Association of Thyroid Hormone Therapy with Mortality in Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis.

CONTEXT: Benefits of thyroid hormone therapy on mortality in adults with subclinical hypothyroidism remain undetermined. OBJECTIVE: To summarize the impact of thyroid hormone therapy on mortality in adults with subclinical hypothyroidism. DATA SOURCES: PubMed, Embase, Scopus, Web of Science, and Clinicaltrials.gov from inception until April 25, 2020. STUDY SELECTION: Studies comparing the effect of thyroid hormone therapy with that of placebo or no therapy in adults with subclinical hypothyroidism on all-cause and/or cardiovascular mortality. DATA EXTRACTION: Two reviewers independently extracted data and performed quality assessments. Random-effects models for meta-analyses were used. DATA SYNTHESIS: Five observational studies and 2 randomized controlled trials with 21 055 adults were included. Overall, thyroid hormone therapy was not significantly associated with all-cause (pooled relative risk [RR] = 0.95, 95% confidence interval [CI]: 0.75-1.22, P = .704) or cardiovascular (pooled RR = 0.99, 95% CI: 0.82-1.20, P = .946) mortality. Subgroup analyses revealed that in younger adults (aged <65-70 years), thyroid hormone therapy was significantly associated with a lower all-cause (pooled RR = 0.50, 95% CI: 0.29-0.85, P = .011) and cardiovascular (pooled RR = 0.54, 95% CI: 0.37-0.80, P = .002) mortality. However, no significant association between thyroid hormone therapy and mortality was observed in older adults (aged ≥65-70 years). CONCLUSIONS: Use of thyroid hormone therapy does not provide protective effects on mortality in older adults with subclinical hypothyroidism. However, thyroid hormone therapy for subclinical hypothyroidism may show benefits on morality in adults aged <65 to 70 years.

Fracture Risks in Patients Treated With Different Oral Anticoagulants: A Systematic Review and Meta-Analysis.

Background Evidence on the differences in fracture risk associated with non-vitamin K antagonist oral anticoagulants (NOAC) and warfarin is inconsistent and inconclusive. We conducted a systematic review and meta-analysis to assess the fracture risk associated with NOACs and warfarin. Methods and Results We searched PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov from inception until May 19, 2020. We included studies presenting measurements (regardless of primary/secondary/tertiary/safety outcomes) for any fracture in both NOAC and warfarin users. Two or more reviewers independently screened relevant articles, extracted data, and performed quality assessments. Data were retrieved to synthesize the pooled relative risk (RR) of fractures associated with NOACs versus warfarin. Random-effects models were used for data synthesis. We included 29 studies (5 cohort studies and 24 randomized controlled trials) with 388 209 patients. Patients treated with NOACs had lower risks of fracture than those treated with warfarin (pooled RR, 0.84; 95% CI, 0.77-0.91; P<0.001) with low heterogeneity (I2=38.9%). NOACs were also associated with significantly lower risks of hip fracture than warfarin (pooled RR, 0.89; 95% CI, 0.81-0.98; P=0.023). A nonsignificant trend of lower vertebral fracture risk in NOAC users was also observed (pooled RR, 0.74; 95% CI, 0.54-1.01; P=0.061). Subgroup analyses for individual NOACs demonstrated that dabigatran, rivaroxaban, and apixaban were significantly associated with lower fracture risks. Furthermore, the data synthesis results from randomized controlled trials and real-world cohort studies were quite consistent, indicating the robustness of our findings. Conclusions Compared with warfarin, NOACs are associated with lower risks of bone fracture.

Effects of Proton Pump Inhibitors on Glycemic Control and Incident Diabetes: A Systematic Review and Meta-analysis.

CONTEXT: Whether proton pump inhibitors (PPI) can improve glycemic control among individuals with diabetes or decrease the risk of incident diabetes in the general population is unclear. OBJECTIVE: To evaluate the impact of PPI therapy on glycemic control among individuals with diabetes and the risk of diabetes among those without diabetes. RESULTS: PubMed, Embase, Scopus, and ClinicalTrials.gov were searched from inception to November 21, 2020. We included studies comparing glycosylated hemoglobin (HbA1c) or fasting blood glucose (FBG) among individuals with diabetes treated with and without PPI therapy as an add-on to standard therapy. Studies evaluating the risk of incident diabetes among individuals taking PPI were assessed. We performed dual independent review, data extraction, and quality assessment. Weighted mean differences between groups or relative risks were imputed using random-effects models. RESULTS: Seven studies (n = 342) for glycemic control and 5 studies (n = 244 439) for risk of incident diabetes were included. Compared with standard therapy, add-on PPI was associated with a significant decrease in HbA1c (WMD, -0.36 %; 95% CI, -0.68 to -0.05; P = 0.025) and FBG (WMD, -10.0 mg/dL; 95% CI, -19.4 to -0.6; P = 0.037). PPI use did not reduce the risk of incident diabetes (pooled RR, 1.10; 95% CI, 0.89 to 1.34; P = 0.385). CONCLUSION: Add-on PPI improved glycemic indices among individuals with diabetes but did not alter the risk of incident diabetes. The effects of PPI on glycemic control should be considered when prescribing antacids to patients with diabetes.

Association of Hypothyroidism and Mortality in the Elderly Population: A Systematic Review and Meta-Analysis.

CONTEXT: The evidence of whether hypothyroidism increases mortality in the elderly population is currently inconsistent and conflicting. OBJECTIVE: The objective of this meta-analysis is to determine the impact of hypothyroidism on mortality in the elderly population. DATA SOURCES: PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases were searched from inception until May 10, 2019. STUDY SELECTION: Studies evaluating the association between hypothyroidism and all-cause and/or cardiovascular mortality in the elderly population (ages ≥ 60 years) were eligible. DATA EXTRACTION: Two reviewers independently extracted data and assessed the quality of the studies. Relative risk (RR) was retrieved for synthesis. A random-effects model for meta-analyses was used. DATA SYNTHESIS: A total of 27 cohort studies with 1 114 638 participants met the inclusion criteria. Overall, patients with hypothyroidism experienced a higher risk of all-cause mortality than those with euthyroidism (pooled RR = 1.26, 95% CI: 1.15-1.37); meanwhile, no significant difference in cardiovascular mortality was found between patients with hypothyroidism and those with euthyroidism (pooled RR = 1.10, 95% CI: 0.84-1.43). Subgroup analyses revealed that overt hypothyroidism (pooled RR = 1.10, 95% CI: 1.01-1.20) rather than subclinical hypothyroidism (pooled RR = 1.14, 95% CI: 0.92-1.41) was associated with increased all-cause mortality. The heterogeneity primarily originated from different study designs (prospective and retrospective) and geographic locations (Europe, North America, Asia, and Oceania). CONCLUSIONS: Based on the current evidence, hypothyroidism is significantly associated with increased all-cause mortality instead of cardiovascular mortality among the elderly. We observed considerable heterogeneity, so caution is needed when interpreting the results. Further prospective, large-scale, high-quality studies are warranted to confirm these findings.

Roles and Role Ambiguity in Patient- and Caregiver-Performed Outpatient Parenteral Antimicrobial Therapy.

BACKGROUND: Complicated medical therapies traditionally performed in acute care hospitals are increasingly moving to the home, requiring patients and informal caregivers to perform complicated medical tasks. For example, in outpatient parenteral antimicrobial therapy (OPAT), patients and caregivers perform antimicrobial infusions and venous catheter care. The objective of this study was to characterize patient understanding of patient, caregiver, and health care worker roles in OPAT and barriers to fulfilling these roles, with the goal of understanding how to best support patients and their caregivers. METHODS: A qualitative study using 40 semistructured telephone interviews and 20 contextual inquiries of patients and caregivers performing OPAT tasks was performed. Eligible participants were discharged from two academic medical centers on OPAT. Interview transcripts and notes from contextual inquiry were coded based on a human factors engineering model. RESULTS: Four main roles are described: communicator, advocate, learner-trainer, and lay health care worker doing "high-skilled tasks." Patients and caregivers experienced role ambiguity about OPAT task performance at the time of hospital discharge. Patients noted that their health care workers experienced role ambiguity as well, particularly regarding who was managing their care. Patients and caregivers used role transitions to achieve workload management, in which patients and caregivers transitioned OPAT tasks or non-OPAT tasks from one person to another. CONCLUSION: Clear delineation of roles in complicated home-based medical therapies and training of all who may perform these tasks could improve the safety and quality of home-based care.