Severe Hypercalcemia Caused by Calcium-Alkali Syndrome after 15 Years of Postoperative Hypoparathyroidism in a Patient with Undiagnosed Hyperaldosteronism.

Introduction: The triad of hypercalcemia, metabolic alkalosis, and acute kidney injury associated with ingesting high doses of calcium and absorbable bases characterizes the calcium-alkali syndrome. Clinical Case. We report the case of a patient with postthyroidectomy hypoparathyroidism 15 years ago due to differentiated thyroid cancer who presented with severe hypercalcemia. He had adequate control of calcemia for many years on treatment with calcitriol and calcium carbonate and hypertension treated with amlodipine, losartan, and hydrochlorothiazide. After a period of loss to follow-up, he suddenly presents with severe hypercalcemia, metabolic alkalosis, and loss of renal function. Upon hydration and withdrawal of calcitriol and calcium replacements, hypercalcemia resolved. The etiological investigation identified no granulomatous or neoplastic diseases, but an aldosterone-producing adrenal incidentaloma was found. The cause of hypercalcemia in this patient was calcium-alkali syndrome due to calcium carbonate replacement potentiated by hydrochlorothiazide and primary aldosteronism. Six months after the hospitalization and suspension of calcium and vitamin D, the patient returned to hypocalcemia, reinforcing the diagnosis. Conclusion: Although seldom described, the calcium-alkali syndrome is an expected complication for individuals with postoperative hypoparathyroidism, as they require lifelong calcium and vitamin D supplementation. This case also shows the importance of hydrochlorothiazide use and primary aldosteronism as possible triggers of life-threatening hypercalcemia.

Length of stay in the clinical wards in a hospital after introducing a multiprofessional discharge team: An effectiveness improvement report.

INTRODUCTION: Emergency overcrowding is a problem in hospitals worldwide. The expansion of wards has limitations. Hospital administrative leaders are constantly looking for opportunities to improve the efficiency of resource use. METHODS: This is a care improvement study with a quasi-experimental design. We created a hospital discharge team (HDT) to solve the issues of prolonged hospital stays. The main interventions were active search and resolution of prolongation of stay and multi-disciplinary huddles. We developed strategies with different hospital units to expedite the processing of patients near discharge. Length of stay (LOS), morning hospital discharges, readmission rates, and bed usage were compared before (2018) and after (2019) HDT implementation. RESULTS: There was a reduction in the mean LOS of 1.8 days (95% confidence interval [CI] -0.9 to -2.6; p < .001). The rate of hospital discharges before noon increased by 7.0% (95% CI 4%-11%; p < .001). The readmission rate was similar between 2018 and 2019 (+0.7%; 95% CI -0.1% to 1.9%; p = .358). We observed higher bed turnover, with 0.5 more hospitalizations per bed per month (95% CI 0.1-0.7; p = .01; mean of 3.7 ± 0.3 in 2018 and 4.1 ± 0.3 in 2019). CONCLUSION: HDT brought benefits to our hospital, reducing the length of stay and increasing bed turnover. However, there is a need for a team focused on the project and support from managers to overcome resistance and integrate units until they are fully operational.

A telemedicine strategy to reduce waiting lists and time to specialist care: A retrospective cohort study.

INTRODUCTION: The demand for specialty care is rising worldwide. In the state of Rio Grande do Sul, Brazil, more than 150,000 people were waiting for specialist consultations in 2013. A telemedicine programme (RegulaSUS) developed referral protocols, audited waitlisted cases, authorised/prioritised referrals by risk and discuss deferred cases primary-care physician. This study assesses the effectiveness of RegulaSUS. METHODS: A retrospective cohort analysis with contemporaneous controls was performed from June 2014 to June 2016. Six medical specialties included in RegulaSUS (50,185 patients) were compared to 50,124 control patients waitlisted according to the usual routine (scheduled for specialty consultation at the next available date). The groups were matched (1:1) by semester and year of waitlisting and by the specialty demand-to-supply ratio. Primary outcomes were referral-to-consultation time and number of waitlisted patients. RESULTS: The mean referral-to-consultation time was 584.8 days in the intervention group and 607.0 days in controls (p<0.001). For specialties regulated by RegulaSUS, the mean referral-to-consultation time was 237.6 days for higher-risk patients. At the end of the observation, 26,708 control patients had been unlisted compared to 31,050 patients in the intervention group (reduction of 53.5% vs. 61.9%, respectively; p<0.001). The number of cancelled referrals was lower in the control group (n=14,403; 28.7%) than in the intervention group (n=16,387; 32.7%; p<0.001). DISCUSSION: Telemedicine support for primary care effectively decreased the time to specialty consultation, reduced the number of waitlisted patients and allowed sicker patients to reach a specialist faster.

Dose-ranging effects of SGLT2 inhibitors in patients with type 2 diabetes: a systematic review and meta-analysis.

The lowest dosage of empagliflozin (10 mg) showed similar benefits on glycated hemoglobin (HbA1c) level, body weight, blood pressure, and total and cardiovascular mortality in comparison with the highest available dose (25 mg) in the EMPAREG trial. These findings have not been clearly demonstrated for canagliflozin and dapagliflozin. The objective was to compare the effect of different doses of SGLT2 inhibitors commercially available in Brazil on HbA1c and body weight of patients with type 2 diabetes. MEDLINE, Cochrane and Embase databases were searched from inception until 11th October 2021 for randomized controlled trials of SGLT2 inhibitors in type 2 diabetes patients, lasting at least 12 weeks. HbA1c and body weight variations were described using standard mean difference. We performed direct and indirect meta-analysis, as well as a meta-regression with medication doses as covariates. Eighteen studies were included, comprising 16,095 patients. In the direct meta-analysis, SGLT2 inhibitors reduced HbA1c by 0.62% (95% CI -0.66 to -0.59) and body weight by 0.60 kg (95% CI -0.64 to -0.55). In the indirect meta-analysis, canagliflozin 300 mg ranked the highest regarding reductions in HbA1c and body weight. The remaining medications and dosages were clinically similar, despite some statistically significant differences among them. Canagliflozin 300 mg seems to be more potent in reducing HbA1c and body weight in patients with type 2 diabetes. The remaining SGLT2 inhibitors at different doses lead to similar effects for both outcomes. Whether these glycemic and weight effects are reflected in lower mortality and cardiovascular events is still uncertain and may be a topic for further studies.

Dose-ranging effects of SGLT2 inhibitors in patients with type 2 diabetes: a systematic review and meta-analysis

ABSTRACT The lowest dosage of empagliflozin (10 mg) showed similar benefits on glycated hemoglobin (HbA1c) level, body weight, blood pressure, and total and cardiovascular mortality in comparison with the highest available dose (25 mg) in the EMPAREG trial. These findings have not been clearly demonstrated for canagliflozin and dapagliflozin. The objective was to compare the effect of different doses of SGLT2 inhibitors commercially available in Brazil on HbA1c and body weight of patients with type 2 diabetes. MEDLINE, Cochrane and Embase databases were searched from inception until 11th October 2021 for randomized controlled trials of SGLT2 inhibitors in type 2 diabetes patients, lasting at least 12 weeks. HbA1c and body weight variations were described using standard mean difference. We performed direct and indirect meta-analysis, as well as a meta-regression with medication doses as covariates. Eighteen studies were included, comprising 16,095 patients. In the direct meta-analysis, SGLT2 inhibitors reduced HbA1c by 0.62% (95% CI −0.66 to −0.59) and body weight by 0.60 kg (95% CI −0.64 to −0.55). In the indirect meta-analysis, canagliflozin 300 mg ranked the highest regarding reductions in HbA1c and body weight. The remaining medications and dosages were clinically similar, despite some statistically significant differences among them. Canagliflozin 300 mg seems to be more potent in reducing HbA1c and body weight in patients with type 2 diabetes. The remaining SGLT2 inhibitors at different doses lead to similar effects for both outcomes. Whether these glycemic and weight effects are reflected in lower mortality and cardiovascular events is still uncertain and may be a topic for further studies.

Reducing central vein catheterization complications with a focused educational program: a retrospective cohort study.

Central venous catheters (CVCs) are frequently used, but the rate of complications is high. This study evaluates the effects of a short training program for CVC insertion in a university-based teaching hospital. A sample of adults with CVCs inserted outside the intensive care unit was selected from two academic years: 2015, year without structured training, and 2016, year with structured training. Clinical and laboratory information, as well as the procedure's characteristics and complications (mechanical and infectious) were collected. The incidence of complications before and after the training was compared. A total of 1502 punctures were evaluated. Comparing the pre- and post-training period, there was an increase in the choice for jugular veins and the use of ultrasound. A numerical reduction in the rate of complications was identified (RR 0.732; 95% CI 0.48-1.12; P = 0.166). This difference was driven by a statistically significant lower rate of catheter-related infections (RR 0.78; 95% CI 0.64-0.95; P = 0.047). In the multivariate analysis, aspects regarding technique (ultrasound use, multiple punctures) and year of training were associated with outcomes. Structured training reduces the rate of complications related to CVC insertion, especially regarding infections.

Patient-centered Management of Type 2 Diabetes Mellitus Based on Specific Clinical Scenarios: Systematic Review, Meta-analysis and Trial Sequential Analysis.

INTRODUCTION: New antihyperglycemic medications have been proven to have cardiovascular (CV) and renal benefits in type 2 diabetes mellitus (T2DM); however, an evidence-based decision tree in specific clinical scenarios is lacking. MATERIALS AND METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs), with trial sequential analysis (TSA). Randomized controlled trial inclusion criteria were patients with T2DM from 1 of these subgroups: elderly, obese, previous atherosclerotic CV disease (ASCVD), previous coronary heart disease (CHD), previous heart failure (HF), or previous chronic kidney disease (CKD). Randomized controlled trials describing those subgroups with at least 48 weeks of follow-up were included. Outcomes: 3-point major adverse cardiovascular events (MACE), CV death, hospitalization due to HF, and renal outcomes. We performed direct meta-analysis with the number of events in the intervention and control groups in each subset, and the relative risk of the events was calculated. RESULTS: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) were the only antihyperglycemic agents related to a reduction in CV events in different populations. For obese and elderly populations, GLP-1 RA were associated with benefits in 3-point MACE; for patients with ASCVD, both SGLT2i and GLP-1 RA had benefits in 3-point MACE, while for patients with CHD, only SGLT2i were beneficial. CONCLUSIONS: SGLT2i and GLP-1 RA reduced CV events in selected populations: SGLT2i led to a reduction in events in patients with previous CHD, ASCVD, and HF. GLP-1 RA led to a reduction in CV events in patients with ASCVD, elderly patients, and patients with obesity. Trial sequential analysis shows that these findings are conclusive. This review opens a pathway towards evidence-based, personalized treatment of T2DM. REGISTRATION: PROSPERO CRD42019132807.

Glucagon-like peptide-1 receptor agonists and pancreatic cancer: a meta-analysis with trial sequential analysis.

We aimed to assess if GLP-1 agonists are associated with pancreatic cancer. Systematic review and meta-analysis of randomized trials with GLP-1 agonists as an intervention was performed. Trial sequential analysis (TSA) was performed to assess if the available information is sufficient to reject this association. Twelve trials met the study criteria, with a total of 36, 397 patients. GLP-1 analogues did not increase the risk for pancreatic cancer when compared to other treatments (OR 1.06; 95% CI 0.67 to 1.67; I2 14%). TSA confirmed that enough patients were randomized and again no association of the medications and pancreatic cancer was observed considering a NNH of 1000 and the short mean follow-up of the included trials (1.7 years). Larger studies with longer duration would be required to exclude a greater NNH and to aside concerns regarding possible influence of study duration and the outcome.

Distance Education to Improve the Quality of Asthma Treatment in Primary Health Care: Cluster Randomized Clinical Trial - RESPIRANET / Educação a distância para melhorar a qualidade do tratamento da asma na Atenção Primária à Saúde: ensaio clínico randomizado em cluster - RESPIRANET / Educación a distancia para mejorar la calidad del tratamiento del asma en la atención primaria de salud: ensayo clínico aleatorizado grupal - RESPIRANET

Objective: The mere dissemination of standard care recommendations has been insufficient to improve clinical results in patients with asthma. The objective of the present study was to evaluate the clinical effectiveness of a multifaceted asthma distance education for primary care providers. Methods: Cluster randomized controlled trial. Full primary care teams were included if they had access to telehealth support and free basic asthma treatment. Before randomization, selected teams indicated asthma patients between 5-45 years old for inclusion. The intervention group received three interactive online sessions, printed educational material, reminders, booklet for patients, and frequent stimulus to use consulting services. The control group received no intervention. Symptomfree days per two weeks was the primary result. Controlled asthma, unscheduled asthma doctor visits, and preventive inhaled corticosteroid use were the secondary results. Six months after intervention, the results were compared with baseline data using generalized estimating equations for repeated measures and clustering effect. Results: Were enrolled 71 primary care teams and 443 individuals. Most patients (60.3%) were female, and 44% were younger than 12 years old. The attendance of interactive sessions by the teams was 50%. The odds ratio (OR) for additional symptom-free day was 1.31 (95%CI 0.61-2.82; p=0.49). For the secondary results, the results were: controlled asthma OR 1.29 (95%CI 0.89-1.87; p=0.18); unscheduled asthma doctor visits OR 0.81 (95%CI 0.60-1.10; p=0.17); and preventive inhaled corticosteroid use OR 1.02 (95%CI 0.71-1.47; p=0.91). Conclusions: Multifaceted distance education in asthma care for primary care providers was not effective to improve patients' results. Telemedicine needs to deal with significant obstacles in professional education. ClinicalTrials.gov registry: NCT01595971.

Objetivo: A mera disseminação de recomendações de cuidados padronizados tem sido insuficiente para melhorar os desfechos clínicos em pacientes com asma. O objetivo do presente estudo foi avaliar a eficácia clínica de uma intervenção educativa multifacetada a distância sobre asma para profissionais da atenção primária à saúde. Métodos: Ensaio clínico randomizado por cluster. Equipes completas de atenção primária foram incluídas se tinham acesso a suporte de telessaúde e tratamento básico gratuito para asma. Antes da randomização, as equipes selecionadas indicaram pacientes asmáticos entre 5-45 anos para inclusão. O grupo de intervenção recebeu três sessões online interativas, material educativo impresso, lembretes, folheto para pacientes e estímulos frequentes para o uso de serviços de consultoria. O grupo controle não recebeu intervenção. O desfecho primário foi dias sem sintomas por duas semanas. Asma controlada, consultas médicas não programadas para asma e uso preventivo de corticosteroides inalatórios foram os desfechos secundários. Seis meses após a intervenção, os resultados foram comparados com a linha de base, usando equações de estimativas generalizadas para medidas repetidas e efeito de agrupamento. Resultados: Foram inscritas 71 equipes de atenção primária e 443 indivíduos. A maioria dos pacientes (60,3%) era do sexo feminino e 44% tinha menos de 12 anos de idade. A frequência das equipes nas sessões interativas foi de 50%. O odds ratio (OR) para dias sem sintomas adicionais foi de 1,31 (IC 95% 0,61-2,82; p=0,49). Para os desfechos secundários, os resultados foram: asma controlada 1,29 (IC 95% 0,89-1,87; p=0,18); visitas não programadas de asma ao médico OR 0,81 (IC 95% 0,60-1,10; p=0,17); e uso preventivo de corticosteroides inalatórios OR 1,02 (IC 95% 0,71-1,47; p=0,91). Conclusões: Ações multifacetadas de educação a distância em cuidados de asma para profissionais de saúde da atenção primária não foram eficazes para melhorar os resultados nos pacientes. A telemedicina precisa lidar com obstáculos significativos na educação profissional. Registro ClinicalTrials.gov: NCT01595971.

Objetivo: La mera difusión de las recomendaciones de atención estándar ha sido insuficiente para mejorar los resultados clínicos en pacientes con asma. El objetivo del presente estudio fue evaluar la efectividad clínica de una educación multifacética a distancia sobre el asma para los proveedores de atención primaria. Métodos: Ensayo controlado aleatorizado por grupos. Se incluyeron equipos completos de atención primaria si tenían acceso a apoyo de telesalud y tratamiento básico gratuito para el asma. Antes de la aleatorización, los equipos seleccionados indicaron pacientes con asma entre 5-45 años de edad para inclusión. El grupo de intervención recibió tres sesiones interactivas en línea, material educativo impreso, recordatorios, folleto para los pacientes y estímulos frecuentes para utilizar los servicios de consultoría. El grupo control no recibió ninguna intervención. El resultado primario fue días sin síntomas por dos semanas. Los resultados secundarios fueron asma controlada, visitas médicas no programadas para el asma y el uso preventivo de corticosteroides inhalados. Seis meses después de la intervención, los resultados se compararon con los datos de referencia utilizando ecuaciones de estimación generalizadas para medidas repetidas y efecto de agrupación. Resultados: Se inscribieron 71 equipos de atención primaria y 443 personas. La mayoría de los pacientes (60,3%) eran mujeres y el 44% eran menores de 12 años. La asistencia a sesiones interactivas por parte de los equipos fue del 50%. La razón de probabilidades (OR) para un día sin síntomas adicional fue de 1.31 (IC del 95%: 0.61 a 2.82; p=0.49). Para los resultados secundarios, los resultados fueron: asma controlada O 1.29 (IC del 95%: 0.89 a 1.87; p=0.18); visitas al médico para el asma no programadas O 0,81 (IC del 95%: 0,60 a 1,10; p=0,17); y el uso preventivo de corticosteroides inhalados OR 1.02 (IC del 95%: 0.71 a 1.47; p=0.91). Conclusiones: La educación a distancia multifacética en el cuidado del asma para los proveedores de atención primaria no fue efectiva para mejorar los resultados de los pacientes. La telemedicina debe enfrentar obstáculos significativos en la educación profesional. Registro de ClinicalTrials.gov: NCT01595971.

Dipeptidyl peptidase-4 inhibitors, pancreatic cancer and acute pancreatitis: A meta-analysis with trial sequential analysis.

The use of dipeptidyl peptidase-4 (DPP-4) inhibitors may be associated with pancreatic cancer and acute pancreatitis. Recent meta-analyses have reported conflicting findings. Therefore, we performed a meta-analysis to assess the risk of both pancreatic cancer and acute pancreatitis associated with the use of DPP-4 inhibitors. We also used trial sequential analysis to evaluate whether the number of patients included was enough to reach conclusions. We included randomised controlled trials lasting 24 weeks or more that compared DPP-4 inhibitors with placebo or other antihyperglycaemic agents. A total of 59,404 patients were included. There was no relationship between the use of DPP-4 inhibitors and pancreatic cancer (Peto odds ratio 0.65; 95% CI 0.35-1.21), and the optimal sample size was reached to determine a number needed to harm (NNH) of 1000 patients. DPP-4 inhibitors were associated with increased risk for acute pancreatitis (Peto odds ratio 1.72; 95% CI 1.18-2.53), with an NNH of 1066 patients, but the optimal sample size for this outcome was not reached. In conclusion, there is no association between DPP-4 inhibitors and pancreatic cancer, and a small risk for acute pancreatitis was observed with DPP-4 inhibitor use, although the latter finding is not definitive.

Screening for coronary artery disease in patients with type 2 diabetes: a meta-analysis and trial sequential analysis.

OBJECTIVE: To evaluate the efficacy of coronary artery disease screening in asymptomatic patients with type 2 diabetes and assess the statistical reliability of the findings. METHODS: Electronic databases (MEDLINE, EMBASE, Cochrane Library and clinicaltrials.org) were reviewed up to July 2016. Randomised controlled trials evaluating coronary artery disease screening in asymptomatic patients with type 2 diabetes and reporting cardiovascular events and/or mortality were included. Data were summarised with Mantel-Haenszel relative risk. Trial sequential analysis (TSA) was used to evaluate the optimal sample size to detect a 40% reduction in outcomes. Main outcomes were all-cause mortality and cardiac events (non-fatal myocardial infarction and cardiovascular death); secondary outcomes were non-fatal myocardial infarction, myocardial revascularisations and heart failure. RESULTS: One hundred thirty-five references were identified and 5 studies fulfilled the inclusion criteria and totalised 3315 patients, 117 all-cause deaths and 100 cardiac events. Screening for coronary artery disease was not associated with decrease in risk for all-cause deaths (RR 0.95(95% CI 0.66 to 1.35)) or cardiac events (RR 0.72(95% CI 0.49 to 1.06)). TSA shows that futility boundaries were reached for all-cause mortality and a relative risk reduction of 40% between treatments could be discarded. However, there is not enough information for firm conclusions for cardiac events. For secondary outcomes no benefit or harm was identified; optimal sample sizes were not reached. CONCLUSION: Current available data do not support screening for coronary artery disease in patients with type 2 diabetes for preventing fatal events. Further studies are needed to assess the effects on cardiac events. PROSPERO: CRD42015026627.

Genetics of diabetic nephropathy.

The increasing prevalence of diabetes mellitus has led to a growing number of chronic complications including diabetic nephropathy (DN). In addition to its high prevalence, DN is associated with high morbidity and mortality especially due to cardiovascular diseases. It is well established that genetic factors play a role in the pathogenesis of DN and genetically susceptible individuals can develop it after being exposed to environmental factors. DN is probably a complex, polygenic disease. Two main strategies have been used to identify genes associated to DN: analysis of candidate genes, and more recently genome-wide scan. Great efforts have been made to identify these main genes, but results are still inconsistent with different genes associated to a small effect in specific populations. The identification of the main genes would allow the detection of those individuals at high risk for DN and better understanding of its pathophysiology as well.

Genetics of diabetic nephropathy / Bases genéticas da nefropatia diabética

The increasing prevalence of diabetes mellitus has led to a growing number of chronic complications including diabetic nephropathy (DN). In addition to its high prevalence, DN is associated with high morbidity and mortality especially due to cardiovascular diseases. It is well established that genetic factors play a role in the pathogenesis of DN and genetically susceptible individuals can develop it after being exposed to environmental factors. DN is probably a complex, polygenic disease. Two main strategies have been used to identify genes associated to DN: analysis of candidate genes, and more recently genome-wide scan. Great efforts have been made to identify these main genes, but results are still inconsistent with different genes associated to a small effect in specific populations. The identification of the main genes would allow the detection of those individuals at high risk for DN and better understanding of its pathophysiology as well.

A crescente elevação na prevalência do diabetes melito (DM) acarretou em um aumento de suas complicações crônicas, entre elas a nefropatia diabética (ND). Além da elevada prevalência, a ND está associada à importante morbidade e mortalidade, principalmente por doenças cardiovasculares. É notória a contribuição genética na patogênese da ND, em que, na presença de fatores ambientais propícios, aqueles indivíduos geneticamente predispostos desenvolverão a doença. Trata-se de uma doença com provável transmissão genética do tipo poligênica e complexa. Duas estratégias principais têm sido utilizadas na busca dos genes associados à ND: a avaliação de genes candidatos e, mais recentemente, a utilização de genoma wide scan. Grande empenho tem sido realizado para identificar os principais genes associados à ND, mas os resultados ainda são heterogêneos com diferentes genes apresentando um efeito pequeno em populações específicas. A identificação dos principais genes permitiria prever os indivíduos de maior risco para o desenvolvimento da ND, além de possibilitar um melhor entendimento fisiopatológico da doença.