Utility of shaking chills as a diagnostic sign for bacteremia in adults: a systematic review and meta-analysis.

BACKGROUND: Accurate prediction of bacteremia is essential for guiding blood culture collection and optimal antibiotic treatment. Shaking chills, defined as a subjective chill sensation with objective body shivering, have been suggested as a potential predictor of bacteremia; however, conflicting findings exist. To address the evidence gap, we conducted a systematic review and meta-analysis of studies to assess the diagnostic accuracy of shaking chills for predicting bacteremia among adult patients. METHODS: We included studies reporting the diagnostic accuracy of shaking chills or chills for bacteremia. Adult patients with suspected bacteremia who underwent at least one set of blood cultures were included. Our main analysis focused on studies that assessed shaking chills. We searched these studies through CENTRAL, MEDLINE, Embase, the World Health Organization ICTRP Search Portal, and ClinicalTrials.gov. Study selection, data extraction, evaluation for risk of bias, and applicability using the QUADAS-2 tool were conducted by two independent investigators. We estimated a summary receiver operating characteristic curve and a summary point of sensitivity and specificity of the index tests, using a hierarchical model and the bivariate model, respectively. RESULTS: We identified 19 studies with a total of 14,641 patients in which the accuracy of shaking chills was evaluated. The pooled sensitivity and specificity of shaking chills were 0.37 (95% confidence interval [CI], 0.29 to 0.45) and 0.87 (95% CI, 0.83 to 0.90), respectively. Most studies had a low risk of bias in the index test domain and a high risk of bias and a high applicability concern in the patient-selection domain. CONCLUSIONS: Shaking chills are a highly specific but less sensitive predictor of bacteremia. Blood cultures and early initiation of antibiotics should be considered for patients with an episode of shaking chills; however, the absence of shaking chills must not lead to exclusion of bacteremia and early antibiotic treatment.

Beta-lactam allergy and drug challenge test in children: a systematic review and meta-analysis.

BACKGROUND: Most cases of beta-lactam allergy in children are likely to be mislabeled. This study aimed to assess the prevalence of true positives, as determined by drug challenge tests, and the rate of false negatives in children with suspected allergies and confirm the safety of the drug challenge test. METHODS: We conducted a systematic review and meta-analysis according to established procedures. Study participants were children with suspected beta-lactam allergy who underwent a drug challenge. PubMed MEDLINE, Dialog EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and clinicaltrials.gov were searched from inception until March 5, 2021. RESULTS: The pooled prevalence of (a) positive results in the first challenge was 0.049 (95% CI, 0.041-0.057; I2 = 71%) from 78 studies; (b) serious adverse events was 0.00 (95% CI, 0.00-0.00; I2 = 0.0%) from 62 studies; and (c) positive results in the second challenge after the first negative result was 0.028 (95% CI, 0.016-0.043; I2 = 38%) from 18 studies. CONCLUSIONS: The prevalence of children with suspected beta-lactam allergy with true-positive results and false-negative results from the drug challenge test was very low. Serious adverse events resulting from drug challenge tests were also very rare. IMPACT: Most children with suspected beta-lactam allergy were likely to be mislabeled. Serious adverse events caused by the drug challenge test were rare. Few false-negative results were obtained from the drug challenge test.

Efficacy of intravenous dexamethasone on postoperative pain after caesarean delivery under spinal anaesthesia with an intrathecal long-acting opioid: a systematic review and meta-analysis.

PURPOSE: Intravenous dexamethasone is recommended in elective caesarean delivery to decrease postoperative pain. However, the efficacy of spinal anaesthesia with an intrathecal long-acting opioid such as morphine or diamorphine for caesarean delivery has not been systematically investigated. METHODS: We searched all randomized controlled trials (RCTs) of pregnant women undergoing caesarean delivery under spinal anaesthesia with an intrathecal morphine or diamorphine via MEDLINE, CENTRAL, EMBASE, ICTRP, and ClinicalTrials.gov on May 18, 2022. Primary outcomes were time to first rescue analgesia, consumption of oral morphine equivalents, and incidence of drug-related adverse reactions. We evaluated the risk of bias for each outcome using the Risk of Bias 2. We conducted a meta-analysis using a random effects model. We evaluated the certainty of evidence with the GRADE approach. RESULTS: Five RCTs (455 patients) were included. The results of intravenous dexamethasone were as follows: time to first rescue analgesia (mean difference [MD] 0.99 h, 95% confidence interval [CI] - 0.86 to 2.84; very low certainty) and consumption of oral morphine equivalents (MD - 6.55 mg, 95% CI - 17.13 to 4.02; moderate certainty). No incidence of drug-related adverse reactions was reported (very low certainty). CONCLUSION: The evidence was very uncertain about the efficacy of intravenous dexamethasone on time to first rescue analgesia and the incidence of drug-related adverse reactions. Intravenous dexamethasone probably reduces the consumption of oral morphine equivalents. Anaesthesiologists might want to consider intravenous dexamethasone for postoperative pain after caesarean delivery under spinal anaesthesia with an intrathecal long-acting opioid.

Performance of an ambulatory electroencephalogram sleep monitor in patients with psychiatric disorders.

Key clinical symptoms observed among individuals with psychiatric disorders include difficulty falling asleep or maintaining sleep, poor sleep quality and nightmares. Those suffering from sleep disorders often present with symptoms of discontent with regard to sleep quality, timing and quantity, and these symptoms have an adverse impact on function and quality of life. A minimally invasive technique would be preferable in patients with psychiatric disorders, who tend to be sensitive to environmental change. Accordingly, we evaluated the performance of Zmachine Insight Plus, an ambulatory electroencephalography sleep monitor, in patients with psychiatric disorders. One hundred and three patients undergoing polysomnography were enrolled in this study. Zmachine Insight Plus was performed simultaneously with polysomnography. Total sleep time, sleep efficiency, wake after sleep onset, rapid eye movement (REM) sleep, light sleep (stages N1 and N2) and deep sleep (stage N3) were assessed. Total sleep time, sleep efficiency, wake after sleep onset, REM sleep duration and non-REM sleep duration of Zmachine Insight Plus showed a significant correlation with those of polysomnography. Lower sleep efficiency and increased frequency of waking after sleep onset, the arousal index and the apnea-hypopnea index on polysomnography were significantly associated with the difference in sleep parameters between the two methods. Among patients with psychiatric disorders who are sensitive to environmental change, Zmachine Insight Plus would be a useful technique to objectively evaluate sleep quality.

Neonatal jaundice, phototherapy and childhood allergic diseases: An updated systematic review and meta-analysis.

BACKGROUND: Neonatal jaundice and phototherapy have been associated with the development of allergic diseases. It has been suggested, however, that effect estimates of the associations might be smaller than expected. We sought to update the evidence of their associations including recently published large longitudinal studies. METHODS: We sought published and unpublished observational studies through the major databases. We used a random-effect meta-analysis model weighted by the inverse variance estimate, the Quality in Prognosis Studies tool to assess the methodological quality for each study, and the Grading of Recommendations, Assessment, Development, and Evaluation approach to assess the certainty of evidence (COE). RESULTS: Nineteen studies were enrolled in the qualitative syntheses, and fourteen studies were synthesized in the meta-analyses. Neonatal jaundice was associated with a higher risk of childhood-onset asthma (odds ratio [OR], 1.46; 95% confidence interval [95% CI], 1.39-1.53; COE, moderate), atopic dermatitis (AD; OR, 1.30; 95% CI, 1.07-1.57; COE, moderate), and allergic rhinitis (AR; OR, 3.01; 95% CI, 0.8810.30; COE, low). Neonatal phototherapy was also associated with a higher risk of childhood-onset asthma (OR, 1.24; 95% CI, 1.11-1.38; COE, moderate), AD (OR, 1.31; 95% CI, 1.24-1.39; COE, moderate), and AR (OR, 1.38; 95% CI, 0.93-2.04; COE, very low). There were no studies that reported effect estimates of the associations between childhood-onset food allergies and neonatal jaundice and phototherapy. CONCLUSION: Neonatal jaundice and phototherapy were probably a prognostic factor of childhood-onset allergic diseases; however, the associations were likely to be smaller than previously estimated.

Humour-based interventions for people with schizophrenia.

BACKGROUND: Humour-based interventions are defined as any intervention that promotes health and wellness by stimulating a playful discovery, expression, or appreciation of the absurdity or incongruity of life's situations. Humour-based interventions can be implemented in different settings, including hospitals, nursing homes and day care centres. They have been posed as an adjunct to usual care for people with schizophrenia, but a summary of the evidence is lacking. OBJECTIVES: To examine the effects of humour-based interventions as an add-on intervention to standard care for people with schizophrenia. SEARCH METHODS: On 31 July 2019 and 10 February 2021 we searched the Cochrane Schizophrenia Group's study-based register of trials, which is based on CENTRAL, CINAHL, ClinicalTrials.Gov, Embase, ISRCTN, MEDLINE, PsycINFO, PubMed, and WHO ICTRP. SELECTION CRITERIA: We included all randomised controlled trials comparing humour-based interventions with active controls, other psychological interventions, or standard care for people with schizophrenia. We excluded studies fulfilling our prespecified selection criteria but without useable data from further quantitative synthesis. DATA COLLECTION AND ANALYSIS: Two review authors independently inspected citations, selected studies, extracted data and appraised study quality, following the guidance from the Cochrane Handbook for Systematic Reviews of Interventions. For binary outcomes we calculated risk ratios (RRs) and their 95% confidence intervals (CIs). For continuous outcomes we calculated the mean differences (MDs) and their 95% CIs. We assessed risks of bias for included studies and created summary of findings tables using the GRADE approach. MAIN RESULTS: We included three studies in this review for qualitative synthesis, although one study did not report any relevant outcomes. We therefore include two studies (n = 96) in our quantitative synthesis. No data were available on the following prespecified primary outcomes: clinically-important change in general mental state, clinically-important change in negative symptoms, clinically-important change in overall quality of life, and adverse effects. As compared with active control, humour-based interventions may not improve the average endpoint score of a general mental state scale (Positive and Negative Syndrome Scale (PANSS) total score: MD -1.70, 95% CI -17.01 to 13.61; 1 study, 30 participants; very low certainty of evidence); positive symptoms (PANSS positive symptom score: MD 0.00, 95% CI -2.58 to 2.58; 1 study, 30 participants; low certainty of evidence), negative symptoms (PANSS negative symptom score: MD -0.70, 95% CI -4.22 to 2.82; 1 study, 30 participants; very low certainty of evidence) and anxiety (State-Trait Anxiety Inventory (STAI): MD -2.60, 95% CI -5.76 to 0.56; 1 study, 30 participants; low certainty of evidence). Due to the small sample size, we remain uncertain about the effect of humour-based interventions on leaving the study early as compared with active control (no event, 1 study, 30 participants; very low certainty of evidence). On the other hand, humour-based interventions may reduce depressive symptoms (Beck Depression Inventory (BDI): MD -6.20, 95% CI -12.08 to -0.32; 1 study, 30 participants; low certainty of evidence). Compared with standard care, humour-based interventions may not improve  depressive symptoms (BDI second edition: MD 0.80, 95% CI -2.64 to 4.24; 1 study, 59 participants; low certainty of evidence). We are uncertain about the effect of humour-based interventions on leaving the study early for any reason compared with standard care (risk ratio 0.38, 95% CI 0.08 to 1.80; 1 study, 66 participants; very low certainty of evidence). AUTHORS' CONCLUSIONS: We are currently uncertain whether the evidence supports the use of humour-based interventions in people with schizophrenia. Future research with rigorous and transparent methodology investigating clinically important outcomes is warranted.

A model six-month workshop for developing systematic review protocols at teaching hospitals: action research and scholarly productivity.

BACKGROUND: Research engagement contributes to the improvement of patient care. A systematic review is a suitable first scholarly activity because it entails summarization of publicly available data and usually requires neither rigorous ethical review nor research funding. METHODS: This study aimed to develop a model workshop for healthcare staff to acquire skills in creating systematic review protocols based on their own clinical questions at teaching hospitals. We used an action research method to create a model workshop at four hospitals in Japan from April 2015 to March 2017. To improve the program, we solicited reflections using participant questionnaires for each lecture and examined the quality of homework submitted by participants after each lecture. We administered a revised final version of the workshop at five hospitals from April 2016 to March 2017. We evaluated the participants' scholarly productivity related to these workshops. The observation period was a minimum of 2 years following the workshops. RESULTS: Most participants had never developed a formal clinical research protocol and voluntarily participated in the workshop. The action research was developed and implemented at nine teaching hospitals in Japan, including one university hospital. The study developed a model nine-step workshop curriculum: 1) Research question development, 2) Search strategy development, 3) Search strategy brush-up, 4) Exclusion and inclusion criteria development, 5) Risk of bias assessment planning, 6) Meta-analysis planning, 7) Subgroup and sensitivity analysis planning, 8) Planning the presentation of results, and 9) Presentation protocols. A total of 233 participants, including medical doctors and other health professionals, produced 414 research questions. Seventy-nine participants (34%) completed the workshop, and 47 review teams accomplished systematic review protocols. The participants published 13 peer-reviewed articles as a result of the workshop. CONCLUSIONS: We developed a structured scholarly productive model workshop for healthcare staff working at hospitals. We found healthcare staff with clinical subspecialties were able to develop an unexpectedly high number of research questions through this workshop. Medical teachers at hospitals with prior systematic review experience could teach how to develop systematic review protocols using this model. Further research is needed to increase the academic productivity of such workshops. TRIAL REGISTRATION: UMIN (https://www.umin.ac.jp/ctr/), UMIN000017107 (4/15/2015), UMIN000025580 (1/10/2017).

Using the Cochrane Central Register of Controlled Trials to identify clinical trial registration is insufficient: a cross-sectional study.

BACKGROUND: While conducting systemic reviews, searching for ongoing or unpublished trials is critical to address publication bias. As of April 2019, records of ongoing or unpublished randomized and/or quasi-randomized controlled trials registered in the International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov are available in the Cochrane Central Register of Controlled Trials (CENTRAL). These records registered in CENTRAL include studies published since the inception of ICTRP and ClinicalTrials.gov . Whether systematic reviewers can search CENTRAL to identify ongoing or unpublished trials instead of ICTRP and ClinicalTrials.gov is unknown. METHODS: This was a cross-sectional study. A consecutive sample of ongoing or unpublished studies published from June 1, 2019 to December 27, 2019 was selected from the Cochrane Reviews. The sensitivity and the number needed to read (NNR) were assessed from among the studies selected from CENTRAL instead of ICTRP and ClinicalTrials.gov and also assessed the characteristics of studies not identified by searching CENTRAL. RESULTS: In total, 247 records from 50 Cochrane reviews were included; of these, 200 were identified by searching CENTRAL, whereas the remaining 47 records were not. The sensitivity of searching CENTRAL was 0.81 (95% confidence interval [CI]: 0.76, 0.85). The NNR was 115 (95% CI: 101, 133). The 47 unidentified studies were registered through ClinicalTrials.gov or ICTRP. Sixteen unidentified studies were not indexed in CENTRAL. CONCLUSIONS: For systematic reviewers, searching CENTRAL could not substitute for searching ClinicalTrials.gov and/or ICTRP. Systematic reviewers should not only search CENTRAL but also ICTRP and ClinicalTrials.gov to identify unpublished trials. TRIAL REGISTRATION: A pre-specified protocol was applied to conduct this study. The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR). TRIAL REGISTRATION NUMBER: UMIN000038981 .

Correction to: Voice rehabilitation for laryngeal cancer after radiotherapy: a systematic review and meta-analysis.

In the original publication of the article, the reference 14 was published incorrectly. The correct reference is given below.

Videolaryngoscopy for transesophageal echocardiography probe insertion: a systematic review and meta-analysis of randomized controlled trials.

Transesophageal echocardiography (TEE) is a well-established procedure, but serious complications may occur. This systematic review and meta-analysis assessed the utility of videolaryngoscopy-assisted technique in TEE probe insertion. We performed a systematic search in MEDLINE, EMBASE, CENTRAL, and ICTRP. We included RCTs comparing TEE probe insertion techniques assisted with videolaryngoscopy and with any other insertion technique in adult patients. Primary outcome measures were (1) the number of attempts before successful TEE probe insertion, and (2) the risk of any procedural injury to related structures. The secondary outcome measure was time to TEE probe insertion. In total, three studies (n = 266) were included in this systematic review. Overall, a significantly less number of attempts were required with videolaryngoscopy-assisted insertion (mean difference [MD] - 0.60; 95% confidence interval [CI] - 0.73, - 0.46; low quality of evidence). Videolaryngoscopy-assisted technique was also associated with smaller risk of complications (risk ratio [RR] 0.17; 95% CI 0.05, 0.62; low quality of evidence). There was no significant difference in time to probe insertion (MD - 8.57; 95% CI - 26.31, 9.16; very low quality of evidence). The use of videolaryngoscopy for TEE probe insertion is associated with a significant reduction in the number of attempts and complication rate.

Voice rehabilitation for laryngeal cancer after radiotherapy: a systematic review and meta-analysis.

PURPOSE: We aimed to determine whether voice rehabilitation after radiotherapy improves the quality of life (QOL), voice function, and self-rated voice function in patients with laryngeal cancer. METHODS: We searched CENTRAL, MEDLINE, EMBASE, PEDro, and World Health Organization International Clinical Trials Registry Platform for randomized controlled trials published between inception and October 2018. The primary outcome was QOL, adverse events and mortality. Secondary outcomes included voice function and self-rated voice function. The quality of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Three trials (enrolling 122 patients) compared voice rehabilitation to usual care or no intervention after radiotherapy. Voice rehabilitation did not significantly improve any QOL scores. Data on adverse events and mortality were not available in any of the trials. Voice rehabilitation did not improve any voice function scores, such as jitter (mean difference: - 0.48 [- 1.27 to 0.32]), shimmer (mean difference: - 0.04 [- 0.27 to 0.19]), maximum phonation time (mean difference: 1.54 [- 1.13 to 4.22]), and the grade, roughness, breathiness, asthenia, and strain scale (mean difference: - 0.39 [- 2.59 to 1.80]). Voice rehabilitation also did not improve the voice handicap index, which was used as a self-rated voice function score (mean difference: 5.54 [- 2.07 to 13.16]). The certainty of the evidence was graded as low for primary and secondary outcomes. CONCLUSION: Voice rehabilitation for patients with laryngeal cancer after radiotherapy might not improve QOL, voice function, and self-rated voice function. Pre-specified voice rehabilitation programs may not be necessary for all patients with laryngeal cancer after radiotherapy.

Effects of hypnotics on prefrontal cortex activity during a verbal fluency task in healthy male subjects: A near-infrared spectroscopy study.

OBJECTIVE: To assess the effects of hypnotics on prefrontal cortex activity in healthy subjects using near-infrared spectroscopy (NIRS) in a double-blind, placebo-controlled crossover trial. METHODS: Eighteen healthy males received acute doses of ramelteon (8 mg), triazolam (0.125 mg), or placebo in a predetermined randomization schedule, with a washout period of more than 1 week. All subjects performed a verbal fluency task during NIRS assessments at baseline and at 1 and 4 hr post-dose. The number of words correctly generated during the task (behavioral performance) and scores on the Stanford Sleepiness Scale (SSS) were also recorded at each test time. RESULTS: Compared with the placebo, triazolam (0.125 mg) significantly decreased oxyhemoglobin (oxy-Hb) concentration change in NIRS during the posttask period and significantly increased behavioral performance, whereas triazolam (0.125 mg) and ramelteon (8 mg) significantly increased SSS scores. CONCLUSIONS: The differential effects of two types of hypnotics on oxy-Hb change measured by NIRS were observed in acute dosing, suggesting that when assessing brain activity of patients with psychiatric disorders, researchers should consider how certain types of hypnotics can influence brain function. This would also provide useful information to clinicians when prescribing hypnotics suitable for their patients' conditions.

Influence of sleep duration on cortical oxygenation in elderly individuals.

AIM: Short sleep duration is a risk factor for cardiovascular diseases. Cerebral blood flow and its regulation are affected by pathological conditions commonly observed in the elderly population, such as dementia, atherosclerosis, diabetes mellitus (DM), stroke, and hypertension. The purpose of this study was to examine the influence of sleep duration on cortical oxygenated hemoglobin (OxyHb) using near-infrared spectroscopy (NIRS). METHODS: Seventy-three individuals (age, 70.1 ± 3.9 years, 51 men and 22 women) participated in this study. Cortical OxyHb levels were measured with NIRS. We evaluated age, body mass index (BMI), smoking status, alcohol intake, sleep duration, hypertension, DM, and hyperlipidemia using a questionnaire. Blood pressure was measured using plethysmography. RESULTS: Peak OxyHb and area under the NIRS curve significantly decreased in participants with sleep duration <7 h compared with those with sleep duration ≥7 h (0.136 ± 0.212 mM·mm vs 0.378 ± 0.342 mM·mm, P = 0.001; 112.0 ± 243.6 vs 331.7 ± 428.7, P = 0.012, respectively). Sleep duration was significantly correlated with peak OxyHb level and area under the NIRS curve (r = 0.378, P = 0.001; r = 0.285, P = 0.015, respectively). Multiple regression analysis, including age, BMI, sex, smoking status, alcohol intake, sleep duration, hypertension, DM, and hyperlipidemia revealed that sleep duration was the only significant independent factor associated with peak OxyHb and area under the NIRS curve (ß = 0.343, P = 0.004; ß = 0.244, P = 0.049, respectively), and smoking status was independently correlated with time to the peak OxyHb (ß = -0.319, P = 0.009). CONCLUSION: Sleep duration may be an important factor that influences cortical oxygenation in the elderly population.

Investigation of single-nucleotide variants in MBD5 associated with autism spectrum disorders and schizophrenia phenotypes.

MBD5 (Methyl-CpG-binding domain 5) is a critical gene for normal development. While deletion or duplication of MBD5 may contribute to a genetic predisposition to autism spectrum disorders (ASD), intellectual disability, or epilepsy, the impact of rare MBD5 single nucleotide variants (SNVs) on neurodevelopmental features, particularly features with late onset, has not been fully explored. In this study, we conducted exon-targeted resequencing of MBD5 with next-generation sequencing technology in 562 Japanese patients (192 with idiopathic ASD and 370 with schizophrenia (SCZ)) and detected 16 MBD5 SNVs with allele frequencies of ≤1%. We then performed phenotype analyses with 12 novel variants of these 16 SNVs. SCZ patients with these variants exhibited mainly within normal development ranges until the first psychosis and ASD patients with SNVs did not precisely overlap with the core characteristics described in previous literature as being associated with MBD5 SNVs. Our results suggested that MBD5 variants might contribute to a broad spectrum of neurodevelopmental pathophysiology. Further research and assessment of clinical diagnostic screening are necessary for understanding the burden of rare MBD5 SNVs for these neurodevelopmental disorders.