Corruption is making people sick.

According to Transparency International, of the US$7.5 trillion spent globally on health each year, US$500 billion is lost to corruption.1 This article deals with the topic of corruption in the health sector in sub-Saharan Africa with a focus on how it affects persons living with HIV and their families. It begins with a definition of corruption and outlines the types of activities, people and institutions that fall within that definition in the context of HIV/AIDS. Examples are provided of what happens in practice and the types of persons (in terms of their societal roles) who yield to corruption, and how and why they commit it. The effects of corruption in health and in the fight against HIV/AIDS are then considered, drawing on published research on the costs to institutions and society. For example, HIV prevalence among women is higher than men, yet their reliance on health services plagued by corruption makes them vulnerable to abuse, blocking access to vital contraceptive, HIV testing, and reproductive and child health services. Attention is then focused on the factors that encourage the adoption of corrupt practices and what approaches have been taken to try to counter them. This includes a review and analysis of the steps that have been taken to strengthen compliance, governance and accountability and why attempts to deal with corruption have met with little success. This article suggests a new approach - harnessing digitalisation - to combat corruption more quickly and effectively, pointing out that corruption is both a major factor contributing to inefficiency and is harming peoples' health. This article aims to raise interest and renew efforts in fighting corruption in health.

Delivery of drinking, eating and mobilising (DrEaMing) and its association with length of hospital stay after major noncardiac surgery: observational cohort study.

BACKGROUND: Enhanced recovery pathways are associated with improved postoperative outcomes. However, as enhanced recovery pathways have become more complex and varied, compliance has reduced. The 'DrEaMing' bundle re-prioritises early postoperative delivery of drinking, eating, and mobilising. We investigated relationships between DrEaMing compliance, postoperative hospital length of stay (LOS), and complications in a prospective multicentre major surgical cohort. METHODS: We interrogated the UK Perioperative Quality Improvement Programme dataset. Analyses were conducted in four stages. In an exploratory cohort, we identified independent predictors of DrEaMing. We quantified the association between delivery of DrEaMing (and its component variables) and prolonged LOS in a homogenous colorectal subgroup and assessed generalisability in multispecialty patients. Finally, LOS and complications were compared across hospitals, stratified by DrEaMing compliance. RESULTS: The exploratory cohort comprised 22 218 records, the colorectal subgroup 7230, and the multispecialty subgroup 5713. DrEaMing compliance was 59% (13 112 patients), 60% (4341 patients), and 60% (3421), respectively, but varied substantially between hospitals. Delivery of DrEaMing predicted reduced odds of prolonged LOS in colorectal (odds ratio 0.51 [0.43-0.59], P<0.001) and multispecialty cohorts (odds ratio 0.47 [0.41-0.53], P<0.001). At the hospital level, complications were not the primary determinant of LOS after colorectal surgery, but consistent delivery of DrEaMing was associated with significantly shorter LOS. CONCLUSIONS: Delivery of bundled and unbundled DrEaMing was associated with substantial reductions in postoperative LOS, independent of the effects of confounder variables. Consistency of process delivery, and not complications, predicted shorter hospital-level length of stay. DrEaMing may be adopted by perioperative health systems as a quality metric to support improved patient outcomes and reduced hospital length of stay.

A Peptide-Duocarmycin Conjugate Targeting the Thomsen-Friedenreich Antigen Has Potent and Selective Antitumor Activity.

Solid-phase synthesis allowed the rapid generation of a peptide-drug conjugate. A peptide targeting the Thomsen-Friedenreich antigen (TFα) was conjugated to the alkylating subunit of the potent cytotoxin duocarmycin SA. The compound, containing a cathepsin B cleavable linker, was shown to be active and selective against TFα expressing tumor cell lines.

Older patients undergoing emergency laparotomy: observations from the National Emergency Laparotomy Audit (NELA) years 1-4.

BACKGROUND: older patients aged ≥65 years constitute the majority of the National Emergency Laparotomy Audit (NELA) population. To better understand this group and inform future service changes, this paper aims to describe patient characteristics, outcomes and process measures across age cohorts and temporally in the 4-year period (2014-2017) since NELA was established. METHODS: patient-level data were populated from the NELA data set years 1-4 and linked with Office of National Statistics mortality data. Descriptive data were compared between groups delineated by age, NELA year and geriatrician review. Primary outcomes were 30- and 90-day mortality, length of stay (LOS) and discharge to care-home accommodation. RESULTS: in total, 93,415 NELA patients were included in the analysis. The median age was 67 years. Patients aged ≥65 years had higher 30-day (15.3 versus 4.9%, P < 0.001) and 90-day mortality (20.4 versus 7.2%, P < 0.001) rates, longer LOS (median 15.2 versus 11.3 days, P < 0.001) and greater likelihood of discharge to care-home accommodation compared with younger patients (6.7 versus 1.9%, P < 0.001). Mortality rate reduction over time was greater in older compared with younger patients. The proportion of older NELA patients seen by a geriatrician post-operatively increased over years 1-4 (8.5 to 16.5%, P < 0.001). Post-operative geriatrician review was associated with reduced mortality (30-day odds ratio [OR] 0.38, confidence interval [CI] 0.35-0.42, P < 0.001; 90-day OR 0.6, CI 0.56-0.65, P < 0.001). CONCLUSIONS: older NELA patients have poorer post-operative outcomes. The greatest reduction in mortality rates over time were observed in the oldest cohorts. This may be due to several interventions including increased perioperative geriatrician input.

Diagnostic value of conventional chest radiography in intrathoracic goiters-retrospective analysis of 2570 patients.

PURPOSE: Since intrathoracic goiters (IG), either cervico-mediastinal goiters (CMGs) or mediastinal nodules (MNs), can lead to sternotomies and/or evitable reoperations, their detection is mandatory before thyroid surgery. A systematic screening by CT scan or MRI is not conceivable because of their expensiveness. We tested if conventional chest radiography (CCR) could remain a good screening tool for IG before thyroid surgery. METHODS: In this retrospective study (2554 patients), CCR usefulness was evaluated in relation with patients' complaints, clinical examination, neck US, and anatomical and surgical findings. RESULTS: CMGs (n = 67) and MNs (n = 42) were symptomatic in 10 and 5 patients, respectively. Clinical examination or neck US suspected their existence in 25 and 13 and 45 and 17 patients, respectively. Among the 50 IG detected by CCR (42 CMGs and 8 MNs), 4 CMGs and 2 MNs were missed by clinical examination or neck US. CCR failed to detect IG in 59 patients (54%): 25 CMGs (37%) and 34 MNs (80%). Twenty-eight IG (9 CMGs and 19 MNs) were discovered during surgery. CCR resulted in false positive in 88 out of 2445 patients (3.5%). CCR potentially avoided reoperation in two patients (a maximum saving of 6160 €, whereas the total cost of CCR was 54,895 €). CONCLUSIONS: CCR should not be used routinely for the preoperative detection of IG. Surgeons should preferably use clinical examination or neck US and directly perform CT scan when a mediastinal extension is suspected.

The magnitude of nephron number reduction mediates intrauterine growth-restriction-induced long term chronic renal disease in the rat. A comparative study in two experimental models.

BACKGROUND: Intrauterine growth restriction (IUGR) is a risk factor for hypertension (HT) and chronic renal disease (CRD). A reduction in the nephron number is proposed to be the underlying mechanism; however, the mechanism is debated. The aim of this study was to demonstrate that IUGR-induced HT and CRD are linked to the magnitude of nephron number reduction, independently on its cause. METHODS: Systolic blood pressure (SBP), glomerular filtration rate (GFR), proteinuria, nephron number, and glomerular sclerosis were compared between IUGR offspring prenatally exposed to a maternal low-protein diet (9% casein; LPD offspring) or maternal administration of betamethasone (from E17 to E19; BET offspring) and offspring with a normal birth weight (NBW offspring). RESULTS: Both prenatal interventions led to IUGR and a similar reduction in birth weight. In comparison to NBW offspring, BET offspring had a severe nephron deficit (-50% in males and -40% in females, p < 0.01), an impaired GFR (-33%, p < 0.05), and HT (SBP+ 17 mmHg, p < 0.05). Glomerular sclerosis was more than twofold higher in BET offspring than in NBW offspring (p < 0.05). Long-term SBP, GFR, and glomerular sclerosis were unchanged in LPD offspring while the nephron number was moderately reduced only in males (-28% vs. NBW offspring, p < 0.05). CONCLUSION: In this study, the magnitude of nephron number reduction influences long term renal disease in IUGR offspring: a moderate nephron number is an insufficient factor. Extremely long-term follow-up of adults prenatally exposed to glucocorticoids are required.

Analgesia for emergency laparotomy: a systematic review.

Aims/Background Poorly controlled pain is common after emergency laparotomy. It causes distress, hinders rehabilitation, and predisposes to complications: prolonged hospitalisation, persistent pain, and reduced quality of life. The aim of this systematic review was to compare the relative efficacies of pre-emptive analgesia for emergency laparotomy to inform practice. Methods We performed a search of MEDLINE, MEDLINE In-Process, Embase, PubMed, Web of Science and SCOPUS for comparator studies of preoperative/intraoperative interventions to control/reduce postoperative pain in adults undergoing emergency laparotomy (EL) for general surgical pathologies. Exclusion criteria: surgery including non-abdominal sites; postoperative sedation and/or intubation; non-formal assessment of pain; non-English manuscripts. All manuscripts were screened by two investigators. Results We identified 2389 papers. Following handsearching and removal of duplicates, 1147 were screened. None were eligible for inclusion, with many looking at elective and/or laparoscopic surgeries. Conclusion Our findings indicate there is no evidence base for pre-emptive analgesic strategies in emergency laparotomy. This contrasts substantially with elective cohorts. Potential reasons include variation in practice, management of physiological derangement taking priority, and perceived contraindications to neuraxial techniques. We urge a review of contemporary practice, with analysis of clinical data, to generate expert consensus.

Clonidine-induced growth hormone and growth-hormone-releasing hormone release is mediated by tachykinin NK2 receptors in sheep.

Clonidine is an α(2)-adrenergic agonist, historically known to treat high blood pressure. Further studies showed that it could be used in the treatment of neuropsychiatric disorders. Afterwards, it has been reported that clonidine stimulated growth hormone (GH) release in many species including man. Using a transnasal surgery technique in awake sheep that allowed accessing hypothalamopituitary portal vessels, our laboratory previously reported that the injection of clonidine in sheep induced a significant, immediate and short-lasting increase in peripheral GH and portal GH-releasing hormone (GHRH) levels. In this study, we show that the clonidine-induced peripheral GH and portal GHRH increase in sheep appears to be mediated by the tachykinin NK2 receptor.

Not All Piggybacks Are Equal: A Retrospective Cohort Analysis of Variation in Anhepatic Transcaval Pressure Gradient and Acute Kidney Injury During Liver Transplant.

OBJECTIVES: Complete inferior vena cava clamping in cavalreplacement during livertransplantis associated with substantial physiological derangement and postoperative morbidity. Partial clamping in the piggyback technique may be relatively protective, but evidence is lacking. Having observed substantial variation in transhepatic inferior vena cava pressure gradient with piggyback, we hypothesized that the causative mechanism is the extent of caval clamping rather than the surgical approach. MATERIALS AND METHODS: We used internal jugular and femoral catheters to estimate suprahepatic and infrahepatic inferior vena cava pressures during clamping. Pressure gradients were calculated, and distributions were compared by surgical technique. We estimated adjusted odds ratios for pressure gradient on acute kidney injury at 72 hours. RESULTS: In 115 case records, we observed substantial variation in maximum pressure gradient; median values were 18.0 mm Hg(interquartile range, 8.0-25.0 mm Hg) with the piggyback technique and 24.0 mm Hg (interquartile range, 19.5-27.0 mm Hg) with caval replacement. Incidence of acute kidney injury was 25% (29 patients). Pressure gradient was linearly associated with probability of acute kidney injury (odds ratio, 1.06; 95% CI, 1.01-1.13). CONCLUSIONS: We report 2 novel findings. (1) Anhepatic inferior vena cavapressuregradient variedsubstantially in individuals undergoing piggyback, and (2) gradient was positively associatedwith early acute kidney injury. We hypothesize that this (unmeasured) variation explains the conflictingfindings ofprevious studies that compared surgical techniques. Also, we propose that caval pressure gradient could be routinely assessed to optimize real-time piggyback clamp position during livertransplant surgery.

Acoustic neuroma presenting as a hypnic headache.

Hypnic headache (HH) is a rare, primary headache syndrome that invariably occurs during sleep and wakes the patient. Acoustic neuroma (AN) is a benign tumour that uncommonly presents with isolated headache. Here, we describe a patient with AN that presented with an HH-like syndrome. A 40-year-old woman presented with 4 months of generalised, throbbing, nocturnal headaches that woke her from sleep. Neurological examination was unremarkable. Retrospectively, she reported a 4-year history of mild, bilateral tinnitus. Neuroimaging demonstrated a large, left-sided AN in the cerebellopontine angle without obstructive hydrocephalus. Gamma knife radiosurgery controlled tumour growth. One year after radiosurgery, she became nocturnal headache-free. AN has not previously been described as presenting with an HH-like syndrome. There are four previous reports of an HH-like syndrome secondary to intracranial masses. In all cases, patients became headache-free following surgery. This advocates for neuroimaging to exclude structural causes.

Predictors of clinical deterioration in patients with suspected COVID-19 managed in a 'virtual hospital' setting: a cohort study.

OBJECTIVE: Identify predictors of clinical deterioration in a virtual hospital (VH) setting for COVID-19. DESIGN: Real-world prospective observational study. SETTING: VH remote assessment service in West Hertfordshire NHS Trust, UK. PARTICIPANTS: Patients with suspected COVID-19 illness enrolled directly from the community (postaccident and emergency (A&E) or medical intake assessment) or postinpatient admission. MAIN OUTCOME MEASURE: Death or (re-)admission to inpatient hospital care during VH follow-up and for 2 weeks post-VH discharge. RESULTS: 900 patients with a clinical diagnosis of COVID-19 (455 referred from A&E or medical intake and 445 postinpatient) were included in the analysis. 76 (8.4%) of these experienced clinical deterioration (15 deaths in admitted patients, 3 deaths in patients not admitted and 58 additional inpatient admissions). Predictors of clinical deterioration were increase in age (OR 1.04 (95% CI 1.02 to 1.06) per year of age), history of cancer (OR 2.87 (95% CI 1.41 to 5.82)), history of mental health problems (OR 1.76 (95% CI 1.02 to 3.04)), severely impaired renal function (OR for eGFR <30=9.09 (95% CI 2.01 to 41.09)) and having a positive SARS-CoV-2 PCR result (OR 2.0 (95% CI 1.11 to 3.60)). CONCLUSIONS: These predictors may help direct intensity of monitoring for patients with suspected or confirmed COVID-19 who are being remotely monitored by primary or secondary care services. Further research is needed to confirm our findings and identify the reasons for increased risk of clinical deterioration associated with cancer and mental health problems.

Appearance and management of COVID-19 laryngo-tracheitis: two case reports.

We present two cases of coronavirus disease 2019 (COVID-19)-related laryngotracheitis in good-prognosis, ventilated patients who had failed extubation. As the pandemic continues to unfold across the globe and better management of those with respiratory failure develops, this may be an increasingly common scenario. Close ENT-intensivist liaison, meticulous team preparation, early consideration of rigid endoscopy and prospective data collection and case sharing are recommended.

Distance travelled to hospital for emergency laparotomy and the effect of travel time on mortality: cohort study.

OBJECTIVES: To evaluate whether distance and estimated travel time to hospital for patients undergoing emergency laparotomy is associated with postoperative mortality. DESIGN: National cohort study using data from the National Emergency Laparotomy Audit. SETTING: 171 National Health Service hospitals in England and Wales. PARTICIPANTS: 22 772 adult patients undergoing emergency surgery on the gastrointestinal tract between 2013 and 2016. MAIN OUTCOME MEASURES: Mortality from any cause and in any place at 30 and 90 days after surgery. RESULTS: Median on-road distance between home and hospital was 8.4 km (IQR 4.7-16.7 km) with a median estimated travel time of 16 min. Median time from hospital admission to operating theatre was 12.7 hours. Older patients live on average further from hospital and patients from areas of increased socioeconomic deprivation live on average less far away.We included estimated travel time as a continuous variable in multilevel logistic regression models adjusting for important confounders and found no evidence for an association with 30-day mortality (OR per 10 min of travel time=1.02, 95% CI 0.97 to 1.06, p=0.512) or 90-day mortality (OR 1.02, 95 % CI 0.97 to 1.06, p=0.472).The results were similar when we limited our analysis to the subgroup of 5386 patients undergoing the most urgent surgery. 30-day mortality: OR=1.02 (95% CI 0.95 to 1.10, p=0.574) and 90-day mortality: OR=1.01 (95% CI 0.94 to 1.08, p=0.858). CONCLUSIONS: In the UK NHS, estimated travel time between home and hospital was not a primary determinant of short-term mortality following emergency gastrointestinal surgery.

Early postnatal overfeeding induces early chronic renal dysfunction in adult male rats.

Low birth weight is associated with an increased risk of hypertension and renal dysfunction at adulthood. Such an association has been shown to involve a reduction of nephron endowment and to be enhanced by accelerated postnatal growth in humans. However, while low-birth-weight infants often undergo catch-up growth, little is known about the long-term vascular and renal effects of accelerated postnatal growth. We surimposed early postnatal overfeeding (OF; reduction of litter size during the suckling period) to appropriate-birth-weight (NBW+OF) and intrauterine growth restriction (IUGR; IUGR+OF) pups, obtained after a maternal gestational low-protein diet. Blood pressure (systolic blood pressure; SBP) and renal function (glomerular filtration rate; GFR) were measured in young and aging offspring. Glomerulosclerosis and nephron number were determined in aging offspring (22 mo). Nephron number was reduced in both IUGR and IUGR+OF male offspring (by 24 and 26%). GFR was reduced by 40% in 12-mo-old IUGR+OF male offspring, and both NBW+OF and IUGR+OF aging male offspring had sustained hypertension (+25 mmHg) and glomerulosclerosis, while SBP and renal function were unaffected in IUGR aging offspring. Female offspring were unaffected. In conclusion, in this experimental model, early postnatal OF in the neonatal period has major long-lasting effects. Such effects are gender dependent. Reduced nephron number alone, associated with IUGR, may not be sufficient to induce long-lasting physiological alterations, and early postnatal OF acts as a "second hit." Early postnatal OF is a suitable model with which to study the long-term effects of postnatal growth in the pathogenesis of vascular disorders and renal disease.

Impact of Environmental Modifications to Enhance Day-Night Orientation on Behavior of Nursing Home Residents With Dementia.

OBJECTIVES: To determine whether environmental rearrangements of the long-term care nursing home can affect disruptive behavioral and psychological symptoms of dementia (BPSD) in residents with dementia. DESIGN: Prospective 6-month study. SETTING: The study was conducted before (phase 1) and after (phase 2) environmental rearrangements [skylike ceiling tiles in part of the shared premises, progressive decrease of the illuminance at night together with soothing streaming music, reinforcement of the illuminance during the day, walls painted in light beige, oversized clocks in corridors, and night team clothes color (dark blue) different from that of the day team (sky blue)]. PARTICIPANTS: All of the patients (n = 19) of the protected unit were included in the study. They were aged 65 years or older and had an estimated life expectancy above 3 months. MEASURES: Number and duration of disruptive BPSD were systematically collected and analyzed over 24 hours or during late hours (6:00-12:00 pm) during each 3-month period. RESULTS: There was no significant change in the patients' dependency, risk of fall, cognitive or depression indexes, or treatment between phase 1 and 2. Agitation/aggression and screaming were observed mainly outside the late hours as opposed to wandering episodes that were noticed essentially within the late hours. The number of patients showing wandering was significantly lower over 24 hours during phase 2. The number of agitation/physical aggression, wandering, and screaming and the mean duration of wandering episodes were significantly (P = .039, .002, .025, and .026 respectively) decreased over 24 hours following environmental rearrangements. Similarly, a significant reduction in the number and mean duration of wandering was noticed during the late hours (P = .031 and .007, respectively). CONCLUSIONS: Our study demonstrates that BPSD prevalence can be reduced following plain environmental rearrangements aimed at improving spatial and temporal orientation.

Risk of infection associated with intravenous iron preparations: protocol for updating a systematic review.

INTRODUCTION: The benefits and risk of intravenous iron have been documented in previous systematic reviews and continue to be the subject of randomised controlled trials (RCTs). An ongoing issue that continues to be raised is the relationship between administering iron and developing infection. This is supported by biological plausibility from animal models. We propose an update of a previously published systematic review and meta-analysis with the primary focus being infection. METHODS AND ANALYSIS: We will include RCTs and non-randomised studies (NRS) in this review update. We will search the relevant electronic databases. Two reviewers will independently extract data. Risk of bias for RCTs and NRS will be assessed using the relevant tools recommended by The Cochrane Collaboration. Data extracted from RCTs and NRS will be analysed and reported separately. Pooled data from RCTs will be analysed using a random effects model. We will also conduct subgroup analyses to identify any patient populations that may be at increased risk of developing infection. We will provide a narrative synthesis on the definitions, sources and responsible pathogens for infection in the included studies. Overall quality of evidence on the safety outcomes of mortality and infection will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: This systematic review will only investigate published studies and therefore ethical approval is not required. The results will be broadly distributed through conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: PROSPERO (CRD42018096023).

A small molecule drug conjugate (SMDC) of DUPA and a duocarmycin built on the solid phase.

In a proof-of-concept study, solid phase synthesis allowed the rapid generation of a small molecule drug conjugate in which the glutamate carboxypeptidase II (GCPII) targeting small molecule DUPA was conjugated to the alkylating subunit of the potent cytotoxin duocarmycin SA. The targeted SMDC contained a cathepsin B cleavable linker, which was shown to be active and selective against cathepsin B over-expressing and GCPII-expressing tumour cell lines.

Postnatal diet-induced obesity in rats upregulates systemic and adipose tissue glucocorticoid metabolism during development and in adulthood: its relationship with the metabolic syndrome.

In humans, a hyperactivity of glucocorticoid metabolism was postulated to be involved in the intrauterine programming of the metabolic syndrome in adulthood. We studied in rats the effects of overfeeding, obtained by reducing the size of the litter in the immediate postnatal period, a time crucial for neuroendocrine maturation such as late gestation in humans. Overfeeding induced early-onset obesity and accelerated the maturation of the hypothalamo-pituitary-adrenal (HPA) axis together with an upregulation of adipose tissue glucocorticoid receptor (GR) mRNA. In adulthood, neonatally overfed rats presented with moderate increases in basal and stress-induced corticosterone secretion and striking changes in visceral adipose tissue glucocorticoid signaling, that is, enhanced GR and 11beta-hydroxysteroid dehydrogenase type 1 mRNA levels. The above-mentioned alterations in the endocrine status of overfed rats were accompanied by a moderate overweight status and significant metabolic disturbances comparable to those described in the metabolic syndrome. Our data demonstrate for the first time that postnatal overfeeding accelerates the maturation of the HPA axis and leads to permanent upregulation of the HPA axis and increased adipose tissue glucocorticoid sensitivity. Thus, the experimental paradigm of postnatal overfeeding is a powerful tool to understand the pathophysiology of glucocorticoid-induced programming of metabolic axes.