Systematic differences in effect estimates between observational studies and randomized control trials in meta-analyses in nephrology.

The limited availability of randomized controlled trials (RCTs) in nephrology undermines causal inferences in meta-analyses. Systematic reviews of observational studies have grown more common under such circumstances. We conducted systematic reviews of all comparative observational studies in nephrology from 2006 to 2016 to assess the trends in the past decade. We then focused on the meta-analyses combining observational studies and RCTs to evaluate the systematic differences in effect estimates between study designs using two statistical methods: by estimating the ratio of odds ratios (ROR) of the pooled OR obtained from observational studies versus those from RCTs and by examining the discrepancies in their statistical significance. The number of systematic reviews of observational studies in nephrology had grown by 11.7-fold in the past decade. Among 56 records combining observational studies and RCTs, ROR suggested that the estimates between study designs agreed well (ROR 1.05, 95% confidence interval 0.90-1.23). However, almost half of the reviews led to discrepant interpretations in terms of statistical significance. In conclusion, the findings based on ROR might encourage researchers to justify the inclusion of observational studies in meta-analyses. However, caution is needed, as the interpretations based on statistical significance were less concordant than those based on ROR.

Level of Low Back Pain-Related Disability Is Associated with Risk of Subsequent Falls in an Older Population: Locomotive Syndrome and Health Outcomes in Aizu Cohort Study (LOHAS).

OBJECTIVES: To examine the longitudinal association between baseline disability due to low back pain (LBP) and future risk of falls, particularly significant falls requiring treatment, in a community-dwelling older population. METHODS: This was a prospective population-based cohort study using data from the Locomotive Syndrome and Health Outcomes in Aizu Cohort Study (LOHAS; 2008-2010). A total of 2,738 residents aged ≥60 years were enrolled. LBP was assessed using the Roland-Morris Disability Questionnaire (RMDQ), and the level of LBP-related disability was divided into three categories (none, low, and medium to high). Incidence of falls over the following year was determined using a self-reported questionnaire after the one-year follow-up period. The risk ratio (RR) for LBP-related disability associated with any fall and any fall requiring treatment was estimated using log binomial regression models. RESULTS: Data were analyzed for 1,358 subjects. The prevalence of LBP at baseline was 16.4%, whereas 122 (8.9%) participants reported a low level of LBP-related disability and 101 (7.4%) reported medium to high levels of LBP-related disability. Incidence of any fall and falls requiring treatment was reported by 22.1% and 4.6% of participants, respectively. Subjects with medium to high levels of disability were more likely to experience subsequent falls (adjusted RR = 1.53, 95% confidence interval [CI] = 1.21-1.95) and falls requiring treatment (adjusted RR = 2.55, 95% CI = 1.41-4.60) than those with no LBP-related disability. CONCLUSIONS: Level of LBP-related disability was associated with an increased risk of serious falls in a general population of community-living older adults. These findings can alert health care providers involved in fall prevention efforts to the important issue of activity-related disability due to LBP.

Direct oral anticoagulants versus warfarin for preventing stroke and systemic embolic events among atrial fibrillation patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for atrial fibrillation (AF), which is more prevalent among CKD patients than the general population. AF causes stroke or systemic embolism, leading to increased mortality. The conventional antithrombotic prophylaxis agent warfarin is often prescribed for the prevention of stroke, but risk of bleeding necessitates regular therapeutic monitoring. Recently developed direct oral anticoagulants (DOAC) are expected to be useful as alternatives to warfarin. OBJECTIVES: To assess the efficacy and safety of DOAC including apixaban, dabigatran, edoxaban, and rivaroxaban versus warfarin among AF patients with CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register (up to 1 August 2017) through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) which directly compared the efficacy and safety of direct oral anticoagulants (direct thrombin inhibitors or factor Xa inhibitors) with dose-adjusted warfarin for preventing stroke and systemic embolic events in non-valvular AF patients with CKD, defined as creatinine clearance (CrCl) or eGFR between 15 and 60 mL/min (CKD stage G3 and G4). DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed quality, and extracted data. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for the association between anticoagulant therapy and all strokes and systemic embolic events as the primary efficacy outcome and major bleeding events as the primary safety outcome. Confidence in the evidence was assessing using GRADE. MAIN RESULTS: Our review included 12,545 AF participants with CKD from five studies. All participants were randomised to either DOAC (apixaban, dabigatran, edoxaban, and rivaroxaban) or dose-adjusted warfarin. Four studies used a central, interactive, automated response system for allocation concealment while the other did not specify concealment methods. Four studies were blinded while the other was partially open-label. However, given that all studies involved blinded evaluation of outcome events, we considered the risk of bias to be low. We were unable to create funnel plots due to the small number of studies, thwarting assessment of publication bias. Study duration ranged from 1.8 to 2.8 years. The large majority of participants included in this study were CKD stage G3 (12,155), and a small number were stage G4 (390). Of 12,545 participants from five studies, a total of 321 cases (2.56%) of the primary efficacy outcome occurred per year. Further, of 12,521 participants from five studies, a total of 617 cases (4.93%) of the primary safety outcome occurred per year. DOAC appeared to probably reduce the incidence of stroke and systemic embolism events (5 studies, 12,545 participants: RR 0.81, 95% CI 0.65 to 1.00; moderate certainty evidence) and to slightly reduce the incidence of major bleeding events (5 studies, 12,521 participants: RR 0.79, 95% CI 0.59 to 1.04; low certainty evidence) in comparison with warfarin. AUTHORS' CONCLUSIONS: Our findings indicate that DOAC are as likely as warfarin to prevent all strokes and systemic embolic events without increasing risk of major bleeding events among AF patients with kidney impairment. These findings should encourage physicians to prescribe DOAC in AF patients with CKD without fear of bleeding. The major limitation is that the results of this study chiefly reflect CKD stage G3. Application of the results to CKD stage G4 patients requires additional investigation. Furthermore, we could not assess CKD stage G5 patients. Future reviews should assess participants at more advanced CKD stages. Additionally, we could not conduct detailed analyses of subgroups and sensitivity analyses due to lack of data.

Clinical characteristics of adrenal crisis in adult population with and without predisposing chronic adrenal insufficiency: a retrospective cohort study.

BACKGROUND: Adrenal crisis (AC) occurs in various clinical conditions but previous epidemiological studies in AC are limited to chronic adrenal insufficiency (AI) and sepsis. The aim of this study was to investigate characteristics of AC patients, including predisposing diseases and to describe candidate risk factors for AC such as comorbidities and glucocorticoid (GC) therapy. METHODS: We conducted a retrospective cohort study using a claims database on 7.4 million patients from 145 acute care hospitals between January 1, 2003 and April 30, 2014. We identified AC patients who met the following criteria: 1) disease name with ICD-10 corresponded with AI; 2) therapeutic GC administration (hydrocortisone equivalent dose ≥100 mg/day); 3) admission; and 4) age ≥18 years. RESULTS: We identified 504 patients with AC (median age, 71 years; interquartile range, 59 to 80; 50.6% male). As predisposing conditions, primary AI and central AI accounted for 23 (4.6%) and 136 patients (27.0%), respectively. In the remaining AC patients (68.5%), comorbidities such as cancer, autoimmune diseases, and renal failure were frequent. The most frequent indication for hospitalization was AC (16.3%), followed by pituitary disease (14.7%), cancer (14.7%), AI-related clinical symptoms (11.5%), and infection (11.1%). Admission under oral GC treatment was reported in 104 patients (20.6%). Twenty-six patients were admitted within 14 days after GC cessation (5.2%). CONCLUSIONS: These findings present an overview of patients with AC in general practice settings, clarifying that predisposing factors for AC were complicated and that patients other than those with chronic AI were older and had more comorbid conditions than those with primary and central AI.

Effects of 50 mg vildagliptin twice daily vs. 50 mg sitagliptin once daily on blood glucose fluctuations evaluated by long-term self-monitoring of blood glucose.

To date, several clinical trials have compared differences in glucose fluctuation observed with dipeptidyl peptidase-4 inhibitor treatment in patients with type 2 diabetes mellitus. However, most patients were assessed for limited periods or during hospitalization. The aim of the present study was to evaluate the effects of switching from sitagliptin to vildagliptin, or vice versa, on 12-week glucose fluctuations using self-monitoring of blood glucose in the standard care setting. We conducted a multicenter, prospective, open-label controlled trial in Japanese patients with type 2 diabetes. Thirty-two patients were treated with vildagliptin (50 mg) twice daily or sitagliptin (50 mg) once daily and were allocated to one of two groups: vildagliptin treatment for 12 weeks before switching to sitagliptin for 12 weeks, or vice versa. Daily profiles of blood glucose were assessed several times during each treatment period, and the mean amplitude of glycemic excursions and M-value were calculated. Metabolic biomarkers such as hemoglobin A1c (HbA1c), glycated albumin, and 1,5-anhydroglucitol were also assessed. With vildagliptin treatment, mean amplitude of glycemic excursions was significantly improved compared with sitagliptin treatment (57.9 ± 22.2 vs. 68.9 ± 33.0 mg/dL; p=0.0045). M-value (p=0.019) and mean blood glucose (p=0.0021) were also lower with vildagliptin, as were HbA1c, glycated albumin, and 1,5-anhydroglucitol. There were no significant differences in other metabolic parameters evaluated. Reduction of daily blood glucose profile fluctuations by vildagliptin was superior to that of sitagliptin in Japanese patients with type 2 diabetes.

Ovarian morphology and prevalence of polycystic ovary syndrome in Japanese women with type 1 diabetes mellitus.

AIMS/INTRODUCTION: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder including polycystic ovary morphology (PCOM), ovulatory dysfunction and hyperandrogenism. PCOS is frequently associated with type 2 diabetes mellitus; however, it is unknown whether PCOM and PCOS are prevalent in Japanese patients with type 1 diabetes mellitus. The purpose of our study was to determine the frequency of PCOM and PCOS in women with type 1 diabetes mellitus. MATERIALS AND METHODS: We evaluated clinical, hormonal and ovarian ultrasound data from 21 type 1 diabetes mellitus patients whose average glycated hemoglobin levels were 7.9 ± 1.5%. RESULTS: Ultrasound identified PCOM in 11 patients (52.4%) and these patients also had higher levels of the androgen dehydroepiandrosterone sulfate (DHEA-S) than those without PCOM (P < 0.05). Of the patients with PCOM, five presented menstrual irregularities (45.5%) and three met the Japanese criteria for PCOS (27.2%); whereas all patients without PCOM had a normal menstrual cycle (P < 0.05). CONCLUSIONS: Japanese premenopausal women with type 1 diabetes mellitus had a high frequency of PCOM as well as PCOS. This is the first research of this area carried out in an Asian population.

[A case of symptomatic pituitary metastases from renal cell carcinoma].

Symptomatic metastases to the pituitary from renal cell carcinoma are rare. We present a case of pituitary metastases from renal cell carcinoma showing panhypopituitarism. A 50-year-old man who had renal cell carcinoma with distant metastases in skin, bone and lymph nodes was referred to our department. Clinically he showed severe cognitive function disorder. Endocrinological evaluation revealed central adrenal and gonadal insufficiencies. Brain magnetic resonance imaging demonstrated a hemorrhagic mass in left frontal lobe and a sellar mass with supra sellar cistern extension. After hormonal replacement and surgical removal of the frontal tumor, he immediately recovered from his cognitive function disorder. Subsequently, whole brain radiotherapy for metastatic pituitary tumor was performed. At present, he is being treated with molecular targeting drugs for other distant metastases and he presents no neurological deficit. Palliative therapy for CNS metastases from renal cell carcinoma may result in better quality of life for patients with advanced stage of renal cell carcinoma.