Distinct phenotypes of hospitalized patients with hyperkalemia by machine learning consensus clustering and associated mortality risks.

BACKGROUND: Hospitalized patients with hyperkalemia are heterogeneous, and cluster approaches may identify specific homogenous groups. This study aimed to cluster patients with hyperkalemia on admission using unsupervised machine learning (ML) consensus clustering approach, and to compare characteristics and outcomes among these distinct clusters. METHODS: Consensus cluster analysis was performed in 5133 hospitalized adult patients with admission hyperkalemia, based on available clinical and laboratory data. The standardized mean difference was used to identify each cluster's key clinical features. The association of hyperkalemia clusters with hospital and 1-year mortality was assessed using logistic and Cox proportional hazard regression. RESULTS: Three distinct clusters of hyperkalemia patients were identified using consensus cluster analysis: 1661 (32%) in cluster 1, 2455 (48%) in cluster 2 and 1017 (20%) in cluster 3. Cluster 1 was mainly characterized by older age, higher serum chloride and acute kidney injury (AKI), but lower estimated glomerular filtration rate (eGFR), serum bicarbonate and hemoglobin. Cluster 2 was mainly characterized by higher eGFR, serum bicarbonate and hemoglobin, but lower comorbidity burden, serum potassium and AKI. Cluster 3 was mainly characterized by higher comorbidity burden, particularly diabetes and end-stage kidney disease, AKI, serum potassium, anion gap, but lower eGFR, serum sodium, chloride and bicarbonate. Hospital and 1-year mortality risk was significantly different among the three identified clusters, with highest mortality in cluster 3, followed by cluster 1 and then cluster 2. CONCLUSION: In a heterogeneous cohort of hyperkalemia patients, three distinct clusters were identified using unsupervised ML. These three clusters had different clinical characteristics and outcomes.

Gastrointestinal bleeding among hospitalizations for salicylate poisoning in the United States.

BACKGROUND: This study aimed to determine the incidence, as well as evaluate risk factors, and impact of gastrointestinal bleeding on outcomes and resource use in patients admitted for salicylate poisoning. METHODS: We used the National Inpatient Sample to construct a cohort of patients hospitalized primarily for salicylate poisoning from 2003 to 2014. We compared clinical characteristics, in-hospital treatments, outcomes and resource use between salicylate poisoning patients with and without gastrointestinal bleeding. RESULTS: Of 13 805 hospital admissions for salicylate poisoning, gastrointestinal bleeding occurred in 482 (3.5%) admissions. The risk factors for gastrointestinal bleeding included older age, history of atrial fibrillation and cirrhosis. After adjusting for difference in baseline characteristics, patients with gastrointestinal bleeding required more gastric lavage, gastrointestinal endoscopy, invasive mechanical ventilation and red blood cell transfusion. Gastrointestinal bleeding was significantly associated with increased risk of anemia, circulatory, liver and hematological failure but was not significantly associated with increased in-hospital mortality. The length of hospital stay and hospitalization cost was significantly higher in patients with gastrointestinal bleeding. CONCLUSION: Gastrointestinal bleeding occurred in about 4% of patients admitted for salicylate poisoning. Gastrointestinal bleeding was associated with higher morbidity and resource use but not mortality.

Incidence and mortality of acute kidney injury in patients undergoing hematopoietic stem cell transplantation: a systematic review and meta-analysis.

BACKGROUND: While acute kidney injury (AKI) is commonly reported following hematopoietic stem cell transplant (HCT), the incidence and impact of AKI on mortality among patients undergoing HCT are not well described. We conducted this systematic review to assess the incidence and impact of AKI on mortality risk among patients undergoing HCT. METHODS: Ovid MEDLINE, EMBASE and the Cochrane Databases were searched from database inceptions through August 2019 to identify studies assessing the incidence of AKI and mortality risk among adult patients who developed AKI following HCT. Random-effects and generic inverse variance method of DerSimonian-Laird were used to combine the effect estimates obtained from individual studies. RESULTS: We included 36 cohort studies with a total of 5144 patients undergoing HCT. Overall, the pooled estimated incidence of AKI and severe AKI (AKI Stage III) were 55.1% (95% confidence interval (CI) 46.6-63.3%) and 8.3% (95% CI 6.0-11.4%), respectively. The pooled estimated incidence of AKI using contemporary AKI definitions (RIFLE, AKIN and KDIGO criteria) was 49.8% (95% CI 41.6-58.1%). There was no significant correlation between study year and the incidence of AKI (P = 0.12) or severe AKI (P = 0.97). The pooled odds ratios of 3-month mortality and 3-year mortality among patients undergoing HCT with AKI were 3.05 (95% CI 2.07-4.49) and 2.23 (95% CI 1.06-4.73), respectively. CONCLUSION: The incidence of AKI among patients who undergo HCT remains high, and it has not changed over the years despite advances in medicine. AKI after HCT is associated with increased short- and long-term mortality.

Nonsteroidal anti-inflammatory drugs and incidence of atrial fibrillation: a meta-analysis.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for many inflammatory disorders and pain-related illnesses. Despite their widespread use, the association between NSAIDs and the incidence of atrial fibrillation (AF) remains unclear. The aim of this systematic review and meta-analysis is to investigate this association. METHODS: A systematic review was conducted in MEDLINE, EMBASE and Cochrane databases from inception through August 2019 to identify studies that evaluated the risk of AF among patients using NSAIDs. Pooled risk ratios (RRs) and 95% CI were calculated using a random-effect, generic inverse variance method. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42019141609). RESULTS: Eight observational studies (four case-control studies and four cohort studies) with a total of 14 806 420 patients were enrolled. When compared with nonNSAIDs users, the pooled RR of AF in patients with NSAIDs use was 1.29 (95% CI 1.19-1.39). Meta-analyses based on the type of study were additionally performed. Subgroup analysis by study design revealed a significant association between the use of NSAIDs and AF for both case-control studies (pooled RR 1.37; 95% CI, 1.15-1.63) and cohort studies (pooled RR 1.22; 95% CI, 1.14-1.31). Sub-analyses based on specific NSAIDs showed pooled RRs of AF in patients using ibuprofen of 1.30 (95% CI 1.22-1.39), naproxen of 1.44 (95% CI 1.18-1.76) and diclofenac of 1.37 (95% CI 1.10-1.71), respectively. Funnel plot and Egger's regression asymmetry tests were performed and showed no publication bias. CONCLUSION: NSAID use is associated with incident AF. Our study also demonstrated a consistent result among different NSAIDs.

Impacts of admission serum albumin levels on short-term and long-term mortality in hospitalized patients.

AIM: The aim of this study is to assess the association between admission serum albumin and short- and long-term mortality in all hospitalized patients. DESIGN: A single-center cohort study. METHODS: A retrospective cohort of all adult hospitalized patients at a tertiary referral hospital between January 2009 and December 2013 were analysed. Admission serum albumin was stratified into six groups: ≤2.4, 2.5-2.9, 3.0-3.4, 3.5-3.9, 4.0-4.4 and ≥4.5 g/dl. The outcomes of interest were in-hospital mortality, length of hospital stay and 1-year mortality. Serum albumin of 4-4.4 g/dl was selected as a reference group for outcome comparison. RESULTS: A total of 14 075 patients were studied. Admission serum albumin of ≥4.5 g/dl had the lowest in-hospital and 1-year mortality with progressively increased in-hospital mortality observed with decreased admission serum albumin. In adjusted analysis, compared with serum albumin of 4.0-4.4 g/dl, serum albumin of ≤2.4, 2.5-2.9, 3.0-3.4 and 3.5-3.9 were significantly associated with increased in-hospital and 1-year mortality. In contrast, serum albumin of ≥4.5 g/dl was significantly associated with lower 1-year mortality but not in-hospital mortality. Admission serum albumin <4.0 g/dl was significantly associated with a prolonged hospital stay, while admission serum albumin of ≥4.5 g/dl was significantly associated with shorter hospital stay, compared with serum albumin of 4.0-4.4 g/dl. CONCLUSION: Low albumin level at admission was progressively associated with increased short- and long-term mortality in all hospitalized patients even when albumin level was considered in normal range.

Effects of aspirin and non-steroidal anti-inflammatory drugs on the risk of cholangiocarcinoma: a meta-analysis.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) can suppress the proliferation of cholangiocarcinoma (CCA) cells in vitro through inhibition of cyclooxygenase-2. However, the effects of aspirin and NSAIDs on the risk of CCA remain unclear. We performed this meta-analysis to assess the risk of biliary tract cancers in patients who take aspirin and/or NSAIDs. METHODS: A systematic review was conducted utilizing MEDLINE, EMBASE, Cochrane databases from inception through October 2017 to identify studies that assessed the association of aspirin and/or NSAIDs use with risk of biliary tract cancers including CCA, gallbladder cancer and ampulla of Vater cancer. Effect estimates from the studies were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Five observational studies with a total of 9 200 653 patients were enrolled. The pooled OR of CCA in patients with aspirin use was 0.56 (95% CI, 0.32-0.96). Egger's regression asymmetry test was performed and showed no publication bias for the association between aspirin use and CCA with P = 0.42. There was no significant association between NSAIDs use and CCA, with a pooled OR of 0.79 (95% CI, 0.28-2.21). One study showed a significant association between aspirin use and reduced risk of gallbladder cancer with OR of 0.37 (0.17-0.80). However, there was no significant association between aspirin and ampulla of Vater cancer with OR of 0.22 (0.03-1.65). CONCLUSIONS: Our study demonstrates a significant association between aspirin use and a 0.56-fold decreased risk of CCA. However, there is no association between the use of NSAIDs and CCA.

Peripheral arterial disease and risk of hip fracture: A systematic review and meta-analysis of cohort studies.

Background: Previous studies have suggested an increased risk of hip fracture among patients with peripheral arterial disease (PAD), however, the results have been inconsistent. This meta-analysis was conducted with the aim to summarize all available evidence to better characterize the risk of incident hip fracture among these patients. Materials and Methods: A comprehensive literature review was conducted using the MEDLINE and EMBASE databases through October 2017 to identify all cohort and case-control studies that compared the risk of subsequent hip fracture between patients with PAD and individuals without PAD. Effect estimates of the included studies were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. Results: The systematic review process yielded six eligible cohort studies comprising 15,895 patients with PAD. There was a significant association between incident hip fracture and PAD with the pooled relative risk (RR) of 1.64 (95% CI, 1.17-2.29; I2, 80%), comparing patients with PAD and individuals without PAD. Subgroup analysis by study design revealed significant results for both prospective studies (pooled RR 1.60; 95% CI, 1.12-2.28; I2, 0%) and retrospective studies (pooled RR 1.72; 95% CI, 1.07-2.77; I2, 92%). The funnel plot is relatively asymmetric suggesting publication bias. Conclusion: This study found a significant association between PAD and hip fracture with the pooled RR of 1.64 (95% CI, 1.17-2.29) on comparing patients with PAD and individuals without PAD. Major limitations include high between-study heterogeneity, possibility of publication bias, and lack of data on the characteristics and type of hip fracture which may limit the clinical significance of the observations.

Hypocalcemia and bone mineral density changes following denosumab treatment in end-stage renal disease patients: a meta-analysis of observational studies.

The incidence of hypocalcemia and bone mineral density (BMD) changes in end-stage renal disease (ESRD) patients on denosumab remains unclear. We performed this meta-analysis to assess the incidence of denosumab-associated hypocalcemia and effects of denosumab on BMD in ESRD patients. A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through November 2017 to identify studies evaluating incidence of denosumab-associated hypocalcemia and changes in serum calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and BMD from baseline to post-treatment course of denosumab in ESRD patients. Study results were pooled and analyzed using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017081074). Six observational studies with a total of 84 ESRD patients were enrolled. The pooled estimated incidence of hypocalcemia during denosumab treatment was 42% (95% CI 29-55%, I2 = 0%). Hypocalcemia occurred approximately 7 to 20 days after the first dose and reached nadir of low calcium levels in the first 2 weeks up to 2 months. However, there were no significant changes in serum calcium or phosphate from baseline to post-treatment course (≥ 3 months after treatment) with mean differences [MDs] of 0.20 mg/dL (95% CI, - 0.30 to 0.69 mg/dL) and - 0.10 mg/dL (95% CI, - 0.70 to 0.49 mg/dL). There were significant reductions in ALP and PTH levels with standardized mean differences (SMDs) of - 0.65 (95% CI - 1.13 to - 0.16) and - 1.89 (95% CI - 3.44 to - 0.34), respectively. There were significant increases in T-scores with MDs of 0.39 (95% CI 0.10 to 0.69) and 0.79 (95% CI 0.60 to 0.98) for lumbar spine and femoral neck, respectively. Our study demonstrates the estimated incidence of denosumab-associated hypocalcemia in dialysis patients of 42%. From baseline to post-treatment course, although there are no differences in serum calcium and phosphate, our findings suggest significant reductions in ALP and PTH and a significant increase in BMD. Currently, denosumab should not be considered as the treatment of choice in ESRD patients until more safety and efficacy data are available.

Osteoporosis and bone mineral density in patients with Wilson's disease: a systematic review and meta-analysis.

This systematic review aims to assess the occurrence and risks of osteopenia and osteoporosis in patientswith Wilson's disease (WD). A literature search was conducted utilizing EMBASE and MEDLINE frominception through April 2017. Studies assessing the occurrence or risk of osteopenia and/or osteoporosis inWD patients were included. Effect estimates from the individual study were extracted and combined usingrandom-effect, generic inverse variance method of DerSimonian and Laird. Of 754 studies, four studies with283 WD patients met the eligibility criteria and were included in the data analysis. The pooled prevalencerates of osteopenia and osteoporosis in WD patients were 36.5% (95% confidence interval [CI]: 14.8%-65.7%) and 27.7% (95%CI: 8.6%-60.9%), respectively. When meta-analysis was limited only to adults, the estimated prevalence rates of osteopenia, osteoporosis, and vertebral fracture were 50.0% (95%CI: 42.0%-58.0%), 17.6% (95%CI: 6.7%-38.6%) and 8.01% (95%CI: 4.05%-15.2%), respectively. Meta-regressionshowed significant impacts of age (negative correlation; P=0.002) and male status (positive correlation;P < 0.001) on the prevalence of osteoporosis. The data on risks of osteopenia and osteoporosis in WDpatients were limited. We suggests that there are potential associations of WD with osteopenia and/orosteoporosis. Also, young age and male status are correlated with the higher prevalence of osteoporosis inWD patients.

Smoking and risk of colonic diverticulosis: A meta-analysis.

BACKGROUND/OBJECTIVES: The possible relationship between smoking and risk of colonic diverticulosis has been suggested by recent epidemiological studies, although the results were inconsistent. This meta-analysis was conducted to summarize all available data. METHODS: A comprehensive literature review was conducted using the MEDLINE and EMBASE databases through May 2017 to identify all studies that compared the risk of colonic diverticulosis among current and former smokers versus nonsmokers. Effect estimates from each study were extracted and combined together using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Of 465 potentially eligible articles, three prospective cohort studies with 130,520 participants met the eligibility criteria and were included in the meta-analysis. The risk of colonic diverticulosis in current smokers was significantly higher than nonsmokers with the pooled risks ratio of 1.46 (95% confidence interval [CI], 1.13-1.89). However, the risk of colonic diverticulosis in former smokers was not significantly higher than nonsmokers with the pooled risk ratio of 1.13 (95% CI, 0.88-1.44). CONCLUSIONS: A significantly increased risk of colonic diverticulosis among current smokers is demonstrated in this study.

Insomnia and risk of nonalcoholic fatty liver disease: A systematic review and meta-analysis.

AIM: This sudy aims to investigate the association between insomnia or excessive daytime sleepiness (EDS) and risk of nonalcoholic fatty liver disease (NAFLD). METHODS: We searched published studies indexed in MEDLINE and EMBASE database from inception to December 2015. Studies that reported odds ratios (ORs), risk ratios, hazard ratios or standardized incidence ratio with 95% confidence intervals (CI) comparing the risk of NAFLD among participants who had insomnia or EDS versus those without insomnia or EDS were included. Pooled ORs and 95% CI were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. Cochran's Q test and I2 statistic were used to determine the between-study heterogeneity. RESULTS: Our search strategy yielded 2117 potentially relevant articles (781 articles from MEDLINE and 1336 articles from EMBASE). After comprehensive review, seven studies (three cross-sectional studies and four case-control studies) were found to be eligible and were included in the meta-analysis. The risk of NAFLD in participants who had insomnia was significantly higher with the pooled OR of 1.13 (95% CI, 1.00-1.27). The statistical heterogeneity was moderate with an I2 of 62%. Elevated risk of NAFLD was also observed among participants with EDS even though the 95% CI was wider and did not reach statistical significance (pooled OR 2.21; 95% CI, 0.84-5.82). The statistical heterogeneity was moderate with an I2 of 62%. CONCLUSIONS: Our study demonstrated an increased risk of NAFLD among participants who had insomnia or EDS. Whether this association is causal needs further investigations.

Impact of admission serum potassium on mortality in patients with chronic kidney disease and cardiovascular disease.

BACKGROUND: Little is known about the effect of admission potassium (K) on risk of in-hospital mortality in chronic kidney disease (CKD) and cardiovascular disease (CVD) patients. AIM: The aim of this study was to assess the relationship between admission serum K and in-hospital mortality in all hospitalized patients stratified by CKD and/or CVD status. DESIGN AND METHODS: All adult hospitalized patients who had admission serum K between years 2011 and 2013 were enrolled. Admission serum K was categorized into seven groups (<3.0, 3.0-3.5, 3.5-4.0, 4.0-4.5, 4.5-5.0, 5.0-5.5 and ≥5.5 mEq/L). The odds ratio (OR) of in-hospital mortality by admission serum K, using K 4.0-4.5 mEq/L as the reference group, was obtained by logistic regression analysis. RESULTS: 73,983 patients were studied. The lowest incidence of in-hospital mortality was associated with serum K within 4.0-4.5 mEq/L. A U-shaped curve emerged demonstrating higher in-hospital mortality associated with both serum K < 4.0 and >4.5 mEq/L. After adjusting for potential confounders, both serum K < 4.0 mEq/L and >5.0 mEq/L were associated with increased in-hospital mortality with ORs of 3.26 (95% CI 2.03-4.98), 2.40 (95% CI 1.89-3.04), 1.38 (95%CI 1.15-1.66), 1.89 (95% CI 1.49-2.38) and 3.62 (95%CI 2.73-4.76) when serum K were within <3.0, 3.0-3.5, 3.5-4.0, 5.0-5.5, and ≥5.5 mEq/L, respectively. In CVD patients, the highest in-hospital mortality was associated with serum K < 3.0 mEq/L (OR 1.70, 95%CI 1.31-2.18). In CKD patients, the highest in-hospital mortality was associated with serum K ≥ 5.5 mEq/L (OR 3.26, 95%CI 2.14-4.90). CONCLUSION: Admission serum K < 4.0 mEq/L and >5.0 mEq/L were associated with increased in-hospital mortality. The mortality risk among patients with various admission potassium levels was affected by CKD and/or CVD status.

Sugar and artificially sweetened beverages linked to obesity: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Artificial sweeteners are used widely to replace caloric sugar as one of the strategies to lessen caloric intake. However, the association between the risk of obesity and artificially sweetened soda consumption is controversial. The objective of this meta-analysis aimed to assess the association between consumption of sugar and artificially sweetened soda and obesity. METHODS: A literature search was performed using MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception through May 2015. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of obesity in patients consuming either sugar or artificially sweetened soda vs. those who did not consume soda were included. Pooled risk ratios (RRs) and 95% CI were calculated using a random-effect, generic inverse variance method. RESULTS: Eleven studies were included in our analysis to assess the association between consumption of sugar-sweetened soda and obesity. The pooled RR of obesity in patients consuming sugar-sweetened soda was 1.18 (95% CI, 1.10-1.27). Three studies were included to assess the association between consumption of artificially sweetened soda and obesity. The pooled RR of obesity in patients consuming artificially sweetened soda was 1.59 (95% CI, 1.22-2.08). CONCLUSIONS: Our study demonstrated a significant association between sugar and artificially sweetened soda consumption and obesity. This finding raises awareness and question of negative clinical impact on both sugar and artificially sweetened soda and the risk of obesity.

Associations of sugar- and artificially sweetened soda with nonalcoholic fatty liver disease: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the major concern of public health worldwide. The risk of NAFLD in subjects who regularly drink soda is controversial. The aim of this study was to assess the association between consumption of sugar-sweetened soda and NAFLD. METHODS: A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through June 2015. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of NAFLD in patients consuming a significant amount of either sugar or artificially sweetened soda vs. those who did not consume soda were included. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Seven observational studies were included in our analysis to assess the association between consumption of sugar-sweetened soda and NAFLD. The pooled RR of NAFLD in patients consuming sugar-sweetened soda was 1.53 (95% CI: 1.34-1.75, I(2) = 0). When meta-analysis was limited only to studies with adjusted analysis, the pooled RR of NAFLD was 1.55 (95% CI: 1.36-1.78, I(2) = 0). The data on association between consumption of artificially sweetened soda and NAFLD were limited; one observational study reported no significant increased risk of NAFLD in artificially sweetened soda consumption. CONCLUSIONS: Our study demonstrates statistically significant association between sugar-sweetened soda consumption and NAFLD. This finding may impact clinical management and primary prevention of NAFLD.