Sparing confirmatory testing in primary aldosteronism (SCIPA): a multicenter retrospective diagnostic accuracy study.

BACKGROUND: The diagnosis of primary aldosteronism (PA) is comprehensive, which includes case-detection testing, case confirmation followed by subtype classification. In certain instances, such as in the setting of spontaneous hypokalemia, suppressed renin activity (PRA) plus plasma aldosterone concentration (PAC) of > 15 ng/dL, one may not proceed with confirmatory tests. However, the quality of evidence behind this approach is very low. This study sought to evaluate the proposed "simplified confirmatory pathway" that can spare confirmatory testing for primary aldosteronism by evaluating the diagnostic performances of the various pre-specified PAC thresholds in combination with findings of suppressed renin and spontaneous hypokalemia. METHODS: This is a multi-center, retrospective diagnostic accuracy cohort-selected cross-sectional study. A total of 133 participants aged 18 years and above underwent saline infusion test between January 2010 to March 2024. The outcome measures comprise of the diagnostic performances of the different index test combinations (baseline PAC, baseline PRA and presence of spontaneous hypokalemia): sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic accuracy. Data analysis was performed using SPSS 29.0.1.0 & MedCalc 20.218. RESULTS: Of the 133 patients who underwent saline infusion test, 88 (66.17%) were diagnosed with PA. A PAC of > 25 ng/dL plus PRA < 1.0 ng/dL/hr with spontaneous hypokalemia showed the highest specificity at 100% (95% CI 90.51%, 100.00%) and positive predictive value at 100% (85.18 - 100.00%). The minimum acceptable combination criteria were determined to be a PAC of > 20 ng/dL plus PRA < 0.6 ng/dL/hr, and presence of spontaneous hypokalemia. It has high specificity (94.59%; 95% CI 81.81%, 99.34%), positive predictive value (93.55%, 95% CI 78.49%, 98.29%), and moderate positive likelihood ratio (LR+) (6.39, 95% CI 1.61, 25.38) CONCLUSION: A hypertensive patient with spontaneous hypokalemia and screening findings of PAC > 20 ng/dL and suppressed PRA of < 0.6 ng/ml/hr, may be classified as "overt primary aldosteronism confirmed" and may not need to proceed with dynamic confirmatory testing. PROTOCOL REGISTRATION NUMBER: SRCTN34186253.

Efficacy of sodium glucose cotransporter 2 inhibitors on hepatic fibrosis and steatosis in non-alcoholic fatty liver disease: an updated systematic review and meta-analysis.

Non-alcoholic fatty liver disease (NAFLD) is a substantial contributor to liver-related morbidity worldwide, and yet, there are no standard, universal pharmacologic therapies approved for this indication. The aim of this systematic review and meta-analysis is to evaluate the effectiveness of SGLT-2 inhibitors in improving hepatic steatosis and hepatic fibrosis in patients with NAFLD. An extensive electronic database search was done to identify studies published from inception until December 2023, without any language restrictions. All randomized controlled trials (RCT) that evaluated the use of SGLT-2 inhibitors for patients with NAFLD, regardless of diabetes mellitus status, were included. The Cochrane Risk of Bias 2.0 tool was used to assess the risk of bias of each study included. Evidence from all studies were synthesized as mean differences for continuous data, and as risk ratio for dichotomous outcomes. An inverse variance or Mantel-Haenszel test was used in conjunction with a random-effects meta-analysis model, where necessary. 18 eligible RCTs involving 1330 participants were analyzed, all of which had risk of bias ranging from low to some concerns. Significant difference in means was observed for controlled attenuation parameter (6 trials, n = 372; MD: - 10.59 dB/m, 95% CI [- 18.25, - 2.92], p = 0.007, I2 = 0%); L/S ratio (3 trials, n = 163; MD: 0.11, 95% CI [0.01, 0.21], p = 0.04, I2 = 78%); LSM (7 trials, n = 447; MD: - 0.67 kPa, 95% CI [- 1.19, - 0.16], p = 0.010, I2 = 69%); MRI-PDFF (5 trials, n = 330; MD: - 2.61%, 95% CI [- 5.05, - 0.17], p = 0.04, I2 = 78%), and FIB-4 index (10 trials, n = 648; MD: - 0.12, 95% CI [- 0.21, - 0.04], p = 0.005, I2 = 16%) after SGLT-2 inhibitor treatment as compared to controls. In conclusion, the use of SGLT-2 inhibitors may lead to slight improvement of hepatic steatosis and/or fibrosis as compared to controls in patients with NAFLD and Type 2 diabetes mellitus based on imaging and histopathology biomarkers with low to moderate certainty of evidence.

Symptomatic treatment (using NSAIDS) versus antibiotics in uncomplicated lower urinary tract infection: a meta-analysis and systematic review of randomized controlled trials.

BACKGROUND: Current guidelines recommend empiric antibiotics as first-line treatment for uncomplicated UTI. Despite proven benefits in treatment, antibiotic resistance rates remain on the rise. This meta-analysis aims to determine whether non-steroidal anti-inflammatory drugs can serve as an effective and safe option in the treatment of uncomplicated lower UTI among non-pregnant women compared to antibiotics. METHODS: A systematic literature search in PUBMED, CENTRAL, and ACP databases from inception to April 2021 was conducted to identify randomized controlled trials that compare the use of non-steroidal anti-inflammatory drugs versus antibiotics in non-pregnant women ≥18 years old with uncomplicated lower urinary tract infection. Primary outcomes were symptom resolution of UTI by Day 3 or 4 of intervention, and upper UTI complications. Secondary outcomes include persistence of positive urine culture despite treatment and need for another rescue antibiotic. Random and fixed-effects model for dichotomous data using Mantel-Haenszel and Peto odds method were reported at 95% CI followed by sensitivity analysis for substantial heterogeneity. RESULTS: Four RCTs involving 1165 patients were analyzed. The probability of having a symptom resolution by Day 3 or 4 with NSAID use is only less than three-fourths of that with antibiotic treatment (RR: 0.69, 95% CIs [0.55, 0.86], p = 0.0008, I2 = 73%, moderate certainty of evidence). The odds of developing upper UTI complications with use of NSAIDs are 6.49 to 1 for antibiotics (Peto OR: 6.49, 95% CIs [3.02, 13.92], p < 0.00001, I2 = 0%, moderate certainty of evidence). Secondary analysis showed that the NSAID group is 2.77x more likely to have persistence of a positive microbiologic urine culture than the antibiotic group (RR: 2.77, 95% CIs [1.95, 3.94], p < 0.00001, I2 = 36%, moderate certainty of evidence). Treatment with NSAIDs are three times more likely to use a secondary or rescue antibiotic due to persistent or worsening symptoms as compared to antibiotics (RR: 3.16, 95% CIs [2.24, 4.44], p < 0.00001, I2 = 47%, low certainty of evidence). CONCLUSION: Antibiotic treatment was more effective than use of non-steroidal anti-inflammatory drugs for acute uncomplicated lower urinary tract infection with an overall moderate certainty of evidence.