Incidence of self-reported tuberculosis treatment with community-wide universal testing and treatment for HIV and tuberculosis screening in Zambia and South Africa: A planned analysis of the HPTN 071 (PopART) cluster-randomised trial.

BACKGROUND: HIV is a potent risk factor for tuberculosis (TB). Therefore, community-wide universal testing and treatment for HIV (UTT) could contribute to TB control, but evidence for this is limited. Community-wide TB screening can decrease population-level TB prevalence. Combining UTT with TB screening could therefore significantly impact TB control in sub-Saharan Africa, but to our knowledge there is no evidence for this combined approach. METHODS AND FINDINGS: HPTN 071 (PopART) was a community-randomised trial conducted between November 2013 to July 2018; 21 Zambian and South African communities (with a total population of approximately 1 million individuals) were randomised to arms A (community-wide UTT and TB screening), B (community-wide universal HIV testing with treatment following national guidelines and TB screening), or C (standard-of-care). In a cohort of randomly selected adults (18 to 44 years) enrolled between 2013 and 2015 from all 21 communities (total size 38,474; 27,139 [71%] female; 8,004 [21%] HIV positive) and followed-up annually for 36 months to measure the population-level impact of the interventions, data on self-reported TB treatment in the previous 12 months (self-reported TB) were collected by trained research assistants and recorded using a structured questionnaire at each study visit. In this prespecified analysis of the trial, self-reported TB incidence rates were measured by calendar year between 2014 and 2017/2018. A p-value ≤0.05 on hypothesis testing was defined as reaching statistical significance. Between January 2014 and July 2018, 38,287 individuals were followed-up: 494 self-reported TB during 104,877 person-years. Overall incidence rates were similar across all arms in 2014 and 2015 (0.33 to 0.46/100 person-years). In 2016 incidence rates were lower in arm A compared to C overall (adjusted rate ratio [aRR] 0.48 [95% confidence interval (95% CI) 0.28 to 0.81; p = 0.01]), with statistical significance reached. In 2017/2018, while incidence rates were lower in arm A compared to C, statistical significance was not reached (aRR 0.58 [95% CI 0.27 to 1.22; p = 0.13]). Among people living with HIV (PLHIV) incidence rates were lower in arm A compared to C in 2016 (RR 0.56 [95% CI 0.29 to 1.08; p = 0.08]) and 2017/2018 (RR 0.50 [95% CI 0.26 to 0.95; p = 0.04]); statistical significance was only reached in 2017/2018. Incidence rates in arms B and C were similar, overall and among PLHIV. Among HIV-negative individuals, there were too few events for cross-arm comparisons. Study limitations include the use of self-report which may have been subject to under-reporting, limited covariate adjustment due to the small number of events, and high losses to follow-up over time. CONCLUSIONS: In this study, community-wide UTT and TB screening resulted in substantially lower TB incidence among PLHIV at population-level, compared to standard-of-care, with statistical significance reached in the final study year. There was also some evidence this translated to a decrease in self-reported TB incidence overall in the population. Reduction in arm A but not B suggests UTT drove the observed effect. Our data support the role of UTT in TB control, in addition to HIV control, in high TB/HIV burden settings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01900977.

Determining the influence of the primary and specialist network of care on patient and system outcomes among patients with a new diagnosis of chronic obstructive pulmonary disease (COPD).

INTRODUCTION: Care for patients with chronic obstructive pulmonary disease (COPD) is provided by both family physicians (FP) and specialists. Ideally, patients receive comprehensive and coordinated care from this provider team. The objectives for this study were: 1) to describe the family and specialist physician network of care for Ontario patients newly diagnosed with COPD and 2) to determine the associations between selected characteristics of the physician network and unplanned healthcare utilization. METHODS: We conducted a retrospective cohort study using Ontario health administrative data housed at ICES (formerly the Institute for Clinical Evaluative Sciences). Ontario patients, ≥ 35 years, newly diagnosed with COPD were identified between 2005 and 2013. The FP and specialist network of care characteristics were described, and the relationship between selected characteristics (i.e., continuity of care) with unplanned healthcare utilization during the first 5 years after COPD diagnosis were determined in multivariate models. RESULTS: Our cohort consisted of 450,837 patients, mean age 61.5 (SD 14.6) years. The FP was the predominant provider of care for 86.4% of the patients. Using the Bice-Boxerman's Continuity of Care Index (COCI), a measure reflecting care across different providers, 227,082 (50.4%) were categorized in a low COCI group based on a median cut-off. In adjusted analyses, patients in the low COCI group were more likely to have a hospital admission (OR = 2.27, 95% CI 2.20,2.22), 30-day readmission (OR = 2.44, 95% CI 2.39, 2.49) and ER visit (OR = 2.27, 95% CI 2.25, 2.29). CONCLUSION: Higher indices of continuity of care are associated with reduced unplanned hospital use for patients with COPD. Primary care-based practice models to enhance continuity through coordination and integration of both primary and specialist care have the potential to enhance the health experience for patients with COPD and should be a health service planning priority.

The systemic treatment of recurrent ovarian cancer revisited.

Treatment approaches for relapsed ovarian cancer have evolved over the past decade from a calendar-based decision tree to a patient-oriented biologically driven algorithm. Nowadays, platinum-based chemotherapy should be offered to all patients with a reasonable chance of responding to this therapy. The treatment-free interval for platinum is only one of many factors affecting patients' eligibility for platinum re-treatment. Bevacizumab increases the response to chemotherapy irrespective of the cytotoxic regimen and can be valuable in patients with an urgent need for symptom relief (e.g. pleural effusion, ascites). For patients with recurrent high-grade ovarian cancer, which responds to platinum-based treatment, maintenance therapy with a poly(ADP-ribose) polymerase inhibitor can be offered, regardless of the BRCA mutation status. Here we review contemporary decision-making processes in the systemic treatment of relapsed ovarian cancer.

Routine testing of close contacts of confirmed COVID-19 cases - National COVID-19 Contact Management Programme, Ireland, May to August 2020.

OBJECTIVES: The objective of this study was to inform public health practitioners who are designing, adapting and implementing testing and tracing strategies for Coronavirus disease (COVID-19) control. STUDY DESIGN: The study design is monitoring and evaluation of a national public health protection programme. METHODS: All close contacts of laboratory-confirmed cases of COVID-19 identified between the 19th May and 2nd August were included; secondary attack rates and numbers needed to test were estimated. RESULTS: Four thousand five hundred eighty six of 7272 (63%) close contacts of cases were tested with at least one test. The secondary attack rate in close contacts who were tested was 7% (95% Confidence Interval [CI]: 6.3 - 7.8%). At the 'day 0' test, 14.6% (95% CI: 11.6-17.6%) of symptomatic close contacts tested positive compared with 5.2% (95% CI: 4.4-5.9%) of asymptomatic close contacts. CONCLUSIONS: The application of additional symptom-based criteria for testing in this high-incidence population (close contacts) is of limited utility because of the low negative predictive value of absence of symptoms.

Evolution of Octupole Deformation in Radium Nuclei from Coulomb Excitation of Radioactive

There is sparse direct experimental evidence that atomic nuclei can exhibit stable "pear" shapes arising from strong octupole correlations. In order to investigate the nature of octupole collectivity in radium isotopes, electric octupole (E3) matrix elements have been determined for transitions in ^{222,228}Ra nuclei using the method of sub-barrier, multistep Coulomb excitation. Beams of the radioactive radium isotopes were provided by the HIE-ISOLDE facility at CERN. The observed pattern of E3 matrix elements for different nuclear transitions is explained by describing ^{222}Ra as pear shaped with stable octupole deformation, while ^{228}Ra behaves like an octupole vibrator.

Characteristics of COPD in never-smokers and ever-smokers in the general population: results from the CanCOLD study.

BACKGROUND: There is limited data on the risk factors and phenotypical characteristics associated with spirometrically confirmed COPD in never-smokers in the general population. AIMS: To compare the characteristics associated with COPD by gender and by severity of airway obstruction in never-smokers and in ever-smokers. METHOD: We analysed the data from 5176 adults aged 40 years and older who participated in the initial cross-sectional phase of the population-based, prospective, multisite Canadian Cohort of Obstructive Lung Disease study. Never-smokers were defined as those with a lifetime exposure of <1/20 pack year. Logistic regressions were constructed to evaluate associations for 'mild' and 'moderate-severe' COPD defined by FEV1/FVC <5th centile (lower limits of normal). Analyses were performed using SAS V.9.1 (SAS Institute, Cary, North Carolina, USA). RESULTS: The prevalence of COPD (FEV1/FVC

Exacerbation-like respiratory symptoms in individuals without chronic obstructive pulmonary disease: results from a population-based study.

RATIONALE: Exacerbations of COPD are defined clinically by worsening of chronic respiratory symptoms. Chronic respiratory symptoms are common in the general population. There are no data on the frequency of exacerbation-like events in individuals without spirometric evidence of COPD. AIMS: To determine the occurrence of 'exacerbation-like' events in individuals without airflow limitation, their associated risk factors, healthcare utilisation and social impacts. METHOD: We analysed the cross-sectional data from 5176 people aged 40 years and older who participated in a multisite, population-based study on lung health. The study cohort was stratified into spirometrically defined COPD (post-bronchodilator FEV1/FVC < 0.7) and non-COPD (post bronchodilator FEV1/FVC ≥ 0.7 and without self-reported doctor diagnosis of airway diseases) subgroups and then into those with and without respiratory 'exacerbation-like' events in the past year. RESULTS: Individuals without COPD had half the frequency of 'exacerbation-like' events compared with those with COPD. In the non-COPD group, the independent associations with 'exacerbations' included female gender, presence of wheezing, the use of respiratory medications and self-perceived poor health. In the non-COPD group, those with exacerbations were more likely than those without exacerbations to have poorer health-related quality of life (12-item Short-Form Health Survey), miss social activities (58.5% vs 18.8%), miss work for income (41.5% vs 17.3%) and miss housework (55.6% vs 16.5%), p<0.01 to <0.0001. CONCLUSIONS: Events similar to exacerbations of COPD can occur in individuals without COPD or asthma and are associated with significant health and socioeconomic outcomes. They increase the respiratory burden in the community and may contribute to the false-positive diagnosis of asthma or COPD.

Blurring the boundaries: decays of multiparticle isomers at the proton drip line.

A multiparticle spin-trap isomer has been discovered in the proton-unbound nucleus (73)(158)Ta85 . The isomer mainly decays by γ-ray emission with a half-life of 6.1(1) µs. Analysis of the γ-ray data shows that the isomer lies 2668 keV above the known 9+ state and has a spin 10ℏ higher and negative parity. This 19- isomer also has an 8644(11) keV, 1.4(2)% α-decay branch that populates the 9+ state in (154)Lu. No proton-decay branch from the isomer was identified, despite the isomer being unbound to proton emission by 3261(14) keV. This remarkable stability against proton emission is compared with theoretical predictions, and the implications for the extent of observable nuclides are considered.

A guide to assessing physical activity using accelerometry in cancer patients.

Increased physical activity (PA) has been associated with a decreased risk for the occurrence and recurrence of many cancers. PA is an important outcome measure in rehabilitation interventions within cancer and may be used as a proxy measure of recovery or deterioration in health status following treatment and in the palliative care setting. PA is a complex multi-dimensional construct which is challenging to measure accurately. Factors such as technical precision and feasibility influence the choice of PA measurement tool. Laboratory-based methods are precise and mainly used for validation purposes, but their clinical applicability is limited. Self-report methods such as questionnaires are widely used due to their simplicity and reasonable cost; however, accuracy can be questionable. Objective methods such as pedometers measure step count but do not measure intensity, frequency or duration of activity. Accelerometers can measure PA behaviour at both ends of the movement spectrum from sedentary to vigorous levels of activity and can also provide objective data about the frequency, intensity, type and duration of PA. Balancing precision with ease of use, accelerometry may be the best measure of PA in cancer-based studies, but only a small number of studies have incorporated this measurement. This review will provide a background to PA and an overview of accelerometer measurement as well as technical and practical considerations, so this useful tool could be more widely incorporated into clinical trial research within cancer.

Testing the 'teachable moment' premise: does physical activity increase in the early survivorship phase?

PURPOSE: Little is known about objectively measured physical activity during the early survivorship period. This study measured physical activity, fatigue, and quality of life (QOL) in breast cancer patients over the first year after completion of chemotherapy and compared results to a matched non-cancer group. METHODS: Data was obtained from 24 breast cancer subjects (mean ± SD) 50.9 ± 12.8 years at time points of 6 weeks, 6 months and 1 year after completion of adjuvant chemotherapy and from 20 matched women. The following variables were assessed, physical activity (RT3 accelerometer and International Physical Activity Questionnaire), quality-of-life (EORTC QLQ C-30) and fatigue (Brief Fatigue Inventory). RESULTS: At 6 weeks after completion of chemotherapy, high levels of sedentary behaviour were found (6.8 ± 1.9 h sedentary per day), which did not improve, and was no different to the comparison group (6.5 ± 1.4 h). Less light activity was performed in the cancer cohort compared to the comparison group (p = 0.003). Body mass index (BMI) increased significantly in the cancer cohort (p = 0.015) and 1 year after chemotherapy finished only 13% (n = 3) had a BMI <25, while the comparable value was 45% (n = 9) in the non-cancer group. The QOL domain of cognitive function improved over the first 6 months (p = 0.034) but physical functioning declined (p = 0.008) over this time period. Fatigue did not change, and at the 1-year time point, 38% of the cancer patients (n = 11) reported high levels of fatigue. CONCLUSION: This study highlighted the unchanging sedentary behaviour and weight gain of breast cancer survivors during the first year after completion of chemotherapy, which may inform rehabilitation models in this population.

Static end-expiratory and dynamic forced expiratory tracheal collapse in COPD.

AIM: To determine the range of tracheal collapse at end-expiration among chronic obstructive pulmonary disease (COPD) patients and to compare the extent of tracheal collapse between static end-expiratory and dynamic forced-expiratory multidetector-row computed tomography (MDCT). MATERIALS AND METHODS: After institutional review board approval and obtaining informed consent, 67 patients meeting the National Heart, Lung, and Blood Institute (NHLBI)/World Health Organization (WHO) Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD were sequentially imaged using a 64-detector-row CT machine at end-inspiration, during forced expiration, and at end-expiration. Standardized respiratory coaching and spirometric monitoring were employed. Mean percentage tracheal collapse at end-expiration and forced expiration were compared using correlation analysis, and the power of end-expiratory cross-sectional area to predict excessive forced-expiratory tracheal collapse was computed following construction of receiver operating characteristic (ROC) curves. RESULTS: Mean percentage expiratory collapse among COPD patients was 17 ± 18% at end-expiration compared to 62 ± 16% during forced expiration. Over the observed range of end-expiratory tracheal collapse (approximately 10-50%), the positive predictive value of end-expiratory collapse to predict excessive (≥80%) forced expiratory tracheal collapse was <0.3. CONCLUSION: COPD patients demonstrate a wide range of end-expiratory tracheal collapse. The magnitude of static end-expiratory tracheal collapse does not predict excessive dynamic expiratory tracheal collapse.

The effect of aerobic exercise on metabolic and inflammatory markers in breast cancer survivors--a pilot study.

PURPOSE: Physical activity is associated with a reduced risk of breast cancer development and recurrence. There are several hypothesised mechanisms for this including positive effects on metabolic and inflammatory biomarkers and favourable changes in anthropometric variables. This pilot study examined the effect of an 8-week aerobic exercise intervention on several of these outcomes, including body composition, the metabolic syndrome, C-reactive protein (CRP) and physical activity, in breast cancer survivors 2-6 months post-chemotherapy. METHODS: Assessments were completed at baseline, at 8-weeks and 3-months post-intervention. Measures taken following a 12-h fast included body composition (bioimpedance analysis), metabolic syndrome (waist circumference, blood pressure, high-density lipoprotein cholesterol, triglycerides and fasting glucose), insulin resistance (homeostatic model assessment), CRP and physical activity (accelerometry and questionnaire). Participants were randomized to either an 8-week moderate-intensity aerobic exercise group or a usual-care control group. Analysis was completed using repeated-measures analysis of variance (ANOVA) (p = 0.05). RESULTS: Twenty-six breast cancer survivors participated (mean (standard deviation) age 48.1 (8.8) years, exercise group; n = 16, control group; n = 10). At baseline, 13 participants were overweight, 6 were obese and 19 centrally obese. Intention-to-treat analysis revealed no significant differences between the exercise and control groups in any of the outcomes measures; however, analysis of those who adhered to >90 % of the supervised exercise class showed a significant decrease in waist circumference (p = 0.05) and a significant increase in subjectively reported "total weekly" (p = 0.005) activity. CONCLUSION: While this 8-week aerobic exercise pilot intervention did not elicit significant improvements in biomarkers of breast cancer risk, there was some suggestion of improvements in waist circumference and subjectively measured physical activity in participants with >90 % adherence to the programme. A trial of longer duration and greater subject numbers is warranted.

Long-term clinical response to cardiac resynchronisation therapy under a multidisciplinary model.

BACKGROUND: Cardiac resynchronisation therapy (CRT) is established in the management of cardiac failure in patients with systolic dysfunction. Clinical response to CRT is not uniform, and response has been difficult to predict. AIM: Patient management within a high volume, multidisciplinary service focused on optimal delivery of CRT would improve response rates. METHODS: Four hundred and thirty-five consecutive patients who underwent CRT under a multidisciplinary heart failure service were enrolled prospectively over a 5-year period. Medically optimised, symptomatic patients with an ejection fraction (EF) <35%, widened QRS or abnormal dyssynchrony index were included. Left ventricular lead position was targeted anatomically to the segment of latest mechanical activation, and electrically to a site with maximal intrinsic intracardiac electrogram separation. Routine device and clinical follow up, as well as CRT optimisations, were performed at baseline and at 3-monthly intervals. Responders were defined as having an absolute reduction in left ventricular end-diastolic diameter >10% and an improvement in EF >5%. RESULTS: With a mean follow up of 53 ± 11 months, response rate to CRT was 81%. Mean EF improved from 26 ± 10% to 37 ± 11%, and mean left ventricular end-diastolic diameter reduced from 68.6 ± 9.2 mm to 57.8 ± 9.3 mm. Predictors of response were sinus rhythm, high dyssynchrony index and intrinsic electrical dyssynchrony >80 ms. Successful LV lead implantation at initial procedure was achieved in 99.1%, and at latest follow up 94.6% of initial LV leads were still active. CONCLUSION: CRT undertaken with a unit focus on optimal LV lead positioning and device optimisation, along with a multidisciplinary follow-up model, results in an excellent response rate to CRT.

Evaluation of plant and fungal extracts for their potential antigingivitis and anticaries activity.

The link between diet and health has lead to the promotion of functional foods which can enhance health. In this study, the oral health benefits of a number of food homogenates and high molecular mass and low molecular mass fractions were investigated. A comprehensive range of assays were performed to assess the action of these foods on the development of gingivitis and caries using bacterial species associated with these diseases. Both antigingivitis and anticaries effects were investigated by assays examining the prevention of biofilm formation and coaggregation, disruption of preexisting biofilms, and the foods' antibacterial effects. Assays investigating interactions with gingival epithelial cells and cytokine production were carried out to assess the foods' anti- gingivitis properties. Anti-caries properties such as interactions with hydroxyapatite, disruption of signal transduction, and the inhibition of acid production were investigated. The mushroom and chicory homogenates and low molecular mass fractions show promise as anti-caries and anti-gingivitis agents, and further testing and clinical trials will need to be performed to evaluate their true effectiveness in humans.

The receptor for the orexigenic peptide melanin-concentrating hormone is a G-protein-coupled receptor.

Gene-knockout studies of melanin-concentrating hormone (MCH) and its effect on feeding and energy balance have firmly established MCH as an orexigenic (appetite-stimulating) peptide hormone. Here we identify MCH as the ligand for the orphan receptor SLC-1. The rat SLC-1 is activated by nanomolar concentrations of MCH and is coupled to the G protein G alpha i/o. The pattern of SLC-1 messenger RNA expression coincides with the distribution of MCH-containing nerve terminals and is consistent with the known central effects of MCH. Our identification of an MCH receptor could have implications for the development of new anti-obesity therapies.

Are there adverse consequences of quizzing during informed consent for HIV research?

INTRODUCTION: While quizzing during informed consent for research to ensure understanding has become commonplace, it is unclear whether the quizzing itself is problematic for potential participants. In this study, we address this issue in a multinational HIV prevention research trial enrolling injection drug users in China and Thailand. METHODS: Enrolment procedures included an informed consent comprehension quiz. An informed consent survey followed. RESULTS: 525 participants completed the informed consent survey (Heng County, China»255, Xinjiang, China»229, Chiang Mai, Thailand»41). Mean age was 33 and mean educational level was 8 yrs. While quizzing was felt to be a good way to determine if a person understands the nature of clinical trial participation (97%) and participants did not generally find the quiz to be problematic, minorities of respondents felt pressured (6%); anxious (5%); bored (5%); minded (5%); and did not find the questions easy (13%). In multivariate analysis, lower educational level was associated with not minding the quizzing (6e10 yrs vs 0e5 yrs: OR»0.27, p»0.03; more than 11 yrs vs 0e5 yrs: OR»0.18, p»0.03). There were also site differences (Heng County vs Xinjiang) in feeling anxious (OR»0.07; p»<0.01), not minding (OR»0.26; p»0.03), being bored (OR»0.25; p»0.01) and not finding the questions easy (OR»0.10; p»<0.01). CONCLUSIONS: Quizzing during the informed consent process can be problematic for a minority of participants. These problems may be associated with the setting in which research takes place and educational level. Further research is needed to develop, test and implement alternative methods of ensuring comprehension of informed consent. TRIAL REGISTRATION: clinicaltrials.gov number NCT00270257.

Community-based health workers implementing universal access to HIV testing and treatment: lessons from South Africa and Zambia-HPTN 071 (PopART).

The global expansion of HIV testing, prevention and treatment services is necessary to achieve HIV epidemic control and promote individual and population health benefits for people living with HIV (PLHIV) in sub-Saharan Africa. Community-based health workers (CHWs) could play a key role in supporting implementation at scale. In the HPTN 071 (PopART) trial in Zambia and South Africa, a cadre of 737 study-specific CHWs, working closely with government-employed CHW, were deployed to deliver a 'universal' door-to-door HIV prevention package, including an annual offer of HIV testing and referral services for all households in 14 study communities. We conducted a process evaluation using qualitative and quantitative data collected during the trial (2013-2018) to document the implementation of the CHW intervention in practice. We focused on the recruitment, retention, training and support of CHWs, as they delivered study-specific services. We then used these descriptions to: (i) analyse the fidelity to design of the delivery of the intervention package, and (ii) suggest key insights for the transferability of the intervention to other settings. The data included baseline quantitative data collected with the study-specific CHWs (2014-2018); and qualitative data from key informant interviews with study management (n = 91), observations of CHW training events (n = 12) and annual observations of and group discussions (GD) with intervention staff (n = 68). We show that it was feasible for newly recruited CHWs to implement the PopART intervention with good fidelity, supporting the interpretation of the trial outcome findings. This was despite some challenges in managing service quality and CHW retention in the early years of the programme. We suggest that by prioritizing the adoption of key elements of the in-home HIV services delivery intervention model-including training, emotional support to workers, monitoring and appropriate remuneration for CHWs-these services could be successfully transferred to new settings.