A Choosing Wisely top-5 list to support general practitioners in Austria.

From a pool of 147 reliable recommendations, ten experts from the Austrian Society of General Practice and Family Medicine selected 21 relevant recommendations as the basis for the Delphi process. In two Delphi rounds, eleven experts established a top­5 list of recommendations designed for Austrian family practice to reduce medical overuse. Three of the chosen recommendations address the issue of antibiotic usage in patients with viral upper respiratory tract infections, in children with mild otitis media, and in patients with asymptomatic bacteriuria. The other two "do not do" recommendations concern imaging studies for nonspecific low back pain and routine screening to detect prostate cancer. A subsequent survey identified the reasons for selecting these top­5 recommendations: the frequency of the issue, potential harms, costs, and patients' expectations. Experts hope the campaign will save time in educating patients and provide legal protection for omitting measures.

Long-term effects of weight-reducing diets in people with hypertension.

BACKGROUND: All major guidelines for antihypertensive therapy recommend weight loss. Dietary interventions that aim to reduce body weight might therefore be a useful intervention to reduce blood pressure and adverse cardiovascular events associated with hypertension. OBJECTIVES: Primary objectives To assess the long-term effects of weight-reducing diets in people with hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events). Secondary objectives To assess the long-term effects of weight-reducing diets in people with hypertension on change from baseline in systolic blood pressure, change from baseline in diastolic blood pressure, and body weight reduction. SEARCH METHODS: For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to April 2020: the Cochrane Hypertension Specialised Register, CENTRAL (2020, Issue 3), Ovid MEDLINE, Ovid Embase, and ClinicalTrials.gov. We also contacted authors of relevant papers about further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of at least 24 weeks' duration that compared weight-reducing dietary interventions to no dietary intervention in adults with primary hypertension. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risks of bias and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using a fixed-effect meta-analysis. In case of moderate or larger heterogeneity as measured by Higgins I2, we used a random-effects model. MAIN RESULTS: This second review update did not reveal any new trials, so the number of included trials remains the same: eight RCTs involving a total of 2100 participants with high blood pressure and a mean age of 45 to 66 years. Mean treatment duration was 6 to 36 months. We judged the risks of bias as unclear or high for all but two trials. No study included mortality as a predefined outcome. One RCT evaluated the effects of dietary weight loss on a combined endpoint consisting of the necessity of reinstating antihypertensive therapy and severe cardiovascular complications. In this RCT, weight-reducing diet lowered the endpoint compared to no diet: hazard ratio 0.70 (95% confidence interval (CI) 0.57 to 0.87). None of the trials evaluated adverse events as designated in our protocol. The certainty of the evidence was low for a blood pressure reduction in participants assigned to weight-loss diets as compared to controls: systolic blood pressure: mean difference (MD) -4.5 mm Hg (95% CI -7.2 to -1.8 mm Hg) (3 studies, 731 participants), and diastolic blood pressure: MD -3.2 mm Hg (95% CI -4.8 to -1.5 mm Hg) (3 studies, 731 participants). We judged the certainty of the evidence to be high for weight reduction in dietary weight loss groups as compared to controls: MD -4.0 kg (95% CI -4.8 to -3.2) (5 trials, 880 participants). Two trials used withdrawal of antihypertensive medication as their primary outcome. Even though we did not consider this a relevant outcome for our review, the results of these RCTs strengthen the finding of a reduction of blood pressure by dietary weight-loss interventions. AUTHORS' CONCLUSIONS: In this second update, the conclusions remain unchanged, as we found no new trials. In people with primary hypertension, weight-loss diets reduced body weight and blood pressure, but the magnitude of the effects are uncertain due to the small number of participants and studies included in the analyses. Whether weight loss reduces mortality and morbidity is unknown. No useful information on adverse effects was reported in the relevant trials.

Long-term effects of weight-reducing drugs in people with hypertension.

BACKGROUND: This is the third update of this review, first published in July 2009. All major guidelines on treatment of hypertension recommend weight loss; anti-obesity drugs may be able to help in this respect. OBJECTIVES: Primary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events).. Secondary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on change from baseline in systolic and diastolic blood pressure, and on body weight reduction. SEARCH METHODS: For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The searches had no language restrictions. We contacted authors of relevant papers about further published and unpublished work. SELECTION CRITERIA: Randomised controlled trials of at least 24 weeks' duration in adults with hypertension that compared approved long-term weight-loss medications to placebo.  DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risks of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using a fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of the heterogeneity. MAIN RESULTS: This third update of the review added one new trial, investigating the combination of naltrexone/bupropion versus placebo. Two medications, which were included in the previous versions of this review (rimonabant and sibutramine) are no longer considered relevant for this update, since their marketing approval was withdrawn in 2010 and 2009, respectively. The number of included studies in this review update is therefore six (12,724 participants in total): four RCTs comparing orlistat to placebo, involving a total of 3132 participants with high blood pressure and a mean age of 46 to 55 years; one trial comparing phentermine/topiramate to placebo, involving 1305 participants with high blood pressure and a mean age of 53 years; and one trial comparing naltrexone/bupropion to placebo, involving 8283 participants with hypertension and a mean age of 62 years. We judged the risks of bias to be unclear for the trials investigating orlistat or naltrexone/bupropion. and low for the trial investigating phentermine/topiramate. Only the study of naltrexone/bupropion included cardiovascular mortality and morbidity as predefined outcomes. There were no differences in the rates of all-cause or cardiovascular mortality, major cardiovascular events, or serious adverse events between naltrexone/bupropion and placebo. The incidence of overall adverse events was significantly higher in participants treated with naltrexone/bupropion. For orlistat, the incidence of gastrointestinal side effects was consistently higher compared to placebo. The most frequent side effects with phentermine/topiramate were dry mouth and paraesthesia. After six to 12 months, orlistat reduced systolic blood pressure compared to placebo by mean difference (MD) -2.6 mm Hg (95% confidence interval (CI) -3.8 to -1.4 mm Hg; 4 trials, 2058 participants) and diastolic blood pressure by MD -2.0 mm Hg (95% CI -2.7 to -1.2 mm Hg; 4 trials, 2058 participants). After 13 months of follow-up, phentermine/topiramate decreased systolic blood pressure compared to placebo by -2.0 to -4.2 mm Hg (1 trial, 1030 participants) (depending on drug dosage), and diastolic blood pressure by -1.3 to -1.9 mm Hg (1 trial, 1030 participants) (depending on drug dosage). There was no difference in the change in systolic or diastolic blood pressure between naltrexone/bupropion and placebo (1 trial, 8283 participants). We identified no relevant studies investigating liraglutide or lorcaserin in people with hypertension. AUTHORS' CONCLUSIONS: In people with elevated blood pressure, orlistat, phentermine/topiramate and naltrexone/bupropion reduced body weight; the magnitude of the effect was greatest with phentermine/topiramate. In the same trials, orlistat and phentermine/topiramate, but not naltrexone/bupropion, reduced blood pressure. One RCT of naltrexone/bupropion versus placebo showed no differences in all-cause mortality or cardiovascular mortality or morbidity after two years. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while for lorcaserin the application for European marketing authorisation was withdrawn due to a negative overall benefit/risk balance. In 2020 lorcaserin was also withdrawn from the US market. Two other medications (rimonabant and sibutramine) had already been withdrawn from the market in 2009 and 2010, respectively.

Management of non-specific low back pain in primary care - A systematic overview of recommendations from international evidence-based guidelines.

AIM: Systematic identification, characterization and analysis of recommendations concerning the diagnosis and treatment of non-specific low back pain (LBP) in primary care provided in international evidence-based guidelines from high-income countries. BACKGROUND: LBP is one of the most common reasons for consulting a primary care physician and its prevalence is higher in high-income than in middle- or low-income countries. The majority of LBP is non-specific and treatment recommendations are not often based on high-quality and patient-oriented evidence. METHODS: We systematically searched PubMed and major guideline databases from 2013 to 2020. Two independent reviewers performed literature selection and the quality assessment of included guidelines using the AGREE II tool. We extracted all relevant recommendations including the corresponding Grade of Recommendation. We grouped all included recommendations by topic and compared them to each other. FINDINGS: This overview includes 10 current guidelines and overall 549 relevant recommendations. Recommendations covered aspects of assessment and diagnosis (15%), non-pharmacological interventions (46%), pharmacological interventions (26%), invasive treatments (8%) and multimodal pain management (5%). In total, 30% of all recommendations were strong and 57% weak or very weak. The proportion of recommendations for and against an intervention was 45% and 38%, respectively. The recommendations from the different guidelines were largely in good agreement. We identify only a small number of contradictory recommendations, mostly dealing with very specific interventions. CONCLUSION: In conclusion, current evidence-based guidelines published in high-income countries provide recommendations for all major aspects of the management of people with LBP in primary care. Recommendations from different guidelines were largely consistent. More than 50% of these recommendations were weak or very weak and a high proportion of recommendation advised against an intervention.

(Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus.

BACKGROUND: Evidence that antihyperglycaemic therapy is beneficial for people with type 2 diabetes mellitus is conflicting. While the United Kingdom Prospective Diabetes Study (UKPDS) found tighter glycaemic control to be positive, other studies, such as the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, found the effects of an intensive therapy to lower blood glucose to near normal levels to be more harmful than beneficial. Study results also showed different effects for different antihyperglycaemic drugs, regardless of the achieved blood glucose levels. In consequence, firm conclusions on the effect of interventions on patient-relevant outcomes cannot be drawn from the effect of these interventions on blood glucose concentration alone. In theory, the use of newer insulin analogues may result in fewer macrovascular and microvascular events. OBJECTIVES: To compare the effects of long-term treatment with (ultra-)long-acting insulin analogues (insulin glargine U100 and U300, insulin detemir and insulin degludec) with NPH (neutral protamine Hagedorn) insulin (human isophane insulin) in adults with type 2 diabetes mellitus. SEARCH METHODS: For this Cochrane Review update, we searched CENTRAL, MEDLINE, Embase, ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was 5 November 2019, except Embase which was last searched 26 January 2017. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the effects of treatment with (ultra-)long-acting insulin analogues to NPH in adults with type 2 diabetes mellitus. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed risk of bias, extracted data and evaluated the overall certainty of the evidence using GRADE. Trials were pooled using random-effects meta-analyses. MAIN RESULTS: We identified 24 RCTs. Of these, 16 trials compared insulin glargine to NPH insulin and eight trials compared insulin detemir to NPH insulin. In these trials, 3419 people with type 2 diabetes mellitus were randomised to insulin glargine and 1321 people to insulin detemir. The duration of the included trials ranged from 24 weeks to five years. For studies, comparing insulin glargine to NPH insulin, target values ranged from 4.0 mmol/L to 7.8 mmol/L (72 mg/dL to 140 mg/dL) for fasting blood glucose (FBG), from 4.4 mmol/L to 6.6 mmol/L (80 mg/dL to 120 mg/dL) for nocturnal blood glucose and less than 10 mmol/L (180 mg/dL) for postprandial blood glucose, when applicable. Blood glucose and glycosylated haemoglobin A1c (HbA1c) target values for studies comparing insulin detemir to NPH insulin ranged from 4.0 mmol/L to 7.0 mmol/L (72 mg/dL to 126 mg/dL) for FBG, less than 6.7 mmol/L (120 mg/dL) to less than 10 mmol/L (180 mg/dL) for postprandial blood glucose, 4.0 mmol/L to 7.0 mmol/L (72 mg/dL to 126 mg/dL) for nocturnal blood glucose and 5.8% to less than 6.4% HbA1c, when applicable. All trials had an unclear or high risk of bias for several risk of bias domains. Overall, insulin glargine and insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH insulin. Changes in HbA1c were comparable for long-acting insulin analogues and NPH insulin. Insulin glargine compared to NPH insulin had a risk ratio (RR) for severe hypoglycaemia of 0.68 (95% confidence interval (CI) 0.46 to 1.01; P = 0.06; absolute risk reduction (ARR) -1.2%, 95% CI -2.0 to 0; 14 trials, 6164 participants; very low-certainty evidence). The RR for serious hypoglycaemia was 0.75 (95% CI 0.52 to 1.09; P = 0.13; ARR -0.7%, 95% CI -1.3 to 0.2; 10 trials, 4685 participants; low-certainty evidence). Treatment with insulin glargine reduced the incidence of confirmed hypoglycaemia and confirmed nocturnal hypoglycaemia. Treatment with insulin detemir compared to NPH insulin found an RR for severe hypoglycaemia of 0.45 (95% CI 0.17 to 1.20; P = 0.11; ARR -0.9%, 95% CI -1.4 to 0.4; 5 trials, 1804 participants; very low-certainty evidence). The Peto odds ratio for serious hypoglycaemia was 0.16, 95% CI 0.04 to 0.61; P = 0.007; ARR -0.9%, 95% CI -1.1 to -0.4; 5 trials, 1777 participants; low-certainty evidence). Treatment with detemir also reduced the incidence of confirmed hypoglycaemia and confirmed nocturnal hypoglycaemia. Information on patient-relevant outcomes such as death from any cause, diabetes-related complications, health-related quality of life and socioeconomic effects was insufficient or lacking in almost all included trials. For those outcomes for which some data were available, there were no meaningful differences between treatment with glargine or detemir and treatment with NPH. There was no clear difference between insulin-analogues and NPH insulin in terms of weight gain. The incidence of adverse events was comparable for people treated with glargine or detemir, and people treated with NPH. We found no trials comparing ultra-long-acting insulin glargine U300 or insulin degludec with NPH insulin. AUTHORS' CONCLUSIONS: While the effects on HbA1c were comparable, treatment with insulin glargine and insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH insulin. Treatment with insulin detemir also reduced the incidence of serious hypoglycaemia. However, serious hypoglycaemic events were rare and the absolute risk reducing effect was low. Approximately one in 100 people treated with insulin detemir instead of NPH insulin benefited. In the studies, low blood glucose and HbA1c targets, corresponding to near normal or even non-diabetic blood glucose levels, were set. Therefore, results from the studies are only applicable to people in whom such low blood glucose concentrations are targeted. However, current guidelines recommend less-intensive blood glucose lowering for most people with type 2 diabetes in daily practice (e.g. people with cardiovascular diseases, a long history of type 2 diabetes, who are susceptible to hypoglycaemia or older people). Additionally, low-certainty evidence and trial designs that did not conform with current clinical practice meant it remains unclear if the same effects will be observed in daily clinical practice. Most trials did not report patient-relevant outcomes.

[Antibody tests for COVID-19: What the results tell us]. / Antikörpertests bei COVID-19 - Was uns die Ergebnisse sagen.

INTRODUCTION: In the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the detection of virus-specific antibodies (AB) will play an increasing role. The presence or absence of such antibodies can potentially lead to considerations regarding immunity and infection. ISSUE: How reliable are inferences from positive or negative test results regarding the actual presence of SARS-CoV-2 specific antibodies? METHODS: Calculation of the probability that, depending on the pretest probability (prevalence of SARS-CoV-2 infection) and test properties, antibodies are present or absent in the case of positive or negative test results. RESULTS: Sensitivity and specificity of different SARS-CoV-2 AB test systems vary between 53 % and 94 % and between 91 % and 99.5 %, respectively. When using a test with high test quality, the positive predictive value (PPV) is 42 % and 7 9%, respectively, with a pre-test probability of 1 % to 5 %, as can currently be assumed for the general population in Austria or Germany. For persons with an increased pre-test probability of 20 %, e. g. persons from high-risk professions, the PPW is 95 %, with a pre-test probability of 80 % the PPW is almost 100 %. The negative predictive value (NPV) is at least 99.7 % for persons with a low pre-test probability of up to 5 % and 79.1 % for persons with a pre-test probability of 80 %. When using test systems with lower sensitivity and specificity, the reliability of the results decreases considerably. The PPV is 5.9 % with a pre-test probability of 1 %. CONCLUSIONS: A sufficiently high sensitivity and specificity are prerequisites for the application of antibody test systems. Positive test results are often false if the pre-test probability is low. Depending on the assumed prevalence of a SARS-CoV-2 infection, there are substantial differences in the significance of a concrete test result for the respective affected persons.

Written patient information materials used in general practices fail to meet acceptable quality standards.

BACKGROUND: Patient information materials and decision aids are essential tools for helping patients make informed decisions and share in decision-making. The aim of this study was to investigate the quality of the written patient information materials available at general practices in Styria, Austria. METHODS: We asked general practitioners to send in all patient information materials available in their practices and to answer a short questionnaire. We evaluated the materials using the Ensuring Quality Information for Patients (EQIP-36) instrument. RESULTS: A total of 387 different patient information materials were available for quality assessment. These materials achieved an average score of 39 out of 100. The score was below 50 for 78% of all materials. There was a significant lack of information on the evidence base of recommendations. Only 9 % of the materials provided full disclosure of their evidence sources. We also found that, despite the poor quality of the materials, 89% of general practitioners regularly make active use of them during consultations with patients. CONCLUSION: Based on international standards, the quality of patient information materials available at general practices in Styria is poor. The vast majority of the materials are not suitable as a basis for informed decisions by patients. However, most Styrian general practitioners use written patient information materials on a regular basis in their daily clinical practice. Thus, these materials not only fail to help raise the health literacy of the general population, but may actually undermine efforts to enable patients to make shared informed decisions. To increase health literacy, it is necessary to make high quality, evidence-based and easy-to-understand information material available to patients and the public. For this, it may be necessary to set up a centralized and independent clearinghouse.

Patients with healed diabetic foot ulcer represent a cohort at highest risk for future fatal events.

Patients with previous diabetic foot ulcer are prone to re-ulceration and (re)amputation, to various comorbidities, have significantly impaired quality of life and increased mortality. We aimed to evaluate the risk of foot related complications and mortality in a high-risk population of patients with healed diabetic foot syndrome over a decade. 91 patients with recently healed diabetic foot ulcer were invited for follow-up at 1, 6 and 11 years after inclusion. Patient characteristics at inclusion were: 40 women, 65 ± 11 years, diabetes type 1 (n = 6) or 2 (n = 85), BMI 28.5 ± 4.4 kg/m2, and HbA1c 68 ± 17 mmol/mol. Comorbidities included neuropathy (n = 91), peripheral artery disease (PAD), history of minor (n = 25) or major (n = 5, 5.5%) amputation, nephropathy (n = 40) and retinopathy (n = 53). Ulceration recurred in 71 (65%) patients, time to first recurrence was 1.8 ± 2.4 years (mean ± SD). 21 patients had to undergo (re)amputation (minor n = 19, major n = 2), time to amputation was 3.6 ± 1.9 years. Over time, 3 further major amputations were required in patients with an initial minor amputation. Thirty-three (36%) of the initially included patients completed the follow-up period of 11.0 ± 0.6 years. 58 patients (64%) died during the observational period, time to death was 5 ± 3 years in this group. We found overall high mortality of 64% throughout the follow-up period of 11 years in high-risk patients with healed diabetic foot syndrome. Presence of PAD, prior amputation and nephropathy as well as poor glycemic control were significantly predictive for death.

Management of overweight and obesity in primary care-A systematic overview of international evidence-based guidelines.

Overweight and obesity are increasing worldwide. In general practice, different approaches exist to treat people with weight problems. To provide the foundation for the development of a structured clinical pathway for overweight and obesity management in primary care, we performed a systematic overview of international evidence-based guidelines. We searched in PubMed and major guideline databases for all guidelines published in World Health Organization (WHO) "Stratum A" nations that dealt with adults with overweight or obesity. Nineteen guidelines including 711 relevant recommendations were identified. Most of them concluded that a multidisciplinary team should treat overweight and obesity as a chronic disease. Body mass index (BMI) should be used as a routine measure for diagnosis, and weight-related complications should be taken into account. A multifactorial, comprehensive lifestyle programme that includes reduced calorie intake, increased physical activity, and measures to support behavioural change for at least 6 to 12 months is recommended. After weight reduction, long-term measures for weight maintenance are necessary. Bariatric surgery can be offered to people with a BMI greater than or equal to 35 kg/m2 when all non-surgical interventions have failed. In conclusion, there was considerable agreement in international, evidence-based guidelines on how multidisciplinary management of overweight and obesity in primary care should be performed.

Optimizing medical care for geriatric patients in Austria: defining a top five list of "Choosing Wisely" recommendations using the Delphi technique.

PURPOSE: Inappropriate use of diagnostic and therapeutic medical procedures is common and potentially harmful for older patients. The Austrian Society of Geriatrics and Gerontology defined a consensus of five recommendations to avoid overuse of medical interventions and to improve care of geriatric patients. METHODS: From an initial pool of 147 reliable recommendations, 20 were chosen by a structured selection process for inclusion in a Delphi process to define a list of five top recommendations for geriatric medicine. 12 experts in the field of geriatric medicine scored the recommendations in two Delphi rounds. RESULTS: The final five recommendations are concerning urinary catheters in elderly patients, percutaneous feeding tubes in patients with advanced dementia, antipsychotics as the first choice to treat behavioral and psychological symptoms of dementia, and screening for breast, colorectal, prostate, or lung cancer, and the use of antimicrobials to treat asymptomatic bacteriuria. CONCLUSIONS: The selected recommendations have the potential to improve medical care for older patients, to reduce side effects caused by unnecessary medical procedures, and to save costs in the health care system.

Short-acting insulin analogues versus regular human insulin for adult, non-pregnant persons with type 2 diabetes mellitus.

BACKGROUND: The use of short-acting insulin analogues (insulin lispro, insulin aspart, insulin glulisine) for adult, non-pregnant people with type 2 diabetes is still controversial, as reflected in many scientific debates. OBJECTIVES: To assess the effects of short-acting insulin analogues compared to regular human insulin in adult, non-pregnant people with type 2 diabetes mellitus. SEARCH METHODS: For this update we searched CENTRAL, MEDLINE, Embase, the WHO ICTRP Search Portal, and ClinicalTrials.gov to 31 October 2018. We placed no restrictions on the language of publication. SELECTION CRITERIA: We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared short-acting insulin analogues to regular human insulin in the treatment of people with type 2 diabetes, who were not pregnant. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias. We assessed dichotomous outcomes by risk ratios (RR), and Peto odds ratios (POR), with 95% confidence intervals (CI). We assessed continuous outcomes by mean differences (MD) with 95% CI. We assessed trials for certainty of the evidence using the GRADE approach. MAIN RESULTS: We identified 10 trials that fulfilled the inclusion criteria, randomising 2751 participants; 1388 participants were randomised to receive insulin analogues and 1363 participants to receive regular human insulin. The duration of the intervention ranged from 24 to 104 weeks, with a mean of about 41 weeks. The trial populations showed diversity in disease duration, and inclusion and exclusion criteria. None of the trials were blinded, so the risk of performance bias and detection bias, especially for subjective outcomes, such as hypoglycaemia, was high in nine of 10 trials from which we extracted data. Several trials showed inconsistencies in the reporting of methods and results.None of the included trials defined all-cause mortality as a primary outcome. Six trials provided Information on the number of participants who died during the trial, with five deaths out of 1272 participants (0.4%) in the insulin analogue groups and three deaths out of 1247 participants (0.2%) in the regular human insulin groups (Peto OR 1.66, 95% CI 0.41 to 6.64; P = 0.48; moderate-certainty evidence). Six trials, with 2509 participants, assessed severe hypoglycaemia differently, therefore, we could not summarise the results with a meta-analysis. Overall, the incidence of severe hypoglycaemic events was low, and none of the trials showed a clear difference between the two intervention arms (low-certainty evidence).The MD in glycosylated haemoglobin A1c (HbA1c) change was -0.03% (95% CI -0.16 to 0.09; P = 0.60; 9 trials, 2608 participants; low-certainty evidence). The 95% prediction ranged between -0.31% and 0.25%. The MD in the overall number of non-severe hypoglycaemic episodes per participant per month was 0.08 events (95% CI 0.00 to 0.16; P = 0.05; 7 trials, 2667 participants; very low-certainty evidence). The 95% prediction interval ranged between -0.03 and 0.19 events per participant per month. The results provided for nocturnal hypoglycaemic episodes were of questionable validity. Overall, there was no clear difference between the two short-acting insulin analogues and regular human insulin. Two trials assessed health-related quality of life and treatment satisfaction, but we considered the results for both outcomes to be unreliable (very low-certainty evidence).No trial was designed to investigate possible long term effects (all-cause mortality, microvascular or macrovascular complications of diabetes), especially in participants with diabetes-related complications. No trial reported on socioeconomic effects. AUTHORS' CONCLUSIONS: Our analysis found no clear benefits of short-acting insulin analogues over regular human insulin in people with type 2 diabetes. Overall, the certainty of the evidence was poor and results on patient-relevant outcomes, like all-cause mortality, microvascular or macrovascular complications and severe hypoglycaemic episodes were sparse. Long-term efficacy and safety data are needed to draw conclusions about the effects of short-acting insulin analogues on patient-relevant outcomes.

Visceral leishmaniasis in a patient with diabetes mellitus type 2 and discrete bicytopenia.

An Austrian patient with diabetes mellitus type 2 developed visceral leishmaniasis after trips to Spain and Crete, presenting with slight bicytopenia, later developing severe pancytopenia. Travel history taking is important due to an extended incubation period. Coexistence of diabetes mellitus can impair T lymphocyte function and cause higher relapse rates.

The Choosing Wisely Initiative: A critical analysis with a special focus on primary care.

The Choosing Wisely initiative (CWI), a campaign led by the American Board of Internal Medicine (ABIM) Foundation, promotes doctor-patient communication and reducing waste in healthcare. At present, many of the top 5 lists from the Choosing Wisely Initiative appear to be primarily eminence-based and influenced by self-interest. The implementation of recommendations from these lists may mean taking a step backwards to the time before evidence-based medicine. On the other hand, despite all the challenges that the Choosing Wisely initiatives are currently facing, it is difficult to deny that they also hold great potential in terms of making healthcare systems more efficient and beneficial to patients. The aim of the ongoing work in Germany and Austria is to create conditions that are necessary if CW initiatives are to evolve into a model tool that will help introduce the principles of evidence-based medicine into daily practice.

Choosing Wisely: assessment of current US top five list recommendations' trustworthiness using a pragmatic approach.

OBJECTIVES: Identification of sufficiently trustworthy top 5 list recommendations from the US Choosing Wisely campaign. SETTING: Not applicable. PARTICIPANTS: All top 5 list recommendations available from the American Board of Internal Medicine Foundation website. MAIN OUTCOME MEASURES/INTERVENTIONS: Compilation of US top 5 lists and search for current German highly trustworthy (S3) guidelines. Extraction of guideline recommendations, including grade of recommendation (GoR), for suggestions comparable to top 5 list recommendations. For recommendations without guideline equivalents, the methodological quality of the top 5 list development process was assessed using criteria similar to that used to judge guidelines, and relevant meta-literature was identified in cited references. Judgement of sufficient trustworthiness of top 5 list recommendations was based either on an 'A' GoR of guideline equivalents or on high methodological quality and citation of relevant meta-literature. RESULTS: 412 top 5 list recommendations were identified. For 75 (18%), equivalents were found in current German S3 guidelines. 44 of these recommendations were associated with an 'A' GoR, or a strong recommendation based on strong evidence, and 26 had a 'B' or a 'C' GoR. No GoR was provided for 5 recommendations. 337 recommendations had no equivalent in the German S3 guidelines. The methodological quality of the development process was high and relevant meta-literature was cited for 87 top 5 list recommendations. For a further 36, either the methodological quality was high without any meta-literature citations or meta-literature citations existed but the methodological quality was lacking. For the remaining 214 recommendations, either the methodological quality was lacking and no literature was cited or the methodological quality was generally unsatisfactory. CONCLUSIONS: 131 of current US top 5 list recommendations were found to be sufficiently trustworthy. For a substantial number of current US top 5 list recommendations, their trustworthiness remains unclear. Methodological requirements for developing top 5 lists are recommended.

Short-acting insulin analogues versus regular human insulin for adults with type 1 diabetes mellitus.

BACKGROUND: Short-acting insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. OBJECTIVES: To assess the effects of short-acting insulin analogues versus regular human insulin in adults with type 1 diabetes. SEARCH METHODS: We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). SELECTION CRITERIA: We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared short-acting insulin analogues with regular human insulins in the treatment of adults with type 1 diabetes who were not pregnant. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. MAIN RESULTS: We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results.The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the insulin analogue, insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable.We also found no clear evidence for a substantial effect of insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. AUTHORS' CONCLUSIONS: Our analysis suggests only a minor benefit of short-acting insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of short acting insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

Successful Medical Treatment of Adult Nesidioblastosis With Pasireotide over 3 Years: A Case Report.

Nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. Diagnosis is often challenging and therapeutic options are scarce.In 2009, a 46-year-old female patient presented with recurrent severe hypoglycemia and immediate recovery after glucose ingestion. Although 72-h-fasting test was positive, various imaging technologies (sonography, computed tomography, somatostatin receptor scintigraphy, dopamine receptor positron emission tomography [DOPA-PET]) were negative. Endoscopic ultrasound revealed a lesion in the pancreatic corpus, whereas selective arterial calcium stimulation test, portal venous sampling and GLP-1-receptor scintigraphy were indicative of a lesion in the pancreatic tail, which was surgically removed. The histopathologic examination revealed beta cell hyperplasia and microadenomas expressing glucagon. After surgery, the patient was free of symptoms for 6 months, after which hypoglycemic episodes recurred. After unsuccessful treatment with corticosteroids and somatostatin analogs, treatment with pasireotide, a novel somatostatin analog with high affinity to somatostatin receptor 5 and a possible side effect of hyperglycemia, was initiated (0.6 mg BID). To date, our patient has been free of severe hypoglycemic episodes ever since. Yearly repeated imaging procedures have shown no abnormities over the last 3 years.We report for the first time that pasireotide was successfully used in the treatment of adult nesidioblastosis.

Long-term effects of weight-reducing diets in people with hypertension.

BACKGROUND: All major guidelines for antihypertensive therapy recommend weight loss. Thus dietary interventions that aim to reduce body weight might be a useful intervention to reduce blood pressure and adverse cardiovascular events associated with hypertension. OBJECTIVES: Primary objectivesTo assess the long-term effects of weight-reducing diets in people with hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events). Secondary objectivesTo assess the long-term effects of weight-reducing diets in people with hypertension on change from baseline in systolic blood pressure, change from baseline in diastolic blood pressure, and body weight reduction. SEARCH METHODS: We obtained studies from computerised searches of the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Hypertension Specialised Register, Ovid MEDLINE, and Ovid EMBASE, and from searches in reference lists, systematic reviews, and the clinical trials registry ClinicalTrials.gov (status as of 2 February 2015). SELECTION CRITERIA: We included randomised controlled trials (RCTs) of at least 24 weeks' duration that compared weight-reducing dietary interventions to no dietary intervention in adults with primary hypertension. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias and extracted data. We pooled studies using fixed-effect meta-analysis. In case of moderate or larger heterogeneity as measured by Higgins I(2), we used a random-effects model. MAIN RESULTS: This review update did not reveal any new studies, so the number of included studies remained the same: 8 studies involving a total of 2100 participants with high blood pressure and a mean age of 45 to 66 years. Mean treatment duration was 6 to 36 months. We judged the risk of bias as unclear or high for all but two trials. No study included mortality as a predefined outcome. One RCT evaluated the effects of dietary weight loss on a combined endpoint consisting of the necessity of reinstating antihypertensive therapy and severe cardiovascular complications. In this RCT, weight-reducing diet lowered the endpoint compared to no diet: hazard ratio 0.70 (95% confidence interval (CI), 0.57 to 0.87). None of the studies evaluated adverse events as designated in our protocol. There was low-quality evidence for a blood pressure reduction in participants assigned to weight loss diets as compared to controls: systolic blood pressure: mean difference (MD) -4.5 mm Hg (95% CI -7.2 to -1.8 mm Hg) (3 of 8 studies included in analysis), and diastolic blood pressure: MD -3.2 mm Hg (95% CI -4.8 to -1.5 mm Hg) (3 of  8  studies included in analysis). There was moderate-quality evidence for weight reduction in dietary weight loss groups as compared to controls: MD -4.0 kg (95% CI -4.8 to -3.2) (5 of 8 studies included in analysis). Two studies used withdrawal of antihypertensive medication as their primary outcome. Even though we did not consider this a relevant outcome for our review, the results of these studies strengthen the finding of reduction of blood pressure by dietary weight loss interventions. AUTHORS' CONCLUSIONS: In this update, the conclusions remain the same, as we found no new trials. In people with primary hypertension, weight loss diets reduced body weight and blood pressure, however the magnitude of the effects are uncertain due to the small number of participants and studies included in the analyses. Whether weight loss reduces mortality and morbidity is unknown. No useful information on adverse effects was reported in the relevant trials.

Long-term effects of weight-reducing drugs in people with hypertension.

BACKGROUND: All major guidelines on antihypertensive therapy recommend weight loss; anti-obesity drugs may be able to help in this respect. PRIMARY OBJECTIVES: To assess the long-term effects of pharmacologically induced reduction in body weight in adults with essential hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events). SECONDARY OBJECTIVES: To assess the long-term effects of pharmacologically induced reduction in body weight in adults with essential hypertension on change from baseline in systolic blood pressure, change from baseline in diastolic blood pressure, and body weight reduction. SEARCH METHODS: We obtained studies using computerised searches of the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid EMBASE, the clinical trials registry ClinicalTrials.gov, and from handsearches in reference lists and systematic reviews (status as of 13 April 2015). SELECTION CRITERIA: Randomised controlled trials in hypertensive adults of at least 24 weeks' duration that compared long-term pharmacologic interventions for weight loss with placebo.  DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of heterogeneity. MAIN RESULTS: After updating the literature search, which was extended to include four new weight-reducing drugs, we identified one additional study of phentermine/topiramate, bringing the total number of studies to nine that compare orlistat, sibutramine, or phentermine/topiramate to placebo and thus fulfil our inclusion criteria. We identified no relevant studies investigating rimonabant, liraglutide, lorcaserin, or naltrexone/bupropion. No study included mortality and cardiovascular morbidity as predefined outcomes. Incidence of gastrointestinal side effects was consistently higher in those participants treated with orlistat versus those treated with placebo. The most frequent side effects were dry mouth, constipation, and headache with sibutramine, and dry mouth and paresthaesia with phentermine/topiramate. In participants assigned to orlistat, sibutramine, or phentermine/topiramate body weight was reduced more effectively than in participants in the usual-care/placebo groups. Orlistat reduced systolic blood pressure as compared to placebo by -2.5 mm Hg (mean difference (MD); 95% confidence interval (CI): -4.0 to -0.9 mm Hg) and diastolic blood pressure by -1.9 mm Hg (MD; 95% CI: -3.0 to -0.9 mm Hg). Sibutramine increased diastolic blood pressure compared to placebo by +3.2 mm Hg (MD; 95% CI: +1.4 to +4.9 mm Hg). The one trial that investigated phentermine/topiramate suggested it lowered blood pressure. AUTHORS' CONCLUSIONS: In people with elevated blood pressure, orlistat and sibutramine reduced body weight to a similar degree, while phentermine/topiramate reduced body weight to a greater extent. In the same trials, orlistat and phentermine/topiramate reduced blood pressure, while sibutramine increased it. We could include no trials investigating rimonabant, liraglutide, lorcaserin, or naltrexone/bupropion in people with elevated blood pressure. Long-term trials assessing the effect of orlistat, liraglutide, lorcaserin, phentermine/topiramate, or naltrexone/bupropion on mortality and morbidity are unavailable and needed. Rimonabant and sibutramine have been withdrawn from the market, after long-term trials on mortality and morbidity have confirmed concerns about the potential severe side effects of these two drugs. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while the application for European marketing authorisation for lorcaserin was withdrawn by the manufacturer after the Committee for Medicinal Products for Human Use judged the overall benefit/risk balance to be negative.

[Breast cancer screening in Austria: Key figures, age limits, screening intervals and evidence]. / Brustkrebs-Screening in Österreich: Kennzahlen, Altersgrenzen, Screening-Intervalle und Evidenzbasis.

In January 2014, the first nationwide quality-assured breast cancer screening program addressing women aged ≥ 40 years was introduced in Austria. As part of the process of developing a patient information leaflet, the Evidence Based Medicine (EBM) Review Center of the Medical University of Graz was charged with the task of assessing the potential benefits and harms of breast cancer screening from the available evidence. Based on these results, key figures were derived for mortality, false-positive and false-negative mammography results, and overdiagnosis, considering Austria-specific incidence rates for breast cancer and breast cancer mortality. Furthermore, the current evidence regarding age limits and screening interval, which were the subjects of controversial public discussions, was analyzed. A systematic search for primary and secondary literature was performed and additional evidence was screened, e. g., evaluation reports of European breast cancer screening programs. On the basis of the available evidence and of the Austrian breast cancer mortality and incidence rates, it can be assumed that - depending on the age group - 1 to 4 breast cancer deaths can be avoided per 1,000 women screened in a structured breast cancer screening program, while the overall mortality remains unchanged. On the other hand, 150 to 200 of these 1,000 women will be affected by false-positive results and 1 to 9 women by overdiagnosis due to the structured breast cancer screening. Therefore, the overall benefit-harm balance is uncertain. If women from 40 to 44 or above 70 years of age are considered, who can also participate in the Austrian screening program, even a negative benefit-harm balance seems possible. However, with the implementation of quality standards in breast cancer screening and the dissemination of a patient information leaflet, an improvement in the medical treatment situation, specifically in terms of informed decision-making, can be expected.

Relevance to family practice of English-language guidelines on breast, colorectal and prostate cancer: a review.

BACKGROUND: GPs regard cancer guidelines as useful yet criticise their limited applicability to the primary care setting. OBJECTIVES: To determine the extent to which English-language breast, colorectal and prostate cancer guidelines contain recommendations that are relevant to GPs and to find out which of the GPs' roles in cancer care the recommendations refer to. METHODS: Evidence- and consent-based English-language breast, colorectal and prostate cancer guidelines were searched for in guideline databases and selected guideline providers' web pages, and checked against inclusion and exclusion criteria. Relevant recommendations were identified, extracted and examined. The involvement of GPs in guideline development as well as whether they were named as a target group was further investigated. RESULTS: Of the 65 identified guidelines, 35 were eligible and contained recommendations applicable to GPs. GPs were directly involved in the development of the majority of only breast cancer guidelines and were explicitly named as a target group in fewer than 50% of guidelines. The majority of recommendations dealt with patient-physician communication, with a focus on cancer therapy. Rarer procedural recommendations predominantly concentrated on follow-up/survivorship care. Less than one-third of all relevant recommendations concerned diagnosis. Only breast cancer guidelines provided a high number of recommendations on transitions between primary and secondary care. CONCLUSION: Greater consideration of GPs would increase their acceptance of guidelines, promote delivery of high-quality cancer care and clarify responsibilities between cancer care providers. The GP's role in cancer diagnosis is not appropriately reflected in cancer guideline recommendations.