Japanese guidelines for the treatment of idiopathic pulmonary fibrosis 2023:Revised edition.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a poor prognosis and an unknown cause that generally progresses to pulmonary fibrosis and leads to irreversible tissue alteration. The "Guidelines for the treatment of idiopathic pulmonary fibrosis 2017," specializing in the treatment of IPF for the first time in Japan and presenting evidence-based standard treatment methods suited to the state of affairs in Japan, was published in 2017, in line with the 2014 version of "Formulation procedure for Minds Clinical Practice Guidelines." Because new evidence had accumulated, we formulated the "Guidelines for the treatment of Idiopathic Pulmonary Fibrosis 2023 (revised 2nd edition)." While keeping the revision consistent with the ATS/ERS/JRS/ALAT IPF treatment guidelines, new clinical questions (CQs) on pulmonary hypertension were added to the chronic stage, in addition to acute exacerbation and comorbid lung cancer, which greatly affect the prognosis but are not described in the ATS/ERS/JRS/ALAT IPF guidelines. Regarding the advanced stages, we additionally created expert consensus-based advice for palliative care and lung transplantation. The number of CQs increased from 17 in the first edition to 24. It is important that these guidelines be used not only by respiratory specialists but also by general practitioners, patients, and their families; therefore, we plan to revise them appropriately in line with ever-advancing medical progress.

Impact of fibrosis on liver-related event incidence in nonalcoholic fatty liver disease: A multicenter observational study.

AIM: There are few reports on the prognosis of liver-related events in Japanese patients with nonalcoholic fatty liver disease (NAFLD). We undertook an observational study to compare the prognosis between fibrotic and nonfibrotic groups in Japanese NAFLD patients. METHODS: Prognosis in 393 NAFLD patients who underwent liver biopsy between April 2013 and April 2015 at multiple centers were investigated. The time to onset of liver-related events, cardiovascular events, development of extrahepatic cancers, and death were compared between the pathologically fibrotic nonalcoholic steatohepatitis (NASH) group and nonalcoholic fatty liver (NAFL) + nonfibrotic NASH group. A similar analysis was carried out based on the fibrotic classification diagnosed using four noninvasive fibrosis prediction models. RESULTS: The mean age and body mass index at the time of liver biopsy was 55.7 years old and 28.04 kg/m2 , respectively The cumulative incidence of liver-related events at 1080 days after liver biopsy was 5.79% in the pathologically fibrotic NASH group and 0% in the NAFL + nonfibrotic NASH group, with a significant difference (p = 0.0334). The cumulative incidence of liver-related events was significantly higher in the positive group for the prediction model than in the negative group in all four models (all p values were <0.0001). There was no significant difference between the pathologically fibrotic NASH group and NAFL + nonfibrotic NASH group in terms of cumulative incidence of cardiovascular events, development of extrahepatic cancers, and death. CONCLUSIONS: The incidence of liver-related events was significantly higher in the fibrotic NASH group than that of the NAFL + nonfibrotic NASH group in Japanese NAFLD patients.

Comparison of Minimally Invasive Surgery with Open Surgery for Remnant Gastric Cancer: A Multi-institutional Cohort Study.

BACKGROUND: Despite growing evidence of the effectiveness of minimally invasive surgery (MIS) for primary gastric cancer, MIS for remnant gastric cancer (RGC) remains controversial due to the rarity of the disease. This study aimed to evaluate the surgical and oncological outcomes of MIS for radical resection of RGC. PATIENTS AND METHODS: Patients with RGC who underwent surgery between 2005 and 2020 at 17 institutions were included, and a propensity score matching analysis was performed to compare the short- and long-term outcomes of MIS with open surgery. RESULTS: A total of 327 patients were included in this study and 186 patients were analyzed after matching. The risk ratios for overall and severe complications were 0.76 [95% confidence interval (CI): 0.45, 1.27] and 0.65 (95% CI: 0.32, 1.29), respectively. The MIS group had significantly less blood loss [mean difference (MD), -409 mL; 95% CI: -538, -281] and a shorter hospital stay (MD, -6.5 days; 95% CI: -13.1, 0.1) than the open surgery group. The median follow-up duration of this cohort was 4.6 years, and the 3-year overall survival were 77.9% and 76.2% in the MIS and open surgery groups, respectively [hazard ratio (HR), 0.78; 95% CI: 0.45, 1.36]. The 3-year relapse-free survival were 71.9% and 62.2% in the MIS and open surgery groups, respectively (HR, 0.71; 95% CI: 0.44, 1.16). CONCLUSIONS: MIS for RGC showed favorable short- and long-term outcomes compared to open surgery. MIS is a promising option for radical surgery for RGC.

Recent Declining Trend of Incidence Rate of Subarachnoid Hemorrhage in Shimane, Japan: The Japan Incidence of Subarachnoid Hemorrhage (JIS) Study.

The "Izumo Study" revealed the incidence rate of subarachnoid hemorrhage (SAH) in Izumo City, Shimane Prefecture, Japan, from 1980 to 1998. However, no study has been published regarding the incidence of SAH in Shimane Prefecture after 1998. Most studies reporting the incidence of SAH in Japan have been conducted before 2000, although a few have been reported after 2000. This study aimed to assess the estimated age-adjusted incidence rate (AAIR) of SAH in Shimane Prefecture after 1998, following the Izumo Study. A retrospective study was conducted to identify the estimated AAIR of SAH in Shimane Prefecture, using the age-adjusted SAH mortality rate for this population from 1999 to 2017 and assuming that the case-fatality rate of SAH decreased by 0.7% annually from 45% in 1999 to 32.4% in 2017. We used linear regression analysis for trend to the estimated AAIR of SAH. Sensitivity analyses were also conducted by various case-fatality rates of SAH using assuming case-fatality rate based on previous reports. The estimated AAIR of SAH in Shimane Prefecture declined from 33.6 (95% confidence interval [CI]: 29.7-37.9) per 100,000 person-years in 1999, by 26.5%, to 24.7 (95% CI: 21.4-28.5) in 2017 (p < 0.01, r = 0.58). Declining trend of incidence rate of SAH in Shimane Prefecture from 1999 to 2017 was confirmed in this study.

Diagnostic advantage of thin slice 2D MRI and multiplanar reconstruction of the knee joint using deep learning based denoising approach.

The purpose of this study is to evaluate whether thin-slice high-resolution 2D fat-suppressed proton density-weighted image of the knee joint using denoising approach with deep learning-based reconstruction (dDLR) with MPR is more useful than 3D FS-PD multi planar voxel image. Twelve patients who underwent MRI of the knee at 3T and 13 knees were enrolled. Denoising effect was quantitatively evaluated by comparing the coefficient of variation (CV) before and after dDLR. For the qualitative assessment, two radiologists evaluated image quality, artifacts, anatomical structures, and abnormal findings using a 5-point Likert scale between 2D and 3D. All of them were statistically analyzed. Gwet's agreement coefficients were also calculated. For the scores of abnormal findings, we calculated the percentages of the cases with agreement with high confidence. The CV after dDLR was significantly lower than the one before dDLR (p < 0.05). As for image quality, artifacts and anatomical structure, no significant differences were found except for flow artifact (p < 0.05). The agreement was significantly higher in 2D than in 3D in abnormal findings (p < 0.05). In abnormal findings, the percentage with high confidence was higher in 2D than in 3D (p < 0.05). By applying dDLR to 2D, almost equivalent image quality to 3D could be obtained. Furthermore, abnormal findings could be depicted with greater confidence and consistency, indicating that 2D with dDLR can be a promising imaging method for the knee joint disease evaluation.

Prevalence and prognosis of chronic fibrosing interstitial lung diseases with a progressive phenotype.

BACKGROUND AND OBJECTIVE: The development of clinically progressive fibrosis complicates a wide array of interstitial lung diseases (ILDs). However, there are limited data regarding its prevalence and prognosis. METHODS: We analysed consecutive patients seen for initial evaluation of a fibrosing form of ILD (FILD). Patients were evaluated for evidence of progressive fibrosis over the first 24 months of follow-up. We defined a progressive phenotype as the presence of at least one of the following: a relative decline in forced vital capacity (FVC) of ≥10%; a relative decline in FVC of ≥5%-<10% with a relative decline in diffusing capacity of the lung for carbon monoxide of ≥15%, increased fibrosis on HRCT or progressive symptoms. RESULTS: Eight hundred and forty-four patients (397 with idiopathic pulmonary fibrosis [IPF] and 447 non-IPF FILD) made up the final analysis cohort. Three hundred and fifty-five patients (42.1%) met the progressive phenotype criteria (59.4% of IPF patients and 26.6% of non-IPF FILD patients, p <0.01). In both IPF and non-IPF FILD, transplantation-free survival differed between patients with a progressive phenotype and those without (p <0.01). Multivariable analysis showed that a progressive phenotype was an independent predictor of transplantation-free survival (hazard ratio [HR]: 3.36, 95% CI: 2.68-4.23, p <0.01). Transplantation-free survival did not differ between non-IPF FILD with a progressive phenotype and IPF (HR: 1.12, 95% CI: 0.85-1.48, p = 0.42). CONCLUSION: Over one-fourth of non-IPF FILD patients develop a progressive phenotype compared to approximately 60% of IPF patients. The survival of non-IPF FILD patients with a progressive phenotype is similar to IPF.

Prevalence of type 2 diabetes by age, sex and geographical area among two million public assistance recipients in Japan: a cross-sectional study using a nationally representative claims database.

BACKGROUND: Recognising the importance of the social determinants of health, the Japanese government introduced a health management support programme targeted at type 2 diabetes (T2D) for public assistance recipients (PAR) in 2018. However, evidence of the T2D prevalence among PAR is lacking. We aimed to estimate T2D prevalence by age and sex among PAR, compared with the prevalence among health insurance enrollees (HIE). Additionally, regional differences in T2D prevalence among PAR were examined. METHODS: This was a cross-sectional study using 1-month health insurance claims of both PAR and HIE. The Fact-finding Survey data on Medical Assistance and the National Database of Health Insurance Claims data were used. T2D prevalence among PAR and HIE were assessed by age and sex, respectively. Moreover, to examine regional differences in T2D prevalence of inpatients and outpatients among PAR, T2D crude prevalence and age-standardised prevalence were calculated by prefecture. Multilevel logistic regression analysis was also conducted at the city level. RESULTS: T2D crude prevalence was 7.7% in PAR (inpatients and outpatients). Among outpatients, the prevalence was 7.5% in PAR and 4.1% in HIE, respectively. The mean crude prevalence and age-standardised prevalence of T2D (inpatients and outpatients) among 47 prefectures were 7.8% and 3.9%, respectively. In the city-level analysis, the OR for the prevalence of T2D by region ranged from 0.31 to 1.51. CONCLUSION: The prevalence of T2D among PAR was higher than HIE and there were regional differences in the prevalence of PAR. Measures to prevent the progression of diabetes among PAR by region are needed.

Association of prenatal maternal blood lead levels with birth outcomes in the Japan Environment and Children's Study (JECS): a nationwide birth cohort study.

BACKGROUND: Despite dramatic declines in prenatal maternal blood lead levels (BLLs) in most developed countries, little is known about the effects of extremely low-level (<1.0 µg/dL) lead exposure on fetal growth. METHODS: We measured maternal BLL during the second or third trimester of pregnancy and assessed birth outcomes, including birthweight, preterm birth (<37 gestational weeks) risk, small for gestational age births (SGA; birthweight <10th percentile) and low birthweight (LBW; <2500 g). The association between birthweight and maternal BLL was estimated using linear and quadratic spline models. Multivariable logistic models were used to examine the risk of binary responses. RESULTS: From 103 099 pregnant women, 20 000 blood samples were randomly selected for analysis. The maternal BLL range was 0.16-7.4 µg/dL, and the median was 0.63 µg/dL. After adjusting for covariates, the linear model showed that each 0.1 µg/dL increase in maternal BLL was associated with a 5.4 g decrease in mean birthweight [95% confidence interval (CI), 3.4 to 7.5 g]. The risk of SGA [adjusted odds ratio (aOR), 1.03; 95% CI, 1.02 to 1.05) and LBW (aOR, 1.03; 95% CI, 1.02 to 1.05) increased, whereas the risk of preterm delivery did not (aOR, 0.99; 95% CI, 0.97 to 1.02). CONCLUSIONS: Even at a maternal BLL below 1.0 µg/dL, prenatal lead exposure was associated with decreased birthweight and increased risk of SGA and LBW, but not preterm delivery. The adverse effect estimates of prenatal lead exposure on birth outcomes were quantitatively small and clinically limited at this low level.

A register-based SAH study in Japan: high incidence rate and recent decline trend based on lifestyle.

OBJECTIVE: Japan has been reported to have the highest (and increasing) incidence of subarachnoid hemorrhage (SAH) in the world. However, there has never been a report on the nationwide incidence rate and recent trends for SAH in Japan. In this register-based study, the authors aimed to clarify the estimated nationwide SAH incidence rate and the recent trend in SAH incidence in Japan and the reasons for any changes in this trend. METHODS: The authors compiled data from the Japanese Ministry of Health, Labour and Welfare and from the records of the Japan Neurosurgical Society. They reviewed the age-standardized nationwide SAH mortality rate, the estimated age-standardized SAH incidence rate according to the age-standardized SAH mortality rate, and the estimated crude SAH incidence rate, including the 95% confidence intervals, from 2003 to 2015. The trends in the number of treatments for unruptured and ruptured cerebral aneurysms, as well as the prevalence of hypertension, current smoking status, and use of cholesterol-lowering drugs, were assessed. The estimated treatment rate for unruptured cerebral aneurysms (UCAs) was also calculated along with the 95% confidence interval. RESULTS: The estimated age-standardized nationwide SAH incidence rate significantly declined from 31.34 cases (95% CI 31.32-31.34) to 27.63 (95% CI 27.59-27.63; decrease by 11.8%) per 100,000 person-years. This decline was based on the 2010 population as the reference from 2003 through 2015 and a case-fatality rate of SAH that was assumed to decrease by 1% annually from 44% in 2003 to 32% in 2015. According to sensitivity analysis, the change rate of the estimated age-standardized SAH incidence rate ranged from -56.69% to 23.27%, with a mean of -30.91% (SD 20.52%), and there were decline trends in 92% of all trends. The estimated nationwide crude SAH incidence rate also showed a significant decline from 23.79 (95% CI 23.78-23.79) to 20.25 (95% CI 20.24-20.25; decrease by 14.9%) per 100,000 person-years. The trend in treatment numbers for UCAs increased significantly (p < 0.0001) from 2003 through 2015; however, the estimated treatment rate for UCAs was only 0.19 (95% CI 0.19-0.20) to 0.51 (95% CI 0.50-0.51) among all UCA patients. The prevalence of hypertension (males, p = 0.0003; females, p < 0.0001) and current smoking status (males, p < 0.0001; females, p = 0.0002) declined significantly from 2003 through 2015, while the use of cholesterol-lowering drugs increased significantly (males, p < 0.0001; females, p = 0.0005) during the same period. CONCLUSIONS: The estimated nationwide SAH incidence rate in Japan was higher than rates in other countries, although it has declined recently. An improving lifestyle may have contributed to the declining rate of SAH incidence in Japan.

Updates to and quality of clinical practice guidelines for high-priority diseases in Japan.

PURPOSE: To examine the update status of clinical practice guidelines (CPGs) for 24 main diseases in Japan, and to clarify the quality of and issues pertaining to the most recent versions of CPGs for each disease. DATA SOURCES: CPGs were searched in two Japanese guideline databases. STUDY SELECTION: All relevant Japanese CPGs published between January 1999 and July 2016 were selected. DATA EXTRACTION: The developer and issue date were extracted for all target CPGs. The most recent CPGs were assessed using the Appraisal of Guidelines for Research and Evaluation-II (AGREE II) instrument. RESULTS OF DATA SYNTHESIS: Among 106 target CPGs, 24 most recent CPGs were subjected to assessment using the AGREE II instrument. CPGs for 11 diseases (46%) had a mean time interval for update of ≥5 years. Among the 24 CPGs subjected to AGREE II assessment, median domain scores were 74% for "Domain 1: Scope and Purpose," 43% for "Domain 2: Stakeholder Involvement," 46% for "Domain 3: Rigor of Development," 69% for "Domain 4: Clarity of Presentation," 24% for "Domain 5: Applicability" and 27% for "Domain 6: Editorial Independence." CONCLUSIONS: The systematic assessment of CPGs for 24 major diseases in Japan revealed a trend for a delay in timing of update for many CPGs. Moreover, the 24 most recent CPGs had low domain scores for domains 2, 3, 5 and 6. In the future, concrete measures will need to be considered in order to improve the quality of CPGs.

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.

Public subsidies and the recommendation of child vaccines among primary care physicians: a nationwide cross-sectional study in Japan.

OBJECTIVE: Although public subsidies and physician recommendations for vaccination play key roles in increasing childhood vaccination coverage, the association between them remains uncertain. This study aimed to identify the association between awareness of public subsidies and recommendations for Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (pneumococcal conjugate vaccine (PCV)) and human papillomavirus (HPV) vaccinations among primary care physicians in Japan. DESIGN: This is a cross-sectional study. SETTING: In 2012, a questionnaire was distributed among 3000 randomly selected physicians who were members of the Japan Primary Care Association. PARTICIPANTS: From the questionnaire, participants were limited to physicians who administered childhood vaccinations. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary measures were participants' awareness of public subsidies and their recommendation levels for Hib, PCV and HPV vaccines. Multiple logistic regression analysis was performed to investigate the association between awareness and recommendation, with adjustment for possible confounders. RESULTS: The response rate was 25.8% (743/2880). Of 743 physician respondents, 434 were included as analysis subjects. The proportions of those who recommended vaccinations were 57.1% for Hib, 54.1% for PCV and 58.1% for HPV. For each vaccine, multivariable analyses showed physicians who were aware of the subsidy were more likely to recommend vaccination than those who were not aware: the adjusted ORs were 4.21 (95% CI 2.47 to 7.15) for Hib, 4.96 (95% CI 2.89 to 8.53) for PCV and 4.17 (95% CI 2.00 to 8.70) for HPV. CONCLUSIONS: Primary care physicians' awareness of public subsidies was found to be associated with their recommendations for the Hib, PCV and HPV vaccines. Provision of information about public subsidies to these physicians may increase their likelihood to recommend vaccination.

Japanese guideline for the treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology which accounts for a large proportion of cases of idiopathic interstitial pneumonia. It has a very poor prognosis with a 5-year survival rate of 30% or below, and so far there has been no guideline in Japan offering an established effective therapy based on evidence. In addition to the establishment of basic therapies, there is also an urgent need to establish therapies to deal with complications, as death occurs in many cases due to acute exacerbation or comorbid lung cancer. It was therefore decided to formulate a guideline in order to promote evidence-based clinical practice, to further improve the quality of medical treatment in the clinical setting, and to allow the benefits to be enjoyed by the public.

Accuracy of non-invasive scoring systems for diagnosing non-alcoholic steatohepatitis-related fibrosis: Multicenter validation study.

AIM: Hepatic fibrosis is the most important factor for estimating the prognosis of patients with non-alcoholic fatty liver disease (NAFLD). A novel non-invasive scoring system, the FM-fibro index, showed high accuracy in a pilot study. The purpose of this study was to validate the efficacy of the FM-fibro index in a multicenter cohort. METHODS: Among 18 institutions, we analyzed 400 Japanese patients with biopsy-proven NAFLD. We evaluated the accuracies of the FM-fibro index, CA-fibro index, and European Liver Fibrosis (ELF) panel by area under the receiver operator characteristics curves (AUROC). The FM-fibro index includes three formulas for type IV collagen 7S, hyaluronic acid, and vascular cell adhesion molecule-1. RESULTS: Among 400 patients, 205 were women, and the median age was 56 years. The histological distribution of Matteoni types 1, 2, 3, and 4 was 11, 40, 15, and 334, and the distribution of hepatic fibrosis stages 0 to 4 was 67, 183, 55, 63, and 32, respectively. The AUROCs of the FM-fibro index, CA-fibro index, and ELF panel for non-alcoholic steatohepatitis (NASH)-related fibrosis were 0.7178/0.7095/0.7065, 0.7093, and 0.7245, respectively. The sensitivity and specificity of the FM-fibro index for predicting NASH-related fibrosis was 0.5359/0.5210/0.4641 and 0.8333/0.8182/0.8788, respectively. The accuracy of the FM-fibro index was not significantly different from that of the CA-fibro index or the ELF panel. CONCLUSIONS: The FM-fibro index can predict NASH-related fibrosis with sufficient accuracy compared with previous scoring systems. Further analyses that verify the accuracy of the FM-fibro index to distinguish significant or advanced fibrosis in patients with NAFLD are awaited. (UMIN-CTR: UMIN000018158).

Characteristics of the Japanese Diet Described in Epidemiologic Publications: A Qualitative Systematic Review.

CONTEXT: International interest in the Japanese diet has grown in recent years. OBJECTIVE: The aim of this systematic review was to evaluate and organize the Japanese diet and dietary characteristics from an epidemiological perspective, mainly focusing on the nutritional and dietary elements. DATA SOURCES: PubMed, Web of Science, Japan Medical Abstracts Society, JDream III, and CiNii databases were searched. STUDY SELECTION: The eligibility criteria included research with an epidemiological study design that was either cross-sectional, cohort, or case-control-based that defined the dietary patterns of the Japanese diet using dietary pattern analysis. A total of 39 research articles that described the Japanese diet were included. DATA EXTRACTION: The data that were extracted included the following: implementing country, location, study design, participant characteristics, key outcomes, methods used in the analysis of dietary patterns, and descriptions of the Japanese diet. DATA SYNTHESIS: As a result of the systematic review analyzing the descriptions of the Japanese diet from 39 selected articles, we were able to aggregate the descriptions into 16 categories from 33 factors. After performing a content analysis using a further aggregation of categories, we found that the top three applicable categories were soybeans/soybean-derived products, seafood, and vegetables; these were followed by rice and miso soup. CONCLUSION: The Japanese dietary content was found to be diverse based on an examination of epidemiological studies; however, we were able to aggregate the content into 16 categories. The Japanese diet is considered to be a dietary pattern that contains a combination of factors: the dietary staple, side dishes, and soup.

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.

Routine blood cultures in the management of pyelonephritis in pregnancy for improving outcomes.

BACKGROUND: Pyelonephritis is a type of urinary tract infection (UTI) that affects the upper urinary tract and kidneys, and is one of the most common conditions for hospitalisation among pregnant women, aside from delivery. Samples of urine and blood are obtained and used for cultures as part of the diagnosis and management of the condition. Acute pyelonephritis requires hospitalisation with intravenous administration of antimicrobial agents. Several studies have questioned the necessity of obtaining blood cultures in addition to urine cultures, citing cost and questioning whether blood testing is superfluous. Pregnant women with bacteraemia require a change in the initial empirical treatment based on the blood culture. However, these cases are not common, and represent approximately 15% to 20% of cases. It is unclear whether blood cultures are essential for the effective management of the condition. OBJECTIVES: To assess the effectiveness of routine blood cultures to improve health outcomes in the management of pyelonephritis in pregnant women. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register without language or date restrictions (31 December 2014). SELECTION CRITERIA: Randomised controlled trials and quasi-randomised trials comparing outcomes among pregnant women with pyelonephritis who received initial management with or without blood cultures. Cluster-randomised trials were eligible for inclusion in this review but none were identified. Clinical trials using a cross-over design were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed one trial report for inclusion. MAIN RESULTS: We identified one trial report but this was excluded. No clinical trials met the inclusion criteria for this review. AUTHORS' CONCLUSIONS: There are no large-scale randomised controlled trials to assess outcomes in the management of pyelonephritis in pregnancy with or without blood cultures. Randomised controlled trials are needed to evaluate the effectiveness of managing pyelonephritis in pregnant women with or without blood cultures, and to assess any adverse outcomes as well as the cost-effectiveness of excluding blood cultures from treatment.