zoster and to assess whether zoster vaccination modifies this association. METHODS AND FINDINGS: The self-controlled case series method was used to estimate rates of stroke and acute MI in defined periods after herpes zoster compared to other time periods, within individuals. Participants were fully eligible Medicare beneficiaries aged ≥ 65 y with a herpes zoster diagnosis and either an ischemic stroke (n = 42,954) or MI (n = 24,237) between 1 January 2006 and 31 December 2011. Age-adjusted incidence ratios (IRs) for stroke and MI during predefined periods up to 12 mo after zoster relative to unexposed time periods were calculated using conditional Poisson regression. We observed a marked increase in the rate of acute cardiovascular events in the first week after zoster diagnosis: a 2.4-fold increased ischemic stroke rate (IR 2.37, 95% CI 2.17-2.59) and a 1.7-fold increased MI rate (IR 1.68, 95% CI 1.47-1.92), followed by a gradual resolution over 6 mo. Zoster vaccination did not appear to modify the association with MI (interaction p-value = 0.44). We also found no evidence for a difference in the IR for ischemic stroke between vaccinated (IR 1.14, 95% CI 0.75-1.74) and unvaccinated (IR 1.78, 95% CI 1.68-1.88) individuals during the first 4 wk after zoster diagnosis (interaction p-value = 0.28). The relatively few vaccinated individuals limited the study's power to assess the role of vaccination. CONCLUSIONS: Stroke and MI rates are transiently increased after exposure to herpes zoster. We found no evidence for a role of zoster vaccination in these associations. These findings enhance our understanding of the temporality and magnitude of the association between zoster and acute cardiovascular events

Social determinants of pertussis and influenza vaccine uptake in pregnancy: a national cohort study in England using electronic health records.

OBJECTIVE: To examine the social determinants of influenza and pertussis vaccine uptake among pregnant women in England. DESIGN: Nationwide population-based cohort study. SETTING: The study used anonymised primary care data from the Clinical Practice Research Datalink and linked Hospital Episode Statistics secondary care data. PARTICIPANTS: Pregnant women eligible for pertussis (2012-2015, n=68 090) or influenza (2010/2011-2015/2016, n=152 132) vaccination in England. MAIN OUTCOME MEASURES: Influenza and pertussis vaccine uptake. RESULTS: Vaccine uptake was 67.3% for pertussis and 39.1% for influenza. Uptake of both vaccines varied by region, with the lowest uptakes in London and the North East. Lower vaccine uptake was associated with greater deprivation: almost 10% lower in the most deprived quintiles compared with the least deprived for influenza (34.5% vs 44.0%), and almost 20% lower for pertussis (57.7% vs 76.0%). Lower uptake for both vaccines was also associated with non-white ethnicity (lowest among women of black ethnicity), maternal age under 20 years and a greater number of children in the household. The associations between all social factors and vaccine uptake were broadly unchanged in fully adjusted models, suggesting the social determinants of uptake were largely independent of one another. Among 3111 women vaccinated against pertussis in their first eligible pregnancy and pregnant again, 1234 (40%) were not vaccinated in their second eligible pregnancy. CONCLUSIONS: Targeting promotional campaigns to pregnant women who are younger, of non-white ethnicity, with more children, living in areas of greater deprivation or the London or North East regions, has potential to reduce vaccine-preventable disease among infants and pregnant women, and to reduce health inequalities. Vaccination promotion needs to be sustained across successive pregnancies. Further research is needed into whether the effectiveness of vaccine promotion strategies may vary according to social factors

Alcohol Use and Sustained Virologic Response to Hepatitis C Virus Direct-Acting Antiviral Therapy.

IMPORTANCE: Some payers and clinicians require alcohol abstinence to receive direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection. OBJECTIVE: To evaluate whether alcohol use at DAA treatment initiation is associated with decreased likelihood of sustained virologic response (SVR). DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used electronic health records from the US Department of Veterans Affairs (VA), the largest integrated national health care system that provides unrestricted access to HCV treatment. Participants included all patients born between 1945 and 1965 who were dispensed DAA therapy between January 1, 2014, and June 30, 2018. Data analysis was completed in November 2020 with updated sensitivity analyses performed in 2023. EXPOSURE: Alcohol use categories were generated using responses to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses for alcohol use disorder (AUD): abstinent without history of AUD, abstinent with history of AUD, lower-risk consumption, moderate-risk consumption, and high-risk consumption or AUD. MAIN OUTCOMES AND MEASURES: The primary outcome was SVR, which was defined as undetectable HCV RNA for 12 weeks or longer after completion of DAA therapy. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% CIs of SVR associated with alcohol category. RESULTS: Among 69 229 patients who initiated DAA therapy (mean [SD] age, 62.6 [4.5] years; 67 150 men [97.0%]; 34 655 non-Hispanic White individuals [50.1%]; 28 094 non-Hispanic Black individuals [40.6%]; 58 477 individuals [84.5%] with HCV genotype 1), 65 355 (94.4%) achieved SVR. A total of 32 290 individuals (46.6%) were abstinent without AUD, 9192 (13.3%) were abstinent with AUD, 13 415 (19.4%) had lower-risk consumption, 3117 (4.5%) had moderate-risk consumption, and 11 215 (16.2%) had high-risk consumption or AUD. After adjustment for potential confounding variables, there was no difference in SVR across alcohol use categories, even for patients with high-risk consumption or AUD (OR, 0.95; 95% CI, 0.85-1.07). There was no evidence of interaction by stage of hepatic fibrosis measured by fibrosis-4 score (P for interaction = .30). CONCLUSIONS AND RELEVANCE: In this cohort study, alcohol use and AUD were not associated with lower odds of SVR. Restricting access to DAA therapy according to alcohol use creates an unnecessary barrier to patients and challenges HCV elimination goals

Acute maternal infection and risk of pre-eclampsia: a population-based case-control study.

BACKGROUND: Infection in pregnancy may be involved in the aetiology of pre-eclampsia. However, a clear association between acute maternal infection and pre-eclampsia has not been established. We assessed whether acute urinary tract infection, respiratory tract infection, and antibiotic drug prescriptions in pregnancy (a likely proxy for maternal infection) are associated with an increased risk of pre-eclampsia. METHODS AND FINDINGS: We used a matched nested case-control design and data from the UK General Practice Research Database to examine the association between maternal infection and pre-eclampsia. Primiparous women aged at least 13 years and registered with a participating practice between January 1987 and October 2007 were eligible for inclusion. We selected all cases of pre-eclampsia and a random sample of primiparous women without pre-eclampsia (controls). Cases (n=1533) were individually matched with up to ten controls (n=14236) on practice and year of delivery. We calculated odds ratios and 95% confidence intervals for pre-eclampsia comparing women exposed and unexposed to infection using multivariable conditional logistic regression. After adjusting for maternal age, pre-gestational hypertension, diabetes, renal disease and multifetal gestation, the odds of pre-eclampsia were increased in women prescribed antibiotic drugs (adjusted odds ratio 1.28;1.14-1.44) and in women with urinary tract infection (adjusted odds ratio 1.22;1.03-1.45). We found no association with maternal respiratory tract infection (adjusted odds ratio 0.91;0.72-1.16). Further adjustment for maternal smoking and pre-pregnancy body mass index made no difference to our findings. CONCLUSIONS: Women who acquire a urinary infection during pregnancy, but not those who have a respiratory infection, are at an increased risk of pre-eclampsia. Maternal antibiotic prescriptions are also associated with an increased risk. Further research is required to elucidate the underlying mechanism of this association and to determine whether, among women who acquire infections in pregnancy, prompt treatment or prophylaxis against infection might reduce the risk of pre-eclampsia