Low and middle income countries (LMICs) share a common, emerging, and largely unrecognized challenge: the burden of increasingly prevalent chronic and non-communicable diseases. This emerging challenge compounds the difficulty of responding to the backlog of disease and illness associated with poverty and “underdevelopment” often associated with preventable infections and reproductive health problems. Cancer – itself a complex set of devastating diseases – epitomizes the complexities and inequities of the epidemiological challenge faced by LMICs. Cancer is also a challenge to economic and human development, as it is both a cause and an effect of poverty. The long-term disability and ongoing health care costs of cancer impoverish families and health systems, and contribute to social exclusion. At the same time, poverty, lack of access to education and health care, and discrimination expose populations to additional risks for presenting and dying from many cancers. There are glaring disparities between rich and poor in incidence and death from preventable cancers and death from treatable cancers, as well as in the pain, suffering, and stigma associated with the disease. These disparities constitute a cancer divide and demonstrate that increasing access to cancer care and control is also an issue of equity. Yet, many believe – and these myths persist – that meeting the challenge of cancer in LMICs – with the exception of some basic prevention – is unnecessary, unaffordable, unattainable, and – perhaps the most pernicious – inappropriate because such an effort would take away resources from other high burden, communicable diseases. These four myths plague and undermine the work of the global community in cancer care and control (CCC), as well as on other non-communicable disease (NCD) and chronic illness.

https://papers.ssrn.com/sol3/Delivery.cfm/SSRN_ID2055430_code1833771.pdf?abstractid=2055430&mirid=1

Closing the Cancer Divide: A Blueprint to Expand Access in Low and Middle Income Countries

Purpose
To compare the clinical outcomes of surgical management by posterior only and combined posterior and anterior approaches for thoracic spinal tuberculosis in the elderly.

Surgical management for thoracic spinal tuberculosis in the elderly: posterior only versus combined posterior and anterior approaches.

Background
People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended.

Objectives
To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis.

Search methods
We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015.

Selection criteria
Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB.

Data collection and analysis
Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a meta-analysis. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Main results
We included 13 randomized controlled trials (RCTs) in the review, which enrolled 5824 participants. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants.

Overall there is little or no difference detected between FDCs and single-drug formulations for most outcomes reported. We did not detect a difference in treatment failure between FDCs compared with single-drug formulations (RR 1.28, 95% CI 0.82 to 2.00; 3606 participants, seven trials, moderate quality evidence). Relapse may be more frequent in people treated with FDCs compared to single-drug formulations, although the confidence interval (CI) includes no difference (RR 1.28, 95% CI 1.00 to 1.64; 3621 participants, 10 trials, low quality evidence). We did not detect any difference in death between fixed-dose and single-drug formulation groups (RR 0.96, 95% CI 0.67 to 1.39; 4800 participants, 11 trials, moderate quality evidence).

When we compared FDCs with single-drug formulations we found little or no difference for sputum smear or culture conversion at the end of treatment (RR 0.99, 95% CI 0.96 to 1.02; 2319 participants, seven trials, high quality evidence), for serious adverse events (RR 1.45, 95% CI 0.90 to 2.33; 3388 participants, six trials, moderate quality evidence), and for adverse events that led to discontinuation of therapy (RR 0.96, 95% CI 0.56 to 1.66; 5530 participants, 13 trials, low quality evidence).

We conducted a sensitivity analysis excluding studies at high risk of bias and this did not alter the review findings.

Authors' conclusions
Fixed-dose combinations and single-drug formulations probably have similar effects for treating people with newly diagnosed pulmonary TB.

Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis

SUMMARY OBJECTIVE: To estimate the costs incurred by patients during the intensive and continuation phases of the current 6-month tuberculosis (TB) regimen in Bangladesh and Tanzania, and thus identify potential benefits to patients of a shorter, 4-month treatment regimen. DESIGN: The validated Stop TB patient cost questionnaire was adapted and used in interviews with 190 patients in the continuation phase of treatment with current regimens. RESULTS: In both countries, overall patient costs were lower during 2 months of the continuation phase (US$74 in Tanzania and US$56 in Bangladesh) than during the 2 months of the intensive phase of treatment (US$150 and US$111, respectively). However, continuation phase patient costs still represented 89% and 77% of the 2-month average national income in the respective countries. Direct travel costs in some settings were kept low by local delivery system features such as community treatment observation. Lost productivity and costs for supplementary foods remained significant. CONCLUSIONS: Although it is not a straightforward exercise to determine the exact magnitude of likely savings, a shorter regimen would reduce out-of-pocket expenses incurred by patients in the most recent 2 months of the continuation phase and allow an earlier return to productive activities. KEY W ORDS: patient preferences; treatment costs; poverty; access

/pdf/patient-costs-during-tuberculosis-treatment-in-bangladesh-557gmi77z5.pdf

Patient costs during tuberculosis treatment in Bangladesh and Tanzania: the potential of shorter regimens.

Background 
The potential population-level impact of private-sector initiatives for tuberculosis (TB) case finding in Southeast Asia remains uncertain. In 2011, the Indus Hospital TB Control Program in Karachi, Pakistan, undertook an aggressive case-finding campaign that doubled notification rates, providing an opportunity to investigate potential population-level effects.


Methods 
We constructed an age-structured compartmental model of TB in the intervention area. We fit the model using field and literature data, assuming that TB incidence equaled the estimated nationwide incidence in Pakistan (primary analysis), or 1.5 times greater (high-incidence scenario). We modeled the intervention as an increase in the rate of formal-sector TB diagnosis and evaluated the potential impact of sustaining this rate for five years.


Results 
In the primary analysis, the five-year intervention averted 24% (95% uncertainty range, UR: 18-30%) of five-year cumulative TB cases and 52% (95% UR: 45-57%) of cumulative TB deaths. Corresponding reductions in the high-incidence scenario were 12% (95% UR: 8-17%) and 27% (95% UR: 21-34%), although the absolute number of lives saved was higher. At the end of five years, TB notification rates in the primary analysis were below their 2010 baseline, incidence had dropped by 45%, and annual mortality had fallen by 72%. About half of the cumulative impact on incidence and mortality could be achieved with a one-year intervention.


Conclusions 
Sustained, multifaceted, and innovative approaches to TB case-finding in Asian megacities can have substantial community-wide epidemiological impact.

/pdf/population-level-impact-of-active-tuberculosis-case-finding-530cfg6vte.pdf

Population-level impact of active tuberculosis case finding in an Asian megacity.

BACKGROUND: Experience with past tuberculosis (TB) regimen changes can guide future regimen changes. METHODS: To explore the process, major players and procedural success factors for recent public sector TB regimen changes, we conducted 166 interviews of country stakeholders in 21 of the 22 TB high-burden countries (HBCs). RESULTS: Stakeholders described 40 distinct regimen changes for drug-susceptible TB. Once countries committed to considering a change, the average timing was ~1 year for decision-making and ~2 years for rollout. Stakeholders more often cited concerns that were program-based (e.g., logistics and cost) rather than p atient-focused (e.g., side effects), and patient representatives were seldom part of decision making. Decisionmaking bodies in higher-income HBCs had more formalized procedures and fewer international participants. Pilot studies focused on logistics were more common than effectiveness studies, and the evidence base was often felt to be insuffi cient. Once implementation started, weaknesses in drug management were often exposed, with additional complications if local manufacturing was required. Best practices for regimen change included early engagement of budgeting staff, procurement staff, regulators and manufacturers. CONCLUSIONS: Future decision makers will benefi t

/pdf/tuberculosis-regimen-change-in-high-burden-countries-1vuqxvw2pg.pdf

Tuberculosis regimen change in high-burden countries.

BACKGROUND: The current tuberculosis (TB) treatment landscape has been studied extensively, but researchers rarely consider how it creates challenges or opportunities for future regimen change. METHODS: In 166 stakeholder interviews in the TB high-burden countries (HBCs), we investigated areas of first-line TB treatment and control that would affect, and be affected by, a future TB regimen change. Responses were compared with existing standardized data. RESULTS: Public sector regimens are converging towards a single standard, which facilitates comparison with a single control arm from clinical trials. However, final product design is challenging if the goal is fixed-dose combinations and patient kits, whose current widespread use addresses continuing weaknesses in drug management. Any product must address broad groups, as relatively low levels of drug susceptibility testing (DST) do not allow for individualized therapy. Finally, the protection of new drugs from the development of resistance will be challenging, as the implementation of directly observed therapy and public-private mix programs is incomplete, and substantial private sectors have been identified as early adopters of these drugs. CONCLUSIONS: Health systems for TB treatment and control must be improved not only to allow better implementation of current treatments but also to set the stage for implementation of new, improved TB regimens.

/pdf/implications-of-the-current-tuberculosis-treatment-landscape-1jbhjqwoo9.pdf

Implications of the current tuberculosis treatment landscape for future regimen change

http://www.jidonline.org/article/S0022202X23012642/pdf

1077 Efficacy and safety of ENERGI-F701 solution versus 2% minoxidil solution for female pattern hair loss: a phase II, multi-center, randomized, double-blind, head-to-head, parallel trial

Background The vast majority of residents of high-income countries (>90%) reportedly have high access to safely managed drinking water, the highest level of service under the Sustainable Development Goal (SDG) framework. Owing perhaps to the widely held perception of near universal access to high-quality water services in these countries, the burden of waterborne disease in these contexts is understudied. Methods We conducted a systematic review of estimates of the disease burden attributed to drinking water in countries where >90% of the population has access to safely managed drinking water per official SDG monitoring. We searched PubMed, Web of Science, and SCOPUS for articles published before September 10, 2021. Findings We identified 24 studies reporting estimates for the disease burden attributable to microbial contaminants. Across these studies, the population-weighted average burden of gastrointestinal illness risks attributed to drinking water was about 3,529 annual cases per 100,000 people. Beyond exposure to infectious agents, we also identified 10 studies reporting disease burden, predominantly, cancer risks, associated with chemical contaminants. Across these studies, the pooled population-weighted average of excess cancer cases attributable to drinking water was 1.8 annual cancer cases per 100,000 people. Interpretation These estimates exceed WHO-recommended normative targets for disease burden attributable to drinking water and highlight that there remains important preventable disease burden in these contexts. However, the available literature was scant and limited in geographic scope, disease outcomes, range of microbial and chemical contaminants, and inclusion of subpopulations that could most benefit from water infrastructure investments. These subpopulations include rural, low-income communities; Indigenous or Aboriginal peoples; and populations marginalized due to discrimination by race, ethnicity, or socioeconomic status. Studies quantifying drinking water-associated disease burden in countries with reportedly high access to safe drinking water, with a focus on specific subpopulations and promoting environmental justice, are needed.

Burden of Disease from Contaminated Drinking Water in Countries with High Access to Safely Managed Water: A Systematic Review

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Papers

Tuberculosis regimen change in high-burden countries.

Implications of the current tuberculosis treatment landscape for future regimen change

1077 Efficacy and safety of ENERGI-F701 solution versus 2% minoxidil solution for female pattern hair loss: a phase II, multi-center, randomized, double-blind, head-to-head, parallel trial

Burden of Disease from Contaminated Drinking Water in Countries with High Access to Safely Managed Water: A Systematic Review