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1.
PLoS One ; 19(3): e0299874, 2024.
Article En | MEDLINE | ID: mdl-38498488

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.


Latent Tuberculosis , Students, Nursing , Humans , Interferon-gamma Release Tests , Tuberculin Test , Indonesia/epidemiology , Latent Tuberculosis/diagnosis , Latent Tuberculosis/epidemiology , Latent Tuberculosis/complications
2.
J Med Imaging Radiat Oncol ; 68(1): 94-102, 2024 Feb.
Article En | MEDLINE | ID: mdl-37898955

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.


Lung Neoplasms , Neuroendocrine Tumors , Small Cell Lung Carcinoma , Humans , Neuroendocrine Tumors/radiotherapy , Dose Fractionation, Radiation , Lung Neoplasms/radiotherapy , New Zealand , Retrospective Studies
3.
Sci Rep ; 13(1): 19894, 2023 11 14.
Article En | MEDLINE | ID: mdl-37963989

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%, I2 = 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.


Diabetes Mellitus , Latent Tuberculosis , Tuberculosis , Adult , Humans , Risk Factors , Diabetes Mellitus/epidemiology , Tuberculosis/complications , Tuberculosis/epidemiology , Latent Tuberculosis/complications , Africa/epidemiology , Prevalence
4.
BMJ Glob Health ; 8(8)2023 08.
Article En | MEDLINE | ID: mdl-37532462

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.


Hemorrhagic Fever, Ebola , United States , Humans , Hemorrhagic Fever, Ebola/diagnosis , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/prevention & control , Liberia/epidemiology , Disease Outbreaks/prevention & control , Public Health Surveillance , Surveys and Questionnaires
5.
N Z Med J ; 136(1578): 100-112, 2023 Jul 07.
Article En | MEDLINE | ID: mdl-37414080

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, Manatu 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 - Maori 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.


Delivery of Health Care , Maori People , Humans , New Zealand , Government , Health Facilities
7.
Cancer Immunol Immunother ; 72(7): 2267-2282, 2023 Jul.
Article En | MEDLINE | ID: mdl-36881133

AIM: We have previously reported that polyfunctional T cell responses can be induced to the cancer testis antigen NY-ESO-1 in melanoma patients injected with mature autologous monocyte-derived dendritic cells (DCs) loaded with long NY-ESO-1-derived peptides together with α-galactosylceramide (α-GalCer), an agonist for type 1 Natural Killer T (NKT) cells. OBJECTIVE: To assess whether inclusion of α-GalCer in autologous NY-ESO-1 long peptide-pulsed DC vaccines (DCV + α-GalCer) improves T cell responses when compared to peptide-pulsed DC vaccines without α-GalCer (DCV). DESIGN, SETTING AND PARTICIPANTS: Single-centre blinded randomised controlled trial in patients ≥ 18 years old with histologically confirmed, fully resected stage II-IV malignant cutaneous melanoma, conducted between July 2015 and June 2018 at the Wellington Blood and Cancer Centre of the Capital and Coast District Health Board. INTERVENTIONS: Stage I. Patients were randomised to two cycles of DCV or DCV + α-GalCer (intravenous dose of 10 × 106 cells, interval of 28 days). Stage II. Patients assigned to DCV + α-GalCer were randomised to two further cycles of DCV + α-GalCer or observation, while patients initially assigned to DCV crossed over to two cycles of DCV + α-GalCer. OUTCOME MEASURES: Primary: Area under the curve (AUC) of mean NY-ESO-1-specific T cell count detected by ex vivo IFN-γ ELISpot in pre- and post-treatment blood samples, compared between treatment arms at Stage I. Secondary: Proportion of responders in each arm at Stage I; NKT cell count in each arm at Stage I; serum cytokine levels at Stage I; adverse events Stage I; T cell count for DCV + α-GalCer versus observation at Stage II, T cell count before versus after cross-over. RESULTS: Thirty-eight patients gave written informed consent; 5 were excluded before randomisation due to progressive disease or incomplete leukapheresis, 17 were assigned to DCV, and 16 to DCV + α-GalCer. The vaccines were well tolerated and associated with increases in mean total T cell count, predominantly CD4+ T cells, but the difference between the treatment arms was not statistically significant (difference - 6.85, 95% confidence interval, - 21.65 to 7.92; P = 0.36). No significant improvements in T cell response were associated with DCV + α-GalCer with increased dosing, or in the cross-over. However, the NKT cell response to α-GalCer-loaded vaccines was limited compared to previous studies, with mean circulating NKT cell levels not significantly increased in the DCV + α-GalCer arm and no significant differences in cytokine response between the treatment arms. CONCLUSIONS: A high population coverage of NY-ESO-1-specific T cell responses was achieved with a good safety profile, but we failed to demonstrate that loading with α-GalCer provided an additional advantage to the T cell response with this cellular vaccine design. CLINICAL TRIAL REGISTRATION: ACTRN12612001101875. Funded by the Health Research Council of New Zealand.


Melanoma , Skin Neoplasms , Male , Humans , Adolescent , Skin Neoplasms/therapy , Skin Neoplasms/metabolism , Peptides/metabolism , Antibodies/metabolism , Cytokines/metabolism , Dendritic Cells , Antigens, Neoplasm , Melanoma, Cutaneous Malignant
8.
Int J Prison Health ; 2023 Jan 11.
Article En | MEDLINE | ID: mdl-36622107

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.


Coinfection , HIV Infections , Prisons , Southeast Asian People , Tuberculosis, Pulmonary , Adult , Female , Humans , Male , HIV Infections/complications , HIV Infections/diagnosis , HIV Infections/epidemiology , Malaysia/epidemiology , Prisons/statistics & numerical data , Southeast Asian People/statistics & numerical data , Tuberculosis/epidemiology , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Coinfection/diagnosis , Coinfection/epidemiology , Sputum/microbiology
9.
BMJ Open ; 12(11): e060786, 2022 Nov 08.
Article En | MEDLINE | ID: mdl-36351737

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, I2=94.7%), 38% (95% CI 30 to 46, I2=98.7%) and 42% (95% CI 32 to 52, I2=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, I2=98.2%), 32% (95% CI 28 to 36, I2=98%), 31% (95% CI 22 to 41, I2=99.3%), 19% (95% CI 12 to 25, I2=98.1%) and 11% (95% CI 9 to 14, I2=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.


Diabetes Mellitus, Type 2 , Diabetic Foot , Diabetic Neuropathies , Peripheral Arterial Disease , Retinal Diseases , Adult , Female , Humans , Male , Glycated Hemoglobin , Diabetic Neuropathies/epidemiology , Diabetic Neuropathies/complications , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/therapy , Diabetic Foot/epidemiology , Diabetic Foot/therapy , Diabetic Foot/complications , Africa/epidemiology , Peripheral Arterial Disease/complications
10.
Trials ; 23(1): 480, 2022 Jun 10.
Article En | MEDLINE | ID: mdl-35689272

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.


Diabetes Mellitus, Type 2 , Isoniazid , Latent Tuberculosis , Rifampin , Adult , Antitubercular Agents/adverse effects , Cohort Studies , Diabetes Mellitus, Type 2/epidemiology , HIV Infections/epidemiology , Humans , Isoniazid/adverse effects , Latent Tuberculosis/prevention & control , Randomized Controlled Trials as Topic , Rifampin/adverse effects , Rifampin/analogs & derivatives , Tanzania/epidemiology
11.
J Infect Prev ; 23(2): 49-58, 2022 Mar.
Article En | MEDLINE | ID: mdl-35340927

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.

14.
Trans R Soc Trop Med Hyg ; 116(1): 10-18, 2022 01 20.
Article En | MEDLINE | ID: mdl-33721022

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.


Mycobacterium tuberculosis , Students, Nursing , Tuberculosis , Humans , Indonesia/epidemiology , Interferon-gamma Release Tests/methods , Prospective Studies , Tuberculosis/diagnosis , Tuberculosis/epidemiology
15.
J Infect Prev ; 23(4): 155-166, 2022 Jul.
Article En | MEDLINE | ID: mdl-37256158

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.

17.
J Intern Med ; 290(5): 1028-1038, 2021 11.
Article En | MEDLINE | ID: mdl-34289189

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.


Acute Coronary Syndrome , Bronchodilator Agents , Pulmonary Disease, Chronic Obstructive , Acute Coronary Syndrome/chemically induced , Acute Coronary Syndrome/epidemiology , Administration, Inhalation , Adrenergic beta-2 Receptor Agonists/adverse effects , Bronchodilator Agents/adverse effects , Case-Control Studies , Drug Therapy, Combination , Humans , Muscarinic Antagonists/adverse effects , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/epidemiology
18.
Stat Med ; 40(22): 4751-4763, 2021 09 30.
Article En | MEDLINE | ID: mdl-33990992

It is difficult to estimate sensitivity and specificity of diagnostic tests when there is no gold standard. Latent class models have been proposed as a potential solution as they provide estimates without the need for a gold standard. Using a motivating example of the evaluation of point of care tests for leptospirosis in Tanzania, we show how a realistic violation of assumptions underpinning the latent class model can lead directly to substantial bias in the estimates of the parameters of interest. In particular, we consider the robustness of estimates of sensitivity, specificity, and prevalence, to the presence of additional latent states when fitting a two-state latent class model. The violation is minor in the sense that it cannot be routinely detected with goodness-of-fit procedures, but is major with regard to the resulting bias.


Diagnostic Tests, Routine , Models, Statistical , Bayes Theorem , Bias , Humans , Latent Class Analysis , Prevalence , Sensitivity and Specificity
19.
PLoS One ; 16(4): e0250289, 2021.
Article En | MEDLINE | ID: mdl-33882106

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.


Diabetes Mellitus, Type 2 , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Patient Compliance/statistics & numerical data , Adult , Aged , Cohort Studies , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Female , Humans , Male , Middle Aged , New Zealand/epidemiology , Young Adult
20.
Aust N Z J Obstet Gynaecol ; 61(6): 837-845, 2021 12.
Article En | MEDLINE | ID: mdl-33908042

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 Maori, 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.


Antidepressive Agents , Ethnicity , Antidepressive Agents/therapeutic use , Female , Humans , Infant , Native Hawaiian or Other Pacific Islander , New Zealand , Pregnancy , Pregnancy Trimester, First
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