Improving pharmaceutical practice in diabetes care using point-of-care glycated haemoglobin testing in the community pharmacy.

OBJECTIVES: To evaluate the use of point-of-care testing to detect new cases of diabetes mellitus at a Brazilian public community pharmacy. METHODS: This cross-sectional study included individuals without a previous diagnosis of diabetes mellitus who met the criteria for screening according to the Brazilian Diabetes Society, which were identified during their presence at a Brazilian public community pharmacy. The measurements of HbA1c were performed using a Cobas b101 device (Roche Diagnostics) and were categorized according to the following classification established by the Brazilian Society of Diabetes: HbA1c <5.7%, normal; HbA1c between 5.7% and 6.4%, pre-diabetes; and HbA1c >6.4%, new diagnosis of T2DM. KEY FINDINGS: One hundred and eight users met the inclusion criteria. The patients' mean age was 54.4 (± 15.4) years old, ranging from 22 to 80 years old. Eighty (74.1%) participants presented with glycated haemoglobin levels over the standard threshold, of which 58 (72.5%) were in the pre-diabetes range (glycated haemoglobin levels between 5.7% and 6.4%), and 22 (27.5%) had glycated haemoglobin levels >6.4%, which corresponds to a new diagnosis of type 2 diabetes mellitus. CONCLUSIONS: The use of point-of-care glycated haemoglobin testing allowed community pharmacists at a Brazilian public community pharmacy to identify health system users with glycated haemoglobin alterations that corresponded to the pre-diabetes state or a new diagnosis of type 2 diabetes mellitus. This presented a good opportunity to refer these users to diabetes diagnosis and treatment services.

Predição de choque séptico e hipovolêmico em pacientes de unidade de terapia intensiva com o uso de machine learning / Prediction of septic and hypovolemic shock in intensive care unit patients using machine learning

RESUMO Objetivo: Criar e validar um modelo de predição de choque séptico ou hipovolêmico a partir de variáveis de fácil obtenção coletadas na admissão de pacientes internados em uma unidade de terapia intensiva. Métodos: Estudo de modelagem preditiva com dados de coorte concorrente realizada em um hospital do interior do nordeste brasileiro. Foram incluídos pacientes com 18 anos ou mais sem uso de droga vasoativa no dia da admissão e que foram internados entre novembro de 2020 e julho de 2021. Foram testados os algoritmos de classificação do tipo Decision Tree, Random Forest, AdaBoost, Gradient Boosting e XGBoost para a construção do modelo. O método de validação utilizado foi o k-fold cross validation. As métricas de avaliação utilizadas foram recall, precisão e área sob a curva Receiver Operating Characteristic. Resultados: Foram utilizados 720 pacientes para criação e validação do modelo. Os modelos apresentaram alta capacidade preditiva com área sob a curva Receiver Operating Characteristic de 0,979; 0,999; 0,980; 0,998 e 1,00 para os algoritmos de Decision Tree, Random Forest, AdaBoost, Gradient Boosting e XGBoost, respectivamente. Conclusão: O modelo preditivo criado e validado apresentou elevada capacidade de predição do choque séptico e hipovolêmico desde o momento da admissão de pacientes na unidade de terapia intensiva.

ABSTRACT Objective: To create and validate a model for predicting septic or hypovolemic shock from easily obtainable variables collected from patients at admission to an intensive care unit. Methods: A predictive modeling study with concurrent cohort data was conducted in a hospital in the interior of northeastern Brazil. Patients aged 18 years or older who were not using vasoactive drugs on the day of admission and were hospitalized from November 2020 to July 2021 were included. The Decision Tree, Random Forest, AdaBoost, Gradient Boosting and XGBoost classification algorithms were tested for use in building the model. The validation method used was k-fold cross validation. The evaluation metrics used were recall, precision and area under the Receiver Operating Characteristic curve. Results: A total of 720 patients were used to create and validate the model. The models showed high predictive capacity with areas under the Receiver Operating Characteristic curve of 0.979; 0.999; 0.980; 0.998 and 1.00 for the Decision Tree, Random Forest, AdaBoost, Gradient Boosting and XGBoost algorithms, respectively. Conclusion: The predictive model created and validated showed a high ability to predict septic and hypovolemic shock from the time of admission of patients to the intensive care unit.

Prediction of septic and hypovolemic shock in intensive care unit patients using machine learning. / Predição de choque séptico e hipovolêmico em pacientes de unidade de terapia intensiva com o uso de machine learning.

OBJECTIVE: To create and validate a model for predicting septic or hypovolemic shock from easily obtainable variables collected from patients at admission to an intensive care unit. METHODS: A predictive modeling study with concurrent cohort data was conducted in a hospital in the interior of northeastern Brazil. Patients aged 18 years or older who were not using vasoactive drugs on the day of admission and were hospitalized from November 2020 to July 2021 were included. The Decision Tree, Random Forest, AdaBoost, Gradient Boosting and XGBoost classification algorithms were tested for use in building the model. The validation method used was k-fold cross validation. The evaluation metrics used were recall, precision and area under the Receiver Operating Characteristic curve. RESULTS: A total of 720 patients were used to create and validate the model. The models showed high predictive capacity with areas under the Receiver Operating Characteristic curve of 0.979; 0.999; 0.980; 0.998 and 1.00 for the Decision Tree, Random Forest, AdaBoost, Gradient Boosting and XGBoost algorithms, respectively. CONCLUSION: The predictive model created and validated showed a high ability to predict septic and hypovolemic shock from the time of admission of patients to the intensive care unit.

OBJETIVO: Criar e validar um modelo de predição de choque séptico ou hipovolêmico a partir de variáveis de fácil obtenção coletadas na admissão de pacientes internados em uma unidade de terapia intensiva. MÉTODOS: Estudo de modelagem preditiva com dados de coorte concorrente realizada em um hospital do interior do nordeste brasileiro. Foram incluídos pacientes com 18 anos ou mais sem uso de droga vasoativa no dia da admissão e que foram internados entre novembro de 2020 e julho de 2021. Foram testados os algoritmos de classificação do tipo Decision Tree, Random Forest, AdaBoost, Gradient Boosting e XGBoost para a construção do modelo. O método de validação utilizado foi o k-fold cross validation. As métricas de avaliação utilizadas foram recall, precisão e área sob a curva Receiver Operating Characteristic. RESULTADOS: Foram utilizados 720 pacientes para criação e validação do modelo. Os modelos apresentaram alta capacidade preditiva com área sob a curva Receiver Operating Characteristic de 0,979; 0,999; 0,980; 0,998 e 1,00 para os algoritmos de Decision Tree, Random Forest, AdaBoost, Gradient Boosting e XGBoost, respectivamente. CONCLUSÃO: O modelo preditivo criado e validado apresentou elevada capacidade de predição do choque séptico e hipovolêmico desde o momento da admissão de pacientes na unidade de terapia intensiva.

Improving Access to the Glycated Hemoglobin Test in Rural Communities With Point-of-Care Devices: An Application Study.

Background: Living in a rural or remote area is frequently associated with impaired access to health services, which directly affects the possibility of early diagnosis and appropriate monitoring of diseases, mainly non-communicable ones, because of their asymptomatic onset and evolution. Point-of-care devices have emerged as useful technologies for improving access to several laboratory tests closely patients' beds or homes, which makes it possible to eliminate the distance barrier. Objective: To evaluate the application of point-of-care technology for glycated hemoglobin (HbA1c) estimation in the assessment of glycemic control and identification of new diagnoses of diabetes in primary care among rural communities in a Brazilian municipality. Materials and Methods: We included individuals aged 18 years or older among rural communities in a Brazilian municipality. From September 2019 to February 2020, participants were assessed for anthropometrics, blood pressure, and capillary glycemia during routine primary care team activities at health fairs and in patient groups. Participants previously diagnosed with diabetes but without recent HbA1c test results or those without a previous diagnosis but with random capillary glycemia higher than 140 mg/dL were considered positive and were tested for HbA1c by using a point-of-care device. Results: At the end of the study, 913 individuals were accessed. Of these, 600 (65.7%) had no previous diagnosis of diabetes, 58/600 (9.7%) refused capillary glycemia screening and 542/600 (90.7%) were tested. Among tested individuals, 73/542 (13.5%) cases without a previous diagnosis of diabetes, were positive for capillary glycemia. Among positives, 31/73 (42.5%) had HbA1c levels that were considered indicative of prediabetes and 16/73 (21.9%) were newly diagnosed with diabetes. Among the participants, 313/913 (34.3%) were previously diagnosed with diabetes. Recent HbA1c results were unavailable for 210/313 (67.1%). These individuals were tested using point-of-care devices. Among them, 143/210 (68.1%) had HbA1c levels higher than target levels (>7% and >8% for adults and elderly individuals, respectively. Conclusion: The application of point-of-care devices for HbA1c level measurement improved the access to this test for people living in rural or remote areas. Thus, it was possible to include this technology in the routine activities of primary health care teams, which increased the rates of new diagnoses and identification of patients with uncontrolled glycemia.

Ledipasvir/Sofosbuvir for 8, 12, or 24 Weeks in Hepatitis C Patients Undergoing Dialysis for End-Stage Renal Disease.

INTRODUCTION: We evaluated 8, 12, or 24 weeks of ledipasvir/sofosbuvir in patients with hepatitis C virus and end-stage renal disease undergoing dialysis. METHODS: Primary efficacy end point was sustained virologic response 12 weeks after treatment. Primary safety end point was treatment discontinuation because of adverse events (AEs). RESULTS: Ninety-four percent (89/95) achieved sustained virologic response 12 weeks after treatment. Six patients died during treatment (n = 4) or before study completion (n = 2); no deaths were related to treatment. No patients discontinued treatment because of AEs. Thirteen percent had serious AEs; none were related to treatment. DISCUSSION: Treatment with ledipasvir/sofosbuvir was safe and effective in patients with end-stage renal disease undergoing dialysis.

The Association of Histologic and Noninvasive Tests With Adverse Clinical and Patient-Reported Outcomes in Patients With Advanced Fibrosis Due to Nonalcoholic Steatohepatitis.

BACKGROUND & AIM: Fibrosis is an independent predictor of death in nonalcoholic steatohepatitis (NASH). We assessed the associations between histologic and noninvasive tests (NITs) for fibrosis with clinical and patient-reported outcomes (PROs) in advanced NASH. METHODS: Patients with advanced NASH (NASH Clinical Research Network stage F3 or F4) were enrolled in 4 multinational clinical trials of simtuzumab and selonsertib. Liver biopsy samples, NIT results, and PROs (Short Form-36, Chronic Liver Disease Questionnaire-NASH, EuroQol-5D, and Work Productivity and Activity Impairment) were prospectively collected. RESULTS: A total of 2154 patients with advanced NASH were included: 52.5% with F4 NASH, 40% male, 72% with type 2 diabetes, baseline liver stiffness of 24.1 ± 14.2 kPa in F4 disease and 14.6 ± 8.0 kPa in F3 disease, baseline mean Enhanced Liver Fibrosis score of 11.4 ± 1.2 in F4 disease and 10.3 ± 1.0 in F3 disease, and a median follow-up of 16 months. Of those with baseline F3 disease, 16.7% experienced disease progression to cirrhosis, whereas for those with F4 disease, 7.3% experienced clinical events (39% ascites, 24% hepatic encephalopathy); patients who progressed had higher baseline NIT scores (all P < .0001). Adjusted for baseline levels, increases in NIT scores were also associated with increased risk of disease progression in both the F3 and F4 groups (P < .01 for all NITs in F3 and for ELF, NAFLD Fibrosis Score, Fibrosis-4 (FIB-4), and liver stiffness in F4). Higher NIT scores were found to be associated with impairment in PROs: ELF, ≥10.43; Nonalcoholic Fatty Liver Disease Fibrosis Score, ≥1.80; Fibrotest score, ≥0.54; liver stiffness, ≥23.4 kPa. During treatment, patients with decreases in NIT scores experienced improvement of their PRO scores, whereas those with increase in NIT scores had their PRO scores worsen (P < .05). CONCLUSIONS: Baseline NIT scores and their changes over time are predictors of adverse clinical and PROs in patients with advanced NASH. (ClinicalTrials.gov, Numbers NCT01672866, NCT01672879, NCT03053050, and NCT03053063).

Fatigue and Pruritus in Patients with Advanced Fibrosis Due to Nonalcoholic Steatohepatitis: The Impact on Patient-Reported Outcomes.

Fatigue and pruritus are common in patients with chronic liver diseases of all etiologies, but clinical awareness is mostly restricted to those with cholestatic liver diseases. We assessed the impact of fatigue and pruritus on patient-reported outcomes (PROs) of patients with advanced nonalcoholic steatohepatitis (NASH). Specifically, PROs (Short Form-36, Chronic Liver Disease Questionnaire-NASH, Euro-Qol 5 Dimension, and Work Productivity and Activity Impairment instruments) were assessed at baseline in patients with histologically confirmed bridging fibrosis (F3) or compensated cirrhosis (F4) due to NASH enrolled in STELLAR 3 and 4. Presence of fatigue and pruritus were indicated by a score of 4 or less on the respective items of the Chronic Liver Disease Questionnaire-NASH (scale range, 1-7). Among the included 1,669 patients with advanced NASH (mean age = 58 ± 9 years, 48% F3, 42% with psychiatric comorbidities), 33% and 27% had fatigue and pruritus, respectively. Patients with NASH with fatigue were younger, more likely to be female, cirrhotic, and diabetic, and had higher body mass index and more comorbidities (all P < 0.05). All PRO scores of patients with fatigue were significantly impaired (mean up to -31% of a PRO range size in comparison to patients without fatigue). In multivariate analysis, predictors of fatigue included diabetes, history of depression or nervous system comorbidities, and lower serum albumin (P < 0.05). Patients with pruritus had demographic characteristics similar to those with fatigue, but a higher prevalence of dermatologic comorbidities. All PROs were impaired (by up to -19% of a range size, all P < 0.01) in patients with NASH with pruritus. Female gender, lower serum albumin, and a history of depression, nervous system, and dermatologic comorbidities were associated with increased risk of pruritus (P < 0.05). Conclusion: Clinically significant fatigue and pruritus are common in patients with advanced NASH, and these symptoms negatively affect PROs.

Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: Results from randomized phase III STELLAR trials.

BACKGROUND & AIMS: Apoptosis signal-regulating kinase 1 (ASK1) plays a key role in hepatocyte injury, inflammation, and fibrosis in non-alcoholic steatohepatitis (NASH). We evaluated the safety and antifibrotic effect of selonsertib, a selective inhibitor of ASK1, in patients with advanced fibrosis due to NASH. METHODS: We conducted 2 randomized, double-blind, placebo-controlled, phase III trials of selonsertib in patients with NASH and bridging fibrosis (F3, STELLAR-3) or compensated cirrhosis (F4, STELLAR-4). Patients were randomized 2:2:1 to receive selonsertib 18 mg, selonsertib 6 mg, or placebo once daily for 48 weeks. Liver biopsies were performed at screening and week 48 and non-invasive tests of fibrosis (NITs) were evaluated. The primary efficacy endpoint was the proportion of patients with ≥1-stage improvement in fibrosis without worsening of NASH at week 48. Additional endpoints included changes in NITs, progression to cirrhosis (in STELLAR-3), and liver-related clinical events. RESULTS: Neither trial met the primary efficacy endpoint. In STELLAR-3, fibrosis improvement without worsening of NASH was observed in 10% (31/322, p = 0.49 vs. placebo), 12% (39/321, p = 0.93 vs. placebo), and 13% (21/159) of patients in the selonsertib 18 mg, selonsertib 6 mg, and placebo groups, respectively. In STELLAR-4, the primary endpoint was achieved in 14% (51/354; p = 0.56), 13% (45/351; p = 0.93), and 13% (22/172) of patients, respectively. Although selonsertib led to dose-dependent reductions in hepatic phospho-p38 expression indicative of pharmacodynamic activity, it had no significant effect on liver biochemistry, NITs, progression to cirrhosis, or adjudicated clinical events. The rates and types of adverse events were similar among selonsertib and placebo groups. CONCLUSIONS: Forty-eight weeks of selonsertib monotherapy had no antifibrotic effect in patients with bridging fibrosis or compensated cirrhosis due to NASH. LAY SUMMARY: Patients with non-alcoholic steatohepatitis (NASH) can develop scarring of the liver (fibrosis), including cirrhosis, which increases the risks of liver failure and liver cancer. We tested whether 48 weeks of treatment with selonsertib reduced fibrosis in patients with NASH and advanced liver scarring. We did not find that selonsertib reduced fibrosis in these patients. TRIAL REGISTRATION DETAILS: Clinicaltrials.gov numbers NCT03053050 and NCT03053063.

Estimated glomerular filtration rate and drug dose adjustment in patients in an intensive care unit in Brazil

Objectives. This study sought to compare the estimated glomerular filtration rate and the indication of dose adjustment of antimicrobials when using Cockcroft-Gault or Modification of Diet in Renal Disease. Methods. A cross-sectional study was performed with patients admitted to the intensive care unit of a Brazilian general hospital. The glomerular filtration rate was calculated for patients on all days using the Cockcroft-Gault and Modification of Diet in Renal Disease equations. The difference in estimated glomerular filtration and the dose adjustment indication of antimicrobials were assessed. Results. A total of 631 patients were included in this study. The median estimated glomerular filtration was significantly higher when estimated using Modification of Diet in Renal Disease (100.3 mL/ min/1.73 m2) than the estimation by Cockcroft-Gault (83.2 mL/min) [p<0.001]. Greater differences in estimations produced by the two formulae were observed in patients at extremes of weight and age, and a different dose adjustment was indicated for all antimicrobials assessed. Conclusions. These results demonstrate a significant difference in estimated glomerular filtration rate values when calculated using either Cockcroft-Gault or Modification of Diet in Renal Disease as well as in the indication of dose adjustment in an intensive care unit

Association between increased mortality rate and antibiotic dose adjustment in intensive care unit patients with renal impairment.

PURPOSE: Adjusting the antibiotic dose based on an estimation of the glomerular filtration rate (eGFR) may result in subdosing, which may actually be significantly more problematic for intensive care unit (ICU) patients than not adjusting the dose. The aim of this study was to assess the outcomes of antibiotic dose adjustment in ICU patients with renal impairment. METHODS: A retrospective cohort study was conducted in adult patients admitted to an ICU of a Brazilian hospital from January 2014 to December 2015. The eGFR was determined using Cockcroft-Gault and Modified Diet in Renal Disease equations for each day of hospitalization. Treatment failure was defined based on the clinical, laboratory, and radiological criteria. RESULTS: A total of 126 patients were assessed to meet the inclusion criteria and subsequently enrolled in the study (19.9% of patients admitted to the ICU during the study period). Of the 168 opportunities for dose adjustment, 99 (58.9%) adjustments were made. The mean eGFR in the group with dose adjustment was lower than that in the group without dose adjustment (38.5 vs. 40.7 mL/min/1.73 m2, respectively). The treatment failure rate among patients with dose adjustment and those treated with the usual dose was 59.3 and 38.9%, respectively (p = 0.023), and the mortality rates in the respective groups were 74.1 and 55.5% (p = 0.033). An association between dose adjustment and treatment failure/mortality rates was also observed in the multivariate analysis including the prognostic score. CONCLUSIONS: In ICU patients with renal impairment, adjustments in antibiotic dose based on eGFR, significantly increased the risk of treatment failure and death.

Cost-effectiveness of liposomal amphotericin B in hospitalised patients with mucocutaneous leishmaniasis.

OBJECTIVE: To compare the cost-effectiveness of L-AmB with that of SbV and AmB-D, for the treatment of mucocutaneous leishmaniasis in a hospital in north-east Brazil. METHODS: We developed an economic model based on retrospective data of 73 hospitalised patients in 2006-2012, from hospital and public health system perspectives. RESULTS: In the economic model, 82.2% of patients who started treatment with L-AmB had completed it after 2 months, vs. 22.0% for the SbV and 19.9% for the AmB-D groups. After 12 months of follow-up, these proportions were 100% in the L-AmB, 77.4% in the AmB-D and 72.2% in the SbV group. Markov chain analyses showed that the group that started therapy with SbV had the lowest mean total cost (US$ 3782.38), followed by AmB-D (US$ 5211.27) and L-AmB (US$ 11 337.44). The incremental cost-effectiveness ratio for L-AmB was US$ 18 816.23 against SbV and US$ 24 504.65 against AmB-D. In the sensitivity analysis, the drug acquisition cost of L-AmB significantly influenced the results. CONCLUSIONS: In the treatment of mucocutaneous leishmaniasis, L-AmB is a cost-effective alternative to SbV and AmB-D owing to its higher effectiveness, safety and shorter course.

Goals of Care Ambulatory Resident Education: Training Residents in Advance Care Planning Conversations in the Outpatient Setting.

BACKGROUND: Advance care planning (ACP) discussions often occur in the inpatient setting when patients are too ill to participate in decision making. Although the outpatient setting is the preferred time to begin these discussions, few physicians do so in practice. Many internal medicine (IM) residents report inadequate training as a barrier to having outpatient ACP discussions. OBJECTIVE: To assess whether a novel curriculum entitled Goals of Care Ambulatory Resident Education (GOCARE) improved resident physicians' understanding of and preparedness for conducting ACP discussions in the outpatient setting. DESIGN: The curriculum was delivered over four weekly three-hour small group sessions to IM residents. Each session included didactics, a demonstration of skills, and a simulated patient communication laboratory that emphasized deliberate practice. SETTING/SUBJECTS: IM residents from an urban, academic ambulatory care practice. MEASUREMENTS: Impact of the intervention was evaluated using a retrospective pre-post design. Residents completed surveys immediately after the course and six months later. RESULTS: Forty-two residents participated in the curriculum and 95% completed the postcourse survey. Residents' self-rated level of preparedness increased for ACP discussions overall (4.0 pre vs. 5.2 post on 7-point Likert scale) and for communication steps involved in ACP (p < 0.001). Fifty-nine percent of participants completed the six-month follow-up survey. Residents' self-rated preparedness to engage in outpatient ACP discussions remained high (4.5 pre vs. 5.5 post at six months p < 0.001). Residents also reported increased use of ACP communication skills (p < 0.001) six months later. CONCLUSIONS: The GOCARE curriculum provides an alternative model of communication training that can be integrated into residency training and improve residents' skills in outpatient ACP discussions.

Prophylactic hydration to prevent contrast-induced nephropathy: much ado about nothing?

Clinical guidelines recommend prophylactic hydration to reduce the risk of contrast-induced nephropathy in high-risk patients, including those with chronic kidney disease. A recent single-center randomized trial showed no significant difference in the incidence of contrast-induced nephropathy in ambulatory patients with stage 3 chronic kidney disease who were randomized to no prophylactic hydration versus normal saline hydration. While these results may identify patients who are less likely to benefit from prophylactic hydration, nephrologists and interventionalists should carefully consider the generalizability of these results to individual patients.

Representation and reporting of kidney disease in cerebrovascular disease: A systematic review of randomized controlled trials.

Patients with kidney disease (KD) are at increased risk for cerebrovascular disease (CVD) and CVD patients with KD have worse outcomes. We aimed to determine the representation of KD patients in major randomized controlled trials (RCTs) of CVD interventions. We searched MEDLINE for reports of major CVD trials published through February 9, 2017. We excluded trials that did not report mortality outcomes, enrolled fewer than 100 participants, or were subgroup, follow-up, or post-hoc analyses. Two independent reviewers performed study selection and data extraction. We included 135 RCTs randomizing 194,977 participants. KD patients were excluded in 48 (35.6%) trials, but were less likely to be excluded from trials of class I/II recommended interventions (n = 7; 15.9%; p = 0.001) and more likely to be excluded in trials with registered protocols (45.5% vs. 22.4%; p = 0.007). Exclusion was lower in trials supported by academic or governmental grants compared to industry or combined funding (21.2% vs. 42.0% and 47.8%; p = 0.033 and 0.028, respectively). Among trials excluding KD patients, 24 (50.0%) used serum creatinine, 7 (14.6%) used estimated glomerular filtration rate or creatinine clearance, 7 (14.6%) used renal replacement therapy, and 19 (39.6%) used non-specific kidney-related criteria. Only 4 (3.0%) trials reported baseline renal function. No trials prespecified or reported subgroup analyses by baseline renal function. Although 19 (14.1%) trials reported the incidence of acute kidney injury, no trial examined adverse event rates according to renal function. In summary, more than one third of major CVD trials excluded patients with KD, primarily based on serum creatinine or non-specific criteria, and outcomes were not stratified by renal parameters. Therefore, purposeful efforts to increase inclusion of KD patients in CVD trials and evaluate the impact of renal function on efficacy and safety are needed to improve the quality of evidence for interventions in this vulnerable population.