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The New England Journal of Medicine Jan 2023The 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... (Randomized Controlled Trial)
Randomized Controlled Trial
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 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m 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, a sustained decrease in eGFR of ≥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. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110; EudraCT number, 2017-002971-24.).
Topics: Humans; Benzhydryl Compounds; Cardiovascular Diseases; Creatinine; Diabetes Mellitus, Type 2; Disease Progression; Glomerular Filtration Rate; Kidney; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 36331190
DOI: 10.1056/NEJMoa2204233 -
Health Technology Assessment... Feb 2022Upper limb problems are common after breast cancer treatment. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Upper limb problems are common after breast cancer treatment.
OBJECTIVES
To investigate the clinical effectiveness and cost-effectiveness of a structured exercise programme compared with usual care on upper limb function, health-related outcomes and costs in women undergoing breast cancer surgery.
DESIGN
This was a two-arm, pragmatic, randomised controlled trial with embedded qualitative research, process evaluation and parallel economic analysis; the unit of randomisation was the individual (allocated ratio 1 : 1).
SETTING
Breast cancer centres, secondary care.
PARTICIPANTS
Women aged ≥ 18 years who had been diagnosed with breast cancer and were at higher risk of developing shoulder problems. Women were screened to identify their risk status.
INTERVENTIONS
All participants received usual-care information leaflets. Those randomised to exercise were referred to physiotherapy for an early, structured exercise programme (three to six face-to-face appointments that included strengthening, physical activity and behavioural change strategies).
MAIN OUTCOME MEASURES
The primary outcome was upper limb function at 12 months as assessed using the Disabilities of Arm, Hand and Shoulder questionnaire. Secondary outcomes were function (Disabilities of Arm, Hand and Shoulder questionnaire subscales), pain, complications (e.g. wound-related complications, lymphoedema), health-related quality of life (e.g. EuroQol-5 Dimensions, five-level version; Short Form questionnaire-12 items), physical activity and health service resource use. The economic evaluation was expressed in terms of incremental cost per quality-adjusted life-year and incremental net monetary benefit gained from an NHS and Personal Social Services perspective. Participants and physiotherapists were not blinded to group assignment, but data collectors were blinded.
RESULTS
Between 2016 and 2017, we randomised 392 participants from 17 breast cancer centres across England: 196 (50%) to the usual-care group and 196 (50%) to the exercise group. Ten participants (10/392; 3%) were withdrawn at randomisation and 32 (8%) did not provide complete baseline data. A total of 175 participants (89%) from each treatment group provided baseline data. Participants' mean age was 58.1 years (standard deviation 12.1 years; range 28-88 years). Most participants had undergone axillary node clearance surgery (327/392; 83%) and 317 (81%) had received radiotherapy. Uptake of the exercise treatment was high, with 181 out of 196 (92%) participants attending at least one physiotherapy appointment. Compliance with exercise was good: 143 out of 196 (73%) participants completed three or more physiotherapy sessions. At 12 months, 274 out of 392 (70%) participants returned questionnaires. Improvement in arm function was greater in the exercise group [mean Disabilities of Arm, Hand and Shoulder questionnaire score of 16.3 (standard deviation 17.6)] than in the usual-care group [mean Disabilities of Arm, Hand and Shoulder questionnaire score of 23.7 (standard deviation 22.9)] at 12 months for intention-to-treat (adjusted mean difference Disabilities of Arm, Hand and Shoulder questionnaire score of -7.81, 95% confidence interval -12.44 to -3.17; = 0.001) and complier-average causal effect analyses (adjusted mean difference -8.74, 95% confidence interval -13.71 to -3.77; ≤ 0.001). At 12 months, pain scores were lower and physical health-related quality of life was higher in the exercise group than in the usual-care group (Short Form questionnaire-12 items, mean difference 4.39, 95% confidence interval 1.74 to 7.04; = 0.001). We found no differences in the rate of adverse events or lymphoedema over 12 months. The qualitative findings suggested that women found the exercise programme beneficial and enjoyable. Exercise accrued lower costs (-£387, 95% CI -£2491 to £1718) and generated more quality-adjusted life years (0.029, 95% CI 0.001 to 0.056) than usual care over 12 months. The cost-effectiveness analysis indicated that exercise was more cost-effective and that the results were robust to sensitivity analyses. Exercise was relatively cheap to implement (£129 per participant) and associated with lower health-care costs than usual care and improved health-related quality of life. Benefits may accrue beyond the end of the trial.
LIMITATIONS
Postal follow-up was lower than estimated; however, the study was adequately powered. No serious adverse events directly related to the intervention were reported.
CONCLUSIONS
This trial provided robust evidence that referral for early, supported exercise after breast cancer surgery improved shoulder function in those at risk of shoulder problems and was associated with lower health-care costs than usual care and improved health-related quality of life.
FUTURE WORK
Future work should focus on the implementation of exercise programmes in clinical practice for those at highest risk of shoulder problems.
TRIAL REGISTRATION
This trial is registered as ISRCTN35358984.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 26, No. 15. See the NIHR Journals Library website for further project information.
Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Cost-Benefit Analysis; Exercise; Female; Humans; Lymphedema; Middle Aged; Pain; Quality of Life; Shoulder; Upper Extremity
PubMed: 35220995
DOI: 10.3310/JKNZ2003 -
Nursing Outlook 2020The delivery of emergency, trauma, critical, and intensive care services requires coordination among all members of the care team. Perceived teamwork and role clarity...
BACKGROUND
The delivery of emergency, trauma, critical, and intensive care services requires coordination among all members of the care team. Perceived teamwork and role clarity may vary among physicians (MDs) and nurse practitioners (NPs).
PURPOSE
To examine differences in perceived roles and responsibilities of NPs and MDs practicing in emergency, trauma, critical, and intensive care.
METHODS
Secondary Analysis of the National Survey of Emergency, Intensive, and Critical Care Nurse Practitioners and Physicians, a cross-sectional national survey of clinicians. Mail survey of randomly selected stratified cross-sectional samples of MDs and NPs drawn from national lists of clinicians in eligible specialties working in emergency, trauma, intensive, and critical care units in the United States. 814 clinicians (351 NPs and 463 MDs) were recruited from national by postal mail survey. Our initial sample included n = 2,063 clinicians, n = 1,031 NPs and n = 1,032 MDs in eligible specialties. Of these, 63.5% of NPs and 70.1% of MDs completed and returned the survey excluding those who were ineligible due to lack of current practice in a relevant specialty.
FINDINGS
NPs in ICU/CCU are more likely to be female and report working fewer hours than do MDs and provide direct care to more patients. 55% of NPs and 82% of MDs agree that their individual role in their unit is clear (p < .001); 34% of MDs and 42% of NPs agree that their unit is an example of excellent team work among professionals (p = 0.021); 41% of MD and 37% of NP clinicians (p = 0.061) agree that their teams are "prepared to provide outstanding care in a crisis or disaster." Perceived role clarity was significantly associated with increased perceptions of excellent teamwork and disaster preparedness.
DISCUSSION
At the time of this survey, and majority of NPs and MDs working in emergency, critical and intensive care did not agree that their teams were prepared for a crisis or disaster. Leaders of health organizations should encourage teamwork and professional role clarity to assist units to perform effectively in emergency and disaster preparedness.
Topics: Adult; Critical Care; Cross-Sectional Studies; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Nurse Practitioners; Nurse's Role; Physicians; Surveys and Questionnaires; United States
PubMed: 32622648
DOI: 10.1016/j.outlook.2020.04.010 -
European Urology May 2021Little is known about health-related quality of life (HRQOL) following treatment for bladder cancer (BC).
BACKGROUND
Little is known about health-related quality of life (HRQOL) following treatment for bladder cancer (BC).
OBJECTIVE
To determine this, we undertook a cross-sectional survey covering 10% of the English population.
DESIGN, SETTING, AND PARTICIPANTS
Participants 1-10 yr from diagnosis were identified through national cancer registration data.
INTERVENTION
A postal survey was administered containing generic HRQOL and BC-specific outcome measures. Findings were compared with those of the general population and other pelvic cancer patients.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Generic HRQOL was measured using five-level EQ-5D (EQ-5D-5L) and European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-C30. BC-specific outcomes were derived from EORTC QLQ-BLM30 and EORTC QLQ-NMIBC24.
RESULTS AND LIMITATIONS
A total of 1796 surveys were completed (response rate 55%), including 868 (48%) patients with non-muscle-invasive BC, 893 (50%) patients who received radiotherapy or radical cystectomy, and 35 (1.9%) patients for whom treatment was unknown. Most (69%) of the participants reported at least one problem in any EQ-5D dimension. Age/sex-adjusted generic HRQOL outcomes were similar across all stages and treatment groups, whilst problems increased with age (problems in one or more EQ-5D dimensions: <65 yr [67% {95% confidence interval or CI: 61-74}] vs 85+ yr [84% {95% CI: 81-89}], p = 0.016) and long-term conditions (no conditions [53% {95% CI: 48-58}] vs more than four conditions [94% {95% CI: 90-97}], p < 0.001). Sexual problems were reported commonly in men, increasing with younger age and radical treatment. Younger participants (under 65 yr) reported more financial difficulties (mean score 20 [95% CI: 16-25]) than those aged 85+ yr (6.8 [4.5-9.2], p < 0.001). HRQOL for BC patients (for comparison, males with problems in one or more EQ-5D dimensions 69% [95% CI: 66-72]) was significantly worse than what has been found after colorectal and prostate cancers and in the general population (51% [95% CI: 48-53], all p < 0.05).
CONCLUSIONS
HRQOL following BC appears to be relatively independent of disease stage, treatment, and multimodal care. Issues are reported with sexual function and financial toxicity. HRQOL after BC is worse than that after other pelvic cancers.
PATIENT SUMMARY
Patients living with bladder cancer often have reduced quality of life, which may be worse than that for other common pelvic cancer patients. Age and other illnesses appear to be more important in determining this quality of life than the treatments received. Many men complain of sexual problems. Younger patients have financial worries.
Topics: Cross-Sectional Studies; Humans; Male; Patient Reported Outcome Measures; Pelvic Neoplasms; Quality of Life; Rare Diseases; Surveys and Questionnaires; Urinary Bladder Neoplasms
PubMed: 33581875
DOI: 10.1016/j.eururo.2021.01.032 -
The Lancet. Diabetes & Endocrinology Jan 2024The EMPA-KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The EMPA-KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population.
METHODS
EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m, or 45 to less than 90 mL/min per 1·73 m with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110.
FINDINGS
Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5-2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62-0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (p=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m per year (95% CI 1·16-1·59), representing a 50% (42-58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1).
INTERPRETATION
In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease.
FUNDING
Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council.
Topics: Humans; Diabetes Mellitus, Type 2; Kidney; Renal Insufficiency, Chronic; Benzhydryl Compounds; Renal Insufficiency; Glomerular Filtration Rate; Hypertension; Disease Progression
PubMed: 38061372
DOI: 10.1016/S2213-8587(23)00322-4 -
The Lancet. Oncology Sep 2020The appropriate age range for breast cancer screening remains a matter of debate. We aimed to estimate the effect of mammographic screening at ages 40-48 years on breast... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The appropriate age range for breast cancer screening remains a matter of debate. We aimed to estimate the effect of mammographic screening at ages 40-48 years on breast cancer mortality.
METHODS
We did a randomised, controlled trial involving 23 breast screening units across Great Britain. We randomly assigned women aged 39-41 years, using individual randomisation, stratified by general practice, in a 1:2 ratio, to yearly mammographic screening from the year of inclusion in the trial up to and including the calendar year that they reached age 48 years (intervention group), or to standard care of no screening until the invitation to their first National Health Service Breast Screening Programme (NHSBSP) screen at approximately age 50 years (control group). Women in the intervention group were recruited by postal invitation. Women in the control group were unaware of the study. The primary endpoint was mortality from breast cancers (with breast cancer coded as the underlying cause of death) diagnosed during the intervention period, before the participant's first NHSBSP screen. To study the timing of the mortality effect, we analysed the results in different follow-up periods. Women were included in the primary comparison regardless of compliance with randomisation status (intention-to-treat analysis). This Article reports on long-term follow-up analysis. The trial is registered with the ISRCTN registry, ISRCTN24647151.
FINDINGS
160 921 women were recruited between Oct 14, 1990, and Sept 24, 1997. 53 883 women (33·5%) were randomly assigned to the intervention group and 106 953 (66·5%) to the control group. Between randomisation and Feb 28, 2017, women were followed up for a median of 22·8 years (IQR 21·8-24·0). We observed a significant reduction in breast cancer mortality at 10 years of follow-up, with 83 breast cancer deaths in the intervention group versus 219 in the control group (relative rate [RR] 0·75 [95% CI 0·58-0·97]; p=0·029). No significant reduction was observed thereafter, with 126 deaths versus 255 deaths occurring after more than 10 years of follow-up (RR 0·98 [0·79-1·22]; p=0·86).
INTERPRETATION
Yearly mammography before age 50 years, commencing at age 40 or 41 years, was associated with a relative reduction in breast cancer mortality, which was attenuated after 10 years, although the absolute reduction remained constant. Reducing the lower age limit for screening from 50 to 40 years could potentially reduce breast cancer mortality.
FUNDING
National Institute for Health Research Health Technology Assessment programme.
Topics: Adult; Age Factors; Aged; Breast; Breast Neoplasms; Early Detection of Cancer; Female; Humans; Mammaplasty; Mammography; Middle Aged; Registries; United Kingdom
PubMed: 32800099
DOI: 10.1016/S1470-2045(20)30398-3 -
The Lancet. Diabetes & Endocrinology Jan 2024Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce progression of chronic kidney disease and the risk of cardiovascular morbidity and mortality in a wide range of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce progression of chronic kidney disease and the risk of cardiovascular morbidity and mortality in a wide range of patients. However, their effects on kidney disease progression in some patients with chronic kidney disease are unclear because few clinical kidney outcomes occurred among such patients in the completed trials. In particular, some guidelines stratify their level of recommendation about who should be treated with SGLT2 inhibitors based on diabetes status and albuminuria. We aimed to assess the effects of empagliflozin on progression of chronic kidney disease both overall and among specific types of participants in the EMPA-KIDNEY trial.
METHODS
EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA), and included individuals aged 18 years or older with an estimated glomerular filtration rate (eGFR) of 20 to less than 45 mL/min per 1·73 m, or with an eGFR of 45 to less than 90 mL/min per 1·73 m with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher. We explored the effects of 10 mg oral empagliflozin once daily versus placebo on the annualised rate of change in estimated glomerular filtration rate (eGFR slope), a tertiary outcome. We studied the acute slope (from randomisation to 2 months) and chronic slope (from 2 months onwards) separately, using shared parameter models to estimate the latter. Analyses were done in all randomly assigned participants by intention to treat. EMPA-KIDNEY is registered at ClinicalTrials.gov, NCT03594110.
FINDINGS
Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and then followed up for a median of 2·0 years (IQR 1·5-2·4). Prespecified subgroups of eGFR included 2282 (34·5%) participants with an eGFR of less than 30 mL/min per 1·73 m, 2928 (44·3%) with an eGFR of 30 to less than 45 mL/min per 1·73 m, and 1399 (21·2%) with an eGFR 45 mL/min per 1·73 m or higher. Prespecified subgroups of uACR included 1328 (20·1%) with a uACR of less than 30 mg/g, 1864 (28·2%) with a uACR of 30 to 300 mg/g, and 3417 (51·7%) with a uACR of more than 300 mg/g. Overall, allocation to empagliflozin caused an acute 2·12 mL/min per 1·73 m (95% CI 1·83-2·41) reduction in eGFR, equivalent to a 6% (5-6) dip in the first 2 months. After this, it halved the chronic slope from -2·75 to -1·37 mL/min per 1·73 m per year (relative difference 50%, 95% CI 42-58). The absolute and relative benefits of empagliflozin on the magnitude of the chronic slope varied significantly depending on diabetes status and baseline levels of eGFR and uACR. In particular, the absolute difference in chronic slopes was lower in patients with lower baseline uACR, but because this group progressed more slowly than those with higher uACR, this translated to a larger relative difference in chronic slopes in this group (86% [36-136] reduction in the chronic slope among those with baseline uACR <30 mg/g compared with a 29% [19-38] reduction for those with baseline uACR ≥2000 mg/g; p<0·0001).
INTERPRETATION
Empagliflozin slowed the rate of progression of chronic kidney disease among all types of participant in the EMPA-KIDNEY trial, including those with little albuminuria. Albuminuria alone should not be used to determine whether to treat with an SGLT2 inhibitor.
FUNDING
Boehringer Ingelheim and Eli Lilly.
Topics: Humans; Albuminuria; Diabetes Mellitus, Type 2; Kidney; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2 Inhibitors; Glomerular Filtration Rate
PubMed: 38061371
DOI: 10.1016/S2213-8587(23)00321-2 -
Global Health & Medicine Dec 2021In Japan, HIV testing has been offered anonymously and free-of-charge at local public health centers, together with pre- and post-test counseling since 1993. Since then,...
In Japan, HIV testing has been offered anonymously and free-of-charge at local public health centers, together with pre- and post-test counseling since 1993. Since then, the number of HIV tests increased steadily to reach a peak in 2008 but has since decreased by 30% during the last decade. The number of tests further decreased in 2020 during the COVID-19 pandemic and steeply by 50% this year compared with the previous year, mostly due to a shift in the workload at these centers to COVID-19-related services. To deal with this decline and thinking beyond the current pandemic, more options for HIV testing are needed, such as self-testing/postal delivery of dried blood spot specimen, a method that is yet to be approved in Japan, in addition to the conventional plasma/serum-based HIV testing.
PubMed: 35036615
DOI: 10.35772/ghm.2021.01103