Post-Obstructive Urinary Concentrating Defect A Case Study in the Role of Prostaglandins

ABSTRACT. A child with post-obstructive urinary concentrating defect was studied for the possible pathophysiological role of prostaglandins and an eventual therapeutic approach. Increased urinary excretion of prostaglandins was corrected by indomethacin, with resultant increased nephrogenous cyclic AMP and partial improvement in the concentrating defect. The addition of a thiazide restored urinary concentration. These results add clinical support to the conception of the important role of prostaglandins in the mechanism of post-obstructive hyposthenuria. This therapeutic regimen is advocated for prolonged post-obstructive concentrating defect.     

Candesartan for the prevention and treatment of stroke - results of the SCOPE and ACCESS trials

Stroke is a leading cause of death and disability. The SCOPE clinical trial assessed the effects of the angiotensin Type 1 (AT(1))-receptor antagonist, candesartan, on major cardiovascular events in elderly hypertensive patients. A first major cardiovascular event (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) occurred to a lesser extent in the candesartan group (242 of 2477) than the placebo group (268 of 2460) and this difference represented a reduction in stroke rather than cardiac events. The ACCESS trial was designed to assess the safety of a modest blood pressure reduction with the AT 1 -receptor antagonist, candesartan, in the early treatment of stroke. What ACCESS actually showed was that, in the absence of blood pressure lowering, candesartan treatment for 7 days, started within 24 h of motor deficit associated with stoke, reduced the cumulative 12-month mortality rate (7.2 and 2.9% for placebo and candesartan, respectively) and vascular events (18.7 and 9.8% for placebo and candesartan, respectively). In conclusion, candesartan is safe to use in the prevention and treatment of acute stroke, and may provide therapeutic benefits.     

EFFECT OF NEUROMUSCULAR ELECTRICAL STIMULATION ON THE RECOVERY OF PEOPLE WITH COVID-19 ADMITTED TO THE INTENSIVE CARE UNIT: A NARRATIVE REVIEW

The rehabilitation of patients with COVID-19 after prolonged treatment in the intensive care unit is often complex and challenging. Patients may develop a myriad of long-term multi-organ impairments, affecting the respiratory, cardiac, neurological, digestive and musculoskeletal systems. Skeletal muscle dysfunction of respiratory and limb muscles, commonly referred to as intensive care unit acquired weakness, occurs in approximately 40% of all patients admitted to intensive care. The impact on mobility and return to activities of daily living is severe. Furthermore, many patients experience ongoing symptoms of fatigue, weakness and shortness of breath, in what is being described as “long COVID”. Neuromuscular electrical stimulation is a technique in which small electrical impulses are applied to skeletal muscle to cause contractions when voluntary muscle contraction is difficult or impossible. Neuromuscular electrical stimulation can prevent muscle atrophy, improve muscle strength and function, maintain blood flow and reduce oedema. This review examines the evidence, current guidelines, and proposed benefits of using neuromuscular electrical stimulation with patients admitted to the intensive care unit. Practical recommendations for using electrical muscle stimulation in patients with COVID-19 are provided, and suggestions for further research are proposed.Evidence suggests NMES may play a role in the weaning of patients from ventilators and can be continued in the post-acute and longer-term phases of recovery. As such, NMES may be a suitable treatment modality to implement within rehabilitation pathways for COVID-19, with consideration of the practical and safety issues highlighted within this review. LAY ABSTRACTMany patients with COVID-19 are admitted to the intensive care unit with ongoing symptoms of fatigue, weakness and shortness of breath. Neuromuscular electrical stimulation is a technique in which small electrical impulses are applied to skeletal muscle to cause contractions when voluntary muscle contraction is difficult or impossible. It can prevent muscle atrophy, improve muscle strength and function, maintain blood flow and reduce oedema. This review examines the evidence, current guidelines, and proposed benefits of using neuromuscular electrical stimulation with patients admitted to the intensive care unit. Practical recommendations for using electrical muscle stimulation with COVID-19 patients are provided and suggestions for further research are proposed. Evidence suggests NMES may play a role in the weaning of patients from ventilators and can be continued in the post-acute and longer-term phases of recovery. As such, NMES may be a suitable treatment modality to implement within rehabilitation pathways for COVID-19, with consideration of the practical and safety issues highlighted within this review. Key words: critical care, rehabilitation, neuromuscular electrical stimulation, muscular atrophy, coronavirus infection, COVID-19

The COVID-19 pandemic has seen unprecedented numbers of people being treated in intensive care units (ICUs) worldwide. Many patients have received artificial ventilation, and some have been ventilated for many weeks. Those that survive are often left with long-term disabilities as a result of the effects of both the disease and of the treatments necessary to keep them alive. A myriad of multi-organ impairments is associated with COVID-19 including respiratory, cardiac, neurological, bowel and kidney dysfunction (1). The unexpectedly large number of COVID-19 patients requiring a prolonged stay in ICU additionally increases the risk of dysfunction of both respiratory and skeletal muscle, commonly referred to as ICU-acquired weakness (ICUAW). A conspicuous feature of COVID-19 is the persistence of symptoms, which may appear to resolve, but then recur. As a result, many survivors are left needing significant rehabilitation at a time when such services are under great stress. This has led to the blanket term “long COVID”, which describes ongoing symptoms, which may include fatigue, weakness and delayed recovery (2).Strikingly, in the first 7 months of 2020, there were more than 10,000 COVID-19 admissions to critical care in the UK National Health Service (NHS), which is 4 times greater than historic annual cases of viral pneumonia (3). Our experience of COVID-19 in the UK is that critically unwell patients generally require a longer course of respiratory support, exacerbating other risk factors for ICUAW (3). At present, ICUAW is seen in approximately 20–50% of patients with COVID-19 admitted to the ICU (4). General deconditioning, muscle atrophy, inflammation, and functional disability often necessitate transfer from the ICU to a long-term care facility. Exacerbations of chronic comorbidities and the cycle of prolonged bed rest, ongoing inflammation and malnutrition can lead to continued functional disability, immobility and continued ventilation support. Data from the UK Intensive Care National Audit and Research Centre (ICNARC) database indicates that older age, obesity, multiple deprivation, and the requirement for assistance in activities of daily living (ADL) are predictors for severe disease requiring admission to critical care (3). These risk factors are associated with a reduced level of background fitness, malnutrition and neuropathy. Infection with COVID-19 characteristically causes myalgia, lethargy and a loss of appetite, which are likely to exacerbate this pre-morbid condition. Further deconditioning may result from constrained normal daily activities. This may be due to the disease itself, causing shortness of breath on exertion or delirium (5), or may be the result of supportive interventions and infection control measures. It is also noteworthy that proximal myopathy is associated with the use of therapeutic dexamethasone, a drug that has been shown to reduce 28-day mortality in COVID-19 (6).Table IRisk factors for deconditioning and intensive care unit associated weakness (ICUAW) in patients with COVID-19 in comparison with those with viral pneumonia (3)

A functional variant in ANGPT1 and the risk of pregnancies with hypertensive disorders and small-for-gestational-age infants

Pregnancies complicated by pre-eclampsia and small-for-gestational-age (SGA) infants demonstrate impaired placental vascular remodelling. Angiopoietin-1 (ANG-1) is an angiogenic growth factor which regulates vascular integrity and remodelling. The TT genotype of angiopoietin 1 (ANGPT1) rs2507800 polymorphism has been associated with increased plasma ANG-1 levels compared with the AA genotype. We aimed to investigate the association between ANGPT1 rs2507800 polymorphism and pregnancies complicated by gestational hypertensive disorders and SGA infants. We also aimed to investigate whether the polymorphism was associated with abnormal uterine artery Doppler as a surrogate marker of impaired placental vascular remodelling. Genotyping data of 1361 nulliparous pregnant women, 1226 partners and 1190 infants were analysed. The prevalence of ANGPT1 rs2507800 TT genotype was reduced in women with pre-eclampsia [P = 0.01, adjusted odds ratio (aOR), 0.5; 95% confidence interval (CI), 0.3-0.9], hypertensive SGA (P = 0.04, aOR, 0.5; 95% CI, 0.2-0.9) and SGA with abnormal uterine artery Doppler (P = 0.009, aOR, 0.4. 95% CI, 0.2-0.8) compared with women with uncomplicated pregnancy. The prevalence of maternal ANGPT1 rs2507800 TT genotype was reduced in women with increased uterine artery resistance index (P = 0.03, aOR, 0.7; 95% CI, 0.5-0.9) and bilateral notching of the uterine arteries (P = 0.004, aOR, 0.6; 95% CI, 0.4-0.9). These results remained significant after correcting for multiple testing. Maternal ANGPT1 rs2507800 TT genotype is associated with a reduced risk for pre-eclampsia, hypertensive SGA and abnormal uterine artery Doppler. These findings suggest that the TT genotype may protect against these pregnancy disorders by increasing ANG-1 production at the maternal-fetal interface. The ANGPT1 rs2507800 polymorphism may have a potential role in screening women to predict the risk of these pregnancy complications. TRIAL REGISTRY NAME: Screening nulliparous women to identify the combinations of clinical risk factors and/or biomarkers required to predict pre-eclampsia, SGA babies and spontaneous preterm birth.     

The SCOPE Study: Health-Care Consumption Related to Patients with Chronic Obstructive Pulmonary Disease in France

OBJECTIVE: The main objective of the SCOPE study was to estimate the total direct medical costs of patients with treated chronic obstructive pulmonary disease (COPD) in France according to severity stages. METHODS: Total medical resources consumption of a sample of COPD patients was collected over a 12-month period through a national physician survey (including both general practitioners and lung specialists). This survey was completed for 255 patients. Data were then extrapolated to all patients with diagnosed and treated COPD in France. Average total medical resources consumption of a COPD patient per year was 4366 euros. Among this cost 41% was directly related to COPD follow-up, 25% to COPD-related complications (mainly exacerbations), and 34% to other diseases. More than one-third of the total direct COPD cost was related to hospitalizations and 31% to drug consumption. COPD-related costs increased markedly with severity based on FEV1 (but data suggested the existence of a threshold effect). SCOPE data did not show any evidence of a significant relationship between direct medical cost and patient age, sex, addiction to tobacco, or duration of COPD. The total medical consumption of COPD patients in France was 3.5 billion euros and accounted for 3.5% of the total medical expenditures (prevalence of COPD was estimated 1.3% in the general population). RESULTS: The SCOPE study revealed the high level of medical resources consumption of patients with COPD. CONCLUSIONS: The burden of COPD itself and its complications appeared to be of considerable magnitude in France especially for severe COPD.