6 research outputs found
Lipid Metabolites Enhance Secretion Acting on SNARE Microdomains and Altering the Extent and Kinetics of Single Release Events in Bovine Adrenal Chromaffin Cells
Lipid molecules such as arachidonic acid (AA) and sphingolipid metabolites have been implicated in modulation of neuronal and endocrine secretion. Here we compare the effects of these lipids on secretion from cultured bovine chromaffin cells. First, we demonstrate that exogenous sphingosine and AA interact with the secretory apparatus as confirmed by FRET experiments. Examination of plasma membrane SNARE microdomains and chromaffin granule dynamics using total internal reflection fluorescent microscopy (TIRFM) suggests that sphingosine production promotes granule tethering while arachidonic acid promotes full docking. Our analysis of single granule release kinetics by amperometry demonstrated that both sphingomyelinase and AA treatments enhanced drastically the amount of catecholamines released per individual event by either altering the onset phase of or by prolonging the off phase of single granule catecholamine release kinetics. Together these results demonstrate that the kinetics and extent of the exocytotic fusion pore formation can be modulated by specific signalling lipids through related functional mechanisms
Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries
Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely
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What is the concordance between the medical record and patient self-report as data sources for ambulatory care?
BackgroundThe validity of quality of care assessments relies upon data quality, yet little is known about the relative completeness and validity of data sources for evaluating the quality of care.ObjectivesWe evaluated concordance between ambulatory medical record and patient survey data. Levels of concordance, variations by type of item, sources of disagreement between data sources, and implications for quality of care assessment efforts are discussed.Design and subjectsThis was an observational study that included 1270 patients sampled from 39 West Coast medical organizations with at least 1 of the following: diabetes, ischemic heart disease, asthma or chronic obstructive pulmonary disease, or low back pain.MeasuresItems from both data sources were grouped into 4 conceptual domains: diagnosis, clinical services delivered, counseling and referral, and medication use. We present total agreement, kappa, sensitivity, and specificity at the item and domain-levels and for all items combined.ResultsWe found good concordance between survey and medical records overall, but there was substantial variation within and across domains. The worst concordance was in the counseling and referrals domain, the best in the medication use domain. Patients were able to report with good sensitivity on memorable items.ConclusionsQuality ratings are likely to vary in differing directions, depending on the data source used. The most appropriate data source for analyses of components of and overall quality of care must be considered in light of study objectives and resources. We recommend data collection from multiple sources to most accurately portray the patient and provider experience of medical care
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Does ambulatory process of care predict health-related quality of life outcomes for patients with chronic disease?
ObjectiveThe validity of quality of care measurement has important implications for practicing clinicians, their patients, and all involved with health care delivery. We used empirical data from managed care patients enrolled in west coast physician organizations to test the hypothesis that observed changes in health-related quality of life across a 2.5-year window reflecting process of care.Data sources/study settingPatient self-report data as well as clinically detailed medical record review regarding 963 patients with chronic disease associated with managed care from three west coast states.Study designProspective cohort study of change in health-related quality of life scores across 30 months as measured by change in SF-12 physical component scores.Data collection/extraction methodsPatient self-report and medical record abstraction.Principal findingsWe found a positive relationship between better process scores and higher burden of illness (p<.05). After adjustment for burden of illness, using an instrumental variables approach revealed better process is associated with smaller declines in SF-12 scores across a 30-month observation window (p=.014). The application of the best quartile of process of care to patients currently receiving poor process is associated with a 4.24 increment in delta SF-12-physical component summary scores.ConclusionsThe use of instrumental variables allowed us to demonstrate a significant relationship between better ambulatory process of care and better health-related quality of life. This finding underscores the importance of efforts to improve the process of care
Empagliflozin in Patients with Chronic Kidney Disease
Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo