IMPORTANCEThe burden of cancer falls disproportionally on low-middle-income countries (LMICs). It is not well known how novel therapies are tested in current clinical trials and the extent to which they match global disease burden.OBJECTIVES To describe the design, results, and publication of oncology randomized clinical trials (RCTs) and examine the extent to which trials match global disease burden and how trial methods and results differ across economic settings. DESIGN, SETTING, AND PARTICIPANTSIn this retrospective cohort study, a literature search identified all phase 3 RCTs evaluating anticancer therapies published from 2014 to 2017. Randomized clinical trials were classified based on World Bank economic classification. Descriptive statistics were used to compare RCT design and results from high-income countries (HICs) and low/middle-income countries (LMICs). Statistical analysis was conducted in January 2020.MAIN OUTCOMES AND MEASURES Differences in the design, results, and output of RCTs between HICs and LMICs. RESULTSThe study cohort included 694 RCTs: 636 (92%) led by HICs and 58 (8%) led by LMICs. A total of 601 RCTs (87%) tested systemic therapy and 88 RCTs (13%) tested radiotherapy or surgery. The proportion of RCTs relative to global deaths was higher for breast cancer (121 RCTs [17%] and 7% of deaths) but lower for gastroesophageal cancer (38 RCTs [6%] and 14% of deaths), liver cancer (14 RCTs [2%] and 8% of deaths), pancreas cancer (14 RCTs [2%] and 5% of deaths), and cervical cancer (9 RCTs [1%] and 3% of deaths). Randomized clinical trials in HICs were more likely than those in LMICs to be funded by industry (464 [73%] vs 24 [41%]; P < .001). Studies in LMICs were smaller than those in HICs (median, 219 [interquartile range, 137-363] vs 474 [interquartile range, 262-743] participants; P < .001) and more likely to meet their primary end points (39 of 58 [67%] vs 286 of 636 [45%]; P = .001). The observed median effect size among superiority trials was larger in LMICs compared with HICs (hazard ratio, 0.62 [interquartile range, 0.54-0.76] vs 0.84 [interquartile range, 0.67-0.97]; P < .001). Studies from LMICs were published in journals with lower median impact factors than studies from HICs (7 [interquartile range, 4-21] vs 21 [interquartile range, 7-34]; P < .001). Publication bias persisted when adjusted for whether a trial was positive or negative (median impact factor: LMIC negative trial, 5 [interquartile range, 4-6] vs HIC negative trial, 18 [interquartile range, 6-26]; LMIC positive trial, 9 [interquartile range, 5-25] vs HIC positive trial, 25 [interquartile range, 10-48]; P < .001). CONCLUSIONS AND RELEVANCEThis study suggests that oncology RCTs are conducted predominantly by HICs and do not match the global burden of cancer. Randomized clinical trials from LMICs are more likely to identify effective therapies and have a larger effect size than RCTs from HICs. This study suggests that there is a funding and publication bias against RCTs led by LMICs. Policy makers, research funders, and ...

Emerging water-borne pathogens constitute a major health hazard in both developed and developing nations. A new dimension to the global epidemiology of cholera-an ancient scourge-was provided by the emergence of Vibrio cholerae O139. Also, water-borne enterohaemorrhagic Escherichia coli ( E. coli O157:H7), although regarded as a problem of the industrialized west, has recently caused outbreaks in Africa. Outbreaks of chlorine-resistant Cryptosporidium have motivated water authorities to reassess the adequacy of current water-quality regulations. Of late, a host of other organisms, such as hepatitis viruses (including hepatitis E virus), Campylobacter jejuni, microsporidia, cyclospora, Yersinia enterocolitica, calciviruses and environmental bacteria like Mycobacterium spp, aeromonads, Legionella pneumophila and multidrug-resistant Pseudomonas aeruginosa have been associated with water-borne illnesses. This review critically examines the potential of these as emerging water-borne pathogens. It also examines the possible reasons, such as an increase in the number of immunocompromised individuals, urbanization and horizontal gene transfer, that may underlie their emergence. Further, measures required to face the challenge posed by these pathogens are also discussed.

Nepal is a small, low-income country between India and China with a unique health care delivery system. Cancer is becoming an important public health problem in the country, but a systematic plan to cancer control is lacking. In this article, we aim to provide a systematic assessment of the burden of disease and available resources and suggest prioritization approaches for the future to assist with any such future cancer control plans for the country.

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Severe burns induce a profound hypermetabolic response, leading to a prolonged state of catabolism associated with organ dysfunction and delay of wound healing. Oxandrolone, a synthetic testosterone analog, may alleviate the hypermetabolic catabolic state thereby decreasing associated morbidity. However, current literature has reported mixed outcomes on complications following Oxandrolone use, specifically liver and lung function. We conducted an updated systematic review and meta-analysis studying the effects of Oxandrolone on mortality, length of hospital stay, progressive liver dysfunction, and nine secondary outcomes. We searched Pubmed, EMBASE, Web of Science, CINAHL, and Cochrane Databases of Systematic Reviews and Randomized Controlled Trials. Thirty-one randomized control trials and observational studies were included. Basic science and animal studies were excluded. Only studies comparing Oxandrolone to standard of care, or placebo, were included. Oxandrolone did not affect rates of mortality (relative risk [RR]: 0.72; 95% confidence interval [CI]: 0.47 to 1.08; P = .11) or progressive liver dysfunction (RR: 1.04; 95% CI: 0.59 to 1.85; P = .88), but did decrease length of stay in hospital. Oxandrolone significantly increased weight regain, bone mineral density, percent lean body mass, and decreased wound healing time for donor graft sites. Oxandrolone did not change the incidence of transient liver dysfunction or mechanical ventilation requirements. There is evidence to suggest that Oxandrolone is a beneficial adjunct to the acute care of burn patients; shortening hospital stays and improving several growth and wound healing parameters. It does not appear that Oxandrolone increases the risk of progressive or transient liver injury, although monitoring liver enzymes is recommended.

Our descriptive findings of low MGMT expression in adrenocorticotropin-producing pituitary adenomas, particularly aggressive tumors, suggest that they may be suitable candidates for temozolomide therapy.

BACKGROUND Pediatric craniocerebral gunshot injuries (CGIs) occur both in the context of accidental and intentional trauma. The incidence and physiology of pediatric CGIs merit reexamination of prognostic factors and treatment priorities. This study characterizes the current understanding of mortality and prognostic factors in this patient population. METHODS A systematic search was conducted. Selection criteria included all studies published since 2000, which described civilian isolated CGIs in pediatric patients. Data were analyzed qualitatively and quantitatively to identify factors prognostic for the primary outcome of mortality. Secondary outcomes included functional outcome status, requirement for surgery, and injury complications. Study quality was assessed with the Newcastle-Ottawa Scale. This study was registered with PROSPERO (CRD42019134231). RESULTS Initial search revealed 349 unique studies. Forty underwent full text screening, and eight studies were included in the final synthesis. The overall mortality rate was 44.8%. Most CGIs occurred in older teenagers. Aggressive surgical treatment was recommended by one author, while remaining studies emphasized clinical judgment. Reported prognostic factors include initial Glasgow Coma Scale, pupil reactivity, involvement of multiple lobes or deep nuclei, and bihemispheric injuries. Reported complications from CGIs included seizure, meningitis, abscess, cerebrospinal fluid leak, bullet migration, focal neurological deficits, endocrine abnormalities, cognitive deficits, and neuropsychological deficits. The Glasgow Outcome Scale was the predominant measure of function and demonstrated a moderate recovery in 17.4% and a good recovery in 27.3% of patients. CONCLUSION This systematic review analyzed the existing evidence for prognostic factors in the context of pediatric CGIs. Significant long-term clinical improvement is possible with interventions including urgent surgical therapy. Fixed bilateral pupils and low initial Glasgow Coma Scale correlate with mortality but do not predict all patient outcomes. Patients younger than 15 years are underreported and may have differences in outcome. The literature on pediatric CGIs is limited and requires further characterization. LEVEL OF EVIDENCE Systematic Review, level IV.

MGMT expression in tumors has been correlated with response to treatment with temozolomide therapy. Few medical therapies are available for Nelson syndrome, and the efficacy of such therapeutics remains limited. The aim of the present study was to assess immunohistochemical expression of MGMT in ACTH-secreting pituitary adenomas of patients with Nelson syndrome. Our material consisted of eight specimens from ACTH-secreting pituitary adenomas of patients with Nelson syndrome. Immunohistochemical staining for MGMT was performed using the streptavidin-biotin-peroxidase complex method. MGMT immunoreactivity was assessed microscopically and recorded as an estimated percentage of nuclear MGMT immunostaining (0 = none, 1=<10%, 2=<25%, 3=<50%, 4=>50%). Five of the eight specimens (65%) exhibited no MGMT immunoreactivity, with two out of eight cases (25%) showing slight MGMT staining (<10%) and one out of eight cases (12%) demonstrating moderate MGMT positivity (<25%). Patient male/female ratio was 3:5, with average patient age being 62.4 (range 57–66). Our findings suggest that temozolomide therapy may be of potential use in patients with Nelson syndrome, as these tumors express absent/low levels of MGMT. Absent or low MGMT staining in brain and other neoplasms has been shown to correlate with successful treatment with temozolomide, and recent reports of aggressive pituitary adenomas suggest similar outcomes.