The short-term and long-term adverse effects of melatonin treatment in children and adolescents: a systematic review and GRADE assessment.

Background: Currently, melatonin is used to treat children and adolescents with insomnia without knowing the full extent of the short-term and long-term consequences. Our aim was to provide clinicians and guideline panels with a systematic assessment of serious-and non-serious adverse events seen in continuation of melatonin treatment and the impact on pubertal development and bone health following long-term administration in children and adolescents with chronic insomnia. Methods: We searched PubMed, Embase, Cinahl and PsycINFO via Ovid, up to March 17, 2023, for studies on melatonin treatment among children and adolescents (aged 5-20 years) with chronic insomnia. The language was restricted to English, Danish, Norwegian, and Swedish. Outcomes were non-serious adverse events and serious adverse events assessed 2-4 weeks after initiating treatment and pubertal development and bone health, with no restriction on definition or time of measurement. Observational studies were included for the assessment of long-term outcomes, and serious and non-serious adverse events were assessed via randomised studies. The certainty of the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The protocol is registered with the Danish Health Authority. Findings: We identified 22 randomised studies with 1350 patients reporting on serious-and non-serious adverse events and four observational studies with a total of 105 patients reporting on pubertal development. Melatonin was not associated with serious adverse events, yet the number of patients experiencing non-serious adverse events was increased (Relative risk 1.56, 95% CI 1.01-2.43, 17 studies, I2 = 47%). Three studies reported little or no influence on pubertal development following 2-4 years of treatment, whereas one study registered a potential delay following longer treatment durations (>7 years). These findings need further evaluation due to several methodological limitations. Interpretation: Children who use melatonin are likely to experience non-serious adverse events, yet the actual extent to which melatonin leads to non-serious adverse events and the long-term consequences remain uncertain. This major gap of knowledge on safety calls for caution against complacent use of melatonin in children and adolescents with chronic insomnia and for more research to inform clinicians and guideline panels on this key issue. Funding: The Danish Health Authority. The Parker Institute, Bispebjerg and Frederiksberg Hospital, supported by the Oak Foundation.

Use of melatonin for children and adolescents with chronic insomnia attributable to disorders beyond indication: a systematic review, meta-analysis and clinical recommendation.

Background: Melatonin has become a widely used sleeping aid for young individuals currently not included in existing guidelines. The aim was to develop a recommendation on the use of melatonin in children and adolescents aged 2-20 years, with chronic insomnia due to disorders beyond indication. Methods: We performed a systematic search for guidelines, systematic reviews, and randomised trials (RCTs) in Medline, Embase, Cochrane Library, PsycInfo, Cinahl, Guidelines International Network, Trip Database, Canadian Agency for Drugs and Technologies in Health, American Academy of Sleep Medicine, European Sleep Research Society and Scandinavian Health Authorities databases. A separate search for adverse events was also performed. The latest search for guidelines, systematic reviews, and adverse events was performed on March 17, 2023. The latest search for RCTs was performed on to February 6, 2023. The language was restricted to English, Danish, Norwegian, and Swedish. Eligible participants were children and adolescents (2-20 years of age) with chronic insomnia due to underlying disorders, in whom sleep hygiene practices have been inadequate and melatonin was tested. Studies exclusively on autism spectrum disorders or attention deficit hyperactive disorder were excluded. There were no restrictions on dosage, duration of treatment, time of consumption or release formula. Primary outcomes were quality of sleep, daytime functioning and serious adverse events, assessed at 2-4 weeks post-treatment. Secondary outcomes included total sleep time, sleep latency, awakenings, drowsiness, quality of life, non-serious adverse events, and all-cause dropouts (assessed at 2-4 weeks post-treatment), plus quality of sleep and daytime functioning (assessed at 3-6 months post-treatment). Pooled estimates were calculated using inverse variance random effects model. Statistical heterogeneity was calculated using I2 statistics. Risk of bias was assessed using Cochrane risk of bias tool. Publication bias was assessed using funnel plots. A multidisciplinary guideline panel constructed the recommendation using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The certainty of evidence was considered either high, moderate, low or very low depending on the extent of risk of bias, inconsistency, imprecision, indirectness, or publication bias. The evidence-to-decision framework was used to discuss the feasibility and acceptance of the constructed recommendation and its impact on resources and equity. The protocol is registered with the Danish Health Authority. Findings: We identified 13 RCTs, including 403 patients with a wide range of conditions. Melatonin reduced sleep latency by 14.88 min (95% CI 23.42-6.34, 9 studies, I2 = 60%) and increased total sleep time by 18.97 min (95% CI 0.37-37.57, 10 studies, I2 = 57%). The funnel plot for total sleep time showed no apparent indication of publication bias. No other clinical benefits were found. The number of patients experiencing adverse events was not statistically increased however, safety data was scarce. Certainty of evidence was low. Interpretation: Low certainty evidence supports a moderate effect of melatonin in treating sleep continuity parameters in children and adolescents with chronic insomnia due to primarily medical disorders beyond indication. The off-label use of melatonin for these patients should never be the first choice of treatment, but may be considered by medical specialists with knowledge of the underlying disorder and if non-pharmacological interventions are inadequate. If treatment with melatonin is initiated, adequate follow-up to evaluate treatment effect and adverse events is essential. Funding: The Danish Health Authority. The Parker Institute, Bispebjerg and Frederiksberg Hospital, supported by the Oak Foundation.

Use of melatonin in children and adolescents with idiopathic chronic insomnia: a systematic review, meta-analysis, and clinical recommendation.

Background: Melatonin prescriptions for children and adolescents have increased substantially during the last decade. Existing clinical recommendations focus on melatonin as a treatment for insomnia related to neurodevelopmental disorders. To help guide clinical decision-making, we aimed to construct a recommendation on the use of melatonin in children and adolescents aged 5-20 years with idiopathic chronic insomnia. Methods: A systematic search for guidelines, systematic reviews and randomised controlled trials (RCT) were performed in Medline, Embase, Cochrane Library, PsycInfo, Cinahl, Guidelines International Network, Trip Database, Canadian Agency for Drugs and Technologies in Health, American Academy of Sleep Medicine, European Sleep Research Society and Scandinavian Health Authorities databases. A search for adverse events in otherwise healthy children and adolescents was also performed. The latest search for guidelines, systematic reviews, and adverse events was performed on March 18, 2023. The latest search for RCTs was performed on to February 6, 2023. The language was restricted to English, Danish, Norwegian, and Swedish. Eligible participants were children and adolescents (5-20 years of age) with idiopathic chronic insomnia, in whom sleep hygiene practices have been inadequate and melatonin was tested. There were no restrictions on dosage, duration of treatment, time of consumption, or release formula. Primary outcomes were quality of sleep, daytime functioning and serious adverse events. Secondary outcomes included total sleep time, sleep latency, awakenings, drowsiness, quality of life, all-cause dropouts, and non-serious adverse events. Outcomes were assessed at different time points to assess short-term and long-term effects. Meta-analysis was performed using inverse variance random-effects model and risk of bias was assessed using Cochrane risk of bias tool. If possible, funnel plots would be constructed to investigate publication bias. Heterogeneity was calculated via I2 statistics. A multidisciplinary guideline panel formulated the recommendation according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). The certainty of evidence was considered either high, moderate, low or very low depending on the extent of risk of bias, inconsistency, imprecision, indirectness, or publication bias. The evidence-to-decision framework was subsequently used to discuss the feasibility and acceptance of the constructed recommendation alongside the impact on resources and equity. The protocol is registered with the Danish Health Authority. Findings: We included eight RCTs with 419 children and adolescents with idiopathic chronic insomnia. Melatonin led to a moderate increase in total sleep time by 30.33 min (95% confidence interval (CI) 18.96-41.70, 4 studies, I2 = 0%) and a moderate reduction in sleep latency by 18.03 min (95% CI -26.61 to -9.44, 3 studies, I2 = 0%), both as assessed by sleep diary. No other beneficial effects were found. None of the studies provided information on serious adverse events, yet the number of participants experiencing non-serious adverse events was increased (Relative risk 3.44, 95% CI 1.25-9.42, 4 studies, I2 = 0%). Funnel plots were not constructed due to the low number of studies. The certainty of evidence was very low on the quality of sleep and low for daytime functioning. Interpretation: Evidence of very low certainty shows that benefits are limited and unwanted events are likely when melatonin is used to treat otherwise healthy children and adolescents with chronic insomnia. Melatonin should never be the first choice of treatment for this particular population, yet carefully monitored short-term use may be considered if sleep hygiene practices and non-pharmacological interventions have proven inadequate, and only if daytime function is compromised. Funding: The Danish Health Authority and the Parker Institute, Bispebjerg and Frederiksberg Hospital supported by the Oak Foundation.

Usefulness of Cochrane Reviews in Clinical Guideline Development-A Survey of 585 Recommendations.

The Danish Health Authority develops clinical practice guidelines to support clinical decision-making based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system and prioritizes using Cochrane reviews. The objective of this study was to explore the usefulness of Cochrane reviews as a source of evidence in the development of clinical recommendations. Evidence-based recommendations in guidelines published by the Danish Health Authority between 2014 and 2021 were reviewed. For each recommendation, it was noted if and how Cochrane reviews were utilized. In total, 374 evidence-based recommendations and 211 expert consensus recommendations were published between 2014 and 2021. Of the 374 evidence-based recommendations, 106 included evidence from Cochrane reviews. In 28 recommendations, all critical and important outcomes included evidence from Cochrane reviews. In 36 recommendations, a minimum of all critical outcomes included evidence from Cochrane reviews, but not all important outcomes. In 33 recommendations, some but not all critical outcomes included evidence from Cochrane reviews. Finally, in nine recommendations, some of the important outcomes included evidence from Cochrane reviews. In almost one-third of the evidence-based recommendations, Cochrane reviews were used to inform clinical recommendations. This evaluation should inform future evaluations of Cochrane review uptake in clinical practice guidelines concerning outcomes important for clinical decision-making.

Supervised Training Compared With No Training or Self-training in Patients With Subacromial Pain Syndrome: A Systematic Review and Meta-analysis.

OBJECTIVE: To study the effects of supervised training in adults with subacromial pain syndrome. DATA SOURCES: Embase, MEDLINE, Cochrane Library, Cumulative Index to Nursing and Allied Health, and Physiotherapy Evidence Database were searched from inception to March 2020. STUDY SELECTION: Independent reviewers selected randomized controlled trials comparing supervised training with (1) no training or (2) self-training in adults with subacromial pain syndrome lasting for at least 1 month. Critical outcomes were shoulder pain, function, and patient-perceived effect. Important outcomes included other potential benefits and adverse events at 3-month follow-up. DATA EXTRACTION: Two independent reviewers extracted data for the meta-analysis. Risk of bias was assessed using the Cochrane Risk of Bias tool 1, and certainty of evidence was evaluated using the Grades of Recommendation Assessment, Development, and Evaluation (GRADE). DATA SYNTHESIS: Ten studies (n=597, 43% female) were included. Supervised training resulted in larger improvements than no training on pain (at rest: n=286; mean difference [MD], 1.68; 95% confidence interval [CI], 0.31-3.06 on 0-10 scale; during movement: n=353; MD, 1.84; 95% CI,0.91-2.76), function (n=396; standardized MD, 0.30; 95% CI, 0.07-0.52), and patient-perceived effect (n=118; risk ratio, 1.43; 95% CI, 0.87-2.34). Supervised training had potential benefits regarding quality of life, return to work, dropout, and training adherence, albeit more patients reported mild, transient pain after training. Supervised training and self-training showed equal improvements on pain (n=44) and function (n=76), with no data describing patient-perceived effect. Certainty of evidence was low for critical outcomes and low-moderate for other outcomes. CONCLUSIONS: Supervised training might be superior to no training and equally effective as self-training on critical and important outcomes. Based on low-moderate certainty of evidence, these findings support a weak recommendation for supervised training in adults with subacromial pain syndrome.

Early enteral nutrition within 24 hours of lower gastrointestinal surgery versus later commencement for length of hospital stay and postoperative complications.

BACKGROUND: This is an update of the review last published in 2011. It focuses on early postoperative enteral nutrition after lower gastrointestinal surgery. Traditional management consisted of 'nil by mouth', where patients receive fluids followed by solids after bowel function has returned. Although several trials have reported lower incidence of infectious complications and faster wound healing upon early feeding, other trials have shown no effect. The immediate advantage of energy intake (carbohydrates, protein or fat) could enhance recovery with fewer complications, and this warrants a systematic evaluation. OBJECTIVES: To evaluate whether early commencement of postoperative enteral nutrition (within 24 hours), oral intake and any kind of tube feeding (gastric, duodenal or jejunal), compared with traditional management (delayed nutritional supply) is associated with a shorter length of hospital stay (LoS), fewer complications, mortality and adverse events in patients undergoing lower gastrointestinal surgery (distal to the ligament of Treitz). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library 2017, issue 10), Ovid MEDLINE (1950 to 15 November 2017), Ovid Embase (1974 to 15 November 2017). We also searched for ongoing trials in ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (15 November 2017). We handsearched reference lists of identified studies and previous systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCT) comparing early commencement of enteral nutrition (within 24 hours) with no feeding in adult participants undergoing lower gastrointestinal surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study quality using the Cochrane 'Risk of bias' tool tailored to this review and extracted data. Data analyses were conducted according to the Cochrane recommendations.We rated the quality of evidence according to GRADE.Primary outcomes were LoS and postoperative complications (wound infections, intraabdominal abscesses, anastomotic dehiscence, pneumonia).Secondary outcomes were: mortality, adverse events (nausea, vomiting), and quality of life (QoL).LoS was estimated using mean difference (MD (presented as mean +/- SD). For other outcomes we estimated the common risk ratio (RR) and calculated the associated 95% confidence intervals. For analysis, we used an inverse-variance random-effects model for the primary outcome (LoS) and Mantel-Haenszel random-effects models for the secondary outcomes. We also performed Trial Sequential Analyses (TSA). MAIN RESULTS: We identified 17 RCTs with 1437 participants undergoing lower gastrointestinal surgery. Most studies were at high or unclear risk of bias in two or more domains. Six studies were judged as having low risk of selection bias for random sequence generation and insufficient details were provided for judgement on allocation concealment in all 17 studies. With regards to performance and deception bias; 14 studies reported no attempt to blind participants and blinding of personnel was not discussed either. Only one study was judged as low risk of bias for blinding of outcome assessor. With regards to incomplete outcome data, three studies were judged to be at high risk because they had more than 10% difference in missing data between groups. For selective reporting, nine studies were judged as unclear as protocols were not provided and eight studies had issues with either missing data or incomplete reporting of results.LOS was reported in 16 studies (1346 participants). The mean LoS ranged from four days to 16 days in the early feeding groups and from 6.6 days to 23.5 days in the control groups. Mean difference (MD) in LoS was 1.95 (95% CI, -2.99 to -0.91, P < 0.001) days shorter in the early feeding group. However, there was substantial heterogeneity between included studies (I2 = 81, %, Chi2 = 78.98, P < 0.00001), thus the overall quality of evidence for LoS is low. These results were confirmed by the TSA showing that the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit.We found no differences in the incidence of postoperative complications: wound infection (12 studies, 1181 participants, RR 0.99, 95%CI 0.64 to 1.52, very low-quality evidence), intraabdominal abscesses (6 studies, 554 participants, RR 1.00, 95%CI 0.26 to 3.80, low-quality evidence), anastomotic leakage/dehiscence (13 studies, 1232 participants, RR 0.78, 95%CI 0.38 to 1.61, low-quality evidence; number needed to treat for an additional beneficial outcome (NNTB) = 100), and pneumonia (10 studies, 954 participants, RR 0.88, 95%CI 0.32 to 2.42, low-quality evidence; NNTB = 333).Mortality was reported in 12 studies (1179 participants), and showed no between-group differences (RR = 0.56, 95%CI, 0.21 to 1.52, P = 0.26, I2 = 0%, Chi2 = 3.08, P = 0.96, low-quality evidence). The most commonly reported cause of death was anastomotic leakage, sepsis and acute myocardial infarction.Seven studies (613 participants) reported vomiting (RR 1.23, 95%CI, 0.96 to 1.58, P = 0.10, I2 = 0%, Chi2 = 4.98, P = 0.55, low-quality evidence; number needed to treat for an additional harmful outcome (NNTH) = 19), and two studies (118 participants) reported nausea (RR 0.95, 0.71 to 1.26, low-quality evidence). Four studies reported combined nausea and vomiting (RR 0.94, 95%CI 0.51 to 1.74, very low-quality evidence). One study reported QoL assessment; the scores did not differ between groups at 30 days after discharge on either QoL scale EORTC QLQ-C30 or EORTC QlQ-OV28 (very low-quality evidence). AUTHORS' CONCLUSIONS: This review suggests that early enteral feeding may lead to a reduced postoperative LoS, however cautious interpretation must be taken due to substantial heterogeneity and low-quality evidence. For all other outcomes (postoperative complications, mortality, adverse events, and QoL) the findings are inconclusive, and further trials are justified to enhance the understanding of early feeding for these. In this updated review, only a few additional studies have been included, and these were small and of poor quality.To improve the evidence, future trials should address quality issues and focus on clearly defining and measuring postoperative complications to allow for better comparison between studies. However due to the introduction of fast track protocols which already include an early feeding component, future trials may be challenging. A more feasible trial may be to investigate the effect of differing postoperative energy intake regimens on relevant outcomes.

Early enteral nutrition within 24 hours of lower gastrointestinal surgery versus later commencement for length of hospital stay and postoperative complications.

BACKGROUND: This is an update of the review last published in 2011. It focuses on early postoperative enteral nutrition after lower gastrointestinal surgery. Traditional management consisted of 'nil by mouth', where patients receive fluids followed by solids after bowel function has returned. Although several trials have reported lower incidence of infectious complications and faster wound healing upon early feeding, other trials have shown no effect. The immediate advantage of energy intake (carbohydrates, protein or fat) could enhance recovery with fewer complications, and this warrants a systematic evaluation. OBJECTIVES: To evaluate whether early commencement of postoperative enteral nutrition (within 24 hours), oral intake and any kind of tube feeding (gastric, duodenal or jejunal), compared with traditional management (delayed nutritional supply) is associated with a shorter length of hospital stay (LoS), fewer complications, mortality and adverse events in patients undergoing lower gastrointestinal surgery (distal to the ligament of Treitz). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library 2017, issue 10), Ovid MEDLINE (1950 to 15 November 2017), Ovid Embase (1974 to 15 November 2017). We also searched for ongoing trials in ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (15 November 2017). We handsearched reference lists of identified studies and previous systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCT) comparing early commencement of enteral nutrition (within 24 hours) with no feeding in adult participants undergoing lower gastrointestinal surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study quality using the Cochrane 'Risk of bias' tool tailored to this review and extracted data. Data analyses were conducted according to the Cochrane recommendations.We rated the quality of evidence according to GRADE.Primary outcomes were LoS and postoperative complications (wound infections, intraabdominal abscesses, anastomotic dehiscence, pneumonia).Secondary outcomes were: mortality, adverse events (nausea, vomiting), and quality of life (QoL).LoS was estimated using mean difference (MD (presented as mean +/- SD). For other outcomes we estimated the common risk ratio (RR) and calculated the associated 95% confidence intervals. For analysis, we used an inverse-variance random-effects model for the primary outcome (LoS) and Mantel-Haenszel random-effects models for the secondary outcomes. We also performed Trial Sequential Analyses (TSA). MAIN RESULTS: We identified 17 RCTs with 1437 participants undergoing lower gastrointestinal surgery. Most studies were at high or unclear risk of bias in two or more domains. Six studies were judged as having low risk of selection bias for random sequence generation and insufficient details were provided for judgement on allocation concealment in all 17 studies. With regards to performance and deception bias; 14 studies reported no attempt to blind participants and blinding of personnel was not discussed either. Only one study was judged as low risk of bias for blinding of outcome assessor. With regards to incomplete outcome data, three studies were judged to be at high risk because they had more than 10% difference in missing data between groups. For selective reporting, nine studies were judged as unclear as protocols were not provided and eight studies had issues with either missing data or incomplete reporting of results.LOS was reported in 16 studies (1346 participants). The mean LoS ranged from four days to 16 days in the early feeding groups and from 6.6 days to 23.5 days in the control groups. Mean difference (MD) in LoS was 1.95 (95% CI, -2.99 to -0.91, P < 0.001) days shorter in the early feeding group. However, there was substantial heterogeneity between included studies (I2 = 81, %, Chi2 = 78.98, P < 0.00001), thus the overall quality of evidence for LoS is low. These results were confirmed by the TSA showing that the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit.We found no differences in the incidence of postoperative complications: wound infection (12 studies, 1181 participants, RR 0.99, 95%CI 0.64 to 1.52, very low-quality evidence), intraabdominal abscesses (6 studies, 554 participants, RR 1.00, 95%CI 0.26 to 3.80, low-quality evidence), anastomotic leakage/dehiscence (13 studies, 1232 participants, RR 0.78, 95%CI 0.38 to 1.61, low-quality evidence; number needed to treat for an additional beneficial outcome (NNTB) = 100), and pneumonia (10 studies, 954 participants, RR 0.88, 95%CI 0.32 to 2.42, low-quality evidence; NNTB = 333).Mortality was reported in 12 studies (1179 participants), and showed no between-group differences (RR = 0.56, 95%CI, 0.21 to 1.52, P = 0.26, I2 = 0%, Chi2 = 3.08, P = 0.96, low-quality evidence). The most commonly reported cause of death was anastomotic leakage, sepsis and acute myocardial infarction.Seven studies (613 participants) reported vomiting (RR 1.23, 95%CI, 0.96 to 1.58, P = 0.10, I2 = 0%, Chi2 = 4.98, P = 0.55, low-quality evidence; number needed to treat for an additional harmful outcome (NNTH) = 19), and two studies (118 participants) reported nausea (RR 0.95, 0.71 to 1.26, low-quality evidence). Four studies reported combined nausea and vomiting (RR 0.94, 95%CI 0.51 to 1.74, very low-quality evidence). One study reported QoL assessment; the scores did not differ between groups at 30 days after discharge on either QoL scale EORTC QLQ-C30 or EORTC QlQ-OV28 (very low-quality evidence). AUTHORS' CONCLUSIONS: This review suggests that early enteral feeding may lead to a reduced postoperative LoS, however cautious interpretation must be taken due to substantial heterogeneity and low-quality evidence. For all other outcomes (postoperative complications, mortality, adverse events, and QoL) the findings are inconclusive, and further trials are justified to enhance the understanding of early feeding for these. In this updated review, only a few additional studies have been included, and these were small and of poor quality.To improve the evidence, future trials should address quality issues and focus on clearly defining and measuring postoperative complications to allow for better comparison between studies. However due to the introduction of fast track protocols which already include an early feeding component, future trials may be challenging. A more feasible trial may be to investigate the effect of differing postoperative energy intake regimens on relevant outcomes.

A systematic review and meta-analysis of nutrition therapy compared with dietary advice in patients with type 2 diabetes.

Background: Despite recommendations, many patients with type 2 diabetes receive dietary advice from nurses or doctors instead of individualized nutrition therapy (INT) that is provided by a dietitian.Objective: We performed a meta-analysis to compare the effect of INT that is provided by a registered dietitian with the effect of dietary advice that is provided by other healthcare professionals.Design: A systematic review was conducted of Cochrane library databases, EMBASE, CINAHL, and MEDLINE in the period 2004-2017 for guidelines, reviews, and randomized controlled trials (RCTs) that assessed the outcomes glycated hemoglobin (HbA1c), weight, body mass index (BMI; in kg/m2), and LDL cholesterol. Risk of bias and the quality of evidence were assessed according to the Grading of Recommendations Assessment, Development and Evaluation guidelines.Results: We identified 5 RCTs comprising 912 participants in total. In the first year of intervention (at 6 or 12 mo), nutrition therapy compared with dietary advice was followed by a 0.45% (95% CI: 0.36%, 0.53%) lower mean difference in HbA1c, a 0.55 (95% CI: 0.02, 1.1) lower BMI, a 2.1-kg (95% CI: 1.2-, 2.9-kg) lower weight, and a 0.17-mmol/L (95% CI: 0.11-, 0.23-mmol/L) lower LDL cholesterol. No longer-term data were available. Some of the included studies had a potential bias, and therefore, the quality of the evidence was low or moderate. In addition, it was necessary to pool primary and secondary outcomes.Conclusions: INT that is provided by a dietitian compared with dietary advice that is provided by other health professionals leads to a greater effect on HbA1c, weight, and LDL cholesterol. Because of the potential bias, we recommend considering nutrition therapy that is provided by a dietitian as part of lifestyle intervention in type 2 diabetes, but further randomized studies are warranted.

Chewing gum for postoperative recovery of gastrointestinal function.

BACKGROUND: Ileus commonly occurs after abdominal surgery, and is associated with complications and increased length of hospital stay (LOHS). Onset of ileus is considered to be multifactorial, and a variety of preventative methods have been investigated. Chewing gum (CG) is hypothesised to reduce postoperative ileus by stimulating early recovery of gastrointestinal (GI) function, through cephalo-vagal stimulation. There is no comprehensive review of this intervention in abdominal surgery. OBJECTIVES: To examine whether chewing gum after surgery hastens the return of gastrointestinal function. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via Ovid), MEDLINE (via PubMed), EMBASE (via Ovid), CINAHL (via EBSCO) and ISI Web of Science (June 2014). We hand-searched reference lists of identified studies and previous reviews and systematic reviews, and contacted CG companies to ask for information on any studies using their products. We identified proposed and ongoing studies from clinicaltrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform and metaRegister of Controlled Trials. SELECTION CRITERIA: We included completed randomised controlled trials (RCTs) that used postoperative CG as an intervention compared to a control group. DATA COLLECTION AND ANALYSIS: Two authors independently collected data and assessed study quality using an adapted Cochrane risk of bias (ROB) tool, and resolved disagreements by discussion. We assessed overall quality of evidence for each outcome using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). Studies were split into subgroups: colorectal surgery (CRS), caesarean section (CS) and other surgery (OS). We assessed the effect of CG on time to first flatus (TFF), time to bowel movement (TBM), LOHS and time to bowel sounds (TBS) through meta-analyses using a random-effects model. We investigated the influence of study quality, reviewers' methodological estimations and use of Enhanced Recovery After Surgery (ERAS) programmes using sensitivity analyses. We used meta-regression to explore if surgical site or ROB scores predicted the extent of the effect estimate of the intervention on continuous outcomes. We reported frequency of complications, and descriptions of tolerability of gum and cost. MAIN RESULTS: We identified 81 studies that recruited 9072 participants for inclusion in our review. We categorised many studies at high or unclear risk of the bias' assessed. There was statistical evidence that use of CG reduced TFF [overall reduction of 10.4 hours (95% CI: -11.9, -8.9): 12.5 hours (95% CI: -17.2, -7.8) in CRS, 7.9 hours (95% CI: -10.0, -5.8) in CS, 10.6 hours (95% CI: -12.7, -8.5) in OS]. There was also statistical evidence that use of CG reduced TBM [overall reduction of 12.7 hours (95% CI: -14.5, -10.9): 18.1 hours (95% CI: -25.3, -10.9) in CRS, 9.1 hours (95% CI: -11.4, -6.7) in CS, 12.3 hours (95% CI: -14.9, -9.7) in OS]. There was statistical evidence that use of CG slightly reduced LOHS [overall reduction of 0.7 days (95% CI: -0.8, -0.5): 1.0 days in CRS (95% CI: -1.6, -0.4), 0.2 days (95% CI: -0.3, -0.1) in CS, 0.8 days (95% CI: -1.1, -0.5) in OS]. There was statistical evidence that use of CG slightly reduced TBS [overall reduction of 5.0 hours (95% CI: -6.4, -3.7): 3.21 hours (95% CI: -7.0, 0.6) in CRS, 4.4 hours (95% CI: -5.9, -2.8) in CS, 6.3 hours (95% CI: -8.7, -3.8) in OS]. Effect sizes were largest in CRS and smallest in CS. There was statistical evidence of heterogeneity in all analyses other than TBS in CRS.There was little difference in mortality, infection risk and readmission rate between the groups. Some studies reported reduced nausea and vomiting and other complications in the intervention group. CG was generally well-tolerated by participants. There was little difference in cost between the groups in the two studies reporting this outcome.Sensitivity analyses by quality of studies and robustness of review estimates revealed no clinically important differences in effect estimates. Sensitivity analysis of ERAS studies showed a smaller effect size on TFF, larger effect size on TBM, and no difference between groups for LOHS.Meta-regression analyses indicated that surgical site is associated with the extent of the effect size on LOHS (all surgical subgroups), and TFF and TBM (CS and CRS subgroups only). There was no evidence that ROB score predicted the extent of the effect size on any outcome. Neither variable explained the identified heterogeneity between studies. AUTHORS' CONCLUSIONS: This review identified some evidence for the benefit of postoperative CG in improving recovery of GI function. However, the research to date has primarily focussed on CS and CRS, and largely consisted of small, poor quality trials. Many components of the ERAS programme also target ileus, therefore the benefit of CG alongside ERAS may be reduced, as we observed in this review. Therefore larger, better quality RCTS in an ERAS setting in wider surgical disciplines would be needed to improve the evidence base for use of CG after surgery.