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Background: No gold standard diagnostic test exists for latent tuberculosis infection (LTBI). The intra-dermal tuberculin skin test (TST) has known limitations and Interferon-gamma release assays (IGRA) have been developed as an alternative. We aimed to assess agreement between IGRA and TST, and risk factors for test positivity, in Indonesian healthcare students., Methods: Medical and nursing students starting their clinical training were screened using IGRA and TST. Agreement between the two tests was measured using Cohen's Kappa coefficient. Logistic regression was used to identify factors associated with test positivity., Results: Of 266 students, 43 (16.2%) were IGRA positive and 85 (31.9%) TST positive. Agreement between the two tests was 74.7% (kappa 0.33, 95% CI 0.21-0.45, P<0.0001). Students who had direct contact with family or friends with TB were less likely to be test positive using IGRA (AOR 0.18, 95% CI 0.05-0.64) and using TST (AOR 0.51, 95% CI 0.26-0.99)., Conclusion: Test positivity for LTBI was lower when measured by IGRA than by TST, with poor agreement between the two tests. Known close TB contact was unexpectedly negatively associated with positivity by either test. Longitudinal studies may be required to help determine the best test for LTBI in healthcare students in Indonesia., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Apriani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The outcomes of palliative radiation therapy (RT) for neuroendocrine neoplasms (NEN) are seldom reported. We investigated outcomes following palliative radiotherapy in a cohort of patients with NENs. We hypothesised that well-differentiated NEN will be less likely to have a clinical response than poorly differentiated NEN., Methods: Patients who received at least one course of palliative RT were identified using the New Zealand NETwork! Registry. Patients with Merkel cell carcinoma, pulmonary small cell carcinoma or asymptomatic patients were excluded. Clinical response to RT within 90 days and overall survival were analysed alongside clinical variables (fractionation, RT site, tumour differentiation and tumour primary site)., Results: The cohort comprised 79 patients, with 147 courses of palliative RT delivered. Clinical response was measurable for 100 courses, with clinical response rate of 76%. A course delivered to a well-differentiated NEN was associated with 2.02-fold (95% CI 0.67, 6.12; P = 0.21) increase in odds of a clinical response compared to a poorly differentiated NEN. Median overall survival from the first fraction of RT was 94 days (95% CI 80, 138 days). Overall survival was higher in well-differentiated NEN than in poorly differentiated NEN (HR 0.2, 95% CI 0.10-0.40, P-value < 0.001); 30-day mortality was 7%. There were significantly reduced odds of clinical response for non-bone sites, and for courses >10 fractions compared to a single fraction., Conclusion: Palliative RT is an appropriate option for management of symptoms in patients with both well- and poorly differentiated metastatic NEN., (© 2023 The Authors. Journal of Medical Imaging and Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Radiologists.)

Purpose: This intensified case finding study aimed to evaluate the prevalence of tuberculosis (TB) disease among people with HIV entering the largest prison in Malaysia., Design/methodology/approach: The study was conducted in Kajang prison, starting in July 2013 in the men's prison and June 2015 in the women's prison. Individuals tested positive for HIV infection, during the mandatory HIV testing at the prison entry, were consecutively recruited over five months at each prison. Consented participants were interviewed using a structured questionnaire and asked to submit two sputum samples that were assessed using GeneXpert MTB/RIF (Xpert) and culture, irrespective of clinical presentation. Factors associated with active TB (defined as a positive result on either Xpert or culture) were assessed using regression analyses., Findings: Overall, 214 incarcerated people with HIV were recruited. Most were men (84.6%), Malaysians (84.1%) and people who inject drugs (67.8%). The mean age was 37.5 (SD 8.2) years, and median CD4 lymphocyte count was 376 cells/mL (IQR 232-526). Overall, 27 (12.6%) TB cases were identified, which was independently associated with scores of five or more on the World Health Organization clinical scoring system for prisons (ARR 2.90 [95% CI 1.48-5.68])., Originality/value: Limited data exists about the prevalence of TB disease at prison entry, globally and none from Malaysia. The reported high prevalence of TB disease in the study adds an important and highly needed information to design comprehensive TB control programmes in prisons., (© Emerald Publishing Limited.)

Diabetes mellitus (DM) increases the risk of developing tuberculosis infection (TBI). However, the evidence on the burden and phenotypic characteristics of TBI in African patients with DM is limited. This study aimed to determine the prevalence and characterisation of TBI in native African patients living with DM. We searched PubMed, EMBASE, and African Journals Online for original studies reporting information on the prevalence and characteristics of TBI in adult Africans with DM. A forest plot was used to describe the pooled prevalence estimate of TBI and the corresponding 95% confidence intervals (CI). Six studies conducted in four African countries involving 721 participants with DM were included in this systematic review. The pooled prevalence estimate of TBI was 40% (95% CI 20-60%, I 2  = 98.52%, p < 0.001). Age ≥ 40 years and glycated haemoglobin levels independently predicted TBI positivity in patients with DM in three studies. Africans with DM have a high prevalence of TBI, especially those who are older or with poorly controlled diabetes. This justifies the need for studies to explore how to screen and manage TBI to avert the progression to active TB disease., (© 2023. The Author(s).)

Introduction: Liberia was heavily affected by the 2014-2016 Ebola virus disease (EVD) outbreak. With substantial investments in interventions to combat future outbreaks, it is hoped that Liberia is well prepared for a new incursion. We assessed the performance of the current EVD surveillance system in Liberia, focusing on its ability to promptly detect a new EVD outbreak., Methods: We integrated WHO and US Centers for Disease Control and Prevention guidelines for public health surveillance system evaluation and used standardised indicators to measure system performance. We conducted 23 key informant interviews, 150 health facility assessment surveys and a standardised patient (SP) study (19 visits) from January 2020 to January 2021. Data were summarised and a gap analysis conducted., Results: We found basic competencies of case detection and reporting necessary for a functional surveillance system were in place. At the higher (national, county and district) levels, we found performance gaps in 2 of 6 indicators relating to surveillance system structure, 3 of 14 indicators related to core functions, 1 of 5 quality indicators and 2 of 8 indicators related to support functions. The health facility assessment found performance gaps in 9 of 10 indicators related to core functions, 5 of 6 indicators related to support functions and 3 of 7 indicators related to quality. The SP simulations revealed large gaps between expected and actual practice in managing a patient warranting investigation for EVD. Major challenges affecting the system's operations across all levels included limited access to resources to support surveillance activities, persistent stock out of sample collection materials and attrition of trained staff., Conclusion: The EVD surveillance system in Liberia may fail to promptly detect a new EVD outbreak. Specific improvements are required, and regular evaluations recommended. SP studies could be crucial in evaluating surveillance systems for rarely occurring diseases that are important to detect early., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Clinical trials are a critical element of a modern, high-functioning, learning healthcare system. Clinical trials provide access to novel, as yet unfunded treatments, and deliver cutting-edge healthcare. Evidence from clinical trials ensures appropriateness of healthcare, allows disinvestment from practices that are found not to improve outcomes or be cost-effective, and supports the introduction of new approaches, all of which leads to improvement in health outcomes. In 2020, Manatū Hauora - Ministry of Health and The Health Research Council of New Zealand funded a project to understand the current state of clinical trial activity in Aotearoa New Zealand and to propose the infrastructure required to support equitable clinical trial activity, in order to ensure that trials benefiting from publicly funded infrastructure are responsive to the needs of New Zealanders and ultimately enable equitable delivery of the best healthcare we can achieve to all New Zealanders. This viewpoint reports the process that was undertaken to develop the final proposed infrastructure and the rationale for the approach. The restructuring of the Aotearoa New Zealand health system into Te Whatu Ora - Health New Zealand and Te Aka Whai Ora - Māori Health Authority that will both operate hospital services and commission primary and community healthcare at a national level provides the ideal opportunity to integrate and embed research into Aotearoa New Zealand's healthcare system. Integration of clinical trials and research more broadly into the public healthcare system will require a significant shift in the culture within our healthcare system. Research must be recognised and promoted as a core activity for clinical staff at all levels of the healthcare system, rather than something to be tolerated or even hindered. Strong leadership will be required from the top of Te Whatu Ora - Health New Zealand down to ensure the required cultural shift to recognise the value of clinical trials to all aspects of the healthcare system, and to grow capability and capacity of the health research workforce. The investment required by the Government to implement the proposed clinical trial infrastructure will be substantial, but now is the ideal time for investment in clinical trials infrastructure in Aotearoa New Zealand. We urge the Government to be bold and invest now to ensure the benefits can be reaped for all New Zealanders in years to come., Competing Interests: Lisa K Stamp, Matire Harwood, Stuart Dalziel, Katrina Sharples, and Frank Bloomfield are active clinical triallists. Funding from Health Research Council of New Zealand and the Ministry of Health., (© PMA.)

Objective: Contemporary data on the attainment of optimal diabetes treatment goals and the burden of diabetes complications in adult populations with type 2 diabetes in Africa are lacking. We aimed to document the current status of attainment of three key indicators of optimal diabetes care and the prevalence of five diabetes complications in adult African populations with type 2 diabetes., Methods: We systematically searched Embase, PubMed and the Cochrane library for published studies from January 2000 to December 2020. Included studies reported any information on the proportion of attainment of optimal glycated haemoglobin (HbA1c), blood pressure (BP) and low-density lipoprotein cholesterol (LDLC) goals and/or prevalence of five diabetes complications (diabetic peripheral neuropathy, retinopathy, nephropathy, foot ulcers and peripheral arterial disease). Random effect model meta-analysis was performed to determine the pooled proportion of attainment of the three treatment goals and the prevalence of five diabetes complications., Results: In total, 109 studies with a total of 63 890 participants (53.3% being females) were included in the meta-analysis. Most of the studies were conducted in Eastern African countries (n=44, 40.4%). The pooled proportion of attainment of an optimal HbA1c, BP and LDLC goal was 27% (95% CI 24 to 30, I 2 =94.7%), 38% (95% CI 30 to 46, I 2 =98.7%) and 42% (95% CI 32 to 52, I 2 =97.4%), respectively. The pooled prevalence of diabetic peripheral neuropathy, retinopathy, diabetic nephropathy, peripheral arterial disease and foot ulcers was 38% (95% CI 31 to 45, I 2 =98.2%), 32% (95% CI 28 to 36, I 2 =98%), 31% (95% CI 22 to 41, I 2 =99.3%), 19% (95% CI 12 to 25, I 2 =98.1%) and 11% (95% CI 9 to 14, I 2 =97.4%), respectively., Conclusion: Attainment of optimal diabetes treatment goals, especially HbA1c, in adult patients with type 2 diabetes in Africa remains a challenge. Diabetes complications, especially diabetic peripheral neuropathy and retinopathy, are highly prevalent in adult populations with type 2 diabetes in Africa., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Healthcare workers (HCWs), especially in high tuberculosis (TB) incidence countries, are at risk of Mycobacterium tuberculosis infection and TB disease, likely due to greater exposure to TB cases and variable implementation of infection control measures., Aim: We aimed to estimate the prevalence of tuberculin skin test (TST) positivity, history of TB and to identify associated risk factors in HCWs employed at a tertiary referral hospital in Bandung, Indonesia., Methods: A cross-sectional study was conducted from April to August 2018. A stratified sample of the HCWs were recruited, screened by TST, assessed for TB symptoms, history of TB disease and possible risk factors. Prevalence of positive TST included diagnosis with TB after starting work. HCWs with TB disease diagnosed earlier were excluded. Survey weights were used for all analyses. Possible risk factors were examined using logistic regression; adjusted odds ratios and 95% confidence intervals (CI) are presented., Results: Of 455 HCWs recruited, 42 reported a history of TB disease (25 after starting work) and 395 had a TST result. The prevalence of positive TST was 76.9% (95% CI 72.6-80.8%). The odds increased by 7% per year at work (95% CI 3-11%) on average, with a rapid rise in TST positivity up to 10 years of work and then a plateau with around 80% positive., Discussion: A high proportion of HCWs had a history of TB or were TST positive, increasing with longer duration of work. A package of TB infection control measures is needed to protect HCWs from Mycobacterium tuberculosis infection., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Diabetes mellitus (DM) increases the risk of tuberculosis (TB) and will hamper global TB control due to the dramatic rise in type 2 DM in TB-endemic settings. In this trial, we will examine the efficacy and safety of TB preventive therapy against the development of TB disease in people with DM who have latent TB infection (LTBI), with a 12-week course of rifapentine and isoniazid (3HP)., Methods: The 'Prevention of tuberculosis in diabetes mellitus' (PROTID) consortium will randomise 3000 HIV-negative eligible adults with DM and LTBI, as evidenced by a positive tuberculin skin test or interferon gamma release assay, to 12 weeks of 3HP or placebo. Participants will be recruited through screening adult patients attending DM clinics at referral hospitals in Tanzania and Uganda. Patients with previous TB disease or treatment with a rifamycin medication or isoniazid (INH) in the previous 2 years will be excluded. The primary outcome is the occurrence of definite or probable TB disease; secondary outcome measures include adverse events, all-cause mortality and treatment completion. The primary efficacy analysis will be intention-to-treat; per-protocol analyses will also be carried out. We will estimate the ratio of TB incidence rates in intervention and control groups, adjusting for the study site using Poisson regression. Results will be reported as efficacy estimates (1-rate ratio). Cumulative incidence rates allowing for death as a competing risk will also be reported. Approximately 1000 LTBI-negative, HIV-negative participants will be enrolled consecutively into a parallel cohort study to compare the incidence of TB in people with DM who are LTBI negative vs positive. A number of sub-studies will be conducted among others to examine the prevalence of LTBI and active TB, estimate the population impact and cost-effectiveness of LTBI treatment in people living with DM in these African countries and address gaps in the prevention and therapeutic management of combined TB-DM., Discussion: PROTID is anticipated to generate key evidence to guide decisions over the use of TB preventive treatment among people with DM as an important target group for better global TB control., Trial Registration: ClinicalTrials.gov NCT04600167 . Registered on 23 October 2020., (© 2022. The Author(s).)

Background: Health care workers (HCWs) in low- and middle-income countries (LMICs) continue to have an unacceptably high prevalence and incidence of Mycobacterium tuberculosis infection due to high exposure to tuberculosis (TB) cases at health care facilities and often inadequate infection control measures. This can contribute to an increased risk of transmission not only to HCWs themselves but also to patients and the general population., Aim: We assessed implementation of TB infection control measures in primary health centres (PHCs) in Bandung, Indonesia, and TB knowledge among HCWs., Methods: A cross-sectional study was conducted between May and November 2017 amongst a stratified sample of the PHCs, and their HCWs, that manage TB patients in Bandung . Questionnaires were used to assess TB infection control measures plus HCW knowledge. Summary statistics, linear regression and the Kruskal-Wallis test were used for analysis., Results: The median number of TB infection control measures implemented in 24 PHCs was 21 of 41 assessed. Only one of five management controls was implemented, 15 of 24 administrative controls, three of nine environmental controls and one of three personal respiratory protection controls. PHCs with TB laboratory facilities and high TB case numbers were more likely to implement TB infection control measures than other PHCs ( p =0.003). In 398 HCWs, the median number of correct responses for knowledge was 10 (IQR 9-11) out of 11., Discussion: HCWs had good TB knowledge. TB infection control measures were generally not implemented and need to be strengthened in PHCs to reduce M. tuberculosis transmission to HCWs, patients and visitors., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: Medical and nursing students entering their clinical programmes are at increased risk for tuberculosis (TB) in TB-endemic settings. Relatively little is known about Mycobacterium tuberculosis infection among such students in high-endemic countries., Methods: We examined M. tuberculosis infection among medical and nursing students starting clinical training in Bandung, Indonesia using interferon-γ release assay (IGRA) QuantiFERON-TB Gold Plus. IGRA-negative students had a repeat test after 1 y and logistic regression was used to identify factors associated with IGRA positivity or conversion., Results: There were 379 students included in this study: 248 (65.4%) were medical students and 131 (34.6%) were nursing students. Of 379 students, 70 (18.5%) were IGRA positive at baseline. Of 293 IGRA-negative students with 1-y results, 26 (8.9%) underwent IGRA conversion. Being a medical student (adjusted relative risk [ARR] 5.15 [95% confidence interval {CI} 1.82 to 14.59], p=0.002) and participation in sputum collection or bronchoscopy were associated with IGRA conversion (ARR 2.74 [95% CI 1.29 to 5.79], p=0.008)., Conclusions: Medical and nursing students entering clinical training are at high risk of M. tuberculosis infection and need improved infection prevention and control strategies., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Depression during pregnancy is associated with a number of negative impacts on maternal and infant health, therefore good control of depression in pregnant women is crucial. There is a lack of population-level information about patterns of antidepressant use during pregnancy in New Zealand., Aim: To describe antidepressant dispensing patterns before, during, and after pregnancy in New Zealand, 2005-2014., Materials and Methods: Antidepressant dispensing records from 270 days prior to pregnancy through to 360 days after pregnancy end were linked with 805 990 pregnancies in the New Zealand Pregnancy Cohort. Proportions (and 95% confidence intervals) with at least one dispensing were calculated for the periods before, during, and after pregnancy and compared over time and by maternal characteristics., Results: Dispensing during the first trimester was lower than in the pre-pregnancy and post-pregnancy periods, and dropped further in later trimesters. The proportion of pregnancies during which an antidepressant was dispensed rose from 3.1 to 4.9% over the study years. Around 80% of those with a dispensing received a selective serotonin reuptake inhibitor. Dispensing before, during, and after pregnancy varied by ethnicity, age, smoking status, and body mass index. Among women taking an antidepressant before pregnancy, younger women and those of Māori, Pacific, or Asian ethnicity were less likely to continue therapy during pregnancy., Conclusions: This study has established a baseline for antidepressant use around pregnancy in New Zealand, documented increasing use over time, and demonstrated that known ethnic differences in antidepressant use are also evident in the pregnant population., (© 2021 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Coronary heart disease occurs more frequently among patients with chronic obstructive pulmonary disease (COPD) compared to those without COPD. While some research suggests that long-acting bronchodilators might confer an additional risk of acute coronary syndrome (ACS), information from real-world clinical practice about the cardiovascular impact of using two versus one long-acting bronchodilator for COPD is limited. We undertook a population-based nested case-control study to estimate the risk of ACS in users of both a long-acting muscarinic antagonist (LAMA) and a long-acting beta2-agonist (LABA) relative to users of a LAMA., Methods: The study was based on the primary care PREDICT Cardiovascular Disease Cohort and linked data from regional laboratories and the New Zealand Ministry of Health's national data collections. The underlying cohort (n = 29,993) comprised patients aged 45-84 years, who initiated treatment with a LAMA and/or LABA for COPD between 1 February 2006 and 11 October 2016. 1490 ACS cases were matched to 13,550 controls by date of birth, sex, date of cohort entry (first long-acting bronchodilator dispensing), and COPD severity., Results: Relative to current use of LAMA therapy, current use of LAMA and LABA dual therapy was associated with a significantly higher risk of ACS (adjusted OR = 1.72; [95% CI: 1.28-2.31])., Conclusion: Dual long-acting bronchodilator therapy, rather than LAMA mono-therapy, could increase the risk of ACS by more than 50%. This has important implications for decisions about the potential benefit/harm ratio of COPD treatment intensification, given the modest benefits of dual therapy., (© 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background. A significant proportion of tuberculosis (TB) patients globally make their initial visit for medical care to either an informal provider or a private practitioner, and many are not formally notified. Involvement of private practitioners (PPs) in a public-private mix for TB (TB-PPM) provides an opportunity for improving TB control. However, context-specific interventions beyond public-private agreements and mandatory notification are needed. In this study we will evaluate whether a tailored intervention package can increase TB notifications from PPs in Indonesia. Methods. This is a cluster-randomized trial of a multi-component public health intervention. 36 community health centre (CHC) areas will be selected as study locations and randomly allocated to intervention and control arms (1:1). PPs in the intervention areas will be identified using a mapping exercise and recruited into the study if they are eligible and consent. They will receive a tailored intervention package including in-person education about TB management along with bimonthly electronic refreshers, context-specific selection of referral pathways, and access to a TB-reporting app developed in collaboration with the National TB programme. The primary hypothesis is that the intervention package will increase the TB notification rate. The primary outcome will be measured by collecting notification data from the CHCs in intervention and control arms at the end of a 1-year observation period and comparing with the 1-year pre-intervention. The primary analysis will be intention-to-treat at the cluster level, using a generalised mixed model with repeated measures of TB notifications for 1 year pre- and 1 year post-intervention. Discussion. The results from this study will provide evidence on whether a tailored intervention package is effective in increasing the number of TB notifications, and whether the PPs refer presumptive TB cases correctly. The study results will guide policy in the development of TB-PPM in Indonesia and similar settings., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Hadisoemarto PF et al.)

Aim: To describe the patterns of discontinuation and reinitiation in new users of metformin monotherapy in New Zealand, overall and according to person- and healthcare-related factors., Materials and Methods: We created a cohort (n = 85,066) of all patients in New Zealand with type 2 diabetes mellitus who initiated metformin monotherapy between 1 January 2006 and 30 September 2014 from the national data collections, and followed them until the earlier of their death or 31 December 2015. Discontinuation was defined as a gap in possession of metformin monotherapy of ≥90 days. We explored patterns of discontinuation and reinitiation using competing risks methods., Results: After 1 year of follow-up, 28% of cohort members had discontinued metformin monotherapy at least once; the corresponding figures after 2 and 5 years were 37% and 46%. The proportions who reinitiated metformin monotherapy within 1, 2, and 5 years of their first discontinuation were 23%, 49%, and 73%. Discontinuation after the first reinitiation was common (48% after 1 year). Discontinuation and reinitiation varied by age, ethnicity, and other person- and healthcare-related factors., Discussion: Our findings highlight the dynamic nature of metformin monotherapy use, show that substantial periods of non-use are common, and identify priority populations for interventions to facilitate adherence., Competing Interests: The authors have declared that no competing interests exist.

Background: Cardiovascular comorbidity is common among patients with chronic obstructive pulmonary disease (COPD) and there is concern that long-acting bronchodilators (long-acting muscarinic antagonists (LAMAs) and long-acting beta 2 agonists (LABAs)) may further increase the risk of acute coronary events. Information about the impact of treatment intensification on acute coronary syndrome (ACS) risk in real-world settings is limited. We undertook a nationwide nested case-control study to estimate the risk of ACS in users of both a LAMA and a LABA relative to users of a LAMA., Methods: We used routinely collected national health and pharmaceutical dispensing data to establish a cohort of patients aged > 45 years who initiated long-acting bronchodilator therapy for COPD between 1 February 2006 and 30 December 2013. Fatal and non-fatal ACS events during follow-up were identified using hospital discharge and mortality records. For each case we used risk set sampling to randomly select up to 10 controls, matched by date of birth, sex, date of cohort entry (first LAMA and/or LABA dispensing), and COPD severity., Results: From the cohort (n=83 417), we identified 5399 ACS cases during 281 292 person-years of follow-up. Compared with current use of LAMA therapy, current use of LAMA and LABA dual therapy was associated with a higher risk of ACS (OR 1.28 (95% CI 1.13 to 1.44)). The OR in an analysis restricted to fatal cases was 1.46 (95% CI 1.12 to 1.91)., Conclusion: In real-world clinical practice, use of two versus one long-acting bronchodilator by people with COPD is associated with a higher risk of ACS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To describe prescription medicine dispensing before and during pregnancy in New Zealand, 2005-2015., Methods: Members of the New Zealand Pregnancy Cohort were linked with their dispensing records in a national database of prescription products dispensed from community pharmacies. We identified the proportion of pregnancies during which at least one prescription medicine was dispensed, the number of different medicines used and the most commonly dispensed medicine groups both during pregnancy and in the 270 days before conception. Dispensing during pregnancy was assessed by several maternal characteristics., Results: 874,884 pregnancies were included. Over the study timeframe, the proportion of pregnancies exposed to a non-supplement prescription medicine increased from 38.5% to 67.2%. The mean number of different non-supplement medicines dispensed during pregnancy increased from 2.5 to 3.2. Dispensing during pregnancy was weakly associated with body mass index, smoking status and ethnicity. Pregnancy exposure was highest for Antibacterials (26.0%), Analgesics (16.7%) and Antinausea & Vertigo Agents (11.0%)., Conclusions: From 2005-2015, both the proportion of exposed pregnancies and the number of different medicines dispensed to pregnant women in New Zealand increased., Competing Interests: The authors have declared that no competing interests exist.

Purpose: This study describes dispensing of potentially teratogenic prescription medicines before and during pregnancy in New Zealand over the period 2005-2015., Methods: Records in a national dispensing database were linked with the members of the New Zealand Pregnancy Cohort to determine the proportion of pregnancies with at least one dispensing of a Category D or X medicine, using the Australian pregnancy risk categorisation system. Exposure was examined from 270 days prior to conception through to the end of pregnancy. Pregnancy outcomes of D/X-exposed pregnancies were reviewed., Results: In the study, 874,884 pregnancies were included. Overall, Category D and X medicines were dispensed during 4.3% and 0.058% of pregnancies, respectively. After excluding misoprostol, X exposure decreased to 0.035%. Generally, dispensing declined through the 270-day pre-pregnancy period and continued to decline throughout pregnancy. Dispensing of X medicines increased over the study timeframe, whereas dispensing of D medicines increased from 2005 to 2011 then declined slightly. Smokers were more likely than non-smokers to have been dispensed a D/X medicine, and compared with European women, Māori and Pacific women were less likely to have been dispensed a D/X medicine. Excluding misoprostol, pregnancies exposed to an X medicine were more likely than D/X-unexposed pregnancies to have ended in termination., Conclusion: Dispensing of potentially harmful medicines in pregnancy in New Zealand was low, particularly for Category X medicines. However, exposure did increase over the study timeframe. The inclusion of pregnancies that did not progress past early pregnancy better reflects population-level pregnancy exposure to potentially teratogenic medicines.

Background: A proportion of tuberculosis (TB) case contacts do not become infected, even when heavily exposed. We studied the innate immune responses of TB case contacts to understand their role in protection against infection with Mycobacterium tuberculosis, termed "early clearance.", Methods: Indonesian household contacts of TB cases were tested for interferon-γ release assay (IGRA) conversion between baseline and 14 weeks post recruitment. Blood cell populations and ex vivo innate whole blood cytokine responses were measured at baseline and, in a subgroup, flow cytometry was performed at weeks 2 and 14. Immunological characteristics were measured for early clearers, defined as a persistently negative IGRA at 3 months, and converters, whose IGRA converted from negative to positive., Results: Among 1347 case contacts, 317 were early clearers and 116 were converters. Flow cytometry showed a resolving innate cellular response from 2 to 14 weeks in persistently IGRA-negative contacts but not converters. There were no differences in cytokine responses to mycobacterial stimuli, but compared to converters, persistently IGRA-negative contacts produced more proinflammatory cytokines following heterologous stimulation with Escherichia coli and Streptococcus pneumoniae., Conclusions: Early clearance of M. tuberculosis is associated with enhanced heterologous innate immune responses similar to those activated during induction of trained immunity., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Early clearance of Mycobacterium tuberculosis is the eradication of infection before an adaptive immune response develops. We aimed to identify host factors associated with early clearance., Methods: Indonesian household contacts patients with smear-positive tuberculosis (TB) had an interferon-γ release assay (IGRA) at baseline and 14 weeks later. Early clearance was defined as a persistently negative IGRA. Contact characteristics, exposure, and disease phenotype were assessed for association with a positive IGRA at each time point., Results: Of 1347 contacts of 462 TB cases, 780 (57.9%) were IGRA positive and 490 (36.3%) were IGRA negative. After 14 weeks, 116 of 445 (26.1%) initially negative contacts were IGRA converters; 317 (71.2%) remained persistently negative. BCG vaccination reduced the risk of a positive baseline IGRA (relative risk [RR], 0.89 [95% confidence interval {CI} .83-.97]; P = .01), and strongly reduced the risk of IGRA conversion (RR, 0.56 [95% CI, .40-.77]; P < .001). BCG protection decreased with increasing exposure (P = .05) and increasing age (P = .004). Risk of IGRA conversion was positively associated with hemoglobin concentration (P = .04)., Conclusions: A quarter of household TB case contacts were early clearers. Protection against M. tuberculosis infection was strongly associated with BCG vaccination. Lower protection from BCG with increasing M. tuberculosis exposure and age can inform vaccine development., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background and Objective: Clinical guidelines recommend the use of beta-blockers and other cardiovascular prevention drugs in patients with acute coronary syndrome (ACS). Studies in several countries have found that beta-blockers are underused in patients with chronic obstructive pulmonary disease (COPD) and co-morbid heart disease, although most have only examined use in subgroups of patients. We undertook a nationwide follow-up study in New Zealand to describe the use of beta-blockers and other cardiovascular prevention drugs in patients with COPD and ACS., Methods: National health and pharmaceutical dispensing data were used to derive the study cohort, identify patients who were admitted to hospital with ACS and/or heart failure before cohort entry and during follow-up, and ascertain drug use., Results: The study cohort included 83 435 patients aged ≥45 years, with 290 400 person-years of follow-up. Among 2637 patients with ≥1 ACS admission during follow-up, only 56.6% received a beta-blocker in the 6 months following the first admission, while 87.7% and 81%, respectively, received aspirin and a statin. Patients with higher COPD severity were less likely to receive a beta-blocker than those with lower severity, as were those with no history of previous ACS and/or heart failure., Conclusion: Use of beta-blockers following an ACS admission was much lower than expected based on the findings of general audits of ACS management in New Zealand. Along with the higher proportions using aspirin and statins, and the differences in beta-blocker dispensing by COPD severity, this suggests a particular reluctance to prescribe beta-blockers to patients with COPD., (© 2019 Asian Pacific Society of Respirology.)