American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

Comparative efficacy and safety of biologic therapies for moderate-to-severe Crohn's disease: a systematic review and network meta-analysis.

BACKGROUND: Data are needed to inform the positioning of biologic therapy in the treatment of moderate-to-severe Crohn's disease, both first line and after previous biologic exposure. We aimed to assess the comparative efficacy and safety of biologics in patients with Crohn's disease. METHODS: We did a systematic review and network meta-analysis of phase 2 and phase 3 randomised controlled trials done in adults (≥18 years) with moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220-450) treated with tumour necrosis factor (TNF) antagonists, anti-integrin, anti-interleukin (IL)-12 and IL-23p40, or anti-IL23p19 agents, either alone or in combination with immunosuppressants, as their first-line biologic or after previous biologic exposure, compared with placebo or an active comparator. The minimum duration of therapy was 14 days for trials reporting induction of remission in active disease and 22 weeks in trials reporting maintenance of remission. We searched Medline, EMBASE, the Cochrane CENTRAL Register of Controlled Trials, conference proceedings, trial registries, and unpublished data from inception to June 3, 2021, without any language restrictions. Summary estimates of the primary and secondary outcomes were extracted from the published reports; individual patient-level data were not sought. The primary endpoint was induction of clinical remission in patients with active disease (CDAI <150) and maintenance of remission in patients with response to induction therapy, with data extracted from published reports. A network meta-analysis with multivariate consistency model random-effects meta-regression was done, with rankings based on surface under the cumulative ranking curve (SUCRA) values. FINDINGS: The search strategy yielded 18 382 citations, of which 31 trials were eligible for inclusion. On the basis of 15 randomised controlled trials including 2931 biologic-naive patients, infliximab monotherapy (odds ratio [OR] 4·53 [95% CI 1·49-13·79]), infliximab combined with azathioprine (7·49 [2·04-27·49]), adalimumab (3·01 [1·25-7·27]), and ustekinumab (2·63 [1·10-6·28]) were associated with significantly higher odds of inducing remission compared to certolizumab pegol (all moderate confidence); infliximab and azathioprine combination therapy was also associated with significantly higher odds of inducing remission than vedolizumab (3·76 [1·01-14·03]; low confidence). On the basis of ten randomised controlled trials including 2479 patients with previous biologic exposure, adalimumab after loss of response to infliximab (OR 2·82 [95% CI 1·20-6·62]; low confidence), and risankizumab (2·10 [1·12-3·92]; moderate confidence), were associated with higher odds of inducing remission than vedolizumab. No differences between active interventions were observed in maintenance trials. Most trials were at low or uncertain risk of bias. INTERPRETATION: Although biologic treatment choices in patients with moderate-to-severe Crohn's disease must be individualised for each patient, this analysis suggests that either infliximab with azathioprine or adalimumab might be preferred as a first-line therapy, and adalimumab (after infliximab loss of response) or risankizumab might be preferred as a second-line therapy, for induction of clinical remission. FUNDING: None.

AGA Technical Review on Intragastric Balloons in the Management of Obesity.

Several strategies are available to address the obesity epidemic and range from noninvasive lifestyle interventions to medications and bariatric surgical procedures. Endoscopic bariatric techniques, such as intragastric balloons, have become an attractive alternative as a tool for weight loss that can augment the effect of lifestyle interventions. This technical review includes multiple systematic reviews performed to support a clinical practice guideline by the American Gastroenterological Association on the role of intragastric balloons as a tool for weight loss. The systematic reviews targeted a priori selected clinical questions about the effectiveness and periprocedural care of intragastric balloons and concomitant and subsequent weight-loss strategies.

Effect of omega-3 fatty acids on systemic lupus erythematosus disease activity: A systematic review and meta-analysis.

OBJECTIVE: Omega-3 fatty acids may decrease systemic lupus erythematosus (SLE) disease activity, however randomized controlled trials (RCT) have been small with conflicting findings. We conducted a systematic review and meta-analysis to estimate the effect of omega-3 fatty acids on SLE disease activity in adults. METHODS: A literature search was conducted from database inception to January 2020. RCTs of adults with SLE comparing omega-3 fatty acids supplementation to placebo or standard of care that evaluated SLE disease activity were included. Abstracts, full text reviews, data abstraction and statistical analysis were evaluated independently by two investigators. Study-specific standardized mean differences (SMD) were estimated and combined using random-effects model. RESULTS: Five RCTs with 136 patients in the comparison groups and 138 in the treatment groups, were included. All the studies used ≤3 g of omega-3 fatty acids. The trial follow-up time ranged from 12 to 52 weeks. The mean age of the patients was 43 years and 80% or more were female. Omega-3 fatty acids reduced SLE activity [SMD -0.33 (95CI: -0.57, -0.09), low certainty evidence, moderate effect size]. Transforming the SMD to the SLE Disease Activity Index (SLEDAI) scale, omega-3 fatty acids reduced disease activity by 0.9 (95CI: -1.6, -0.3, I2 = 0%) SLEDAI points compared to placebo. CONCLUSION: This meta-analysis suggests that omega-3 fatty acids could provide therapeutic benefit in addition to immunosuppressive regimens used for SLE.

Targeted Therapy- and Chemotherapy-Associated Skin Toxicities: Systematic Review and Meta-Analysis.

PROBLEM IDENTIFICATION: Preventing and managing skin toxicities can minimize treatment disruptions and improve well-being. This systematic review aimed to evaluate the effectiveness of interventions for the prevention and management of cancer treatment-related skin toxicities. LITERATURE SEARCH: The authors systematically searched for comparative studies published before April 1, 2019. Study selection and appraisal were conducted by pairs of independent reviewers. DATA EVALUATION: The random-effects model was used to conduct meta-analysis when appropriate. SYNTHESIS: 39 studies (6,006 patients) were included; 16 of those provided data for meta-analysis. Prophylactic minocycline reduced the development of all-grade and grade 1 acneform rash in patients who received erlotinib. Prophylaxis with pyridoxine 400 mg in capecitabine-treated patients lowered the risk of grade 2 or 3 hand-foot syndrome. Several treatments for hand-foot skin reaction suggested benefit in heterogeneous studies. Scalp cooling significantly reduced the risk for severe hair loss or total alopecia associated with chemotherapy. IMPLICATIONS FOR RESEARCH: Certainty in the available evidence was limited for several interventions, suggesting the need for future research. SUPPLEMENTAL MATERIAL CAN BE FOUND AT&NBSP;HTTPS: //onf.ons.org/supplementary-material-targeted-therapy-and-chemotherapy-associated-skin-toxicity-systematic-review.

A phase 2B randomised trial of hyperbaric oxygen therapy for ulcerative colitis patients hospitalised for moderate to severe flares.

BACKGROUND: Hyperbaric oxygen has been reported to improve disease activity in hospitalised ulcerative colitis (UC) patients. AIM: To evaluate dosing strategies with hyperbaric oxygen for hospitalised UC patients. METHODS: We enrolled UC patients hospitalised for acute flares (Mayo score 6-12). Initially, all patients received 3 days of hyperbaric oxygen at 2.4 atmospheres (90 minutes with two air breaks) in addition to intravenous steroids. Day 3 responders (reduction of partial Mayo score ≥ 2 points and rectal bleeding score ≥ 1 point) were randomised to receive a total of 5 days vs 3 days of hyperbaric oxygen. RESULTS: We treated 20 patients with hyperbaric oxygen (75% prior biologic failure). Day 3 response was achieved in 55% (n = 11/20), with significant reductions in stool frequency, rectal bleeding and CRP (P < 0.01). A more significant reduction in disease activity was observed with 5 days vs 3 days of hyperbaric oxygen (P = 0.03). Infliximab or colectomy was required in only three patients (15%) despite a predicted probability of 80% for second-line therapy. Day 3 hyperbaric oxygen responders were less likely to require re-hospitalisation or colectomy by 3 months vs non-responders (0% vs 66%, P = 0.002). No treatment-related adverse events were observed. CONCLUSION: Hyperbaric oxygen appears to be effective for optimising response to intravenous steroids in UC patients hospitalised for acute flares, with low rates of re-hospitalisation or colectomy at 3 months. An optimal clinical response is achieved with 5 days of hyperbaric oxygen. Larger phase 3 trials are needed to confirm efficacy and obtain labelled approval.

DOACs Versus VKAs in Older Adults Treated for Acute Venous Thromboembolism: Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTVES: Four direct-acting oral anticoagulants (DOACs) are currently approved by the Food and Drug Administration for the treatment of venous thromboembolism (VTE). Limited efficacy and safety data are available for their use in older adults (aged ≥75 years). METHODS: Medline, Cochrane Central Register of Controlled Trials, Embase, EBSCO, Web of Science, and CINAHL databases were searched for trials comparing DOACs with vitamin K antagonists (VKAs) for the treatment of VTE in older adults from inception through January 1, 2020. Meta-analysis was performed to assess the combined endpoint of recurrent VTE and related deaths and bleeding events (composite of major and clinically relevant nonmajor bleeding). The Mantel-Haenszel relative risk (RR) random effects model was used to pool results across studies. RESULTS: Six randomized controlled trials at low risk of bias met criteria for inclusion with a total of 3,665 patients aged 75 years and older with follow-up of 24 weeks or longer. Data for bleeding events were not available for dabigatran. Overall, DOACs had an improved efficacy over VKAs (RR = .56; 95% confidence interval [CI] = .38-.82). There was no statistically significant difference in the safety outcomes (RR = .77; 95% CI = .56-1.05). No significant heterogeneity was observed for efficacy outcome, and only moderate heterogeneity was observed for safety outcome. CONCLUSION: In older adults with VTE, DOACs appear to improve rates of recurrent VTE and VTE-related deaths compared with VKAs with similar bleeding outcomes.

A Meta-analysis to Guide the Enhancement of CBT for Childhood Anxiety: Exposure Over Anxiety Management.

Cognitive behavior therapy (CBT) is the most empirically supported therapy for childhood anxiety disorders (CADs) but has not reliably outperformed other credible interventions. The current study used meta-analysis to examine the frequency with which the most common treatment components are included in outcome studies and the relation of these components to symptom improvement. Seventy-five studies were identified that included youth with an anxiety disorder treated with CBT or a comparison condition. The protocols for the 111 CBT conditions generally consisted of 12, 1-h sessions delivered to the child with minimal parent inclusion. A greater amount of in-session exposure was related to significantly larger effect sizes between CBT and waitlist control across reporters (- 0.12 to - 0.15; P's < .05) and from pre- to post-treatment for child report (- .06; P < .01). Compared to treatments that omitted relaxation, treatments that included relaxation strategies were associated with significantly smaller pre- to post-treatment effect sizes across reporters (0.38 to 0.80; P's < .05). The current study suggests that CBT protocols for CADs that emphasize in-session exposure and do not include relaxation have the potential to improve the efficacy and effectiveness of therapy. Dismantling studies directly testing these hypotheses are needed.

Spinal Stimulation for the Treatment of Intractable Spine and Limb Pain: A Systematic Review of RCTs and Meta-Analysis.

OBJECTIVE: To synthesize the evidence regarding the effect of spinal stimulation (SS) vs medical therapy (MT) and the effect of newer SS technologies vs conventional SS on pain reduction in patients with intractable spine or limb pain. METHODS: A comprehensive literature search was conducted by a reference librarian. The literature search encompassed January 1, 1995 - December 31, 2017. Reviewers worked independently to select and appraise trials. Random-effect meta-analysis and frequentist indirect comparison methods were used to compare the three interventions. Results were expressed as odds ratio (OR) or weighted mean difference (WMD) with 95% CIs. RESULTS: We identified 12 trials enrolling 980 patients. Compared with MT, SS significantly increased the odds of reducing pain by 50% or more in three trials (OR, 13.01; 95% CI, 4.96-34.17) and significantly reduced pain as measured by visual analogue scale scores in three trials (WMD, 1.43 scale points; 95% CI, 0.16-2.71). Using the common comparator of MT, newer stimulation technology (eg, high-frequency 10 kilohertz spinal stimulation, Burst, dorsal root ganglion) was associated with increased odds of pain relief compared with conventional SS (OR, 2.07; 95% CI, 1.35-3.19). CONCLUSIONS: In patients with intractable spine/limb pain, SS was associated with better pain reduction than MT. New stimulation technology was likely associated with better pain reduction than conventional stimulation.

Effects of Nutritional Supplements and Dietary Interventions on Cardiovascular Outcomes: An Umbrella Review and Evidence Map.

Background: The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear. Purpose: To examine evidence about the effects of nutritional supplements and dietary interventions on mortality and cardiovascular outcomes in adults. Data Sources: PubMed, CINAHL, and the Cochrane Library from inception until March 2019; ClinicalTrials.gov (10 March 2019); journal Web sites; and reference lists. Study Selection: English-language, randomized controlled trials (RCTs) and meta-analyses of RCTs that assessed the effects of nutritional supplements or dietary interventions on all-cause mortality or cardiovascular outcomes, such as death, myocardial infarction, stroke, and coronary heart disease. Data Extraction: Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence. Data Synthesis: Nine systematic reviews and 4 new RCTs were selected that encompassed a total of 277 trials, 24 interventions, and 992 129 participants. A total of 105 meta-analyses were generated. There was moderate-certainty evidence that reduced salt intake decreased the risk for all-cause mortality in normotensive participants (risk ratio [RR], 0.90 [95% CI, 0.85 to 0.95]) and cardiovascular mortality in hypertensive participants (RR, 0.67 [CI, 0.46 to 0.99]). Low-certainty evidence showed that omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) was associated with reduced risk for myocardial infarction (RR, 0.92 [CI, 0.85 to 0.99]) and coronary heart disease (RR, 0.93 [CI, 0.89 to 0.98]). Folic acid was associated with lower risk for stroke (RR, 0.80 [CI, 0.67 to 0.96]; low certainty), whereas calcium plus vitamin D increased the risk for stroke (RR, 1.17 [CI, 1.05 to 1.30]; moderate certainty). Other nutritional supplements, such as vitamin B6, vitamin A, multivitamins, antioxidants, and iron and dietary interventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low- to moderate-certainty evidence). Limitations: Suboptimal quality and certainty of evidence. Conclusion: Reduced salt intake, omega-3 LC-PUFA use, and folate supplementation could reduce risk for some cardiovascular outcomes in adults. Combined calcium plus vitamin D might increase risk for stroke. Primary Funding Source: None.

Noninvasive Ventilation in Patients With Do-Not-Intubate and Comfort-Measures-Only Orders: A Systematic Review and Meta-Analysis.

OBJECTIVES: To assess the effectiveness of noninvasive ventilation in patients with acute respiratory failure and do-not-intubate or comfort-measures-only orders. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science from inception to January 1, 2017. STUDY SELECTION: Studies of all design types that enrolled patients in the ICU or hospital ward who received noninvasive ventilation and had preset do-not-intubate or comfort-measures-only orders. DATA EXTRACTION: Data abstraction followed Meta-analysis of Observational Studies in Epidemiology guidelines. Data quality was assessed using a modified Newcastle-Ottawa Scale. DATA SYNTHESIS: Twenty-seven studies evaluating 2,020 patients with do-not-intubate orders and three studies evaluating 200 patients with comfort-measures-only orders were included. In patients with do-not-intubate orders, the pooled survival was 56% (95% CI, 49-64%) at hospital discharge and 32% (95% CI, 21-45%) at 1 year. Hospital survival was 68% for chronic obstructive pulmonary disease, 68% for pulmonary edema, 41% for pneumonia, and 37% for patients with malignancy. Survival was comparable for patients treated in a hospital ward versus an ICU. Quality of life of survivors was not reduced compared with baseline, although few studies evaluated this. No studies evaluated quality of dying in nonsurvivors. In patients with comfort-measures-only orders, a single study showed that noninvasive ventilation was associated with mild reductions in dyspnea and opioid requirements. CONCLUSIONS: A large proportion of patients with do-not-intubate orders who received noninvasive ventilation survived to hospital discharge and at 1 year, with limited data showing no decrease in quality of life in survivors. Provision of noninvasive ventilation in a well-equipped hospital ward may be a viable alternative to the ICU for selected patients. Crucial questions regarding quality of life in survivors, quality of death in nonsurvivors, and the impact of noninvasive ventilation in patients with comfort-measures-only orders remain largely unanswered.

Effects of Different Models of Dialysis Care on Patient-Important Outcomes: A Systematic Review and Meta-Analysis.

Ongoing payment reform in dialysis necessitates better patient outcomes and lower costs. Suggested improvements to processes of care for maintenance dialysis patients are abundant; however, their impact on patient-important outcomes is unclear. This systematic review included comparative randomized controlled trials or observational studies with no restriction on language, published from 2000 to 2014, involving at least 5 adult dialysis patients who received a minimum of 6 months of follow-up. The effect size was pooled and stratified by intervention strategy (multidisciplinary care [MDC], home dialysis, alternate dialysis settings, and electronic health record implementation). Heterogeneity (I2) was used to assess the variability in study effects related to study differences rather than chance. Of the 1988 articles screened, 25 international studies with 74,833 maintenance dialysis patients were included. Interventions with MDC or home dialysis were associated with a lower mortality (hazard ratio [HR] = 0.72, 95% confidence interval [CI] 0.61, 0.84, I2 = 41.6%; HR = 0.57, 95% CI 0.41, 0.81, I2 = 89.0%; respectively) and hospitalizations (incidence rate ratio [IRR] = 0.68, 95% CI 0.51, 0.91, I2 = NA; IRR = 0.88, 95% CI 0.64, 1.20, I2 = 79.6%; respectively). Alternate dialysis settings also were associated with a reduction in hospitalizations (IRR = 0.41, 95% CI 0.25, 0.69, I2 = 0.0%). This systematic review underscores the importance of multidisciplinary care, and also the value of telemedicine as a means to increase access to providers and enhance outcomes for those dialyzing at home or in alternate settings, including those with limited access to nephrology expertise because of travel distance.

Non-pharmacological treatment of depression: a systematic review and evidence map.

BACKGROUND: The comparative effectiveness of non-pharmacological treatments of depression remains unclear. METHODS: We conducted an overview of systematic reviews to identify randomised controlled trials (RCTs) that compared the efficacy and adverse effects of non-pharmacological treatments of depression. We searched multiple electronic databases through February 2016 without language restrictions. Pairs of reviewers determined eligibility, extracted data and assessed risk of bias. Meta-analyses were conducted when appropriate. RESULT: We included 367 RCTs enrolling ∼20 000 patients treated with 11 treatments leading to 17 unique head-to-head comparisons. Cognitive behavioural therapy, naturopathic therapy, biological interventions and physical activity interventions reduced depression severity as measured using standardised scales. However, the relative efficacy among these non-pharmacological interventions was lacking. The effect of these interventions on clinical response and remission was unclear. Adverse events were lower than antidepressants. LIMITATION: The quality of evidence was low to moderate due to inconsistency and unclear or high risk of bias, limiting our confidence in findings. CONCLUSIONS: Non-pharmacological therapies of depression reduce depression symptoms and should be considered along with antidepressant therapy for the treatment of mild-to-severe depression. A shared decision-making approach is needed to choose between non-pharmacological therapies based on values, preferences, clinical and social context.

Interventions To Prevent Retinopathy of Prematurity: A Meta-analysis.

CONTEXT: The effectiveness of many interventions aimed at reducing the risk of retinopathy has not been well established. OBJECTIVE: To estimate the effectiveness of nutritional interventions, oxygen saturation targeting, blood transfusion management, and infection prevention on the incidence of retinopathy of prematurity (ROP). DATA SOURCES: A comprehensive search of several databases was conducted, including Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through March 2014. STUDY SELECTION: We included studies that evaluated nutritional interventions, management of supplemental oxygen, blood transfusions, or infection reduction and reported the incidence of ROP and mortality in neonates born at <32 weeks. DATA EXTRACTION: We extracted patient characteristics, interventions, and risk of bias indicators. Outcomes of interest were any stage ROP, severe ROP or ROP requiring treatment, and mortality. RESULTS: We identified 67 studies enrolling 21 819 infants. Lower oxygen saturation targets reduced the risk of developing any stage ROP (relative risk [RR] 0.86, 95% confidence interval [CI], 0.77-0.97) and severe ROP or ROP requiring intervention (RR 0.58, 95% CI, 0.45-0.74) but increased mortality (RR 1.15, 95% CI, 1.04-1.29). Aggressive parenteral nutrition reduced the risk of any stage ROP but not severe ROP. Supplementation of vitamin A, E, or inositol and breast milk feeding were beneficial but only in observational studies. Use of transfusion guidelines, erythropoietin, and antifungal agents were not beneficial. LIMITATIONS: Results of observational studies were not replicated in randomized trials. Interventions were heterogeneous across studies. CONCLUSIONS: At the present time, there are no safe interventions supported with high quality evidence to prevent severe ROP.

Applying quality improvement methods in a hyperbaric oxygen program: reducing unnecessary glucose testing.

OBJECTIVE: To describe the implementation of a quality improvement (QI) project that aimed at improving and standardizing glucose checks on patients with diabetes undergoing hyperbaric oxygen (HBO2) therapy. METHODS: This is a prospective cohort study. Following the Model for Improvement, nurses and physicians ran several Plan-Do-Study-Act (PDSA) cycles over a four-month period, with multiple iteration and testing changes. They developed and implemented a nurse-led protocol that was tested prospectively. RESULTS: Compared to the pre-protocol baseline (N = 332), glucose checks per session guided by the protocol decreased by 37.7% (2.84 vs. 1.77 per session, P⟨0.001). Compliance with the new protocol was higher than compliance with the existing protocol (97.3% to 84.2%, P⟨0.001). There were no cases of a symptomatic hypoglycemic event after the implementation of the protocol. CONCLUSIONS: A quality improvement project implemented by a multidisciplinary team in a hyperbaric practice was feasible and has improved the management of diabetic patients undergoing HBO2 therapy. Considering how the hyperbaric community values the culture of safety and considering the feasibility of this project, more QI training and projects in hyperbaric programs should be performed.

The incidence of hypoglycemia during HBO2 therapy: A retrospective review.

BACKGROUND: Hypoglycemia is concerning in patients with diabetes undergoing hyperbaric oxygen (HBO2) therapy. We aimed to estimate the incidence, risk factors and a pretreatment glucose threshold of HBO2-associated hypoglycemia. METHODS: We retrospectively evaluated a patient cohort undergoing HBO2 therapy. We calculated the area under the curve (AUC) and odds ratio (OR) with 95% confidence interval (CI) adjusting for patients' age, gender, diabetes type, insulin use, body mass index, hemoglobin A1c and HBO2 treatment time. RESULTS: During 77 months, 3,136 HBO2 sessions were performed on patients with diabetes. In-chamber glucose was higher than pre-HBO2 glucose in 1,708/3,136 sessions (54%). The incidence of hypoglycemia (defined as ≤ 70 mg/dL) during or immediately after HBO2 treatment was 1.5% (0.8-2.1%). Hypoglycemia that was symptomatic or severe was rare. A glucose value pre-HBO2 of 150 mg/dL best predicted the risk of subsequent hypoglycemia (AUC 0.80; 95% CI, 0.75-0.86). Type 1 diabetes was independently associated with increased risk of hypoglycemia (OR 3.69; 95% CI, 1.67, 8.19) whereas insulin use was not. CONCLUSIONS: In patients with diabetes undergoing HBO2, severe hypoglycemia is rare and occurs more frequently in Type 1 diabetes. Pre-HBO2 glucose values may be used to predict subsequent hypoglycemia and reduce the need for routine glucose monitoring during and after HBO2.

A clinical practice guideline for the use of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers.

BACKGROUND: The role of hyperbaric oxygen (HBO2) for the treatment of diabetic foot ulcers (DFUs) has been examined in the medical literature for decades. There are more systematic reviews of the HBO2/DFU literature than there have been randomized controlled trials (RCTs), but none of these reviews has resulted in a clinical practice guideline (CPG) that clinicians, patients and policy-makers can use to guide decision-making in everyday practice. METHODS: The Undersea and Hyperbaric Medical Society (UHMS), following the methodology of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, undertook this systematic review of the HBO2 literature in order to rate the quality of evidence and generate practice recommendations for the treatment of DFUs. We selected four clinical questions for review regarding the role of HBO2 in the treatment of DFUs and analyzed the literature using patient populations based on Wagner wound classification and age of the wound (i.e., acute post-operative wound vs. non-healing wound of 30 or more days). Major amputation and incomplete healing were selected as critical outcomes of interest. RESULTS: This analysis showed that HBO2 is beneficial in preventing amputation and promoting complete healing in patients with Wagner Grade 3 or greater DFUs who have just undergone surgical debridement of the foot as well as in patients with Wagner Grade 3 or greater DFUs that have shown no significant improvement after 30 or more days of treatment. In patients with Wagner Grade 2 or lower DFUs, there was inadequate evidence to justify the use of HBO2 as an adjunctive treatment. CONCLUSIONS: Clinicians, patients, and policy-makers should engage in shared decision-making and consider HBO2 as an adjunctive treatment of DFUs that fit the criteria outlined in this guideline. The current body of evidence provides a moderate level of evidence supporting the use of HBO2 for DFUs. Future research should be directed at improving methods for patient selection, testing various treatment protocols and improving our confidence in the existing estimates.

Pharmacologic interventions for painful diabetic neuropathy: An umbrella systematic review and comparative effectiveness network meta-analysis.

BACKGROUND: Multiple treatments for painful diabetic peripheral neuropathy are available. PURPOSE: To evaluate the comparative effectiveness of oral and topical analgesics for diabetic neuropathy. DATA SOURCES: Multiple electronic databases between January 2007 and April 2014, without language restriction. STUDY SELECTION: Parallel or crossover randomized, controlled trials that evaluated pharmacologic treatments for adults with painful diabetic peripheral neuropathy. DATA EXTRACTION: Duplicate extraction of study data and assessment of risk of bias. DATA SYNTHESIS: 65 randomized, controlled trials involving 12 632 patients evaluated 27 pharmacologic interventions. Approximately one half of these studies had high or unclear risk of bias. Nine head-to-head trials showed greater pain reduction associated with serotonin-norepinephrine reuptake inhibitors (SNRIs) than anticonvulsants (standardized mean difference [SMD], -0.34 [95% credible interval {CrI}, -0.63 to -0.05]) and with tricyclic antidepressants (TCAs) than topical capsaicin 0.075%. Network meta-analysis showed that SNRIs (SMD, -1.36 [CrI, -1.77 to -0.95]), topical capsaicin (SMD, -0.91 [CrI, -1.18 to -0.08]), TCAs (SMD, -0.78 [CrI, -1.24 to -0.33]), and anticonvulsants (SMD, -0.67 [CrI, -0.97 to -0.37]) were better than placebo for short-term pain control. Specifically, carbamazepine (SMD, -1.57 [CrI, -2.83 to -0.31]), venlafaxine (SMD, -1.53 [CrI, -2.41 to -0.65]), duloxetine (SMD, -1.33 [CrI, -1.82 to -0.86]), and amitriptyline (SMD, -0.72 [CrI, -1.35 to -0.08]) were more effective than placebo. Adverse effects included somnolence and dizziness with TCAs, SNRIs, and anticonvulsants; xerostomia with TCAs; and peripheral edema and burning sensation with pregabalin and capsaicin. LIMITATION: Confidence in findings was limited because most evidence came from indirect comparisons of trials with short (≤3 months) follow-up and unclear or high risk of bias. CONCLUSION: Several medications may be effective for short-term management of painful diabetic neuropathy, although their comparative effectiveness is unclear. PRIMARY FUNDING SOURCE: Mayo Foundation for Medical Education and Research.