-
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. 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 -
The Cochrane Database of Systematic... Nov 2023Self-administered questionnaires are widely used to collect data in epidemiological research, but non-response reduces the effective sample size and can introduce bias.... (Review)
Review
BACKGROUND
Self-administered questionnaires are widely used to collect data in epidemiological research, but non-response reduces the effective sample size and can introduce bias. Finding ways to increase response to postal and electronic questionnaires would improve the quality of epidemiological research.
OBJECTIVES
To identify effective strategies to increase response to postal and electronic questionnaires.
SEARCH METHODS
We searched 14 electronic databases up to December 2021 and manually searched the reference lists of relevant trials and reviews. We contacted the authors of all trials or reviews to ask about unpublished trials; where necessary, we also contacted authors to confirm the methods of allocation used and to clarify results presented.
SELECTION CRITERIA
Randomised trials of methods to increase response to postal or electronic questionnaires. We assessed the eligibility of each trial using pre-defined criteria.
DATA COLLECTION AND ANALYSIS
We extracted data on the trial participants, the intervention, the number randomised to intervention and comparison groups and allocation concealment. For each strategy, we estimated pooled odds ratios (OR) and 95% confidence intervals (CI) in a random-effects model. We assessed evidence for selection bias using Egger's weighted regression method and Begg's rank correlation test and funnel plot. We assessed heterogeneity amongst trial odds ratios using a Chi test and quantified the degree of inconsistency between trial results using the I statistic.
MAIN RESULTS
Postal We found 670 eligible trials that evaluated over 100 different strategies of increasing response to postal questionnaires. We found substantial heterogeneity amongst trial results in half of the strategies. The odds of response almost doubled when: using monetary incentives (odds ratio (OR) 1.86; 95% confidence interval (CI) 1.73 to 1.99; heterogeneity I = 85%); using a telephone reminder (OR 1.96; 95% CI 1.03 to 3.74); and when clinical outcome questions were placed last (OR 2.05; 95% CI 1.00 to 4.24). The odds of response increased by about half when: using a shorter questionnaire (OR 1.58; 95% CI 1.40 to 1.78); contacting participants before sending questionnaires (OR 1.36; 95% CI 1.23 to 1.51; I = 87%); incentives were given with questionnaires (i.e. unconditional) rather than when given only after participants had returned their questionnaire (i.e. conditional on response) (OR 1.53; 95% CI 1.35 to 1.74); using personalised SMS reminders (OR 1.53; 95% CI 0.97 to 2.42); using a special (recorded) delivery service (OR 1.68; 95% CI 1.36 to 2.08; I = 87%); using electronic reminders (OR 1.60; 95% CI 1.10 to 2.33); using intensive follow-up (OR 1.69; 95% CI 0.93 to 3.06); using a more interesting/salient questionnaire (OR 1.73; 95% CI 1.12 to 2.66); and when mentioning an obligation to respond (OR 1.61; 95% CI 1.16 to 2.22). The odds of response also increased with: non-monetary incentives (OR 1.16; 95% CI 1.11 to 1.21; I = 80%); a larger monetary incentive (OR 1.24; 95% CI 1.15 to 1.33); a larger non-monetary incentive (OR 1.15; 95% CI 1.00 to 1.33); when a pen was included (OR 1.44; 95% CI 1.38 to 1.50); using personalised materials (OR 1.15; 95% CI 1.09 to 1.21; I = 57%); using a single-sided rather than a double-sided questionnaire (OR 1.13; 95% CI 1.02 to 1.25); using stamped return envelopes rather than franked return envelopes (OR 1.23; 95% CI 1.13 to 1.33; I = 69%), assuring confidentiality (OR 1.33; 95% CI 1.24 to 1.42); using first-class outward mailing (OR 1.11; 95% CI 1.02 to 1.21); and when questionnaires originated from a university (OR 1.32; 95% CI 1.13 to 1.54). The odds of response were reduced when the questionnaire included questions of a sensitive nature (OR 0.94; 95% CI 0.88 to 1.00). Electronic We found 88 eligible trials that evaluated over 30 different ways of increasing response to electronic questionnaires. We found substantial heterogeneity amongst trial results in half of the strategies. The odds of response tripled when: using a brief letter rather than a detailed letter (OR 3.26; 95% CI 1.79 to 5.94); and when a picture was included in an email (OR 3.05; 95% CI 1.84 to 5.06; I = 19%). The odds of response almost doubled when: using monetary incentives (OR 1.88; 95% CI 1.31 to 2.71; I = 79%); and using a more interesting topic (OR 1.85; 95% CI 1.52 to 2.26). The odds of response increased by half when: using non-monetary incentives (OR 1.60; 95% CI 1.25 to 2.05); using shorter e-questionnaires (OR 1.51; 95% CI 1.06 to 2.16; I = 94%); and using a more interesting e-questionnaire (OR 1.85; 95% CI 1.52 to 2.26). The odds of response increased by a third when: offering survey results as an incentive (OR 1.36; 95% CI 1.16 to 1.59); using a white background (OR 1.31; 95% CI 1.10 to 1.56); and when stressing the benefits to society of response (OR 1.38; 95% CI 1.07 to 1.78; I = 41%). The odds of response also increased with: personalised e-questionnaires (OR 1.24; 95% CI 1.17 to 1.32; I = 41%); using a simple header (OR 1.23; 95% CI 1.03 to 1.48); giving a deadline (OR 1.18; 95% CI 1.03 to 1.34); and by giving a longer time estimate for completion (OR 1.25; 95% CI 0.96 to 1.64). The odds of response were reduced when: "Survey" was mentioned in the e-mail subject (OR 0.81; 95% CI 0.67 to 0.97); when the email or the e-questionnaire was from a male investigator, or it included a male signature (OR 0.55; 95% CI 0.38 to 0.80); and by using university sponsorship (OR 0.84; 95%CI 0.69 to 1.01). The odds of response using a postal questionnaire were over twice those using an e-questionnaire (OR 2.33; 95% CI 2.25 to 2.42; I = 98%). Response also increased when: providing a choice of response mode (electronic or postal) rather than electronic only (OR 1.76 95% CI 1.67 to 1.85; I = 97%); and when administering the e-questionnaire by computer rather than by smartphone (OR 1.62 95% CI 1.36 to 1.94).
AUTHORS' CONCLUSIONS
Researchers using postal and electronic questionnaires can increase response using the strategies shown to be effective in this Cochrane review.
Topics: Male; Humans; Surveys and Questionnaires; Reminder Systems; Sample Size; Smartphone; Electronics
PubMed: 38032037
DOI: 10.1002/14651858.MR000008.pub5 -
JAMA Nov 2023Optimal strategies for increasing cervical cancer screening may differ by patient screening history and health care setting. Mailing human papillomavirus (HPV)... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Optimal strategies for increasing cervical cancer screening may differ by patient screening history and health care setting. Mailing human papillomavirus (HPV) self-sampling kits to individuals who are overdue for screening increases adherence; however, offering self-sampling kits to screening-adherent individuals has not been evaluated in the US.
OBJECTIVE
To evaluate the effectiveness of direct-mail and opt-in approaches for offering HPV self-sampling kits to individuals by cervical cancer screening history (screening-adherent and currently due, overdue, or unknown).
DESIGN, SETTING, AND PARTICIPANTS
Randomized clinical trial conducted in Kaiser Permanente Washington, a US integrated health care delivery system. Individuals aged 30 to 64 years with female sex, a primary care clinician, and no hysterectomy were identified through electronic health records (EHRs) and enrolled between November 20, 2020, and January 28, 2022, with follow-up through July 29, 2022.
INTERVENTIONS
Individuals stratified as due (eg, at the time of randomization, these individuals have been previously screened and are due for their next screening in ≤3 months) were randomized to receive usual care (patient reminders and clinician EHR alerts [n = 3671]), education (usual care plus educational materials about screening [n = 3960]), direct mail (usual care plus educational materials and a mailed self-sampling kit [n = 1482]), or to opt in (usual care plus educational materials and the option to request a kit [n = 3956]). Individuals who were overdue for screening were randomized to receive usual care (n = 5488), education (n = 1408), or direct mail (n = 1415). Individuals with unknown history for screening were randomized to receive usual care (n = 2983), education (n = 3486), or to opt in (n = 3506).
MAIN OUTCOMES AND MEASURES
The primary outcome was screening completion within 6 months. Primary analyses compared direct-mail or opt-in participants with individuals randomized to the education group.
RESULTS
The intention-to-treat analyses included 31 355 randomized individuals (mean [SD] age, 45.9 [10.4] years). Among those who were due for screening, compared with receiving education alone (1885 [47.6%]), screening completion was 14.1% (95% CI, 11.2%-16.9%) higher in the direct-mail group (914 [61.7%]) and 3.5% (95% CI, 1.2%-5.7%) higher in the opt-in group (2020 [51.1%]). Among individuals who were overdue, screening completion was 16.9% (95% CI, 13.8%-20.0%) higher in the direct-mail group (505 [35.7%]) compared with education alone (264 [18.8%]). Among those with unknown history, screening was 2.2% (95% CI, 0.5%-3.9%) higher in the opt-in group (634 [18.1%]) compared with education alone (555 [15.9%]).
CONCLUSIONS AND RELEVANCE
Within a US health care system, direct-mail self-sampling increased cervical cancer screening by more than 14% in individuals who were due or overdue for cervical cancer screening. The opt-in approach minimally increased screening. To increase screening adherence, systems implementing HPV self-sampling should prioritize direct-mail outreach for individuals who are due or overdue for screening. For individuals with unknown screening history, testing alternative outreach approaches and additional efforts to document screening history are warranted.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04679675.
Topics: Female; Humans; Middle Aged; Early Detection of Cancer; Educational Status; Human Papillomavirus Viruses; Papillomavirus Infections; Uterine Cervical Neoplasms; Diagnostic Self Evaluation; United States; Adult; Postal Service
PubMed: 38015219
DOI: 10.1001/jama.2023.21471 -
Medicina Oral, Patologia Oral Y Cirugia... Nov 2023Odontogenic tumours are infrequent lesions. Studies on the frequency of odontogenic tumours from Latin America are scarce. This work aimed to determine the relative... (Review)
Review
BACKGROUND
Odontogenic tumours are infrequent lesions. Studies on the frequency of odontogenic tumours from Latin America are scarce. This work aimed to determine the relative frequency of odontogenic tumours in a Chilean population using the 2022 World Health Organization classification.
MATERIAL AND METHODS
This is a case series retrospective study. We reviewed 35,530 samples from 1975 to 2022 from the Oral Pathology Referral Institute and the Pathological Anatomy Service, Faculty of Dentistry, University of Chile. We utilized the 2022 World Health Organization classification for histological typification.
RESULTS
According to 2022 World Health Organization classification, 544 odontogenic tumours were confirmed. The most frequent odontogenic tumours were: odontoma (n=241; 44.3%), ameloblastoma (n=109; 20.0%) and cemento-ossifying fibroma (n=71; 13.1%). Benign odontogenic tumours corresponded to 538 cases (98.9%) and malignant tumours were only six cases (1.1%).
CONCLUSIONS
In our population, odontoma was the most frequent odontogenic tumour followed by ameloblastoma and cemento-ossifying fibroma. Malignant odontogenic tumours were very rare. The results of this study are similar to reports from America, but there are some differences concerning the data from Africa and Asia.
Topics: Humans; Ameloblastoma; Odontoma; Retrospective Studies; Cementoma; Chile; Odontogenic Tumors; World Health Organization
PubMed: 37823289
DOI: 10.4317/medoral.26008 -
Frontiers in Public Health 2023To implement state policies of zero-markup drug policy and medical service fee adjustment for public hospitals, this study constructed game models of the pharmaceutical...
To implement state policies of zero-markup drug policy and medical service fee adjustment for public hospitals, this study constructed game models of the pharmaceutical supply chain, consisting of a drug supplier and a public hospital. The study obtained the optimal medical service level and pricing under the new state drug policies. In addition, it analyzed the impacts of the degree of public benefit of hospitals on the medical service level, the medical service price, and the drug price. Finally, from the perspective of cooperation between drug suppliers and public hospitals, the specialized coordination contract was designed to maximize overall social welfare. This study found an anomalous but meaningful conclusion: in the background of the zero-markup drug policy, a higher public benefit of hospitals could increase the drug prices, but it could reduce the medical service prices further to cut down on the overall treatment fees for the patients. The novel coordination contract can optimize the pharmaceutical supply chain and achieve a win-win situation for the drug suppliers, public hospitals, and patients. When the public benefit of hospitals is higher, the profit of a decentralized decision-making supply chain is greater than a centralized one, while the pharmaceutical supply chain will not coordinate itself.
Topics: Humans; Public Policy; Hospitals, Public; Costs and Cost Analysis; Pharmaceutical Preparations
PubMed: 37927883
DOI: 10.3389/fpubh.2023.1208994 -
Heliyon Apr 2024Effective restoration strategies play a crucial role in mitigating the environmental impact of mining and colliery activities while promoting ecological resilience and... (Review)
Review
Effective restoration strategies play a crucial role in mitigating the environmental impact of mining and colliery activities while promoting ecological resilience and rejuvenating ecosystem services. However, many organizations find it challenging to understand and balance their efforts in restoring degraded lands. For example, their restoration plans lack clarity and overlook relevant ecosystem services. This study reviews and focuses on the potential restoration of ecosystem services at TATA Steel's Noamundi Iron Ore Mine and West Bokaro Colliery to contribute to Sustainable Development Goals (SDGs), particularly SDG-15, for localization. The approach involved assessing the number of preventive measures being implemented to restore a particular ecosystem service. Moreover, the potential of each preventive measure is to restore that ecosystem service. The findings underscore the significance of preventive measures and comprehensive restoration plans in enhancing carbon sequestration, soil fertility, habitat creation, and genetic diversity conservation. Our results showed that the impact scores and ranks of various ecosystem services demonstrate the positive effects of restoration efforts, emphasizing the importance of reestablishing forests, restoring water bodies and wetlands, and allocating land for agriculture and public use. The research provides valuable insights for decision-makers in developing sustainable land management strategies, ensuring biodiversity conservation and local communities' well-being. By prioritizing ecosystem services in restoration initiatives, stakeholders can contribute to the sustainable management of natural resources and foster a harmonious coexistence between human activities and the environment.
PubMed: 38699718
DOI: 10.1016/j.heliyon.2024.e29877 -
Revue Medicale de Liege Jul 2023Winslow's foramen hernia, or Blandin's hernia, is a rare internal hernia with a non-specific clinical presentation and its diagnosis may be difficult. The hernia occurs...
Winslow's foramen hernia, or Blandin's hernia, is a rare internal hernia with a non-specific clinical presentation and its diagnosis may be difficult. The hernia occurs across the omental hiatus, bounded by the inferior vena cava posteriorly and the portal triad anteriorly. CT imaging provides several diagnostic clues in this condition. Prompt surgical management allows reduction before complications arise. We present a case of caecal internal herniation through Winslow's foramen in a patient who underwent gastrojejunal bypass about ten years ago. Laparoscopy with reduction of the caecal bascule and closure of the foramen is performed successfully.
Topics: Humans; Cecal Diseases; Cecum; Hernia; Plastic Surgery Procedures; Vena Cava, Inferior; Herniorrhaphy
PubMed: 37560954
DOI: No ID Found