BACKGROUND: The implementation of tuberculosis preventive treatment (TPT) is challenging especially in resource-limited settings. As part of a Phase 3 trial on TPT, we described our experience with the use of rifampicin for 4 months (4R) and isoniazid for 9 months (9H) in Indonesia.METHODS: In 2011-2017, children and adults with latent TB infection were randomised to either 4R or 9H and followed until 16 months after randomisation for children and 28 months for adults. The primary outcome was the treatment completion rate. Secondary outcomes were Grade 3-5 adverse events (AEs), active TB occurrence, and health costs.RESULTS: A total of 157 children and 860 adults were enrolled. The 4R treatment completion rate was significantly higher than that of 9H (78.7% vs. 65.5%), for a rate difference of 13.2% (95% CI 7.1-19.2). No Grade 3-5 AEs were reported in children; in adults, it was lower in 4R (0.4%) compared to 9H (2.8%). The incidence of active TB was lower with 4R than with 9H (0.09/100 person-year vs. 0.36/100 person-year) (rate difference: -0.36/100 person-year). The total cost per patient was lower for the 4R regimen than for the 9H regimen (USD151.9 vs. USD179.4 in adults and USD152.9 vs. USD206.5 in children)CONCLUSIONS: Completion and efficacy rates for 4R were better than for 9H. Compared to 9H, 4R was cheaper in all age groups, safer in adults and equally safe in children. The Indonesian TB program could benefit from these benefits of the 4R regimen.

OBJECTIVES:To determine the level of agreement among patients with rheumatoid arthritis (RA) with the principles and recommendations of the treat-to-target (T2T) initiative in New Zealand (NZ) and to further explore specific patient opinions via online iterative surveys.METHODS:Participants with RA were recruited from rheumatology clinics in NZ and invited to receive and reply to surveys administered via the Patient Opinion Real-Time Anonymous Liaison (PORTAL) system. An enrolment survey recorded demographics, disease duration and treatment and then RA T2T surveys were administered weekly. A Likert scale 1-5 measured agreement with the principles and recommendations and further surveys explored responses of interest identified by investigators from each prior survey.RESULTS:One hundred and ninety patients consented to participate in PORTAL and 132 in the RA T2T surveys. Level of agreement with RA T2T principles was: 93.3% to 99.3% and to the recommendations: 77.3%-100%. The lowest level of agreement 77.3% was with recommendation 8, 3 monthly treatment adjustment, and the highest was 100% agreement with recommendation 10, shared decision-making. Patients agreed less with low disease activity as the target compared with remission (91.4% and 98%). Despite high-level agreement for the use of a disease activity score (95.7%), 23% did not feel the individual components reflected their disease control. Patients rated difficulty coping, erosions on imaging, health-related quality of life and pain all significantly higher than C-reactive protein as indicators of worsening arthritis.CONCLUSIONS:Despite a high level of patient agreement with RA T2T this study highlights the importance of patient engagement in the RA T2T process to individualize therapy adjustments, make shared decisions and decide on targets that accurately reflect disease control according to patients.

Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in New Zealand (NZ), accounting for 40% of all deaths, with Maori, Pacific Island and Indo-Asian populations experiencing greater CVD morbidity and mortality. In 2012, the NZ Ministry of Health implemented a program for primary health care to undertake Cardiovascular Disease Risk Assessment’ (CVDRA) in a group defined by age, sex and ethnicity. We wished to better understand factors influencing the uptake of CVDRA and any subsequent recommendations, Methods: We approached consecutive patients admitted to Wellington Hospital with a first presentation of an acute coronary syndrome. We then selected patients who consented to a semi-structured qualitative interview about their knowledge and experience of CVDRA. Interviews were digitally recorded, transcribed verbatim and analysed using grounded theory and thematic coding to identify key themes. Results: Six themes were identified: factors (motivators or barriers) influencing attendance of CVDRA and the uptake of subsequent recommendations; the importance of understanding the implications of the estimated cardiovascular risk; the relevance of the doctor-patient relationship and the necessity of effective discussion regarding CVDRA outcomes. A further widespread theme was the underestimation of personal risk of CVD. Conclusion: Our findings suggest that there is potential to improve the overall effectiveness of CVDRA and translate it into management. Identified motivators and barriers can be used to increase CVDRA attendance and the uptake of interventions. Allowing time for discussion regarding personal risk and the implications of risk scores would also offer potential to improve effectiveness of the process.

Background: In 2012 the New Zealand Ministry of Health made cardiovascular risk assessment (CVDRA) a health target aiming for ∼90% of the eligible population to be screened by 2014. This was reputedly achieved but we wished to assess the understanding of patients about the process. Methods: Patients admitted to Wellington Hospital with their first episode of an acute coronary syndrome (ACS) - including transfers from other hospitals - were interviewed about previous CVDRA. Interviewers used a standardised questionnaire to obtain data regarding CVDRA administration, comprehension and any subsequent health behaviour or medication changes. We wrote to the patient's general practitioner (GP) requesting the date and calculated risk level from any logged CVDRA process. Data was described using simple summary statistics. Results: Of 47 patients recruited to the study, 19 were aware of having received a CVDRA score although 41 were reported by GPs. Of those 19, 63% received lifestyle advice and 63% were prescribed cardio-protective medication compared to 64% and 46% of patients who did not recollect a CVDRA. Of the 19 recollecting a CVDRA, all had followed lifestyle advice compared to 67% of those who did not remember a CVDRA. Equal numbers in both groups were taking cardio-protective medication at the time of ACS. Conclusion: Most patients admitted with a first ACS had received a recent CVDRA according to their GP but fewer patients seemed aware of the formal process. Nevertheless most were aware of risk factors and had taken some action to address these.

The tobacco epidemic and burden from overweight/obesity are major causes of health loss in New Zealand.1 Changes to the obesogenic environment and the use of various price signals are probably the most critical interventions required (eg, tobacco tax increases2,3). But there is potentially a place for the promotion of individual-level interventions, including the use of innovative internet and smartphone technologies. In New Zealand, smartphone access has been increasing, and a survey in 2013 found 59% smartphone ownership or access by New Zealand adults.4 It was even higher, at 71%, for those aged 18 to 54 years, and also for Māori or Pacific peoples compared to New Zealand European (70% vs 55% respectively). There is some New Zealand randomised control trial (RCT) evidence for the effectiveness of mobile phone text messaging for smoking cessation,5 with this being equally effective for Māori as non-Māori.6 Work has also been done in New Zealand on smartphone-mediated cardiovascular management7 (eg, as per a New Zealand trial on ‘Text4Heart’8). Internationally, there is evidence detailed in a systematic review that computer-based and other electronic aids can assist with smoking cessation, and are “highly likely to be cost-effective”.9 Another systematic review of five RCTs has reported that mobile phone interventions are effective for smoking cessation.10 But the evidence from RCTs of ‘smartphone apps’ for smoking cessation is fairly limited (eg, we only identified two trials11,12). For smartphone apps for weight loss, one review reported on 10 RCTs which used text messaging or app interventions to support weight loss in women, with significant improvements being observed in eight studies.13 Another review of 17 studies14 that utilised smartphone applications, text messaging and web resources, reported overall weight loss of 0.43 kg (95% CI 0.25– 0.61, p-value≤0.01). But not included in this review were some other smartphone app specific studies which did not report statistically significant weight loss15-18 (albeit some of these being small pilot studies). Given this background of some promising evidence, we aimed to assess the quality of existing apps for weight loss and smoking cessation available for downloading to smartphones by New Zealanders.

Objective To investigate qualitatively and quantitatively the performance of a programme for managing the child contacts of adult tuberculosis patients in Indonesia.Methods A public health evaluation framework was used to assess gaps in a child contact management programme at a lung clinic. Targets for programme performance indicators were derived from established programme indicator targets, the scientific literature and expert opinion. Compliance with tuberculosis screening, the initiation of isoniazid preventive therapy in children younger than 5 years, the accuracy of tuberculosis diagnosis and adherence to preventive therapy were assessed in 755 child contacts in two cohorts. In addition, 22 primary caregivers and 34 clinic staff were interviewed to evaluate knowledge and acceptance of child contact management. The cost to caregivers was recorded. Gaps between observed and target indicator values were quantified.Findings The gaps between observed and target performance indicators were: 82% for screening compliance; 64 to 100% for diagnostic accuracy, 50% for the initiation of preventive therapy, 54% for adherence to therapy and 50% for costs. Many staff did not have adequate knowledge of, or an appropriate attitude towards, child contact management, especially regarding isoniazid preventive therapy. Caregivers had good knowledge of screening but not of preventive therapy and had difficulty travelling to the clinic and paying costs.Conclusion The study identified widespread gaps in the performance of a child contact management system in Indonesia, all of which appear amenable to intervention. The public health evaluation framework used could be applied in other settings where child contact management is failing.

SETTING:Defaulting from anti-tuberculosis treatment hinders tuberculosis (TB) control.OBJECTIVE:To identify potential defaulters.DESIGN:We conducted a cohort study in newly diagnosed Indonesian TB patients. We administered a questionnaire, prospectively identified defaulters (discontinued treatment ≥ 2 weeks) and assessed risk factors using Cox's regression.RESULTS:Of 249 patients, 39 (16%) defaulted, 61% in the first 2 months. Default was associated with liver disease (HR 3.40, 95%CI 1.02-11.78), chest pain (HR 2.25, 95%CI 1.06-4.77), night sweats (HR 1.98, 95%CI 1.03-3.79), characteristics of the head of the household (self-employed, HR 2.47, 95%CI 1.15-5.34; patient's mother, HR 7.72, 95%CI 1.66-35.88), household wealth (HR 4.24, 95%CI 1.12-16.09), walking to clinic (HR 4.53, 95%CI 1.39-14.71), being unaccompanied at diagnosis (HR 30.49, 95%CI 7.55-123.07) or when collecting medication (HR 3.34, 95%CI 1.24-8.98) and low level of satisfaction with the clinic (HR 3.85, 95%CI 1.17-12.62) or doctors (HR 2.45, 95%CI 1.18-5.10). Health insurance (HR 0.24, 95%CI 0.07-0.74) and paying for diagnosis (HR 0.14, 95%CI 0.04-0.48) were protective.CONCLUSION:Defaulting is common and occurs early. Interventions that improve clinic services, strengthen patient support and increase insurance coverage may reduce default in Indonesia.

BACKGROUND:It is recommended that young child contacts of sputum smear positive tuberculosis cases receive isoniazid preventive therapy (IPT) but reported adherence is low and risk factors for poor adherence in children are largely unknown.METHODS:We prospectively determined rates of IPT adherence in children < 5 yrs in an Indonesian lung clinic. Possible risk factors for poor adherence, defined as ≤3 months prescription collection, were calculated using logistic regression. To further investigate adherence barriers in-depth interviews were conducted with caregivers of children with good and poor adherence.RESULTS:Eighty-two children eligible for IPT were included, 61 (74.4%) of which had poor adherence. High transport costs (OR 3.3, 95% CI 1.1-10.2) and medication costs (OR 20.0, 95% CI 2.7-414.5) were significantly associated with poor adherence in univariate analysis. Access, medication barriers, disease and health service experience and caregiver TB and IPT knowledge and beliefs were found to be important determinants of adherence in qualitative analysis.CONCLUSION:Adherence to IPT in this setting in Indonesia is extremely low and may result from a combination of financial, knowledge, health service and medication related barriers. Successful reduction of childhood TB urgently requires evidence-based interventions that address poor adherence to IPT.

Young children living with a tuberculosis patient are at high risk of Mycobacterium tuberculosis infection and disease. WHO guidelines promote active screening and isoniazid (INH) preventive therapy (PT) for such children under 5 years, yet this well-established intervention is seldom used in endemic countries. We review the literature regarding barriers to implementation of PT and find that they are multifactorial, including difficulties in screening, poor adherence, fear of increasing INH resistance and poor acceptability among primary caregivers and healthcare workers. These barriers are largely resolvable, and proposed solutions such as the adoption of symptom-based screening and shorter drug regimens are discussed. Integrated multicomponent and site-specific solutions need to be developed and evaluated within a public health framework to overcome the policy-practice gap and provide functional PT programmes for children in endemic settings.

SETTING AND OBJECTIVES: The tuberculin skin test (TST) has limitations in diagnosing latent tuberculosis (TB) infection (LTBI). Interferon-gamma release assays may improve diagnostic accuracy. We compared Quanti-FERON (R)-TB Gold In-Tube (QFT-GIT) and TST in Indonesian children.DESIGN: Children aged from 6 months to 9 years exposed to a TB case at household and neighbourhood levels were recruited. The children underwent QFT-GIT and TST. Test responsiveness was assessed according to an exposure gradient.RESULTS: A total of 299 household-exposed and 72 neighbourhood-exposed children were analysed. Overall, respectively 46% and 41% were positive using QFT-GIT and the TST. Test positivity increased with exposure (QFT-GIT P value for trend <0.001, and TST P < 0.001); however, only QFT-GIT responded significantly to a 'within-household' gradient. The TST was less likely to be positive than the QFT-GIT in neighbourhood-exposed children (P = 0.05). BCG-vaccinated children were less likely to be QFT-GIT-positive, while older children were more likely to be QFT-GIT-positive. Both tests had increasing positivity with increasing smear grade.CONCLUSION: QFT-GIT performed similarly to the TST in Indonesian children living with an infectious TB case. Test accuracy was not compromised by young age or BCG vaccination. Our findings suggest that QFT-GIT offers little advantage over the TST in this population. High rates of LTBI diagnosed in household-exposed children by both tests support preventive therapy.

SETTING AND OBJECTIVES Young children living with infectious tuberculosis (TB) cases are at high risk of infection and disease, and screening is recommended. This is rarely conducted in resource-limited settings. Identifying children most at risk of infection may be useful for setting practical screening policies. DESIGN Child contacts of smear-positive adult TB patients were invited for Mycobacterium tuberculosis infection and disease screening by symptoms, tuberculin skin test (TST), QuantiFERON-TB Gold In-Tube assay (QFT-GIT) and chest X-ray. Risk factors for infection were collected using a questionnaire and were calculated separately for TST, for QFT-GIT and for both tests combined. RESULTS Of 304 screened children 145/302 (48%) were positive using TST, 152/299 (51%) by QFT-GIT and 180/304 (59%) were positive using either or both tests. Positivity for both tests was associated with index case infectivity (acid-fast bacilli [AFB] 3+ vs. AFB 1+: TST OR 2.93, 95%CI 1.59-5.39; QFT-GIT OR 2.28, 95%CI 1.06-4.90) and exposure (child contact's parent is the index case: TST OR 7.04, 95%CI 2.23-22.28; QFT-GIT OR 4.30, 95%CI 1.48-12.45). CONCLUSION M. tuberculosis infection according to either test was high, supporting screening and preventive treatment. Children of smear-positive TB cases who accompany their parents to the clinic should be prioritised for immediate screening.

Background. Screening of children who are household contacts of tuberculosis (TB) cases is universally recommended but rarely implemented in TB endemic setting. This paper aims to summarise published data of the prevalence of TB infection and disease among child contacts in South East Asia. Methods. Search strategies were developed to identify all published studies from South East Asia of household contact investigation that included children (0–15 years). Results. Eleven studies were eligible for review. There was heterogeneity across the studies. TB infection was common among child contacts under 15 years of age (24.4–69.2%) and was higher than the prevalence of TB disease, which varied from 3.3% to 5.5%. Conclusion. TB infection is common among children that are household contacts of TB cases in South East Asia. Novel approaches to child contact screening and management that improve implementation in South East Asia need to be further evaluated.

Philip Campbell Hill and colleagues propose using a health needs assessment framework, research tools, and a strategy for clinical evaluation to help better manage child contacts of adult TB cases.

An estimated 9.7 million children under the age of five die every year worldwide, approximately 41% of them in sub-Saharan Africa (SSA). Access to adequate health care is among the factors suggested to be associated with child mortality; improved access holds great potential for a significant reduction in under-five death in developing countries. Theory and corresponding frameworks indicate a wide range of factors affecting access to health care, such as traditionally measured variables (distance to a health provider and cost of obtaining health care) and additional variables (social support, time availability and caregiver autonomy). Few analytical studies of traditional variables have been conducted in SSA, and they have significant limitations and inconclusive results. The importance of additional factors has been suggested by qualitative and recent quantitative studies. We propose that access to health care is multidimensional; factors other than distance and cost need to be considered by those planning health care provision if child mortality rates are to be reduced through improved access. Analytical studies that comprehensively evaluate both traditional and additional variables in developing countries are required.

Background As part of a formal evaluation of the Quantiferon-Gold in-tube assay (QFT-IT) for latent TB infection we compared its sensitivity to the tuberculin skin test (TST) in confirmed adult TB cases in Indonesia. Smear-positive TB disease was used as a proxy gold standard for latent TB infection. Methods and Findings We compared the sensitivity of QFT-IT and TST in 98 sputum smear and chest x-ray positive TB cases and investigated risk factors for negative and discordant results in both tests. Both tests showed high sensitivity; (QFT-IT; 88.7%: TST; 94.9%), not significantly different from each other (p value 0.11). Very high sensitivity was seen when tests were combined (98.9%). There were no variables significantly associated with discordant results or with a negative TST. For QFT-IT which particular staff member collected blood was significantly associated with test positivity (p value 0.01). Study limitations include small sample size and lack of culture confirmation or HIV test results. Conclusions The QFT-IT has similar sensitivity in Indonesian TB cases as in other locations. However, QFT-IT, like the TST cannot distinguish active TB disease from LTBI. In countries such as Indonesia, with high background rates of LTBI, test specificity for TB disease will likely be low. While our study was not designed to evaluate the QFT-IT in the diagnosis of active TB disease in TB suspects, the data suggest that a combination of TST and QFT-IT may prove useful for ruling out TB disease. Further research is required to explore the clinical role of QFT-IT in combination with other TB diagnostic tests.

Une traduction en francais de ce resume figure a, la fin de l'article. Al final de/articulo se facilita una traduccion al espanol Introduction Every year approximately 10 million children under 5 years of age die throughout the world, mostly in developing countries. (1) Of every 1000 children born in sub-Saharan Africa, approximately 170 die, compared with less than 10 of those who are born in developed countries. (2) The fourth Millennium Development Goal is to reduce child and infant mortality in the world by two-thirds by 2015, (2) yet current estimates suggest that at least 44 developing countries have less than a 20% chance of achieving the goal. (1) An understanding of the risk factors associated with child mortality and the design of appropriate interventions are urgently required. Population-based studies suggest that poor access to health care, which results in delayed attendance at a health facility or none at all, may be a key determinant of mortality in children under 5 years of age in developing countries. (3,4) To assess this relationship, researchers have adopted simple traditional measures, such as distance from the household to a health facility, (5-7) availability of transportation (8) and healthcare costs. (9) Their findings have been inconclusive. Recently, qualitative studies (10-12) have suggested the need to consider additional barriers, such as lack of social support for primary caregivers, limited caregiver autonomy in decision-making and financial matters, and social exclusion at health clinics. Studies that assess the relationship between these factors and child death are needed. Therefore, we evaluated traditional measures of access to health care in addition to non-traditional measures to study mortality in children under 5 years of age in the Gambia. Methodology Population and study design We conducted a case-control study within the Farafenni Demographic Surveillance System (FDSS), on the North Bank of the River Gambia. The FDSS was established in 1981 as a platform for research, its location being considered particularly ideal for malaria studies. The FDSS covers approximately 17 000 rural and 26 000 urban dwellers belonging to three main ethnic groups (Wolloff, Mandinka and Fula) among which young age, high fertility, low educational levels, frequent polygamy and widespread poverty prevail. (13) Water is gathered primarily from communal wells with hand pumps, and 12% of the population utilizes uncovered wells. Pit latrines predominate. Villages have no electricity, and transportation routes are dirt roads. (13) The cases were all children under 5 years of age under coverage by the FDSS who had died between 31 December 2003 and 30 April 2006. Children were excluded from the study if their primary caregiver could not be located or had since died or if their cause of death was unrelated to access to health care (e.g. congenital malformations, in-hospital neonatal deaths, immediate death after an injury, etc.). Verbal autopsies, available for 92% of the cases, were conducted within 3 months of death by trained field workers using the standardized INDEPTH form, as part of routine FDSS practice. (14) They were assessed by consensus between two physicians. Controls were children under 5 years of age who were registered in the FDSS and who were alive at the time their respective cases died. They were excluded from the study if the primary caregiver could not be located or had since died. From the FDSS population, 10 controls were randomly identified for and matched with each case by age (within the same birth month) and sex. Only the first five random choices were selected, followed by the next child on the list of random choices in the event of refusal to participate. On the assumption that 70% of the controls would take at least 30 minutes or more to travel to a health-care facility, we estimated that at least 120 cases and 600 controls were required to detect an odds ratio (OR) of 2. …

Objective To assess whether traditional measures of access to health care (distance and travel time to a facility) and non-traditional measures (social and financial support indicators) are associated with mortality among children under 5 years of age in the Gambia.Methods We conducted a case-control study in a population under demographic surveillance. Cases (n = 140) were children under 5 years of age who died between 31 December 2003 and 30 April 2006. Each case was matched in age and sex to five controls (n = 700). Information was gathered by interviewing primary caregivers. The data were analysed using conditional logistic regression.Findings Of traditional measures of access, only rural versus urban/periurban residence was important: children from rural areas were more likely to die (OR: 4.9; 95% confidence interval, CI: 1.2-20.2). For non-traditional measures, children were more likely to die if their primary caregivers; lacked help with meal preparation (OR: 2.3; 95% CI: 1.2-4.1), had no one to relax with (OR: 1.8; 95% CI: 1.1-2.9), had no one who could offer good advice (OR: 23.1; 95% CI: 4.3-123.4), had little say over how earned money was spent (OR: 12.7; 95% CI: 1.3-127.6), were unable to cut spending for health care (OR: 2.5; 95% CI: 1.5-4.2) or had to carry out odd jobs to pay for the care (OR:.3.4; 95% CI: 2.1-5.5). A protective effect was observed when the caregiver had other children to care for (OR: 0.2; 95% CI: 0.1-0.5).Conclusion Improving access to health-care for children in the Gambia and similar settings is not simply a matter of reducing travel time and distance to a health facility, but requires improvements in caregivers' support networks and their access to the financial resources they need.