Estimation of age-specific rates of reactivation and immune boosting of the varicella zoster virus

Studies into the impact of vaccination against the varicella zoster virus (VZV) have increasingly focused on herpes zoster (HZ), which is believed to be increasing in vaccinated populations with decreasing infection pressure. This idea can be traced back to Hope-Simpson's hypothesis, in which a person's immune status determines the likelihood that he/she will develop HZ. Immunity decreases over time, and can be boosted by contact with a person experiencing varicella (exogenous boosting) or by a reactivation attempt of the virus (endogenous boosting). Here we use transmission models to estimate age-specific rates of reactivation and immune boosting, exogenous as well as endogenous, using zoster incidence data from the Netherlands (2002–2011, n = 7026). The boosting and reactivation rates are estimated with splines, enabling these quantities to be optimally informed by the data. The analyses show that models with high levels of exogenous boosting and estimated or zero endogenous boosting, constant rate of loss of immunity, and reactivation rate increasing with age (to more than 5% per year in the elderly) give the best fit to the data. Estimates of the rates of immune boosting and reactivation are strongly correlated. This has important implications as these parameters determine the fraction of the population with waned immunity. We conclude that independent evidence on rates of immune boosting and reactivation in persons with waned immunity are needed to robustly predict the impact of varicella vaccination on the incidence of HZ.PIENTER2 serological stud

The impact of influenza vaccination on infection, hospitalisation and mortality in the Netherlands between 2003 and 2015.

Influenza epidemics annually cause substantial morbidity and mortality. For this reason, vaccination is offered yearly to persons with an elevated risk for complications. Assessments of the impact of vaccination are, however, hampered by year-to-year variation in epidemic size and vaccine effectiveness. We estimate the impact of the current vaccination programme comparing simulations with vaccination to counterfactual simulations without vaccination. The simulations rely on an age- and risk-structured transmission model that tracks the build-up and loss of immunity over successive seasons, and that allows the vaccine match to vary between seasons. The model parameters are estimated with a particle Monte Carlo method and approximate Bayesian computation, using epidemiological data on vaccine effectiveness and epidemic size in the Netherlands over a period of 11 years. The number of infections, hospitalisations and deaths vary greatly between years because waning of immunity and vaccine match may differ every season, which is in line with observed variation in influenza epidemic sizes. At an overall coverage of 21%, vaccination has averted on average 13% (7.2-19%, 95% range) of infections, 24% (16-36%) of hospitalisations, and 35% (16-50%) of deaths. This suggests that vaccination is mainly effective in protecting vaccinees from infection rather than reducing transmission. As the Dutch population continues to grow and age, the vaccination programme is projected (up to 2025) to gain in impact, despite a decreasing infection attack rate

Self-reported medication adherence instruments and their applicability in low-middle income countries:a scoping review

INTRODUCTION: Medication non-adherence is an important public health issue, associated with poor clinical and economic outcomes. Globally, self-reported instruments are the most widely used method to assess medication adherence. However, the majority of these were developed in high-income countries (HICs) with a well-established health care system. Their applicability in low- and middle-income countries (LMICs) remains unclear. The objective of this study is to systematically review the applicability of content and use of self-reported adherence instruments in LMICs.METHOD: A scoping review informed by a literature search in Pubmed, EBSCO, and Cochrane databases was conducted to identify studies assessing medication adherence using self-reported instruments for patients with five common chronic diseases [hypertension, diabetes, dyslipidemia, asthma, or Chronic Obstructive Pulmonary Disease (COPD)] in LMICs up to January 2022 with no constraints on publication year. Two reviewers performed the study selection process, data extraction and outcomes assessment independently. Outcomes focused on LMIC applicability of the self-reported adherence instruments assessed by (i) containing LMIC relevant adherence content; (ii) methodological quality and (iii) fees for use.FINDINGS: We identified 181 studies that used self-reported instruments for assessing medication adherence in LMICs. A total of 32 distinct types of self-reported instruments to assess medication adherence were identified. Of these, 14 self-reported instruments were developed in LMICs, while the remaining ones were adapted from self-reported instruments originally developed in HICs. All self-reported adherence instruments in studies included presented diverse potential challenges regarding their applicability in LMICs, included an underrepresentation of LMIC relevant non-adherence reasons, such as financial issues, use of traditional medicines, religious beliefs, lack of communication with healthcare provider, running out of medicine, and access to care. Almost half of included studies showed that the existing self-reported adherence instruments lack sufficient evidence regarding cross cultural validation and internal consistency. In 70% of the studies, fees applied for using the self-reported instruments in LMICs.CONCLUSION: There seems insufficient emphasis on applicability and methodological rigor of self-reported medication adherence instruments used in LMICs. This presents an opportunity for developing a self-reported adherence instrument that is suitable to health systems and resources in LMICs.SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022302215.</p

Influence of single and multiple doses of amifostine on the efficacy and the pharmacokinetics of carboplatin in mice.

We have previously reported that amifostine potentiates the anti-tumour activity of carboplatin in mice. The present study was carried out in well-established human ovarian cancer xenografts OVCAR-3, A2780 and FMa grown subcutaneously in the nude mouse. It was found that a single dose of amifostine resulted in a higher increase in the anti-tumour activity of carboplatin than three doses of amifostine. A single dose of amifostine increased the AUC (area under the curve) values of total platinum in plasma ultrafiltrate (30.1 vs 18.2 microM x h), liver (307.7 vs 236.4 nmol g(-1) x h), kidney (500.8 vs 368.3 nmol g(-1) x h) and OVCAR-3 tumour tissue (184.0 vs 146.8 nmol g(-1) x h). Despite this increase in total platinum, a decrease in platinum (Pt)-DNA adduct levels was observed in liver, kidney and bone marrow, which was significant in liver. In tumour tissue an insignificant increase in Pt-DNA adduct levels, specifically the Pt-GG adduct, was observed after treatment with a single dose of amifostine, which may explain the increase in anti-tumour activity. The increase in the AUC of total platinum was probably caused by a reduction in body temperature, which was most severe after three doses of amifostine. The extreme hypothermia may be the reason that three doses of amifostine resulted in less potentiation of the efficacy of carboplatin

Empathy Gaps Between Helpers and Help-Seekers: Implications for Cooperation

Help-seekers and potential helpers often experience an “empathy gap” – an inability to understand each other’s unique perspectives. Both parties are concerned about their reputation, self-esteem, and relationships, but these concerns differ in ways that lead to misinterpretation of the other party’s actions, and, in turn, missed opportunities for cooperation. In this article, we review research that describes the role-specific concerns of helpers and help-seekers. We then review studies of emotional perspective-taking, which can help explain why help-seekers and helpers often experience empathy gaps. We go on to discuss recent work that illustrates the consequences of empathy gaps between helpers and help-seekers—social prediction errors that prevent helping and misguided intentions that can lead to unhelpful help. Finally, we discuss some promising directions for future research

Clinical and economic burden of drug-susceptible tuberculosis in Indonesia:national trends 2017-19

BACKGROUND: The global incidence of tuberculosis is decreasing, yet it remains high in Indonesia. The Indonesian National Tuberculosis Program facilitates mandatory notification, which enables early detection and treatment, minimises complications, prevents transmission, and decreases deaths. This study aimed to assess the characteristics, trends, and economic burden of notified drug-susceptible tuberculosis cases registered in this system from 2017 to 2019. METHODS: We performed a multiyear cross-sectional study focusing on drug-susceptible tuberculosis notified cases, incidence, geographical tuberculosis case distribution, treatment outcomes, and costs in Indonesia using data from Sistem Informasi Tuberkulosis (2017-19). The settings were Indonesian health-care facilities that provide tuberculosis control programmes and services. Eligible patients were those who were diagnosed with drug-susceptible tuberculosis and notified to Sistem Informasi Tuberkulosis. FINDINGS: Between 2017 and 2019, notified cases increased from 429 219 to 523 614 individuals, corresponding to an increase in incidence from 167 cases per 100 000 to 196 cases per 100 000. In 2019, more than 250 cases per 100 000 inhabitants were notified in Jakarta, North Sulawesi, Gorontalo, and Papua. Treatment success rate increased from 363 098 (84·60%) of 429 219 in 2017 to 452 966 (86·51%) of 523 614 in 2019, with a relatively stable mortality, changing from 3·15% to 3·05%. HIV status was increasingly confirmed, with unknown status decreasing from 66·21% to 43·68%. The costs of visits and monitoring and drug regimens were relatively stable, with total direct medical costs slightly increasing from US$39·40 to$40·40 per case. INTERPRETATION: Progress was made on drug-susceptible tuberculosis management in Indonesia. However, further intensified efforts, including case-finding, optimising diagnosis, and cost-effective tuberculosis management are required if Indonesia is to achieve the 2025 WHO End Tuberculosis Strategy target incidence of fewer than 55 cases per 100 000 people. These data are an important starting point for understanding drug-susceptible tuberculosis dynamics in Indonesia and optimising its management. FUNDING: Directorate General of Higher Education; Ministry of Education, Culture, Research, and Technology of the Republic of Indonesia

Sex Differences in Incidence of Respiratory Symptoms and Management by General Practioners

Background: Differences between women and men play an important role in lung physiology and epidemiology of respiratory diseases, but also in the health care processes. Objective: To analyse sex differences in patients encountering their general practitioner (GP) with respiratory symptoms with regard to incidence, GP's management and final diagnoses. Methods: Retrospective cohort study, using data of the Dutch Practice Based Research Network. All patients who encountered their GP from 01-07-2013 until 30-06-2018 with a new episode of care starting with a reason for encounter in the respiratory category (R) of the ICPC-2 classification were included (n = 16 773). Multi-level logistic regression was used to analyse influence of patients' sex on management of GPs with adjustment for possible confounders. Results: We found a significant higher incidence of respiratory symptoms in women than in men: 230/1000 patient years [95% confidence interval (CI) 227-232] and 186/1000 patient years (95% CI 183-189), respectively. When presenting with cough, GPs are more likely to perform physical examination [odds ratio (OR) 1.22; 95% CI 1.11-1.35] and diagnostic radiology (OR 1.25; 95% CI 1.08-1.44), but less likely to prescribe medication (OR 0.88; 95% CI 0.82-0.95) in men. When visiting the GP with dyspnoea, men more often undergo diagnostic imaging (OR 1.32; 95% CI 1.05-1.66) and are more often referred to a specialist (OR 1.35; 95% CI 1.13-1.62). Conclusions: Women encounter their GP more frequently with respiratory symptoms than men and GPs perform more diagnostic investigations in men. We suggest more research in general practice focussing on sex differences and possible confounders