Sodium-glucose cotransporter 2 (SGLT-2) inhibitors and microvascular outcomes in patients with type 2 diabetes: systematic review and meta-analysis.

PURPOSE: The effect of the sodium-glucose 2 (SGLT-2) inhibitors on microvascular complications remains uncertain. We performed a systematic review to determine the efficacy of the SGLT-2 inhibitors on microvascular outcomes in patients with type 2 diabetes. METHODS: A comprehensive search was performed using Ovid, MEDLINE, EMBASE, Web of Science, and Scopus from inception to May 2019. Randomized trials comparing SGLT-2 inhibitors with placebo or other medication for type 2 diabetes for ≥ 4 weeks were included. Diabetes-related microvascular complications such as nephropathy, retinopathy, neuropathy, and peripheral vascular disease were evaluated. A random-effect model using mean differences for continuous outcomes and risk ratio for dichotomous outcomes was used to synthesize data. PROSPERO (CRD 42017076460). RESULTS: A total of 40 RCTs with overall moderate quality of evidence were included. SGLT-2 inhibitors reduced the risk of renal-replacement therapy (0.65; 95% CI 0.54-0.79), renal death (0.57; 95% CI 0.49-0.65), and progression of albuminuria (0.69; 95% CI 0.66-0.73). Conversely, they appeared ineffective in maintaining eGFR (0.33; 95% CI - 0.74 to 1.41) or reducing serum creatinine (- 0.07; 95% CI - 0.26 to 0.11), whereas urine albumin-creatinine ratio (- 23.4; 95% CI - 44.6 to - 2.2) was reduced. Risk of amputation was non-significant (1.30; 95% CI 0.93-1.83). No available data were found regarding neuropathy and retinopathy to perform a quantitative analysis. CONCLUSION: SGLT-2 inhibitors may reduce the risk of renal patient-important outcomes but fail to improve surrogate outcomes. Apparently, no increased risk of amputations was observed with these medications. No data were available regarding other microvascular complications.

Comparative efficacy of parathyroidectomy and active surveillance in patients with mild primary hyperparathyroidism: a systematic review and meta-analysis.

Counseling for patients with primary hyperparathyroidism (PHPT) and mild hypercalcemia without indications for surgical intervention requires accurate estimates of the potential benefits of parathyroidectomy. We aim to summarize the available evidence regarding the benefits of parathyroidectomy that patients with mild PHPT without indications for surgery experience compared to observation. We searched multiple databases from inception to August 2015. We included randomized controlled trials (RCT) and observational studies that evaluated changes in bone health, quality of life or neuropsychiatric symptoms, or in the risk of nephrolithiasis, cardiovascular events, or death between patients undergoing parathyroidectomy or active surveillance. Eight studies were eligible. Risk differences were not significant, in part due to lack of events (fractures, nephrolithiasis, cardiovascular events, or deaths). No significant differences were observed across measures of bone health, quality of life, and neuropsychiatric symptoms. A single RCT evaluating bone mineral density (BMD) changes at 5 years found a small statistically significant effect favoring parathyroidectomy. Patients with mild PHPT without indications for surgery experience a limited number of adverse consequences during short-term follow-up limiting our ability to estimate the benefit of surgery during this timeframe. This information is helpful as these patients consider surgery versus active surveillance. Long-term data is warranted to determine who benefits in the long run from surgical intervention and the extent to which this benefit affects outcomes that matter to patients.

Shared decision-making in the care of individuals with diabetes.

People with diabetes often live with other chronic conditions and lead complicated lives. Determining what is the best management decision for a patient requires consideration of each individual's personal, social and biomedical context, what he or she values, the reasons he or she has to value the available options, and the relative contribution of each option in terms of benefits, harms, costs and inconveniences. Empathic conversations between patients and clinicians to diagnose the patient situation that necessitates action and the range of evidence-based actions that best address the situation, so-called shared decision-making, are essential to the personalized care of people with diabetes. The aim of the present review was to present key elements of shared decision-making and propose three different approaches for its application. The first approach focuses on transferring information to patients so that they can make decisions. The second approach, choice, focuses on cultivating the individual's ability to give voice to which choice is best for them. The third approach, conversation, establishes an empathic conversational environment through which the individual with diabetes and their clinician think and talk through how to address the problems of living with diabetes and related illnesses. These approaches are manifest in the design of evidence-based decision aids created to support shared decision-making. In randomized trials, decision aids can efficiently improve patient's knowledge, satisfaction, risk awareness, decisional conflict and involvement. Further research, however, is needed to better understand when and how to promote the empathic conversations, patient, clinician and service and policy contexts necessary to routinely implement shared decision-making in different at scale healthcare systems. In the interim, sufficient evidence and tools exist for persons with diabetes and their clinicians to gain expertise in making decisions together.

Attaining minimally disruptive medicine: context, challenges and a roadmap for implementation.

In this second of two papers on minimally disruptive medicine, we use the language of patient workload and patient capacity from the Cumulative Complexity Model to accomplish three tasks. First, we outline the current context in healthcare, comprised of contrasting problems: some people lack access to care and others receive too much care in an overmedicalised system, both of which reflect imbalances between patients' workloads and their capacity. Second, we identify and address five tensions and challenges between minimally disruptive medicine, the existing context, and other approaches to accessible and patient-centred care such as evidence-based medicine and greater patient engagement. Third, we outline a roadmap of three strategies toward implementing minimally disruptive medicine in practice, including large-scale paradigm shifts, mid-level add-ons to existing reform efforts, and a modular strategy using an existing 'toolkit' that is more limited in scope, but can fit into existing healthcare systems.

Pioglitazone and risk of bladder cancer: a meta-analysis of controlled studies.

AIMS: Pioglitazone, a thiazolidinedione, was approved for treatment of Type 2 diabetes. However, several observational studies suggest an association of pioglitazone with an increased risk of bladder cancer in patients with diabetes. Therefore, we sought to perform a systematic review and meta-analysis to evaluate the magnitude of this association and the quality of the supporting evidence. METHODS: Electronic databases were queried to identify controlled studies of pioglitazone that measured the risk of bladder cancer. RESULTS: Six studies involving 215 142 patients using pioglitazone were included, with a median period of follow-up of 44 months. The hazard of developing bladder cancer was significantly higher in patients using pioglitazone (hazard ratio 1.23; 95% CI 1.09-1.39; I² = 0%) compared with control groups. The risk of bias was moderate across the six studies. Considering an incidence rate of 20.8 per 100 000 person years, the number needed to harm was five additional cases of bladder cancer per 100 000 person years. CONCLUSIONS: Patients treated with pioglitazone have a slight increased risk of bladder cancer compared to general population. Patient involvement and weighing treatment benefits versus risks should be discussed with patient toward shared decision. Patients with type 2 diabetes with risk factors, such as family history, smoking, or exposure to certain forms of chemotherapy may need to consider other anti-hyperglycemic agents. Also, pioglitazone should be discontinued in type 2 diabetes patients with newly diagnosed bladder cancer.

Evidence-based endocrinology: illustrating its principles in the management of patients with pituitary incidentalomas.

Incidentally discovered pituitary lesions are commonly encountered in the current era of ever-increasing imaging. Individualizing a particular approach implies a thorough analysis of existing evidence and balancing it against different patient expectations. We will illustrate the application of principles of Evidence-Based Medicine to a case of a pituitary incidentaloma by formulating questions that are important to patient care and finding related evidence. Our objective is to reflect the opportunities and the challenges that an evidence-based clinical approach offers to clinicians and patients.

Shared decision making: really putting patients at the centre of healthcare.

Although many clinicians feel they already use shared decision making, research shows a perception-reality gap. A M Stiggelbout and colleagues discuss why it is important and highlight some best practices.

Diagnostic performance of body mass index to identify obesity as defined by body adiposity: a systematic review and meta-analysis.

OBJECTIVE: We performed a systematic review and meta-analysis of studies that assessed the performance of body mass index (BMI) to detect body adiposity. DESIGN: Data sources were MEDLINE, EMBASE, Cochrane, Database of Systematic Reviews, Cochrane CENTRAL, Web of Science, and SCOPUS. To be included, studies must have assessed the performance of BMI to measure body adiposity, provided standard values of diagnostic performance, and used a body composition technique as the reference standard for body fat percent (BF%) measurement. We obtained pooled summary statistics for sensitivity, specificity, positive and negative likelihood ratios (LRs), and diagnostic odds ratio (DOR). The inconsistency statistic (I2) assessed potential heterogeneity. RESULTS: The search strategy yielded 3341 potentially relevant abstracts, and 25 articles met our predefined inclusion criteria. These studies evaluated 32 different samples totaling 31 968 patients. Commonly used BMI cutoffs to diagnose obesity showed a pooled sensitivity to detect high adiposity of 0.50 (95% confidence interval (CI): 0.43-0.57) and a pooled specificity of 0.90 (CI: 0.86-0.94). Positive LR was 5.88 (CI: 4.24-8.15), I (2)=97.8%; the negative LR was 0.43 (CI: 0.37-0.50), I (2)=98.5%; and the DOR was 17.91 (CI: 12.56-25.53), I (2)=91.7%. Analysis of studies that used BMI cutoffs >or=30 had a pooled sensitivity of 0.42 (CI: 0.31-0.43) and a pooled specificity of 0.97 (CI: 0.96-0.97). Cutoff values and regional origin of the studies can only partially explain the heterogeneity seen in pooled DOR estimates. CONCLUSION: Commonly used BMI cutoff values to diagnose obesity have high specificity, but low sensitivity to identify adiposity, as they fail to identify half of the people with excess BF%.

Omega-3 polyunsaturated fatty acids (PUFA) for type 2 diabetes mellitus.

BACKGROUND: People with type 2 diabetes mellitus are at increased risk from cardiovascular disease. Dietary omega-3 polyunsaturated fatty acids (PUFAs) are known to reduce triglyceride levels, but their impact on cholesterol levels, glycemic control and vascular outcomes are not well known. OBJECTIVES: To determine the effects of omega-3 PUFA supplementation on cardiovascular outcomes, cholesterol levels and glycemic control in people with type 2 diabetes mellitus. SEARCH STRATEGY: We carried out a comprehensive search of The Cochrane Library, MEDLINE, EMBASE, bibliographies of relevant papers and contacted experts for identifying additional trials. SELECTION CRITERIA: All randomised controlled trials were included where omega-3 PUFA supplementation or dietary intake was randomly allocated and unconfounded in people with type 2 diabetes. Authors of large trials were contacted for missing information. DATA COLLECTION AND ANALYSIS: Trials were assessed for inclusion. Authors were contacted for missing information. Data was extracted and quality assessed independently in duplicate. Fixed-effect meta-analysis was carried out. MAIN RESULTS: Twenty three randomised controlled trials (1075 participants) were included with a mean treatment duration of 8.9 weeks. The mean dose of omega-3 PUFA used in the trials was 3.5 g/d. No trials with vascular events or mortality endpoints were identified. Among those taking omega-3 PUFA triglyceride levels were significantly lowered by 0.45 mmol/L (95% confidence interval (CI) -0.58 to -0.32, P < 0.00001) and VLDL cholesterol lowered by -0.07 mmol/L (95% CI -0.13 to 0.00, P = 0.04). LDL cholesterol levels were raised by 0.11 mmol/L (95% CI 0.00 to 0.22, P = 0.05). No significant change in or total or HDL cholesterol, HbA1c, fasting glucose, fasting insulin or body weight was observed. The increase in VLDL remained significant only in trials of longer duration and in hypertriglyceridemic patients. The elevation in LDL cholesterol was non-significant in subgroup analyses. No adverse effects of the intervention were reported. AUTHORS' CONCLUSIONS: Omega-3 PUFA supplementation in type 2 diabetes lowers triglycerides and VLDL cholesterol, but may raise LDL cholesterol (although results were non-significant in subgroups) and has no statistically significant effect on glycemic control or fasting insulin. Trials with vascular events or mortality defined endpoints are needed.

Fluoroquinolone prophylaxis in patients with neutropenia: a meta-analysis of randomized placebo-controlled trials.

A recent meta-analysis, which included non-placebo open-labeled trials, showed that fluoroquinolone prophylaxis reduces mortality in neutropenic patients, whereas two recent large trials failed to show a similar benefit. Therefore, we performed a meta-analysis of randomized, blinded, placebo-controlled trials of fluoroquinolone prophylaxis in neutropenic patients. We searched several databases for relevant trials in any language. We used random effects models for pooling dichotomous data and assessed the between-study inconsistency with I (2). Two investigators independently assessed the eligibility and quality of the included trials. A total of 2,721 patients were randomized in eight eligible trials. Compared to the placebo, there was a statistically non-significant but consistent decrease in mortality with fluoroquinolone prophylaxis (4.5% vs. 3.9%, relative risk (RR) 0.76, 95% confidence interval (CI) 0.54, 1.08, p = 0.13, I (2) = 0%). Significant inconsistency, however, accompanied the pooled analysis of febrile episode (39% vs. 31%, RR 0.76, 95% CI 0.55, 1.03, p = 0.08, I (2) = 96.5%). To an extent, this inconsistency was explained in the subgroup analyses by the type of patient population studied and the type of fluoroquinolone used (p for interaction

Interventions for smokeless tobacco use cessation.

BACKGROUND: Use of smokeless tobacco (ST) can lead to nicotine addiction and long-term use can lead to health problems including periodontal disease and cancer. OBJECTIVES: To assess the effects of behavioural and pharmacologic interventions for the treatment of ST use. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, Web of Science, PsycINFO, Dissertation Abstracts Online, and Scopus. Date of last search: March, 2007. SELECTION CRITERIA: Randomized trials of behavioural or pharmacological interventions to help users of ST to quit with follow up of at least six months. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. MAIN RESULTS: Two trials of bupropion SR did not detect a benefit of treatment at six months or longer (Odds Ratio (OR) 0.86, 95% Confidence Interval (CI): 0.47 to 1.57). Four trials of nicotine patch did not detect a benefit (OR 1.16, 95% CI: 0.88 to 1.54), nor did two trials of nicotine gum (OR 0.98, 95% CI: 0.59 to 1.63). There was statistical heterogeneity among the results of 12 behavioural interventions included in the meta-analyses. Six trials showed significant benefits of intervention. In post-hoc subgroup analyses, behavioural interventions which include telephone counselling or an oral examination may increase abstinence rates more than interventions without these components. AUTHORS' CONCLUSIONS: Behavioural interventions should be used to help ST users to quit and telephone counselling or an oral examination may increase abstinence rates. Pharmacotherapies have not been shown to affect long-term abstinence.

Interventions for smokeless tobacco use cessation.

BACKGROUND: Use of smokeless tobacco (ST) can lead to nicotine addiction and health problems including periodontal disease and oral cancer OBJECTIVES: To assess the effects of behavioural and pharmacotherapeutic interventions to treat ST use. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register (February 2004), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2004), MEDLINE (January 1966-February 2004), EMBASE (1988-January 2004), CINAHL (1982-February 2004), PsycINFO (1984-February 2004), Database of Abstract of Reviews of Effectiveness (DARE, The Cochrane Library, Issue 1, 2004). SELECTION CRITERIA: Randomized trials of behavioural or pharmacological interventions to help users of ST to quit, with follow-up of at least six months. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. MAIN RESULTS: One trial of bupropion did not detect a benefit of treatment after six months (Odds Ratio (OR) 1.00, 95% Confidence Interval (CI): 0.23 to 4.37). Three trials of nicotine patch did not detect a benefit (OR 1.16, 95% CI: 0.88 to 1.54), nor did two trials of nicotine gum (OR 0.98, 95% CI: 0.59 to 1.63). There was statistical heterogeneity among the results of eight trials of behavioural interventions included in the meta-analysis. Three trials showed significant benefits of intervention. In a post-hoc analysis the trials of interventions which included an oral examination and feedback about ST-induced mucosal changes had homogeneous results and when pooled showed a significant benefit (OR 2.41 95% CI: 1.79 to 3.24). REVIEWERS' CONCLUSIONS: Behavioural interventions should be used to help ST users to quit. Pharmacotherapies have not been shown to affect long-term abstinence but larger trials are needed.

Improving patients' safety locally: changing clinician behaviour.

Safety initiatives in hospitals should focus on common health care interventions that when used appropriately can improve important health outcomes, and when used inappropriately or not at all, result in substantial harm. We suggest that errors of omission should be a safety priority. We focus on preventive health care interventions, and describe five steps that can improve patients' safety by changing clinician behaviour. The steps are to: do an environmental scan; understand current behaviour, target behaviour for change (why, what, when, where, and who); adopt effective strategies to change behaviour; and synergise.

Intermittent compression pump for nonhealing wounds in patients with limb ischemia. The Mayo Clinic experience (1998-2000).

BACKGROUND: The aim of this retrospective observational study was to review the use of an intermittent pneumatic compression device on nonhealing wounds in patients with critical limb ischemia at Mayo Clinic Rochester. METHODS: The setting was a community and referral multidisciplinary wound care clinic. The authors analysed 107 patients, median age 73, with critical limb ischemia and active ulcers started using a compression device between 1998 and 2000; 101 patients had lower extremity ulcers, and 25% had a history of amputation, and 64% had diabetes. Of all the wounds, 64% were multifactorial in etiology, and 60% had associated transcutaneous oxygen tension levels below 20 mmHg. Patients were typically asked to use the device at home on the affected limb(s) for 6 hours daily. The main outcome criterion was complete wound healing with limb preservation. RESULTS: The median follow-up after initiation of treatment was 6 months. Complete wound healing with limb preservation was achieved by 40% of patients with TcPO(2) levels below 20 mmHg; by 48% with osteomyelitis or active wound infection; by 46% with diabetes treated with insulin; and by 28% with a previous amputation. Half of all amputations occurred in patients with prior amputations. Seven patients discontinued the device because of pain experienced with its use. CONCLUSIONS: Patients with critical limb ischemia and nonhealing wounds at high risk of amputation can achieve complete wound healing and limb preservation by using an intermittent pneumatic compression device.

Fish oil in people with type 2 diabetes mellitus.

BACKGROUND: People with type 2 diabetes mellitus are at increased risk from cardiovascular disease. Dietary fish oils are known to reduce triglyceride levels, but their impact on cholesterol levels, glycemic control and vascular outcomes are not well known. OBJECTIVES: To determine the effects of fish oil supplementation on cardiovascular outcomes, cholesterol levels and glycemic control in people with type 2 diabetes mellitus. SEARCH STRATEGY: We carried out a comprehensive search of the Cochrane Controlled Trials Register, Medline, Embase, Lilacs, bibliographies of relevant papers and contacted experts for identifying additional trials. Date of last search: September 2000. SELECTION CRITERIA: All randomized placebo-controlled trials in which fish oil supplementation was the only intervention in people with type 2 diabetes were included. Authors were contacted for missing information. DATA COLLECTION AND ANALYSIS: Three investigators performed data extraction and quality scoring independently with discrepancies resolved by consensus. MAIN RESULTS: Eighteen trials including 823 participants followed for a mean of 12 weeks were included. Doses of fish oil used ranged from 3 to 18 g/day. No trials with vascular event or mortality endpoints were identified. The outcomes studied were glycemic control and lipid levels. Meta-analysis of pooled data demonstrated a statistically significant effect of fish oil in lowering triglycerides by 0.56 mmol/l (95% CI -0.71 to -0.40 mmol/l) and raising LDL cholesterol by 0.21 mmol/l (95% CI 0.02 to 0.41 mmol/l). No statistically significant effect was observed for fasting glucose, HbA1c, total or HDL cholesterol. The triglyceride lowering effect and the elevation in LDL cholesterol were most marked in those trials that recruited people with hypertriglyceridemia and used higher doses of fish oil. No adverse effects of the intervention were reported. REVIEWER'S CONCLUSIONS: Fish oil supplementation in type 2 diabetes lowers triglycerides, may raise LDL cholesterol (especially in hypertriglyceridemic patients on higher doses of fish oil) and has no statistically significant effect on glycemic control. Trials with vascular event or mortality defined endpoints are needed.

What is evidence-based medicine and why should it be practiced?

Responding to the limitations of traditional expert recommendations as a guide to clinical practice, evidence-based medicine has presented a paradigm shift in the way clinicians learn and practice medicine. The practice of evidence-based medicine requires careful examination of the evidence, using a set of formal rules applied in an explicit manner. The clinician then judiciously applies the evidence to decision-making, with an understanding of the patient context and values. Using examples pertinent to respiratory therapists, we discuss evidence-based decision-making as a clinical problem-solving strategy, its basis on a hierarchy of evidence, and the interplay of values, preferences, expertise, and circumstances that affect its application. We briefly describe some resources available to obtain evidence reports and to learn to critically appraise and apply them.

Validity of the aldosterone-renin ratio used to screen for primary aldosteronism.

OBJECTIVE: To determine whether the calculated ratio of plasma aldosterone concentration (PAC) to plasma renin activity (PRA), a proposed screening test for primary aldosteronism, provides a renin-independent measure of circulating aldosterone that is suitable to judge whether PAC is inappropriately elevated relative to PRA. SUBJECTS AND METHODS: This study consisting of 221 black and 276 white subjects with previously diagnosed essential hypertension was conducted between 1996 and 2000. Antihypertensive drugs were withdrawn for at least 4 weeks; PAC and PRA were measured while subjects were supine and then seated after 30 minutes of ambulation. The seated measurements were repeated after 4 weeks of oral diuretic therapy with hydrochlorothiazide (25 mg/d). RESULTS: The variation in the aldosterone-renin ratio was strongly and inversely dependent on PRA (R2=0.71; P<.001). When subjects changed position from supine to seated, the increase in mean +/- SD PRA (from 1.18 +/- 1.06 to 1.31 +/- 1.19 ng x mL(-1) x h(-1); P<.001) was associated with an increase in the mean ratio (from 18.6 +/- 52.8 to 25.8 +/- 38.1 h x 10(2); P<.001), whereas the increase in mean +/- SD PRA in response to diuretic therapy (from 1.31 +/- 1.19 to 2.72 +/- 2.67 ng x mL(-1) x h(-1); P=.007) was associated with a decrease in the mean ratio (from 25.8 +/- 38.1 to 16.4 +/- 31.6 h 10(2); P<.001). CONCLUSION: In patients with previously diagnosed essential hypertension, calculation of the aldosterone-renin ratio does not provide a renin-independent measure of circulating aldosterone that is suitable for determining whether PAC is elevated relative to PRA. Because elevation of the aldosterone-renin ratio is predominantly an indicator of low PRA, its perceived value in screening for primary aldosteronism most likely derives from additional diagnostic tests being done in patients with low-renin hypertension.

From artisan to architect: the specialist and systems of provision of diabetes care in 2001.

OBJECTIVE: To discuss the future role of the diabetes specialist and the endocrinologist in the care of patients with diabetes. METHODS: We reviewed the literature on health care systems, integrated approaches to provision of health care, health care in the primary-care setting for patients with chronic illness, and population-based health care for patients with diabetes. RESULTS: Specialists who care for patients with diabetes will assume a more significant role as caretakers of teams of health care professionals who are responsible for the primary care of patients with diabetes. The integration of specialist care at the primary-care level may lead to improved outcomes at the primary-care level, increased access to specialty care, and decreased costs for the health care system. Alternative systems, such as regulatory barriers to specialist care, are less likely to accomplish these outcomes. CONCLUSION: In the near future, specialists will be expected to care for those who provide primary care for patients with diabetes. Endocrinologists and endocrinology training programs should recognize this emerging role and prepare for it.