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Background: The mechanisms underlying interindividual variability in pain perception and cognitive responses are undefined but highly heritable. alpha(2C)- and alpha(2A)-adrenergic receptors regulate noradrenergic activity and are important mediators of pain perception and analgesia. We hypothesized that common genetic variants in these genes, particularly the ADRA2C 322-325 deletion variant, affect pain perception or cognitive responses.Methods: We studied 73 healthy subjects (37 Caucasians and 36 African-Americans) aged 25.4+/-4.6years. Pain response to a cold pressor test was measured using a 10cm visual analog scale and again on the next day, after three infusions of the selective alpha(2)-agonist dexmedetomidine. Standardized cognitive tests were administered at baseline and after each infusion. The contribution of ADRA2C deletion genotype, dexmedetomidine concentration, and other covariates to pain perception and cognitive responses was determined using multiple linear regression models. Secondary analysis examined the effects of ADRA2A and other ADRA2C variants on pain perception.Results: ADRA2C Del homozygotes had higher pain scores in response to cold at baseline (6.3+/-1.8cm) and after dexmedetomidine (5.6+/-2.2cm) than insertion allele carriers (4.6+/-2.1cm [baseline] and 3.8+/-1.9cm [after dexmedetomidine]; adjusted P-values=0.019 and 0.004, respectively). Cognitive responses were unrelated to ADRA2C Ins/Del genotype. None of the other ADRA2A and ADRA2C variants was significantly related to cold pain sensitivity before dexmedetomidine; after dexmedetomidine, ADRA2A rs1800038 was marginally associated (P=0.03).Conclusion: The common ADRA2C del322-325 variant affected pain perception before and after dexmedetomidine but did not affect other cognitive responses, suggesting that it contributes to interindividual variability in pain perception. [ABSTRACT FROM AUTHOR]

AIM: This was a pilot clinical trial to assess biochemical and clinical effects of an oral probiotic dietary supplement in chronic kidney disease (CKD) patients (stages 3 and 4). METHODS: A prospective, randomized, double-blind, crossover, placebo-controlled, 6-month trial of probiotic bacteria was conducted in 16 outpatients in Ontario, Canada. Primary endpoints included effect on hematologic, biochemical, and fecal variables, and on general well-being as assessed by quality of life (QOL). These outcomes were evaluated from biochemical parameters, mainly blood urea nitrogen (BUN), creatinine, uric acid, and C-reactive protein (CRP) as a general inflammatory marker. QOL was assessed on a subjective scale of 1 to 10 as the secondary parameter. TRIAL REGISTRATION: This pilot study forms part of registered trial NCT00760162. RESULTS: A total of 13 patients completed the study. Three patients dropped out: one was the receiver of a transplant. The second dropped out for unknown reasons and the third died of myocardial infarction (unrelated to probiotic bacteria or the protocol). Among the 13 patients who completed the trial, the mean change in BUN concentration during the probiotic treatment period (-2.93 mmol/L) differed significantly (p = 0.002) from the mean change in BUN concentration during the placebo period (4.52 mmol/L). In addition, the mean changes in uric acid concentration were moderate during the KB period (24.70 micromol/L) versus during the placebo period (50.62 micromol/L, p = 0.050), and the changes in serum creatinine concentration were insignificant. Neither gastrointestinal nor infectious complications were noted in any subject with improved QOL. CONCLUSION: Orally administered probiotic bacteria selected to metabolize nitrogenous wastes may be tolerated for as long as 6 months. A major limitation of this trial is its small size that may have precluded detection of changes in other biochemical or hematologic parameters that would be evident in larger cohorts. Extension of the evaluation of this probiotic bacterial mixture will include a dose escalation trial in a similar prospective, placebo-controlled, and double-blind study site. [ABSTRACT FROM AUTHOR]

This Editorial provides a brief commentary exploring the possibilities of the bowel acting as a substitute for kidney function in chronic kidney disease/end stage renal disease. Three concepts are highlighted as potential means by which bowel function can serve as an alternative to renal filtration: oral sorbents, diarrhea therapy and bacterial-enzyme nitrogen recycling within the gut. [ABSTRACT FROM AUTHOR]

PURPOSE: Morning diabetes management in an inpatient acute care facility was examined. METHODS: A descriptive, nonexperimental research design was used to study the effect of the following variables on patients' prelunch blood glucose: duration of time between (1) blood glucose monitoring and insulin administration, (2) insulin administration and breakfast, and (3) blood glucose monitoring and breakfast. A nonprobability convenience sample was used to examine 40 adults with diabetes who were hospitalized in an urban, academic medical center. RESULTS: The chi2 test and measurements of central tendency were used for statistical analysis. The mean interval of time between (1) blood glucose monitoring and insulin administration was 93 minutes+/-52.82, (2) blood glucose monitoring and breakfast was 121+/-47 minutes, and (3) insulin administration and breakfast was 73+/-37.06 minutes. Insulin was administered in 28% of patients<45 minutes before breakfast, whereas in 39% and 33%, it was administered between 46 and 90 minutes and >90 minutes prior to breakfast, respectively. There was a statistically significant difference (P=.033) between mean prelunch glucose levels for subjects who received insulin>45 minutes before breakfast and mean glucose levels for those who received insulin<45 minutes before breakfast. Eighty percent of patients whose breakfast was >45 minutes following insulin had prelunch glucose values of >180 mg/dL (10 mmol/L) versus 20%<180 mg/dL (10 mmol/L). Of those whose breakfast was <45 minutes before insulin, 43% had blood glucose levels>180 mg/dL, and 57% had blood glucose<180 mg/dL (P=.026). A logistical regression model revealed that patients had a 5.3 times higher risk of having a prelunch blood glucose level>180 mg/dL when their breakfast time was >45 minutes after receiving insulin as compared to those whose insulin was given<45 minutes before breakfast (relative risk, 5.3; 95% confidence interval, 1.2-25; P=.031). CONCLUSION: Current practice suggests patients are at a higher risk of prelunch hyperglycemia, and multiple opportunities exist to improve care for the inpatient with diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To ascertain whether patients at discharge from a municipal teaching hospital knew their discharge diagnoses, treatment plan (names and purpose of their medications), and common side effects of prescribed medications. PATIENTS AND METHODS: From July to October 1999, we surveyed 47 consecutive patients at discharge from the medical service of a municipal teaching hospital in New York City (Brooklyn, NY). Patients were asked to state either the trade or the generic name(s) of their medication(s), their purpose, and the major side effect(s), as well as their discharge diagnoses. Patients were excluded if they were not oriented to person, place, and time, were unaware of the circumstances surrounding their admission to the hospital, and/or did not speak or understand English. RESULTS: Of the 47 patients surveyed, 4 were excluded. Of the remaining 43 patients, 12 (27.9%) were able to list all their medications, 16 (37.2%) were able to recount the purpose of all their medications, 6 (14.0%) were able to state the common side effect(s) of all their medications, and 18 (41.9%) were able to state their diagnosis or diagnoses. The mean number of medications prescribed at discharge was 3.89. CONCLUSIONS: Less than half of our study patients were able to list their diagnoses, the name(s) of their medication(s), their purpose, or the major side effect(s). Lacking awareness of these factors affects a patient's ability to comply fully with discharge treatment plans. Whether lack of communication between physician and patient is actually the cause of patient unawareness of discharge Instructions or if this even affects patient outcome requires further study. [ABSTRACT FROM AUTHOR]

Throughout the industrialized (well-fed) world, diabetes mellitus is the most prevalent cause of end-stage renal disease (ESRD). Diabetic nephropathy is as likely to develop in long-duration non-insulin-dependent diabetes (type 2) as in insulin-dependent diabetes mellitus (type 1). Nephropathy in diabetes follows a well outlined course, starting with microalbuminuria through proteinuria, azotaemia and culminating in ESRD. Renal functional decline in diabetic nephropathy is slowed by establishment of euglycaemia and normalization of hypertensive blood pressure. Diabetic ESRD patients compared with other causes of ESRD, sustain greater mortality and morbidity due to concomitant systemic disorders, especially coronary artery and cerebrovascular disease. A central role for glucose toxicity, especially the adverse impact of accumulated adverse impact of accumulated advanced glycosylated end-products (AGEs), appears likely from experimental data generated both in induced diabetic rodents and diabetic individuals. Treatment with aminoguanidine raises the possibility of blocking end-organ damage in diabetes without the necessity for correcting hyperglycaemia. [ABSTRACT FROM PUBLISHER]

Background: In the United States, the use of polytetraflourotheylene (PTFE) graft compared with native arteriovenous fistula (AVF) for haemodialysis vascular access has been increasing despite a greater than two-fold higher incidence of thrombosis and infection associated with PTFE grafts. [ABSTRACT FROM PUBLISHER]

Objective: To assess the extent of functional and vocational rehabilitation achieved by elderly inner-city patients sustained on maintenance hemodialysis.Design: Inception cohort study of elderly patients who have end-stage renal disease using a modified Karnofsky rating system. The need for a wheelchair, participation in household activities, and effect of comorbid conditions were noted. Current status was compared with patient's recollection of functional activity level 2 years before commencing maintenance hemodialysis.Setting: Seven outpatient, hospital-affiliated and private hemodialysis units in Brooklyn, NY.Patients: One hundred four patients aged 65 years or older who were receiving maintenance hemodialysis for at least 6 months.Main Outcome Measures: A score of 76 or greater on a modified Karnofsky scale indicated independent function at a level that permitted participation in activities beyond those mandated by the hemodialysis regimen. A comorbidity score 6 or greater on a newly constructed index correlated with severe debility. Employment status was also recorded.Results: Present functional activity had deteriorated to a modified Karnofsky score of 66 +/- 12.3 (+/- SD) compared with patients' recollection of a mean score of 84 +/- 14.3 (P < .001) 2 years before initiation of hemodialysis. Diabetic patients had a lower score than nondiabetic patients. The mean comorbidity index of the entire study group was 7.8 +/- 2.9 (mean +/- SD). Within the diabetic subset, severe debility constrained 71 patients (68%) to limit all activity to their residence with the exception of travel to and from their dialysis facility. By contrast, 2 years prior to commencing dialytic therapy, 81 diabetic patients (78%) had interests and activities that took them outside their homes (P < .001). Generalized weakness was the most common explanation given for the lack of outside activity by nine patients (9%) who were wheelchair bound. Erythropoietin, though regularly administered to 87 patients (84%) in the study group, was unsuccessful in raising mean hematocrit reading above 0.28 +/- 0.05 (mean +/- SD).Conclusions: Maintenance hemodialysis does not return inner-city elderly patients to their predialysis level of functioning. Few elderly, diabetic hemodialysis patients conduct any substantive portion of their lives outside their homes. For nondiabetic patients, the modified Karnofsky score of whites (70.4 +/- 11.9) and blacks (66.5 +/- 15.3), though low, was equivalent (P < .4). [ABSTRACT FROM AUTHOR]

Competing Interests: Competing interests: None declared.

The World Health Organization (WHO) was born as a normative agency and has looked to global health law to structure collective action to realize global health with justice. Framed by its constitutional authority to act as the directing and coordinating authority on international health, WHO has long been seen as the central actor in the development and implementation of global health law. However, WHO has faced challenges in advancing law to prevent disease and promote health over the past 75 years, with global health law constrained by new health actors, shifting normative frameworks, and soft law diplomacy. These challenges were exacerbated amid the COVID-19 pandemic, as states neglected international legal commitments in national health responses. Yet, global health law reforms are now underway to strengthen WHO governance, signaling a return to lawmaking for global health. Looking back on WHO's 75th anniversary, this article examines the central importance of global health law under WHO governance, reviewing the past successes, missed opportunities, and future hopes for WHO. For WHO to meet its constitutional authority to become the normative agency it was born to be, we offer five proposals to reestablish a WHO fit for purpose: normative instruments, equity and human rights mainstreaming, sustainable financing, One Health, and good governance. Drawing from past struggles, these reforms will require further efforts to revitalize hard law authorities in global health, strengthen WHO leadership across the global governance landscape, uphold equity and rights at the center of global health law, and expand negotiations in global health diplomacy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gostin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)