Antipsychotic drugs for anorexia nervosa.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of antipsychotic drugs (both first- and second-generation antipsychotics) compared to placebo on body weight gain, psychological symptoms, acceptability, and adverse events for people with anorexia nervosa.

Literature review: prevention of aspiration in the elderly overseas.

Objective: This review seeks to identify trends and issues in preventing aspiration for the elderly overseas in the hopes of gathering information regarding how a similar level of care may be provided in Japan. Materials and Methods: The authors used the CHINAL Ultimate database to review academic publications from December 2012 to December 2022. Four terms, one from each of four sets of keywords, were combined as search criteria: (1) "dysphagia", "aspiration", "choking", "airway obstruction asphyxia", "swallowing function", or "pneumonia", (2) "aged" or "elderly people", (3) "nursing" or "nursing care", and (4) prevention. Papers that did not directly relate to the purpose of this review were excluded. Results: The authors identified fourteen publications regarding preventative care for aspiration in the elderly. According to the reports, preventative care mainly consisted of ensuring proper oral care, screening to assess swallowing function, and taking steps at meals to prevent aspiration. Conclusion: Our research showed that the primary ways of preventing aspiration in the elderly overseas included (1) screening for oral conditions and swallowing function to prevent pneumonia and (2) providing proper oral care coupled with support during meals.

Effect of reduced daily magnesium oxide doses on laxative effect: a single-center retrospective study.

Objective: To investigate the laxative effect of reducing the number of daily doses of magnesium oxide (MgO), while maintaining the total daily dose of MgO in patients with good bowel movements. Patients and Methods: The retrospective analysis involved 11 patients with regular bowel movements who were prescribed MgO for constipation upon admission to a nursing care facility accompanied by home visits by a pharmacist. This investigation was conducted before and after reducing the number of daily doses from three to two, or from two to one, over a two-week period. Results: The number of bowel movements was 7.6 ± 3.4 and 6.6 ± 4.0 times for two weeks before and after the change in dosage frequency, respectively. The difference was not statistically significant (P=0.09). The Bristol Stool Form Scale was 3.9 ± 0.9 and 4.0 ± 0.9 two weeks before and after the change, respectively, which was not significant (P=0.93). Two weeks after the change, the MgO regimen remained unchanged and no on-demand laxatives were administered. Conclusions: The results suggest that reducing the number of daily doses of MgO does not affect its laxative action.

National burden of gambling in Japan: an estimation from an online-based cross-sectional investigation and national epidemiological survey.

BACKGROUND: Gambling is a popular leisure activity in many countries, often expected to boost regional economies. Nevertheless, its negative impacts remain a significant concern. Gambling disorder is recognized as the most severe consequence; however, even non- or low-risk gamblers may also face negative impacts. This study aimed to estimate the number of Japanese gamblers experiencing gambling-related harm (GRH) and its distribution across six life domains, financial, relational, emotional, health, social and other aspects, based on the severity of their problem gambling risk. METHODS: This cross-sectional study relied on an online survey conducted between August 5 and 11, 2020. Participants aged 20 years and above, who engaged in gambling during 2019 were recruited via a market research company. The survey assessed the prevalence of GRH 72 items among four gambler risk groups (non-problem, low-, moderate-, and high-risk), as categorized by the Problem Gambling Severity Index. The data was adjusted for population weighting using representative national survey data: the 2017 Comprehensive Survey of Living Conditions and the 2017 Epidemiological Survey on Gambling Addictions. RESULTS: Out of the 28,016 individuals invited to the survey, 6,124 participated in the screening, 3,113 in the main survey, and 3,063 provided valid responses. After adjusting the survey data, it was estimated that 39.0 million (30.8%) of Japan's 126.8 million citizens gambled in 2019. Among them, 4.44 million (11.4%) experienced financial harm, 2.70 million (6.9%) health harm, 2.54 million (6.5%) emotional harm, 1.31 million (3.4%) work/study harm, 1.28 million (3.3%) relationship harm, and 0.46 million (1.2%) other harm. Although high-risk gamblers experienced severe harm at the individual level, over 60% of gamblers who experienced GRHs were non- and low-risk gamblers, with the exception of other harm, at the population level. CONCLUSIONS: The study highlighted the prevention paradox of gambling in Japan. While national gambling policies primarily focus on the prevention and intervention for high-risk gamblers, a more effective approach would involve minimizing GRH across the entire population.

Interventions to increase time spent outdoors for preventing incidence and progression of myopia in children.

BACKGROUND: Myopia or nearsightedness is a type of refractive error. It causes people to see near objects clearly but distant objects as blurred. Good vision can be obtained if the refractive error is corrected properly but, where this is not possible, impaired vision will remain. The remaining myopia imposes a considerable personal and societal burden. In addition, the progression of myopia is more likely to be accompanied by other ocular diseases such as cataract, glaucoma and retinal detachment. Myopia has emerged as a significant global public health problem in recent years. The World Health Organization (WHO) reported uncorrected or undercorrected myopia to be a major cause of visual impairment worldwide. From both an individual and social perspective, it is important to prevent the onset of myopia and slow down its progression. Observational studies have shown that children who spend more time outdoors have a lower incidence of myopia. Several other non-Cochrane systematic reviews have focused on the association between increasing children's outdoor activity time and the prevention of myopia. However, none of these systematic reviews were limited to randomised controlled trials (RCTs), as they included all types of study designs, including observational studies and non-RCTs, in addition to RCTs. OBJECTIVES: To assess the effects of interventions to increase outdoor time on the incidence and progression of myopia in children. SEARCH METHODS: We searched CENTRAL, MEDLINE Ovid, Embase Ovid, ISRCTN registry, ClinicalTrials.gov, and the WHO ICTRP with no language restrictions. The databases were last searched on 24 June 2022. SELECTION CRITERIA: We included RCTs and cluster-RCTs in which interventions were performed to increase the outdoor time for children with the aim of preventing the incidence and progression of myopia. DATA COLLECTION AND ANALYSIS: We employed the standard methods recommended by Cochrane and assessed the certainty of the evidence using GRADE. We considered the following outcome measures: mean change in refractive error from baseline, incidence of myopia, mean change in the axial length from baseline, mean change in unaided distance visual acuity from baseline, quality of life and adverse event. MAIN RESULTS: We included five RCTs in this review, four of which were cluster-RCTs. The total number of participants was 10,733. The included participants were primary school children, most of whom were in first or second grade (aged six to nine years). Four cluster-RCTs involved school-based interventions to encourage children to spend more time outdoors. The interventions included classroom time outdoors, routine for spending recess outdoors, motivational tools for spending time outdoors, and encouragement through electronic information tools. The intervention groups had less change in refractive errors in the direction of myopia; however, 95% confidence intervals (CIs) included no benefit or both benefit and harm at years one and three, and differences at year two included both clinically important and unimportant benefits (at 1 year: mean difference (MD) 0.08 dioptres (D), 95% CI -0.01 to 0.17; 4 studies, 1656 participants; low-certainty evidence; at 2 years: MD 0.13 D, 95% CI 0.06 to 0.19; 4 studies, 2454 participants; moderate-certainty evidence; at 3 years: MD 0.17 D, 95% CI -0.17 to 0.51; 1 study, 729 participants; low-certainty evidence). Our protocol defined a difference of 0.1 D in the change in refractive error as clinically important. At one year, the difference was less than 0.1 D, but at two and three years it was more than 0.1 D. The incidence of myopia was lower in the intervention groups compared to the control groups, but 95% CIs included no change or clinically unimportant benefits (at 1 year: 7.1% with intervention versus 9.5% with control; risk ratio (RR), 0.82, 95% CI 0.56 to 1.19; 3 studies, 1265 participants; low-certainty evidence; at 2 years: 22.5% with intervention versus 26.7% with control; RR 0.84, 95% CI 0.72 to 0.98; 3 studies, 2104 participants; moderate-certainty evidence; at 3 years: 30.5% with intervention versus 39.8% with control; RR 0.77, 95% CI 0.59 to 1.01; 1 study, 394 participants; moderate-certainty evidence). Our protocol defined a difference of 3% in the incidence of myopia as clinically important. At one year, the difference was 2.4%, but there were clinically important differences between the two groups at two (4.2%) and three years (9.3%). The intervention groups had smaller changes in axial lengths in the direction of myopia than the control groups; however, 95% CIs included no benefit or both benefit and harm at years one and three (at 1 year: MD -0.04 mm, 95% CI -0.09 to 0; 3 studies, 1666 participants; low-certainty evidence; at 2 years: MD -0.04 mm, 95% CI -0.07 to -0.01; 3 studies, 2479 participants; moderate-certainty evidence; at 3 years: MD -0.03 mm, 95% CI -0.13 to 0.07; 1 study, 763 participants; moderate-certainty evidence). No included studies reported changes in unaided distance visual acuity and quality of life. No adverse events were reported. AUTHORS' CONCLUSIONS: The intervention methods varied from adopting outdoor activities as part of school lessons to providing information and motivation for encouraging outdoor activities. The results of this review suggest that long-term interventions to increase the time spent outdoors may potentially reduce the development of myopia in children. However, although the interventions may also suppress the progression of myopia, the low certainty of evidence makes it difficult to draw conclusions. Further research needs to be accumulated and reviewed.

Remote family education and support program for parents of patients with adolescent and early adulthood eating disorders based on interpersonal psychotherapy: study protocol for a pilot randomized controlled trial.

BACKGROUND: In cases of adolescent and early adulthood eating disorders, despite the importance of the patients' relationship with their parents, conflict and confusion frequently occur among them. Interpersonal psychotherapy (IPT) is a present-focused psychotherapy that emphasizes the interpersonal context of symptoms. We developed a remote family education and support program exclusively for parents of patients with eating disorders, based on the principle of IPT. The use of IPT is expected to reduce conflicts in the patient-parent relationship. Consequently, parents will be better able to listen to patients, and patients will be better able to express their thoughts and desires. In this study, we describe the protocol for a randomized controlled trial designed to examine the effectiveness of this program in promoting effective communication in their home based on active listening skills of parents of patients with adolescent and early adulthood eating disorders. METHODS: Participants will be parents of patients aged 12-29 years with adolescent and early adulthood eating disorders. Individually randomized, parallel-group trial design will be employed. Seventy participants will be allocated to one of two treatment conditions: (1) remote family education and support program (four, 150 min weekly group sessions) for parents plus treatment-as-usual for patients (consultation by physicians or no treatment), or (2) waiting for the control condition (parents will wait to start the program for 8 weeks) plus treatment-as-usual for patients. The primary outcome measure will be parents' active listening ability as measured by the Active Listening Attitude Scale at 8 weeks after randomization. Additionally, perception of social support (Social Provision Scale-10 item), loneliness (UCLA Loneliness Scale), mental health status (K6), family function (Family Assessment Device), and parent-evaluated eating disorder symptoms (Anorectic Behavior Observation Scale) will be assessed. Data from the intention-to-treat sample will be analyzed 8 weeks after randomization. DISCUSSION: This is the first study to evaluate the effectiveness of a family education and support program for parents of patients with adolescent and early adulthood eating disorders based on IPT. If this type of intervention is effective, although indirect, it could be a new support method for this patient population. TRIAL REGISTRATION: Clinical Trials. gov ID NCT05840614.

For patients with adolescent and early adulthood eating disorders, although the relationship with their parents is an important interpersonal dynamic, conflicts and confusion often arise between patients and their parents. On the other hand, parents who live with individuals with eating disorders are frequently involved in interpersonal disputes, leading to a heavy psychological burden and elevated levels of depression and anxiety. It has been found that highly depressed or anxious parents tend to have difficulty listening carefully to their patients. Additionally, parental anxiety often promotes an overprotective response. Interpersonal psychotherapy (IPT) is a present-focused psychotherapy that emphasizes the interpersonal context of symptoms. In IPT, the patient and therapist work within interpersonal therapeutic domains, such as interpersonal role disputes with different expectations and role transitions. We developed a remote family education and support program exclusively for parents of patients with eating disorders based on IPT principles. In the present study, we describe the protocol for a randomized controlled trial designed to examine the effectiveness of this program in promoting effective communication within their homes, focusing on the active listening skills of parents of patients with adolescent and early adulthood eating disorders.

Frequency of Myoclonus and its Countermeasures in Terminally Ill Patients with Cancer: A Single-Center Retrospective Study.

Myoclonus is a relatively rare involuntary movement that is often observed in palliative care settings and that can cause patient distress. The purpose of this study is to investigate the occurrence of myoclonus and countermeasures against it in terminally ill patients with cancer diagnosed by palliative care specialists at Komaki City Hospital, Japan. We retrospectively reviewed patients with terminal cancer who received palliative care consultations between January 2018 and May 2019 and who were diagnosed with myoclonus by palliative care specialists, using electronic medical records. Patient demographics, time from onset of myoclonus to death, daily opioid use, countermeasures, and outcome of myoclonus were assessed. Of 360 patients examined during this period, 45 (12.5%) were diagnosed with myoclonus. Median age was 71 (range, 43-88) years; median time from onset of myoclonus to death was 8 days (range, 0-56); opioid usage was present in 39 patients (morphine, oxycodone, and fentanyl: n = 6, 21, and 12, respectively); and median oral morphine equivalent at onset of myoclonus was 60 mg (range, 12-336 mg). Myoclonus treatment was administered to 21 patients (opioid dose reduction, opioid switching, and others: n = 14, 3, and 4, respectively). Myoclonus is a common complication in patients with terminal cancer.

Multicomponent Intervention for Overactive Bladder in Women: A Randomized Clinical Trial.

Importance: Although the cognitive components of behavioral therapy for overactive bladder (OAB) are widely recognized, there is a lack of studies evaluating the effectiveness of multicomponent interventions that include cognitive components as a treatment for OAB. Objective: To examine the efficacy of a multicomponent intervention in improving health-related quality of life (HRQOL) for women with moderate to severe OAB. Design, Setting, and Participants: This multicenter, open-label, randomized clinical trial was conducted in Japan among women aged 20 to 80 years who had moderate to severe OAB. Participants were recruited from 4 institutions between January 16, 2020, and December 31, 2022, through self-referral via advertisement or referral from the participating institutions. Interventions: Participants were randomized 1:1 by minimization algorithm using an internet-based central cloud system to four 30-minute weekly sessions of a multicomponent intervention or waiting list. Both groups continued to receive baseline treatment throughout the study period. Main Outcomes and Measures: The primary outcome was the least-squares mean changes from baseline through week 13 in HRQOL total scores of the OAB questionnaire between 2 groups. Secondary outcomes included OAB symptom score and frequency volume chart. Results: A total of 79 women were randomized to either the intervention group (39 participants; mean [SD] age, 63.5 [14.6] years) or the waiting list control group (40 participants; mean [SD] age, 63.5 [12.9] years). One participant from each group dropped out from the allocated intervention, while 5 participants in the intervention group and 2 in the control group dropped out from the primary outcome assessment at week 13. Thirty-six participants (92.3%) in the intervention group and 35 (87.5%) in the control group had moderate OAB. The change in HRQOL total score from baseline to week 13 was 23.9 points (95% CI, 18.4-29.5 points) in the intervention group and 11.3 points (95% CI, 6.2-16.4 points) in the waiting list group, a significant difference of 12.6 points (95% CI, 6.6-18.6 points; P < .001). Similar superiority of the intervention was confirmed for frequency of micturition and urgency but not for OAB symptom score. Conclusions and Relevance: These findings demonstrate that a multicomponent intervention improves HRQOL for women with moderate to severe OAB and suggest that the cognitive component may be an effective treatment option for women with OAB. Trial Registration: UMIN Clinical Trials Registry Identifier: UMIN000038513.

Anterior versus posterior mediastinal reconstruction after esophagectomy in esophageal cancer patients: a systematic review and meta-analysis.

PURPOSE: Esophagectomy is the primary surgical treatment for esophageal cancer, although other treatment approaches are often incorporated, including preoperative chemotherapy and chemoradiotherapy. The two major routes of esophageal reconstruction after esophagectomy are the anterior mediastinal (retrosternal, heterotopic) and posterior mediastinal (prevertebral, orthotopic) routes. However, which of these two routes of reconstruction is the most appropriate remains controversial. This systematic review aimed to compare the efficacy and safety of anterior mediastinal reconstruction with those of posterior mediastinal reconstruction after esophagectomy in esophageal cancer. METHODS: In January 2022, a literature search of the CENTRAL, MEDLINE, and EMBASE databases was conducted to identify all published and unpublished randomized controlled trials, regardless of language. Eight studies were included for quantitative synthesis. RESULTS: Postoperative death (9/129 and 4/125, risk ratio [RR]: 2.07, 95% confidence interval [CI]: 0.65-6.64) and incidence of anastomotic leak (24/208 and 26/208, RR: 0.95, 95% CI: 0.56-1.62) were not significantly different between the two mediastinal reconstructions. We could not perform a meta-analysis for quality of life, loss of body weight, or postoperative hospital stay due to data limitations. CONCLUSION: Overall, there was low-quality evidence to suggest that the outcomes of the anterior and posterior mediastinal routes of reconstruction are not significantly different in patients with esophageal cancer.

[Xanthan Gum-based Food Thickeners Reduce Disintegration Time of Medical and OTC Loxoprofen Sodium Tablets].

Xanthan gum-based food thickeners have been reported to potentially interfere with tablet disintegration. Loxoprofen sodium (LOX) is widely used as an antipyretic analgesic and is expected to provide rapid pain relief. In this study, we aimed to investigate the impact of a xanthan gum-based food thickener on LOX tablet disintegration. We used four different brands each of medical and OTC-LOX tablets, each containing 60 mg of LOX as the sole active ingredient. Depending on the brand, tablet hardness varied between 50.1-96.6 N and was not associated with the disintegration time. Disintegration times for medical tablets not immersed in the food thickener were 536±215, 621±159, 348±22, 369±42 s and for OTC tablets, were 358±20, 336±13, 292±13, 172±27 s. Immersion in the food thickener for 15 min reduced medical tablet disintegration time to 177±46 and 233±150 s (the third and fourth brands were disintegrated during immersion), and that for OTC tablets to 77±40, 75±110, and 37±85 s (the fourth brand was disintegrated during immersion). Despite each tablet containing different pharmaceutical additives, no correlation was found between disintegration time and presence of superdisintegrants. The OTC tablet with a light anhydrous silicic acid coating exhibited the shortest disintegration time. Thus, the disintegration time of LOX tablets is accelerated when immersed in the xanthan gum-based food thickener, potentially leading to rapid pain relief for patients.

Differences in serum selenoprotein P profile between C57BL/6 and BALB/c mice fed high-fat diet.

BACKGROUND: C57BL/6 mice generally show hyperglycaemia and insulin resistance when fed a high-fat diet (HFD) compared to those of BALB/c mice. However, whether these strains also show different expression profiles of selenoprotein P, a diabetes-related hepatokine, after HFD feeding is unclear. We investigated the effects of HFD on body weight, glucose metabolism, and plasma selenoprotein P levels in C57BL/6 and BALB/c mice. METHODS: Male C57BL/6 and BALB/c mice aged seven weeks were divided into normal diet (ND) and HFD groups. Fasting body weights and blood sugar levels were measured weekly. Blood specimens were collected after 16 h of fasting (in weeks 7, 9, and 11) and after 24 h of subsequent refeeding (in weeks 9 and 11) to analyse plasma selenoprotein P and insulin levels. RESULTS: The mean body weight of the HFD group was consistently higher than that of the ND group for both strains. However, a significant elevation in fasting plasma glucose levels from the early stage was observed only in the HFD group of C57BL/6 mice. In BALB/c mice, a difference in fasting glucose levels between the HFD and ND groups was observed after nine weeks. After seven, nine, and eleven weeks, the fasting plasma insulin levels were higher in the HFD group than in the ND group for both strains. During this period, plasma selenoprotein P levels in the HFD group were significantly higher than those in the ND group of C57BL/6 mice. However, BALB/c mice did not show a significant difference in plasma levels of selenoprotein P between the ND and HFD groups. After refeeding, the plasma insulin and selenoprotein P levels increased compared to those observed during fasting in the ND group for both strains. Elevation of insulin levels, but not of selenoprotein P levels, after refeeding was noticed in the HFD group for both strains. Plasma selenoprotein P level after refeeding was significantly lower than that during fasting in the HFD group of C57BL/6 mice. CONCLUSION: Unlike C57BL/6 mice, BALB/c mice did not show elevated fasting plasma selenoprotein P levels despite HFD feeding. Additionally, the pattern of selenoprotein P levels in the plasma after refeeding differed between C57BL/6 and BALB/c mice. These differences in selenoprotein P expression among strains may be related to different susceptibilities of individuals to diabetes.

Bladder training for treating overactive bladder in adults.

BACKGROUND: Overactive bladder (OAB) is a common chronic and bothersome condition. Bladder training is widely prescribed as a first-line treatment for OAB, but the efficacy has been systematically evaluated for urinary incontinence rather than OAB alone. OBJECTIVES: To evaluate the benefits and harms of bladder training for treating adults with OAB compared to no treatment, anticholinergics, ß3-adrenoceptor agonists, or pelvic floor muscle training (PFMT) alone or in combination. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 6 November 2022. SELECTION CRITERIA: We included randomized controlled trials involving adults aged 18 years or older with non-neurogenic OAB. We excluded studies of participants whose symptoms were caused by factors outside the urinary tract (e.g. neurologic disorders, cognitive impairment, gynecologic diseases). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. participant-reported cure or improvement, 2. symptom- and condition-related quality of life (QoL), and 3. ADVERSE EVENTS: Secondary outcomes included 4. participant-reported satisfaction, 5. number of incontinence episodes, 6. number of urgency episodes, and 7. number of micturition episodes. For the purpose of this review, we considered two time points: immediately after the treatment (early phase) and at least two months after the treatment (late phase). We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We included 15 trials with 2007 participants; participants in these trials were predominantly women (89.3%). We assessed the risk of bias of results for primary and secondary outcomes, which across all studies was similar and predominantly of high risk of bias, and none were at low risk of bias. The certainty of evidence was low to very low, with some moderate, across measured outcomes. Bladder training versus no treatment: three studies involving 92 participants compared bladder training to no treatment. The evidence is very uncertain about the effects of bladder training on cure or improvement at the early phase (risk ratio (RR) 17.00, 95% confidence interval (CI) 1.13 to 256.56; 1 study, 18 participants; very low-certainty evidence). Bladder training may reduce the number of incontinence episodes (mean difference (MD) -1.86, 95% CI -3.47 to -0.25; 1 study, 14 participants; low-certainty evidence). No studies measured symptom- and condition-related QoL, number of adverse events, participant-reported satisfaction, number of urgency episodes, or number of micturition episodes in the early phase. Bladder training versus anticholinergics: seven studies (602 participants) investigated the effects of bladder training versus anticholinergic therapy. Bladder training may be more effective than anticholinergics on cure or improvement at the early phase (RR 1.37, 95% CI 1.10 to 1.70; 4 studies, 258 participants; low-certainty evidence). The evidence is very uncertain about the effects of bladder training on symptom- and condition-related QoL (standardized mean difference (SMD) -0.06, 95% CI -0.89 to 0.77; 2 studies, 117 participants; very low-certainty evidence). Although the evidence is very uncertain, there were fewer adverse events in the bladder training group than in the anticholinergics group (RR 0.03, 95% CI 0.01 to 0.17; 3 studies, 187 participants; very low-certainty evidence). The evidence is very uncertain about the effects of the number of incontinence episodes per 24 hours (MD 0.36, 95% CI -0.27 to 1.00; 2 studies, 117 participants; very low-certainty evidence), the number of urgency episodes per 24 hours (MD 0.70, 95% CI -0.62 to 2.02; 2 studies, 92 participants; very low-certainty evidence), and the number of micturition episodes per 24 hours (MD -0.35, 95% CI -1.90 to 1.20; 3 studies, 175 participants; very low-certainty evidence). No studies measured participant-reported satisfaction in the early phase. Bladder training versus PFMT: three studies involving 203 participants compared bladder training to PFMT. The evidence is very uncertain about the different effects between bladder training and PFMT on symptom- and condition-related QoL at the early phase (SMD 0.10, 95% CI -0.19 to 0.40; 2 studies, 178 participants; very low-certainty evidence). There were no adverse events in either group at the early phase (1 study, 97 participants; moderate-certainty evidence). The evidence is uncertain about the effects of the number of incontinence episodes per 24 hours (MD 0.02, 95% CI -0.35 to 0.39, 1 study, 81 participants; low-certainty evidence) and very uncertain about the number of micturition episodes per 24 hours (MD 0.10, 95% CI -1.44 to 1.64; 1 study, 81 participants; very low-certainty evidence). No studies measured cure or improvement, participant-reported satisfaction, or number of urgency episodes in the early phase. Although we were interested in studies examining bladder training versus ß3-adrenoceptor agonists, in combination with ß3-adrenoceptor agonists versus ß3-adrenoceptor agonists alone, and in combination with PFMT versus PFMT alone, we did not identify any eligible studies for these comparisons. AUTHORS' CONCLUSIONS: This review focused on the effect of bladder training to treat OAB. However, most of the evidence was low or very-low certainty. Based on the low- or very low-certainty evidence, bladder training may cure or improve OAB compared to no treatment. Bladder training may be more effective to cure or improve OAB than anticholinergics, and there may be fewer adverse events. There may be no difference in efficacy or safety between bladder training and PFMT. More well-designed trials are needed to reach a firm conclusion.

Development and validation of a prediction model for rehospitalization among people with schizophrenia discharged from acute inpatient care.

Objective: Relapses and rehospitalization prevent the recovery of individuals with schizophrenia or related psychoses. We aimed to build a model to predict the risk of rehospitalization among people with schizophrenia or related psychoses, including those with multiple episodes. Methods: This retrospective cohort study included individuals aged 18 years or older, with schizophrenia or related psychoses, and discharged between January 2014 and December 2018 from one of three Japanese psychiatric hospital acute inpatient care ward. We collected nine predictors at the time of recruitment, followed up with the participants for 12 months, and observed whether psychotic relapse had occurred. Next, we applied the Cox regression model and used an elastic net to avoid overfitting. Then, we examined discrimination using bootstrapping, Steyerberg's method, and "leave-one-hospital-out" cross-validation. We also constructed a bias-corrected calibration plot. Results: Data from a total of 805 individuals were analyzed. The significant predictors were the number of previous hospitalizations (HR 1.42, 95% CI 1.22-1.64) and the current length of stay in days (HR 1.31, 95% CI 1.04-1.64). In model development for relapse, Harrell's c-index was 0.59 (95% CI 0.55-0.63). The internal and internal-external validation for rehospitalization showed Harrell's c-index to be 0.64 (95% CI 0.59-0.69) and 0.66 (95% CI 0.57-0.74), respectively. The calibration plot was found to be adequate. Conclusion: The model showed moderate discrimination of readmission after discharge. Carefully defining a research question by seeking needs among the population with chronic schizophrenia with multiple episodes may be key to building a useful model.

Health-Related Quality of Life After Percutaneous Coronary Intervention for Stable Ischemic Heart Disease: A Systematic Review and Meta-analysis.

BACKGROUND: There has been no meta-analysis of whether percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) improves health-related quality of life (HRQL) compared with OMT alone in patients with stable ischemic heart disease (SIHD). METHODS: We searched MEDLINE, Cochrane Central Registry of Controlled Trials, Embase, ClinicalTrials.gov, and International Clinical Trials Registry Platform in November 2022. We included randomized controlled trials (RCTs) that compared PCI with OMT vs OMT alone with HRQL in patients with SIHD. The primary outcome was the aggregated physical HRQL, including physical functioning using the Short Form (SF)-36 or RAND-36, physical limitation using the Seattle Angina Questionnaire (SAQ) or SAQ-7, McMaster Health Index Questionnaire, and Duke Activity Status Index within 6 months. Data were analyzed using a random effects model when substantial heterogeneity was identified or a fixed effect model otherwise. RESULTS: Among 14 systematically reviewed RCTs, 12 RCTs with 12,238 patients were meta-analyzed. Only 1 trial had a low risk of bias in all domains. PCI with OMT improved aggregated physical HRQL (standardized mean difference, 0.16; 95% confidence interval [CI], 0.1-0.23; P < 0.0001) at 6 months. Also, PCI with OMT improved physical functioning on the SF-36/RAND-36 (mean difference 3.65; 95% CI, 1.88-5.41) and physical limitation on the SAQ/SAQ-7 (mean difference, 3.09; 95% CI, 0.93-5.24) compared with OMT alone at 6 months. However, all of the aggregated physical HRQL domains were classified into small effects, and no HRQL domain exceeded the prespecified minimal clinically important difference. CONCLUSIONS: These findings showed that PCI with OMT improved HRQL compared with OMT alone in patients with SIHD, but the benefit was not large.

Fenofibrate for diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) remains a major cause of sight loss worldwide, despite new therapies and improvements in the metabolic control of people living with diabetes. Therefore, DR creates a physical and psychological burden for people, and an economic burden for society. Preventing the development and progression of DR, or avoiding the occurrence of its sight-threatening complications is essential, and must be pursued to save sight. Fenofibrate may be a useful strategy to achieve this goal, by reversing diabetes' effects and reducing inflammation in the retina, as well as improving dyslipidaemia and hypertriglyceridaemia.  OBJECTIVES: To investigate the benefits and harms of fenofibrate for preventing the development and progression of diabetic retinopathy in people with type 1 (T1D) or type 2 diabetes (T2D), compared with placebo or observation. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and three trials registers (February 2022). SELECTION CRITERIA: We included randomised controlled trials (RCTs) that included people with T1D or T2D, when these compared fenofibrate with placebo or with observation, and assessed the effect of fenofibrate on the development or progression of DR (or both). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods for data extraction and analysis. Our primary outcome was progression of DR, a composite outcome of 1) incidence of overt retinopathy for participants who did not have DR at baseline, or 2) advancing two or more steps on the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale for participants who had any DR at baseline (or both), based on the evaluation of stereoscopic or non-stereoscopic fundus photographs, during the follow-up period. Overt retinopathy was defined as the presence of any DR observed on stereoscopic or non-stereoscopic colour fundus photographs. Secondary outcomes included the incidence of overt retinopathy, reduction in visual acuity of participants with a reduction in visual acuity of 10 ETDRS letters or more, proliferative diabetic retinopathy, and diabetic macular oedema; mean vision-related quality of life, and serious adverse events of fenofibrate. We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included two studies and their eye sub-studies (15,313 participants) in people with T2D. The studies were conducted in the US, Canada, Australia, Finland, and New Zealand; follow-up period was four to five years. One was funded by the government, the other by industry. Compared to placebo or observation, fenofibrate likely results in little to no difference in progression of DR (risk ratio (RR) 0.86; 95% confidence interval (CI) 0.60 to 1.25; 1 study, 1012 participants; moderate-certainty evidence) in a population with and without overt retinopathy at baseline. Those without overt retinopathy at baseline showed little or no progression (RR 1.00, 95% CI 0.68 to 1.47; 1 study, 804 participants); those with overt retinopathy at baseline found that their DR progressed slowly (RR 0.21, 95% CI 0.06 to 0.71; 1 study, 208 people; test for interaction P = 0.02). Compared to placebo or observation, fenofibrate likely resulted in little to no difference in either the incidence of overt retinopathy (RR 0.91; 95% CI 0.76 to 1.09; 2 studies, 1631 participants; moderate-certainty evidence); or the incidence of diabetic macular oedema (RR 0.39; 95% CI 0.12 to 1.24; 1 study, 1012 participants; moderate-certainty evidence). The use of fenofibrate increased severe adverse effects (RR 1.55; 95% CI 1.05 to 2.27; 2 studies, 15,313 participants; high-certainty evidence). The studies did not report on incidence of a reduction in visual acuity of 10 ETDRS letters or more, incidence of proliferative diabetic retinopathy, or mean vision-related quality of life. AUTHORS' CONCLUSIONS: Current, moderate-certainty evidence suggests that in a mixed group of people with and without overt retinopathy, who live with T2D, fenofibrate likely results in little to no difference in progression of diabetic retinopathy. However, in people with overt retinopathy who live with T2D, fenofibrate likely reduces the progression. Serious adverse events were rare, but the risk of their occurrence was increased by the use of fenofibrate. There is no evidence on the effect of fenofibrate in people with T1D. More studies, with larger sample sizes, and participants with T1D are needed. They should measure outcomes that are important to people with diabetes, e.g. change in vision, reduction in visual acuity of 10 ETDRS letters or more, developing proliferative diabetic retinopathy; and evaluating the requirement of other treatments, e.g. injections of anti-vascular endothelial growth factor therapies, steroids.

Efficacy of Integrated Online Mindfulness and Self-compassion Training for Adults With Atopic Dermatitis: A Randomized Clinical Trial.

Importance: Quality of life (QOL) of patients with atopic dermatitis (AD) is reported to be the lowest among skin diseases. To our knowledge, mindfulness and self-compassion training has not been evaluated for adults with AD. Objective: To evaluate the efficacy of mindfulness and self-compassion training in improving the QOL for adults with AD. Design, Setting, and Participants: This randomized clinical trial conducted from March 2019 through October 2022 included adults with AD whose Dermatology Life Quality Index (DLQI) score, a skin disease-specific QOL measure, was greater than 6 (corresponding to moderate or greater impairment). Participants were recruited from multiple outpatient institutes in Japan and through the study's social media outlets and website. Interventions: Participants were randomized 1:1 to receive eight 90-minute weekly group sessions of online mindfulness and self-compassion training or to a waiting list. Both groups were allowed to receive any dermatologic treatment except dupilumab. Main Outcomes and Measures: The primary outcome was the change in the DLQI score from baseline to week 13. Secondary outcomes included eczema severity, itch- and scratching-related visual analog scales, self-compassion and all of its subscales, mindfulness, psychological symptoms, and participants' adherence to dermatologist-advised treatments. Results: The study randomized 107 adults to the intervention group (n = 56) or the waiting list (n = 51). The overall participant mean (SD) age was 36.3 (10.5) years, 85 (79.4%) were women, and the mean (SD) AD duration was 26.6 (11.7) years. Among participants from the intervention group, 55 (98.2%) attended 6 or more of the 8 sessions, and 105 of all participants (98.1%) completed the assessment at 13 weeks. The intervention group demonstrated greater improvement in the DLQI score at 13 weeks (between-group difference estimate, -6.34; 95% CI, -8.27 to -4.41; P < .001). The standardized effect size (Cohen d) at 13 weeks was -1.06 (95% CI, -1.39 to -0.74). All secondary outcomes showed greater improvements in the intervention group than in the waiting list group. Conclusions and Relevance: In this randomized clinical trial of adults with AD, integrated online mindfulness and self-compassion training in addition to usual care resulted in greater improvement in skin disease-specific QOL and other patient-reported outcomes, including eczema severity. These findings suggest that mindfulness and self-compassion training is an effective treatment option for adults with AD. Trial Registration: https://umin.ac.jp/ctr Identifier: UMIN000036277.

Association between social support for mothers of patients with eating disorders and mothers' active listening attitude: a cohort study.

BACKGROUND: Family members of patients with eating disorders, especially their mothers, experience heavy caregiving burdens associated with supporting the patient. We predict that increasing caregivers' support will have a positive effect on their active listening attitudes, mental health, loneliness, and self-efficacy. This study aimed to investigate differences in mothers' active listening attitudes, mental health, loneliness, and self-efficacy improvements between mothers who did and did not experience increased perceived social support. MAIN BODY: Participants were mothers of patients with eating disorders. Questionnaires for this cohort study were sent to the participants' homes at three time points (baseline, 9 months, and 18 months). The Japanese version of the Social Provision Scale (SPS-10) was used to evaluate social support, the Active Listening Attitude Scale (ALAS) for listening attitude, the UCLA Loneliness Scale (ULS) for loneliness, the General Self-Efficacy Scale (GSES) for self-efficacy, the Beck Depression Inventory (BDI-II) for depression symptoms, and the K6 for psychological distress. An unpaired t-test was used to determine whether participants' status differed between the groups that did and did not experience increased perceived social support. The mean age of the participants was 55.1 ± 6.7 (mean ± SD) years. The duration of their children's eating disorders was 7.6 ± 5.5 years. The degree of improvement for each variable (active listening attitude, loneliness, self-efficacy, depressive symptoms, and mental health) was the difference in each score (ALAS, ULS, GSES, BDI-II, and K6) from T1 to T3. The degree of improvement in active listening attitude and loneliness was significantly greater in the improved social support group than in the non-improved social support group (p < 0.002 and p < 0.012, respectively). CONCLUSIONS: Our findings indicate that increasing mothers' perceptions of social support will be associated with improving their active listening attitudes and loneliness.

Ultrasound guidance versus landmark method for peripheral venous cannulation in adults.

BACKGROUND: Peripheral intravenous cannulation is one of the most fundamental and common procedures in medicine. Securing a peripheral line is occasionally difficult with the landmark method. Ultrasound guidance has become a standard procedure for central venous cannulation, but its efficacy in achieving peripheral venous cannulation is unclear. OBJECTIVES: To evaluate the effectiveness and safety of ultrasound guidance compared to the landmark method for peripheral intravenous cannulation in adults.  SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 29 November 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which participants are systematically allocated based on data such as date of birth or recruitment) comparing the effects of ultrasound guidance to the landmark method for peripheral intravenous cannulation in adults. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were first-pass success of cannulation, overall success of cannulation, and pain. Our secondary outcomes were procedure time for first-pass cannulation, procedure time for overall cannulation, number of attempts, patient satisfaction, and overall complications. We used GRADE to assess the certainty of the evidence.  Placing a peripheral intravenous line in individuals can be classed as 'difficult', 'moderate', or 'easy'. We use the terms 'difficult participants', 'moderate/moderately difficult participants' and 'easy participants' as shorthand to characterise the difficulty level in placing a peripheral line using the landmark method. We used the original studies' definitions of difficulty levels of peripheral intravenous cannulation with the landmark method. We analysed the results in these subgroups: 'difficult participants', 'moderate participants', and 'easy participants'. We did this because we expected the effect of ultrasound-guided peripheral venous cannulation to be largest in participants classed as 'difficult' and smaller in participants classed as 'moderate' and 'easy'.  MAIN RESULTS: We included 14 RCTs and two quasi-RCTs involving 2267 participants undergoing peripheral intravenous cannulation. Participants were classed as 'difficult' in 12 studies (880 participants), 'moderate' in one study (401 participants), and 'easy' in one study (596 participants). Two studies (390 participants) did not restrict by landmark method difficulty level. The overall risk of bias assessments ranged from low to high. We judged studies to be at high risk of bias mainly because of concerns about blinding for subjective outcomes. In difficult participants, ultrasound guidance increased the first-pass success of cannulation (risk ratio (RR) 1.50, 95% confidence interval (95% CI) 1.15 to 1.95; 10 studies, 815 participants; low-certainty evidence), and the overall success of cannulation (RR 1.40, 95% CI 1.10 to 1.77; 10 studies, 670 participants; very low-certainty evidence). There was no clear difference in pain (mean difference (MD) -0.20, 95% CI -1.13 to 0.72; 4 studies, 323 participants; very low-certainty evidence; numerical rating scale (NRS) 0 to 10 where 10 is maximum pain). Ultrasound guidance increased the procedure time for first-pass cannulation (MD 119.9 seconds, 95% CI 88.6 to 151.1; 2 studies, 219 participants; low-certainty evidence), and patient satisfaction (standardised mean difference (SMD) 0.49, 95% CI 0.07 to 0.92; 5 studies, 333 participants; very low-certainty evidence; NRS 0 to 10 where 10 is maximum satisfaction). Ultrasound guidance decreased the number of cannulation attempts (MD -0.33, 95% CI -0.64 to -0.02; 9 studies, 568 participants; very low-certainty evidence). Ultrasound guidance showed no clear difference in the procedure time for overall cannulation (MD -24.9 seconds, 95% CI -323.1 to 273.3; 8 studies, 413 participants; very low-certainty evidence) and overall complications (RR 0.64, 95% CI 0.37 to 1.10; 5 studies, 431 participants; low-certainty evidence).  In moderate participants, ultrasound guidance increased the first-pass success of cannulation (RR 1.14, 95% CI 1.02 to 1.27; 1 study, 401 participants; moderate-certainty evidence). No studies assessed the overall success of cannulation. There was no clear difference in pain (MD 0.10, 95% CI -0.47 to 0.67; 1 study, 401 participants; low-certainty evidence; NRS 0 to 10 where 10 is maximum pain). Ultrasound guidance increased the procedure time for first-pass cannulation (MD 95.2 seconds, 95% CI 72.8 to 117.6; 1 study, 401 participants; high-certainty evidence). Ultrasound guidance showed no clear difference in overall complications (RR 0.83, 95% CI 0.38 to 1.82; 1 study, 401 participants; moderate-certainty evidence). No studies assessed the procedure time for overall cannulation, number of cannulation attempts, or patient satisfaction.  In easy participants, ultrasound guidance decreased the first-pass success of cannulation (RR 0.89, 95% CI 0.85 to 0.94; 1 study, 596 participants; high-certainty evidence). No studies assessed the overall success of cannulation. Ultrasound guidance increased pain (MD 0.60, 95% CI 0.17 to 1.03; 1 study, 596 participants; moderate-certainty evidence; NRS 0 to 10 where 10 is maximum pain). Ultrasound guidance increased the procedure time for first-pass cannulation (MD 94.8 seconds, 95% CI 81.2 to 108.5; 1 study, 596 participants; high-certainty evidence). Ultrasound guidance showed no clear difference in overall complications (RR 2.48, 95% CI 0.90 to 6.87; 1 study, 596 participants; moderate-certainty evidence). No studies assessed the procedure time for overall cannulation, number of cannulation attempts, or patient satisfaction.  AUTHORS' CONCLUSIONS: There is very low- and low-certainty evidence that, compared to the landmark method, ultrasound guidance may benefit difficult participants for increased first-pass and overall success of cannulation, with no difference detected in pain. There is moderate- and low-certainty evidence that, compared to the landmark method, ultrasound guidance may benefit moderately difficult participants due to a small increased first-pass success of cannulation with no difference detected in pain. There is moderate- and high-certainty evidence that, compared to the landmark method, ultrasound guidance does not benefit easy participants: ultrasound guidance decreased the first-pass success of cannulation with no difference detected in overall success of cannulation and increased pain.

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.

Pre-emptive antifungal therapy versus empirical antifungal therapy for febrile neutropenia in people with cancer.

BACKGROUND: Intensive cytotoxic chemotherapy for people with cancer can cause severe and prolonged cytopenia, especially neutropenia, a critical condition that is potentially life-threatening. When manifested by fever and neutropenia, it is called febrile neutropenia (FN). Invasive fungal disease (IFD) is one of the serious aetiologies of chemotherapy-induced FN. In pre-emptive therapy, physicians only initiate antifungal therapy when an invasive fungal infection is detected by a diagnostic test. Compared to empirical antifungal therapy, pre-emptive therapy may reduce the use of antifungal agents and associated adverse effects, but may increase mortality. The benefits and harms associated with the two treatment strategies have yet to be determined.  OBJECTIVES: To assess the relative efficacy, safety, and impact on antifungal agent use of pre-emptive versus empirical antifungal therapy in people with cancer who have febrile neutropenia. SEARCH METHODS: We searched CENTRAL, MEDLINE Ovid, Embase Ovid, and ClinicalTrials.gov to October 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared pre-emptive antifungal therapy with empirical antifungal therapy for people with cancer. DATA COLLECTION AND ANALYSIS: We identified 2257 records from the databases and handsearching. After removing duplicates, screening titles and abstracts, and reviewing full-text reports, we included seven studies in the review. We evaluated the effects on all-cause mortality, mortality ascribed to fungal infection, proportion of antifungal agent use (other than prophylactic use), duration of antifungal use (days), invasive fungal infection detection, and adverse effects for the comparison of pre-emptive versus empirical antifungal therapy. We presented the overall certainty of the evidence for each outcome according to the GRADE approach. MAIN RESULTS: This review includes 1480 participants from seven randomised controlled trials. Included studies only enroled participants at high risk of FN (e.g. people with haematological malignancy); none of them included participants at low risk (e.g. people with solid tumours).  Low-certainty evidence suggests there may be little to no difference between pre-emptive and empirical antifungal treatment for all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.72 to 1.30; absolute effect, reduced by 3/1000); and for mortality ascribed to fungal infection (RR 0.92, 95% CI 0.45 to 1.89; absolute effect, reduced by 2/1000). Pre-emptive therapy may decrease the proportion of antifungal agent used more than empirical therapy (other than prophylactic use; RR 0.71, 95% CI 0.47 to 1.05; absolute effect, reduced by 125/1000; very low-certainty evidence). Pre-emptive therapy may reduce the duration of antifungal use more than empirical treatment (mean difference (MD) -3.52 days, 95% CI -6.99 to -0.06, very low-certainty evidence). Pre-emptive therapy may increase invasive fungal infection detection compared to empirical treatment (RR 1.70, 95% CI 0.71 to 4.05; absolute effect, increased by 43/1000; very low-certainty evidence). Although we were unable to pool adverse events in a meta-analysis, there seemed to be no apparent difference in the frequency or severity of adverse events between groups. Due to the nature of the intervention, none of the seven RCTs could blind participants and personnel related to performance bias. We identified considerable clinical and statistical heterogeneity, which reduced the certainty of the evidence for each outcome. However, the two mortality outcomes had less statistical heterogeneity than other outcomes. AUTHORS' CONCLUSIONS: For people with cancer who are at high-risk of febrile neutropenia, pre-emptive antifungal therapy may reduce the duration and rate of use of antifungal agents compared to empirical therapy, without increasing over-all and IFD-related mortality; but the evidence regarding invasive fungal infection detection and adverse events was inconsistent and uncertain.