In the eye of the beholder: To make global health estimates useful, make them more socially robust

A plethora of new development goals and funding institutions have greatly increased the demand for internationally comparable health estimates in recent years, and have brought important new players into the field of health estimate production. These changes have rekindled debates about the validity and legitimacy of global health estimates. This paper draws on country case studies and personal experience to support our opinion that the production and use of estimates are deeply embedded in specific social, economic, political and ideational contexts, which differ at different levels of the global health architecture. Broadly, most global health estimates tend to be made far from the local contexts in which the data upon which they are based are collected, and where the results of estimation processes must ultimately be used if they are to make a difference to the health of individuals. Internationally standardised indicators are necessary, but they are no substitute for data that meet local needs, and that fit with local ideas of what is credible and useful. In other words, data that are both technically and socially robust for those who make key decisions about health. We suggest that greater engagement of local actors (and local data) in the formulation, communication and interpretation of health estimates would increase the likelihood that these data will be used by those most able to translate them into health gains for the longer term. Besides strengthening national information systems, this requires ongoing interaction, building trust and establishing a communicative infrastructure. Local capacities to use knowledge to improve health must be supported

What Makes a National Pharmaceutical Track and Trace System Succeed?

__Background:__ Track and trace systems are increasingly being implemented as a technological solution to secure pharmaceutical supply chains. Turkey was the first country to implement a full pharmaceutical track and trace system throughout the entire regulated domestic supply chain. This article explores the emergence and functioning of this system and the consequences for substandard and falsified medicine with a focus on the underlying political and economic factors. __Methods:__ This study uses an explanatory case study approach that combined interviews with purposefully selected key informants and document analyses. __Results:__ The main drivers for implementing the pharmaceutical track and trace system in Turkey centered on the elimination of reimbursement fraud and the prevention of falsified medicine in the regulated supply chain. Although stakeholders experienced both physical and software-related problems in implementation, the alignment of incentives of all stakeholders with the power of the state, along with leeway for adaptations, ultimately resulted in a successful process. This track and trace system provides a clean regulated supply chain, minimizes reimbursement fraud, facilitates fast market recalls, and can flag likely medicine shortages. Staff previously engaged in pharmacy inspections now concentrate on ensuring production quality, which reduces the risk of substandard medicines. __Conclusions:__ In Turkey, 4 factors drove the successful implementation of pharmaceutical track and trace: the political determination to eliminate reimbursement fraud, a large pharmaceutical market dominated by a single payer, medicine reimbursement being contingent on verified dispensing and prescription, and flexibility to adapt the system according to the needs of stakeholders during implementation

Identifying market risk for substandard and falsified medicines

__Introduction:__ Substandard and falsified medicines undermine health systems. We sought to unravel the political and economic factors which drive the production of these products, and to explain how they reach patients. __Methods:__ We conducted in-depth case studies in China, Indonesia, Turkey and Romania. We reviewed academic papers and press reports (n = 840), developing semi-structured questionnaires. We interviewed regulators, policy-makers, pharmaceutical manufacturers, physicians, pharmacists, patients and academics (n=88). We coded data using NVivo software, and developed an analytic framework to assess national risks for substandard and falsified medicines. We tested the framework against cases reported to the World Health Organization, from countries at all income levels. __Results:__ We found that increasing political commitment to provision of universal health coverage has led to public procurement policies aimed at lowering prices of medical products. In response, legitimate, profit-driven pharmaceutical companies protect their margins by cutting costs, or withdrawing from less profitable markets, while distributors engage in arbitrage. Meanwhile, health providers sometimes protect profits by 'upselling' patients to medicines not covered by insurers. Cost-cutting can undermine quality assurance, leading to substandard or degraded medicines. Other responses contribute to shortages, irrational demand and high prices. All of these provide market opportunities for producers of falsified products; they also push consumers outside of the regular supply chain, providing falsifiers with easy access to customers. The analytic framework capturing these interactions explained cases in most high and middle-income settings; additional factors operate in the poorest countries. __Conclusions:__ Most efforts to secure medicine quality currently focus on product regulation. However, our research suggests market mechanisms are key drivers for poor quality medicines, including where political commitments to universal health coverage are under-resourced. We have developed a framework to guide country-specific, system-wide analysis. This can flag risks and pinpoint specific actions to protect medicine quality, and thus health

Reconstruction of Family-Level Phylogenetic Relationships within Demospongiae (Porifera) Using Nuclear Encoded Housekeeping Genes

Background: Demosponges are challenging for phylogenetic systematics because of their plastic and relatively simple morphologies and many deep divergences between major clades. To improve understanding of the phylogenetic relationships within Demospongiae, we sequenced and analyzed seven nuclear housekeeping genes involved in a variety of cellular functions from a diverse group of sponges. Methodology/Principal Findings: We generated data from each of the four sponge classes (i.e., Calcarea, Demospongiae, Hexactinellida, and Homoscleromorpha), but focused on family-level relationships within demosponges. With data for 21 newly sampled families, our Maximum Likelihood and Bayesian-based approaches recovered previously phylogenetically defined taxa: Keratosap, Myxospongiaep, Spongillidap, Haploscleromorphap (the marine haplosclerids) and Democlaviap. We found conflicting results concerning the relationships of Keratosap and Myxospongiaep to the remaining demosponges, but our results strongly supported a clade of Haploscleromorphap+Spongillidap+Democlaviap. In contrast to hypotheses based on mitochondrial genome and ribosomal data, nuclear housekeeping gene data suggested that freshwater sponges (Spongillidap) are sister to Haploscleromorphap rather than part of Democlaviap. Within Keratosap, we found equivocal results as to the monophyly of Dictyoceratida. Within Myxospongiaep, Chondrosida and Verongida were monophyletic. A well supported clade within Democlaviap, Tetractinellidap, composed of all sampled members of Astrophorina and Spirophorina (including the only lithistid in our analysis), was consistently revealed as the sister group to all other members of Democlaviap. Within Tetractinellidap, we did not recover monophyletic Astrophorina or Spirophorina. Our results also reaffirmed the monophyly of order Poecilosclerida (excluding Desmacellidae and Raspailiidae), and polyphyly of Hadromerida and Halichondrida. Conclusions/Significance: These results, using an independent nuclear gene set, confirmed many hypotheses based on ribosomal and/or mitochondrial genes, and they also identified clades with low statistical support or clades that conflicted with traditional morphological classification. Our results will serve as a basis for future exploration of these outstanding questions using more taxon- and gene-rich datasets

Field-testing of a rapid survey method to assess the prevalence and causes of hearing loss in Gao'an, Jiangxi province, China.

BACKGROUND: The Rapid Assessment of Hearing Loss (RAHL) survey protocol aims to measure the prevalence and causes of hearing loss in a low cost and rapid manner, to inform planning of ear and hearing services. This paper reports on the first field-test of the RAHL in Gao'an County, Jiangxi Province, China. This study aimed to 1) To report on the feasibility of RAHL; 2) report on the estimated prevalence and causes of hearing loss in Gao'an. METHODS: A cross-sectional population-based survey was conducted in September-October 2018. Forty-seven clusters in Gao'an County were selected using probability-proportionate-to-size sampling. Within clusters, compact segment sampling was conducted to select 30 people aged 50+. A questionnaire was completed covering sociodemographics, hearing health, and risk factors. Automated pure-tone audiometry was completed for all participants, using smartphone-based audiometry (hearTest), at 0.5, 1, 2, 4 kHz (kHz). All participants had their ears examined by an Ear Nose and Throat (ENT) doctor, using otoscopy, and probable causes of hearing loss assigned. Prevalence estimates were age and sex standardised to the Jiangxi population. Feasibility of a cluster size of 30 was examined by assessing the response rate, and the proportion of clusters completed in 1 day. RESULTS: 1344 of 1421 eligible participants completed the survey (94.6%). 100% of clusters were completed in 1 day. The survey was completed in 4.5 weeks. The prevalence of moderate or greater hearing loss (pure-tone average of 0.5, 1, 2, 4 kHz of > = 41dBHL in the better ear) was 16.3% (95% CI = 14.3, 18.5) and for any level of hearing loss (pure-tone average of > = 26dBHL in the better ear) the prevalence was 53.2% (95% CI = 49.2, 57.1). The majority of hearing loss was due to acquired sensorineural causes (91.7% left; 92.1% right). Overall 54.0% of the population aged 50+ (108,000 people) are in need of diagnostic audiology services, 3.4% were in need of wax removal (7000 people), and 4.8% were in need of surgical services (9500 people). Hearing aid coverage was 0.4%. CONCLUSION: The RAHL survey protocol is feasible, demonstrated through the number of people examined per day, and the high response rate. The survey was completed in a much shorter period than previous all-age surveys in China. Some remaining challenges included assignment of causes of probable sensorineural loss. The data obtained from this survey can be used to scale-up hearing services in Gao'an

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049