Carnitine supplements for people with chronic kidney disease requiring dialysis.

BACKGROUND: Carnitine deficiency is common in patients with chronic kidney disease (CKD) who require dialysis. Several clinical studies have suggested that carnitine supplementation is beneficial for dialysis-related symptoms. However, the clinical effectiveness and potential adverse effects of carnitine supplementation in dialysis patients have not been determined. OBJECTIVES: This review aimed to evaluate the effectiveness and safety of carnitine supplementation for the treatment of dialysis-related complications in CKD patients requiring dialysis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 16 August 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the 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) and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth, or other predictable methods) that compared carnitine supplements with placebo or standard care in people with CKD requiring dialysis. DATA COLLECTION AND ANALYSIS: Two authors independently extracted study data and assessed study quality. We used a random-effects model to perform a quantitative synthesis of the data.  We used the I² statistic to measure heterogeneity amongst the studies in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes, mean difference (MD) for continuous outcomes, or standardised mean differences (SMD) if different scales were used, with 95% confidence intervals (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. MAIN RESULTS: We included 52 studies (47 parallel RCTs and five cross-over RCTs) (3398 randomised participants). All studies compared L-carnitine with a placebo, other treatment, or no treatment. Standard care was continued as co-interventions in each group. Most studies were judged to have an unclear or high risk of bias. L-carnitine may have little or no effect on the quality of life (QoL) SF-36 physical component score (PCS) (4 studies, 134 participants: SMD 0.57, 95% CI -0.15 to 1.28; I² = 73%; low certainty of evidence), and the total QoL score (Kidney Disease Quality of Life (KDQOL), VAS (general well-being), or PedsQL) (3 studies, 230 participants: SMD -0.02, 95% CI -0.29 to 0.25; I² = 0%; low certainty of evidence). L-carnitine may improve SF-36 mental component score (MCS) (4 studies, 134 participants: SMD 0.70, 95% CI 0.22 to 1.18; I² = 42%; low certainty of evidence). L-carnitine may have little or no effect on fatigue score (2 studies, 353 participants: SMD 0.01, 95% CI -0.20 to 0.23; I² = 0%; low certainty of evidence), adverse events (12 studies, 1041 participants: RR, 1.14, 95% CI 0.86 to 1.51; I² = 0%; low certainty of evidence), muscle cramps (2 studies, 102 participants: RR, 0.44, 95% CI 0.18 to 1.09; I² = 23%; low certainty of evidence), and intradialytic hypotension (3 studies, 128 participants: RR, 0.76, 95% CI 0.34 to 1.69; I² = 0%; low certainty of evidence). L-carnitine may improve haemoglobin levels (26 studies, 1795 participants: MD 0.46 g/dL, 95% CI 0.18 to 0.74; I² = 86%; low certainty of evidence) and haematocrit values (14 studies, 950 participants: MD 1.78%, 95% CI 0.38 to 3.18; I² = 84%; low certainty of evidence). AUTHORS' CONCLUSIONS: The available evidence does not currently support the use of carnitine supplementation in the treatment of dialysis-related carnitine deficiency. Although carnitine supplementation may slightly improve anaemia-related markers, carnitine supplementation makes little or no difference to adverse events. However, these conclusions are based on limited data and, therefore, should be interpreted with caution.

Primary care physicians' perceptions concerning engagement in cancer survivor care.

Background: Given the growing diversity among cancer survivors and the fact that oncologists typically do not perform long-term care, the expected role of primary care physicians (PCPs) in survivor care is expanding. However, communication and collaboration between oncologists and PCPs are lacking. Therefore, we assessed the perception of cancer survivor care among PCPs. Methods: We sent a questionnaire to 767 Japanese Board-certified PCPs, regardless of facility type (clinics and hospitals), inquiring about PCPs' perceptions of their role in survivor care. Additionally, we included vignette-based scenarios focused on colorectal and prostate cancer survivors to explore factors associated with their clinical decisions. Results: We obtained 91 replies (response rate: 11.9%). A total of 75% of PCPs had encountered at least 1 cancer patient in actual practice. Even for patients actively receiving cancer treatment, >70% of PCPs reported that they were willing to engage in comprehensive survivor care, except for the administration of anticancer drugs. Further, 49% of PCPs considered that both PCPs and oncologists were suited to performing regular screening for cancer recurrence in high-risk patients. Multivariable logistic regression analyses revealed that clinic PCPs were less inclined to conduct screening for recurrence than hospital PCPs in both colorectal (odds ratio, 3.85 [95% confidence interval 1.40-10.6]) and prostate (4.36 [95% confidence interval 1.51-12.6]) cancer scenarios. Conclusions: Our findings suggest that Japanese PCPs are willing to engage in survivor care and encourage closer collaboration between oncologists and PCPs. However, oncologists might need to request cooperation, considering the facility type with which PCPs are affiliated.

Laxative use and mortality in patients on haemodialysis: a prospective cohort study.

BACKGROUND: Patients on haemodialysis (HD) are often constipated. This study aimed to assess the relationship between constipation and mortality in such patients. In this study, constipation was defined as receiving prescription laxatives, based on the investigation results of "a need to take laxatives is the most common conception of constipation" reported by the World Gastroenterology Organization Global Guidelines. METHODS: This cohort study included 12,217 adult patients on HD enrolled in the Japan-Dialysis Outcomes and Practice Patterns study phases 1 to 5 (1998 to 2015). The participants were grouped into two based on whether they were prescribed laxatives during enrolment at baseline. The primary endpoint was all-cause mortality in 3 years, and the secondary endpoint was cause-specific death. Missing values were imputed using multiple imputation methods. All estimations were calculated using a Cox proportional hazards model with an inverse probability of treatment weighting using the propensity score. RESULTS: Laxatives were prescribed in 30.5% of the patients, and there were 1240 all-cause deaths. There was a significant association between laxative prescription and all-cause mortality [adjusted hazard ratio (AHR), 1.12; 95% confidence interval (CI): 1.03 to 1.21]. Because the Kaplan-Meier curves of the two groups crossed over, we examined 8345 patients observed for more than 1.5 years. Laxative prescription was significantly associated with all-cause mortality (AHR, 1.35; 95% CI: 1.17 to 1.55). The AHR of infectious death was 1.62 (95% CI: 1.14 to 2.29), and that of cancerous death was 1.60 (95% CI: 1.08 to 2.36). However, cardiovascular death did not show a significant inter-group difference. CONCLUSIONS: Constipation requiring use of laxatives was associated with an increased risk of death in patients on HD. It is important to prevent patients receiving HD from developing constipation and to reduce the number of patients requiring laxatives.

Intraoperative end-tidal carbon dioxide and postoperative mortality in major abdominal surgery: a historical cohort study.

PURPOSE: There is a paucity of data on the effect of intraoperative end-tidal carbon dioxide (EtCO2) levels on postoperative mortality. The purpose of this study was to investigate the relationship between intraoperative EtCO2 and 90-day mortality in patients undergoing major abdominal surgery under general anesthesia. METHODS: We conducted a historical cohort study of patients undergoing major abdominal surgery under general anesthesia at Kyoto University Hospital. We measured the intraoperative EtCO2, and patients with a mean EtCO2 value < 35 mm Hg were classified as low EtCO2. The time effect was determined based on minutes below an EtCO2 of 35 mm Hg, and cumulative effects were evaluated by measuring the area under the threshold of 35 mm Hg for each patient. RESULTS: Of 4,710 patients, 1,374 (29%) had low EtCO2 and 55 (1.2%) died within 90 days of surgery. Multivariable Cox regression analysis-adjusted for age, American Society of Anesthesiologists Physical Status classification, sex, laparoscopic surgery, emergency surgery, blood loss, mean arterial pressure, duration of surgery, type of surgery, and chronic obstructive pulmonary disease-revealed an association between low EtCO2 and 90-day mortality (adjusted hazard ratio, 2.2; 95% confidence interval [CI], 1.2 to 3.8; P = 0.006). In addition, severity of low EtCO2 was associated with an increased 90-day mortality (area under the threshold; adjusted hazard ratio; 2.9, 95% CI, 1.2 to 7.4; P =0.02); for long-term exposure to an EtCO2 < 35 mm Hg (≥ 226 min), the adjusted hazard ratio for increased 90-day mortality was 2.3 (95% CI, 0.9 to 6.0; P = 0.08). CONCLUSION: A mean intraoperative EtCO2 < 35 mm Hg was associated with increased postoperative 90-day mortality.

RéSUMé: OBJECTIF: Il n'existe que très peu de données s'intéressant à l'effet du niveau peropératoire télé-expiratoire du dioxyde de carbone (EtCO2) sur la mortalité postopératoire. L'objectif de cette étude était d'examiner la relation entre l'EtCO2 peropératoire et la mortalité à 90 jours chez des patients subissant une chirurgie abdominale majeure sous anesthésie générale. MéTHODE: Nous avons réalisé une étude de cohorte historique portant sur des patients subissant une chirurgie abdominale majeure sous anesthésie générale à l'Hôpital universitaire de Kyoto. Nous avons mesuré l'EtCO2 peropératoire, et les patients avec une valeur moyenne d'EtCO2 < 35 mmHg ont été catégorisés comme EtCO2 faible. L'effet temps a été déterminé en fonction de la durée, en minutes, avec une EtCO2 inférieure à 35 mmHg, et les effets cumulatifs ont été évalués en mesurant l'aire sous le seuil de 35 mmHg pour chaque patient. RéSULTATS: Sur 4710 patients, 1374 (29 %) avaient une EtCO2 faible et 55 (1,2 %) sont décédés dans les 90 jours suivant la chirurgie. Une analyse de régression multivariée de Cox, ajustée pour tenir compte des facteurs suivants : âge, statut physique selon l'American Society of Anesthesiologists, sexe, chirurgie par laparoscopie, chirurgie d'urgence, pertes de sang, tension artérielle moyenne, durée de la chirurgie, type de chirurgie et maladie pulmonaire obstructive chronique, a révélé une association entre une EtCO2 faible et la mortalité à 90 jours (rapport de risque ajusté, 2,2; intervalle de confiance [IC] à 95 %, 1,2 à 3,8; P = 0,006). De plus, la sévérité de l'EtCO2 basse était associée à une augmentation de la mortalité à 90 jours (aire sous le seuil; rapport de risque ajusté; 2,9, IC 95 %, 1,2 à 7,4; P =0,02); pour une exposition à long terme à une EtCO2 < 35 mmHg (≥ 226 minutes), le rapport de risque ajusté pour une mortalité accrue à 90 jours était de 2,3 (IC 95 %, 0,9 à 6,0 ; P = 0,08). CONCLUSION: Une EtCO2 peropératoire moyenne < 35 mmHg était associée à une augmentation de la mortalité postopératoire à 90 jours.

Erratum: Interdialytic Weight Gain Effects on Hemoglobin Concentration and Cardiovascular Events.

[This corrects the article DOI: 10.1016/j.ekir.2021.05.015.][This corrects the article DOI: 10.1016/j.ekir.2020.07.027.].

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.

Interdialytic Weight Gain Effects on Hemoglobin Concentration and Cardiovascular Events.

INTRODUCTION: Although predialysis hemoglobin concentration is affected by interdialytic weight gain (IDWG), the interaction between these parameters is not well understood. METHODS: Using data from the Japanese Dialysis Outcomes and Practice Pattern Study phases 1-5, we analyzed patients who underwent maintenance hemodialysis. The exposure variable was hemoglobin concentration, and the effect modifier was IDWG at baseline. These 2 categorical variables were then combined and analyzed. The primary outcome was major adverse cardiovascular events (MACEs). Hazard ratios were estimated using a Cox model for the association between exposure and MACEs after adjusting for potential confounders. We examined additive interactions between hemoglobin concentration and IDWG by calculating the relative excess risk due to interaction, which is defined as a departure from the additivity of effects. RESULTS: A total of 8234 patients were enrolled. During a median follow-up of 2.1 years, 1062 (12.9%) patients developed MACEs. In IDWG categories of <6%, adjusted hazard ratios for MACEs tended to be lower as hemoglobin concentration increased. In IDWG categories of ≥6%, point estimation of MACEs with hemoglobin concentration of ≥11.0 g/dl-<12.0 g/dl was higher than that with hemoglobin concentration of ≥10.0 g/dl-<11.0 g/dl. The relative excess risk due to interaction was 0.22 (95% confidence interval 0.02-0.42) between IDWG category of ≥6% and hemoglobin categories of ≥11.0 g/dl-<12.0 g/dl, indicating a synergistic interaction. CONCLUSIONS: The association between hemoglobin concentration and MACEs differed across IDWG. Consideration should be given to the upper limit of hemoglobin concentration in patients with high IDWG.

Low rather than high mean corpuscular volume is associated with mortality in Japanese patients under hemodialysis.

Recent studies have reported that high mean corpuscular volume (MCV) might be associated with mortality in patients with advanced chronic kidney disease (CKD). However, the question of whether a high MCV confers a risk for mortality in Japanese patients remains unclear. We conducted a longitudinal analysis of a cohort of 8571 patients using data derived from the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS) phases 1 to 5. Associations of all-cause mortality, vascular events, and hospitalization due to infection with baseline MCV were examined via Cox proportional hazard models. Non-linear relationships between MCV and these outcomes were examined using restricted cubic spline analyses. Associations between time-varying MCV and these outcomes were also examined as sensitivity analyses. Cox proportional hazard models showed a significant association of low MCV (< 90 fL), but not for high MCV (102 < fL), with a higher incidence of all-cause mortality and hospitalization due to infection compared with 94 ≤ MCV < 98 fL (reference). Cubic spline analysis indicated a graphically U-shaped association between baseline MCV and all-cause mortality (p for non-linearity p < 0.001). In conclusion, a low rather than high MCV might be associated with increased risk for all-cause mortality and hospitalization due to infection among Japanese patients on hemodialysis.

Association between work schedules and motivation for lifestyle change in workers with overweight or obesity: a cross-sectional study in Japan.

OBJECTIVE: To investigate the association between work schedules and motivation for behavioural change of lifestyle, based on the transtheoretical model (TTM) in workers with overweight or obesity. DESIGN: A cross-sectional observational study. SETTING: A healthcare examination centre in Japan. PARTICIPANTS: Between April 2014 and March 2016, we recruited 9243 participants who underwent healthcare examination and met the inclusion criteria, namely, age 20-65 years, body mass index (BMI) ≥25 kg/m2 and full-time workers. EXPOSURE: Night and shift (night/shift) workers were compared with daytime workers in terms of motivation for behavioural change. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was action and maintenance stages of change (SOC) for lifestyle in TTM. In a subgroup analysis, we investigated interactions between characteristics, including age, sex, BMI, current smoking, alcohol habits, hours of sleep and working hours. RESULTS: Overall, 1390 participants (15.0%) were night/shift workers; night/shift workers were younger (median age (IQR): 46 (40-54) vs 43 (37-52) years) and the proportion of men was lesser (75.4 vs 60.9%) compared with daytime workers. The numbers of daytime and night/shift workers in the action and maintenance SOC were 2113 (26.9%) and 309 (22.2%), respectively. Compared with daytime workers, night/shift workers were less likely to demonstrate action and maintenance SOC (adjusted OR (AOR): 0.85, 95% CI: 0.74 to 0.98). In a subgroup analysis that included only those with long working hours (≥10 hours/day), results revealed a strong inverse association between night/shift work and action and maintenance SOC (AOR: 0.65, 95% CI: 0.48 to 0.86). A significant interaction was observed between long working hours and night/shift work (P for interaction=0.04). CONCLUSIONS: In workers with overweight or obesity, a night/shift work schedule was associated with a lower motivation for behavioural change in lifestyle, and the association was strengthened in those with long working hours.

The Normalized Protein Catabolic Rate and Mortality Risk of Patients on Hemodialysis by Frailty Status: The Japanese Dialysis Outcomes and Practice Pattern Study.

OBJECTIVE: The appropriate protein intake for patients on hemodialysis complicated with frailty remains highly controversial. METHODS: We conducted a prospective cohort study using data from Japanese Dialysis Outcomes and Practice Pattern Study. The patients were separated by their baseline of normalized protein catabolic rate (nPCR) into 3 categories: low (nPCR < 1.0), medium (1.0 ≤ nPCR <1.2), and high (nPCR ≥1.2). The frailty score was calculated based on the 12-item Short Form, and frailty was defined in cases with a total score of ≥2 points. The all-cause mortality was compared between groups using a Cox proportional hazard model. RESULTS: A total of 2,404 patients were included in the longitudinal analysis, 1,096 (45.6%) of whom had frailty. Patients in the low-nPCR group showed a higher prevalence of frailty than those in the other groups. In the Cox proportional hazard model, no significant differences in the all-cause mortality were noted between the low-nPCR and medium-nPCR groups or the high-nPCR and medium-nPCR groups. Furthermore, no significant differences were noted among any groups when subjects were limited to patients with frailty. CONCLUSIONS: Patients with a low nPCR have a higher prevalence of frailty and incidence of mortality than those with a medium nPCR. Patients with a high nPCR did not show a lower survival rate than those with a medium nPCR in this study. To clarify the appropriate protein intake for patients on hemodialysis with frailty, an intervention study or large-scale, long-term cohort study will be needed.

Cumulative network meta-analyses, practice guidelines, and actual prescriptions for postmenopausal osteoporosis: a meta-epidemiological study.

We compared the cumulative network meta-analyses with the recommendations in postmenopausal osteoporosis practice guidelines and actual prescribing practices in the USA. There was no apparent discrepancy between guideline recommendations and drug prescribing rankings, with the exception of vitamin D and calcium, when we used cumulative NMAs as references. PURPOSE: To compare the results of cumulative network meta-analyses (NMAs) with the recommendations in postmenopausal osteoporosis practice guidelines and actual prescribing practices in the USA. METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus were searched to retrieve randomized controlled trials (RCTs) in July 2017. The Agency for Healthcare Research and Quality's National Guideline Clearinghouse and associated society websites were searched to retrieve guidelines in June 2018. We used the Medical Expenditure Panel Survey (MEPS) to analyze prescription data from 1996 to 2015. Two independent investigators selected eligible RCTs. One investigator selected potential eligible guidelines, which were confirmed by another investigator. Two independent investigators extracted data from included RCTs. One investigator extracted recommendations from guidelines, which were confirmed by another investigator. (Registration: UMIN000031894) RESULTS: We analyzed data from 1995, 2000, 2005, 2010, and 2015. We chose hip fracture as the primary outcome of cumulative NMAs. We included 51 trials, 17 guidelines, and 5099 postmenopausal osteoporosis patients from the MEPS. Bisphosphonate, including alendronate, and combination of vitamin D and calcium (vDCa) were consistently recommendable from an efficacy viewpoint in NMAs and recommended in guidelines. Alendronate was the most prescribed drug (more than 30% over the observation period); however, vDCa was seldom prescribed. The maximum proportion was 5.3% from 2011 to 2015. CONCLUSIONS: In postmenopausal osteoporosis, there was no apparent discrepancy between guideline recommendations and drug prescribing rankings, with the exception of vDCa, when we used cumulative NMAs as references.

Low Predialysis Plasma Calculated Osmolality Is Associated with Higher All-Cause Mortality: The Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS).

INTRODUCTION: Patients undergoing hemodialysis (HD) have higher predialysis plasma osmolality. Several studies have suggested lower osmolality to be associated with worse outcomes in patients not undergoing HD. However, no studies have examined the association between osmolality and mortality among patients undergoing HD. OBJECTIVE: We aimed to examine the association between predialysis plasma calculated osmolality and all-cause mortality. METHODS: This was a prospective cohort study of 1,240 patients undergoing HD participating in the Japanese Dialysis Outcomes and Practice Patterns Study phase 5 (2012-2015). The exposure was predialysis plasma osmolality, calculated as 2 × (serum sodium concentration [mmol/L]) + (serum urea nitrogen [mg/dL])/2.8 + (serum glucose [mg/dL])/18. The primary outcome was all-cause mortality. The secondary outcome was the change in systolic blood pressure (SBP) during HD. We used a marginal structural model with stabilized weights to estimate the association between calculated osmolality and all-cause mortality in the presence of time-varying confounders affected by prior exposure. RESULTS: Mean baseline plasma calculated osmolality was 306.8 ± 8.6 mOsm/kg. Low predialysis calculated osmolality was associated with higher mortality (adjusted hazard ratio 1.52, 95% confidence interval [CI]: 1.30-1.78 by each 10 mOsm/L lower osmolality). The association was consistent across clinically relevant subgroups. Predialysis osmolality was significantly associated with intradialytic SBP change (mean difference 0.96 [95% CI: 0.05-1.88] mm Hg per each 10 mOsm/L lower osmolality). CONCLUSIONS: Low predialysis calculated osmolality was an independent risk factor of all-cause mortality.

Intra-Dialytic Hemoglobin Changes and Cardiovascular Events: A Cohort Study on Dialysis Outcomes and Practice Patterns in Japan.

BACKGROUND: Ultrafiltration during hemodialysis (HD) causes hemoconcentration. Little is known about the relationships between intra-dialytic changes in hemoglobin concentration and cardiovascular events. Thus, this study aimed to elucidate the relationships between intra-dialytic changes in hemoglobin concentration and cardiovascular events among HD patients. METHODS: This prospective cohort study was based on the Japanese Dialysis Outcomes and Practice Pattern Study phases 4 and 5. The predictor was the ratio of post-dialysis hemoglobin concentration to pre-dialysis hemoglobin concentration (post-Hb/pre-Hb) at baseline. The primary outcome was major adverse cardiovascular events (MACEs). Hazard ratios (HRs) were estimated using a Cox model for the association between post-Hb/pre-Hb and MACEs, adjusting for potential confounders. RESULTS: A total of 865 patients were enrolled. During a median follow-up of 2.6 years, 145 (16.8%) patients developed MACEs. Patients were divided into 4 categories according to baseline post-Hb/pre-Hb (<1.0, ≥1.0 to <1.1, ≥1.1 to <1.2, and ≥1.2). The multivariable-adjusted HRs for MACEs were 1.69 (95% CI 1.36-2.10), 1.29 (95% CI 1.10-1.51), and 1.31 (95% CI 1.02-1.68) in patients with post-Hb/pre-Hb ratios of <1.0, ≥1.0 to <1.1, and ≥1.2, respectively, compared with the reference post-Hb/pre-Hb ratio of ≥1.1 to <1.2. Cubic spline analyses revealed a U-shaped association between post-Hb/pre-Hb and MACEs. CONCLUSION: High and low intra-dialytic changes in hemoglobin concentration are associated with a high risk of MACEs in patients undergoing HD.

Dialysate temperature reduction for intradialytic hypotension for people with chronic kidney disease requiring haemodialysis.

BACKGROUND: Intradialytic hypotension (IDH) is a common complication of haemodialysis (HD), and a risk factor of cardiovascular morbidity and death. Several clinical studies suggested that reduction of dialysate temperature, such as fixed reduction of dialysate temperature or isothermal dialysate using a biofeedback system, might improve the IDH rate. OBJECTIVES: This review aimed to evaluate the benefits and harms of dialysate temperature reduction for IDH among patients with chronic kidney disease requiring HD, compared with standard dialysate temperature. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised Register up to 14 May 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs), cross-over RCTs, cluster RCTs and quasi-RCTs were included in the review. DATA COLLECTION AND ANALYSIS: Two authors independently extracted information including participants, interventions, outcomes, methods of the study, and risks of bias. We used a random-effects model to perform quantitative synthesis of the evidence. We assessed the risks of bias for each study using the Cochrane 'Risk of bias' tool. We assessed the certainty of evidence using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). MAIN RESULTS: We included 25 studies (712 participants). Three studies were parallel RCTs and the others were cross-over RCTs. Nineteen studies compared fixed reduction of dialysate temperature (below 36°C) and standard dialysate temperature (37°C to 37.5°C). Most studies were of unclear or high risk of bias. Compared with standard dialysate, it is uncertain whether fixed reduction of dialysate temperature improves IDH rate (8 studies, 153 participants: rate ratio 0.52, 95% CI 0.34 to 0.80; very low certainty evidence); however, it might increase the discomfort rate compared with standard dialysate (4 studies, 161 participants: rate ratio 8.31, 95% CI 1.86 to 37.12; very low certainty evidence). There were no reported dropouts due to adverse events. No study reported death, acute coronary syndrome or stroke.Three studies compared isothermal dialysate and thermoneutral dialysate. Isothermal dialysate might improve the IDH rate compared with thermoneutral dialysate (2 studies, 133 participants: rate ratio 0.68, 95% CI 0.60 to 0.76; I2 = 0%; very low certainty evidence). There were no reports of discomfort rate (1 study) or dropouts due to adverse events (2 studies). No study reported death, acute coronary syndrome or stroke. AUTHORS' CONCLUSIONS: Reduction of dialysate temperature may prevent IDH, but the conclusion is uncertain. Larger studies that measure important outcomes for HD patients are required to assess the effect of reduction of dialysate temperature. Six ongoing studies may provide much-needed high quality evidence in the future.

Postdialysis Hypokalemia and All-Cause Mortality in Patients Undergoing Maintenance Hemodialysis.

BACKGROUND AND OBJECTIVES: Almost half of patients on dialysis demonstrate a postdialysis serum potassium ≤3.5 mEq/L. We aimed to examine the relationship between postdialysis potassium levels and all-cause mortality. DESIGN, SETTING, PATIENTS, & MEASUREMENTS: We conducted a cohort study of 3967 participants on maintenance hemodialysis from the Dialysis Outcomes and Practice Patterns Study in Japan (2009-2012 and 2012-2015). Postdialysis serum potassium was measured repeatedly at 4-month intervals and used as a time-varying variable. We estimated the hazard ratio of all-cause mortality rate using Cox hazard regression models, with and without adjusting for time-varying predialysis serum potassium. Models were adjusted for baseline characteristics and time-varying laboratory parameters. We also analyzed associations of combinations of pre- and postdialysis potassium with mortality. RESULTS: The age of participants at baseline was 65±12 years (mean±SD), 2552 (64%) were men, and 96% were treated with a dialysate potassium level of 2.0 to <2.5 mEq/L. The median follow-up period was 2.6 (interquartile range, 1.3-2.8) years. During the follow-up period, 562 (14%) of 3967 participants died, and the overall mortality rate was 6.7 per 100 person-years. Compared with postdialysis potassium of 3.0 to <3.5 mEq/L, the hazard ratios of postdialysis hypokalemia (<3.0 mEq/L) were 1.84 (95% confidence interval, 1.44 to 2.34) in the unadjusted model, 1.44 (95% confidence interval, 1.14 to 1.82) in the model without adjusting for predialysis serum potassium, and 1.10 (95% confidence interval, 0.84 to 1.44) in the model adjusted for predialysis serum potassium. The combination of pre- and postdialysis hypokalemia was associated with the highest mortality risk (hazard ratio, 1.72; 95% confidence interval, 1.35 to 2.19, reference; pre- and postdialysis nonhypokalemia). CONCLUSIONS: Postdialysis hypokalemia was associated with mortality, but this association was not independent of predialysis potassium.

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.

Association between social networks and discussions regarding advance care planning among Japanese older adults.

BACKGROUND: Older adults' discussions with family, or with physicians, or with both, about advance care planning (ACP) are increasingly regarded as important for the management of end-of-life care, and yet the factors that induce older adults to engage in ACP discussions are poorly understood. For example, in older adults, is stronger connectedness with family and friends (stronger "networks") associated with ACP discussions? By facilitating, or by impeding ACP discussions? We sought to evaluate the associations between ACP discussions and social networks in Japanese older adults. METHODS: In July 2016 we conducted a cross-sectional survey on 355 community-dwelling patients aged ≥65 years visiting community hospital clinics in Fukushima, Japan. We used the Lubben Social Network Scale (LSNS-6, the shortest available LSNS scale) to assess social networks and recorded two components of social network structure, marital status (dichotomized as "married" vs. "single / other") and living status ("living with others" vs. "living alone"). One item asked if patients had had ACP discussions. We analyzed the LSNS-6 social network and marital and living status data in relation to the occurrence of ACP discussions using multiple logistic regression models with adjustments for possible confounding factors. RESULTS: Respondents' social network was "limited" in 16% of cases; 61% had had ACP discussions. Respondents with a limited social network had a significantly lower tendency to have had ACP discussions than respondents with an "adequate" social network (adjusted odds ratio [AOR]: 0.35; 95% confidence interval [CI]: 0.18-0.66; P < 0.001). Marital status and living status were not significantly associated with ACP discussion. CONCLUSIONS: Among Japanese older adults, weaker social networks may be associated with a lower tendency to discuss ACP. Our findings may help practitioners to quickly screen populations at risk for inadequate ACP discussion by using the LSNS-6.

Physician characteristics associated with proper assessment of overstated conclusions in research abstracts: A secondary analysis of a randomized controlled trial.

OBJECTIVES: Little is known about the physician characteristics associated with appraisal skills of research evidence, especially the assessment of the validity of study methodology. This study aims to explore physician characteristics associated with proper assessment of overstated conclusions in research abstracts. DESIGN: A secondary analysis of a randomized controlled trial. SETTING AND PARTICIPANTS: We recruited 567 volunteers from the Japan Primary Care Association. METHODS: Participants were randomly assigned to read the abstract of a research paper, with or without an overstatement, and to rate its validity. Our primary outcome was proper assessment of the validity of its conclusions. We investigated the association of physician characteristics and proper assessment using logistic regression models and evaluated the interaction between the associated characteristics and overstatement. RESULTS: We found significant associations between proper assessment and post-graduate year (odds ratio [OR] = 0.67, 95% confidence interval [CI] 0.49 to 0.91, for every 10-year increase) and research experience as a primary investigator (PI; OR = 2.97, 95% CI 1.65 to 5.34). Post-graduate year and PI had significant interaction with overstatement (P = 0.015 and < 0.001, respectively). Among participants who read abstracts without an overstatement, post-graduate year was not associated with proper assessment (OR = 1.04, 95% CI 0.82 to 1.33), and PI experience was associated with lower scores of the validity (OR = 0.58, 95% CI 0.35 to 0.96). CONCLUSION: Physicians who have been in practice longer should be trained in distinguishing overstatements in abstract conclusions. Physicians with research experience might be informed that they tend to rate the validity of research lower regardless of the presence or absence of overstatements. TRIAL REGISTRATION: UMIN000026269.

Association Between the Discrepancy in Self-Reported and Performance-Based Physical Functioning Levels and Risk of Future Falls Among Community-Dwelling Older Adults: The Locomotive Syndrome and Health Outcomes in Aizu Cohort Study (LOHAS).

OBJECTIVES: A discrepancy in self-reported and performance-based physical functioning levels is often observed among older adults. We investigated the association of discrepancy in self-reported and performance-based physical functioning levels with risk of future falls among community-dwelling older adults. DESIGN: Prospective cohort study. SETTING: Two communities in Fukushima Prefecture, Japan. PARTICIPANTS: 1379 older adults who took part in the yearly health checkup in both 2009 and 2010. MEASURES: The performance-based and self-reported physical functioning levels were evaluated by the Timed Up and Go test and the Short-Form 12 Health Survey (Japanese version) physical functioning subscale, respectively. We divided the participants into 4 groups based on the combinations of low or high performance-based and self-reported physical functioning groups, which were classified by age- and sex-specific reference values. The main outcome was the occurrence of any falls within the 1-year follow-up period, assessed using a self-reported questionnaire. RESULTS: A total of 22% of the participants reported the occurrence of a fall during the follow-up period. In multivariable logistic regression analysis, the adjusted odds ratios of the high self-reported and low performance-based, low self-reported and high performance-based, and low self-reported and low performance-based physical functioning groups were 1.10 (95% confidence interval [CI], 0.67-1.82), 1.76 (95% CI, 1.17-2.66), and 1.80 (95% CI, 1.11-2.90), respectively, compared with the high self-reported and high performance-based physical functioning group. CONCLUSIONS: Our findings suggest that the discrepancy as high performance-based but low self-reported physical functioning level is associated with an increased risk of future falls in older adults aged 65-89 years. Clinicians should carefully assess older adults whose subjective perception of their physical functioning capacity is lower than those in similar age and sex groups, even if their actual physical functioning appears to be objectively high.