As pharma is to people, so infrastructure is to cities

The pharmaceutical industry is a profit-making sector of the healthcare system and has grown into a self-regulating complex system over the years. Starting from the pre-clinical to clinical development of drugs to the authorisation and marketing thereof, a typical multi-national pharmaceutical company of today operates in complex ways which partly emerge from the multiple interactions within and without the company. The complexity is further given by the unpredictability of the outcomes: merely 1 out of 10 drugs that are in development are likely to be approved. The plethora of regulations by authorities such as the European Medicines Agency pose a negative feedback on this complex system which is further aggravated by the reimbursement landscape of each country, taking a toll on the innovative side of this privately funded sector.
 By analogy, infrastructure operations with distinct supply systems delivering specific critical products and services, pharmaceutical companies have become the exclusive suppliers of drugs within the healthcare system. Increasingly traditional public sector infrastructure provision has been privatised, as has national health services drug development, resulting in high levels of regulation in each, constraining innovation and profitability, hall-marks of the private sector. Just as infrastructure delivers the life-blood of cities, pharma delivers medicines for the health of individuals: both aim for public health and societal good. Failures in infrastructure delivery, such as unaffordability by the poor, match with pharma failures to provide equitably to all individuals: the poor cannot afford the best drugs. The urban sprawl in cities and the rise of informal settlements without sufficient infrastructure, can be observed in health care by the rise in use of alternative and unreliable medications by sections of the population who are excluded from pharma penetration.
 Our work studies such analogies between infrastructure and pharmaceutical companies in the hope of a better understanding of the operations of and connections with each other and inspirations about finding solutions from these two similar, yet distinct complex systems

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

The effect of hyperemesis gravidarum on the 75g oral glucose tolerance test screening and gestational diabetes mellitus

Objective: To clarify the effect of hyperemesis gravidarum (HG) on the 75g oral glucose tolerance test (OGTT) and gestational diabetes mellitus.Methods: This retrospective cohort study was conducted via an evaluation of the hospital database medical records of 700 pregnant women. Of these, 60 were included in the study group as a result of hospitalization due to HG, 41 were excluded, and the remaining 599 formed a control group. The body mass index (BMI), urine ketone levels, and ages of all participants were separately recorded, both in the initial examination and during the 75g OGTT.Results: At initial examination, no significant differences in maternal age and BMI were observed between the two groups. There was a significant decrease in BMI after 75g OGTT in the study group. No significant difference in fasting serum glucose levels was found between the two groups, but significant differences in first and second hour serum glucose levels were observed.Conclusions: HG may improve in many women in the late second trimester, and loss of fatty tissue may affect the 75g OGTT screening results. The appropriate cutoff value of 75g OGTT for HG should be reevaluated following future, larger, studies

ILC3 deficiency and generalized ILC abnormalities in DOCK8-deficient patients

BackgroundDedicator of cytokinesis 8 (DOCK8) deficiency is the main cause of the autosomal recessive hyper-IgE syndrome (HIES). We previously reported the selective loss of group 3 innate lymphoid cell (ILC) number and function in a Dock8-deficient mouse model. In this study, we sought to test whether DOCK8 is required for the function and maintenance of ILC subsets in humans