Towards transparency: adoption of WHO best practices in clinical trial registration and reporting among top medical research funders in the USA.

OBJECTIVE: To assess to what extent the clinical trial policies of the largest public and philanthropic funders of clinical research in the United States meet WHO best practices in trial registration and reporting. METHODS: Public and philanthropic funders of clinical trials in the USA with >US$50 million annual spend were selected. The funders were assessed using an 11-item scoring tool based on WHO Joint Statement benchmarks. These 11 items fell into 4 categories, namely: trial registration, academic publication, monitoring and sanctions. An additional item captured whether and how funders referred to Consolidated Standards of Reporting Trials (CONSORT) within their trial policies. Each funder was independently assessed by two or three researchers. Funders were contacted to flag possible errors and omissions. Ambiguous or difficult-to-score items were settled by an independent adjudicator. RESULTS: Fourteen funders were assessed. Our cross-sectional study found that, on average, funders have only implemented 4.1/11 (37%) of WHO best practices in clinical trial transparency. The most frequently adopted requirement was open access publishing (14/14 funders). The least frequently adopted were (1) requiring trial ID to appear in all publications (2/14 funders, 14%) and (2) making compliance reports public (2/14 funders, 14%). Public funders, on average, adopted more policy elements (5.2/11 items, 47%) than philanthropic funders (2.8/11 items, 25%). Only one funder's policy documents mentioned the CONSORT statement. CONCLUSIONS: There is a significant variation between the number of best practice policy items adopted by medical research funders in the USA. Many funders fell significantly short of WHO Joint Statement benchmarks. Each funder could benefit from policy revision and strengthening.

Epidural pneumorrhachis, a rare complication of asthma exacerbation.

Introduction: An association between pneumorrhachis and asthma exacerbation is uncommon. However, we present a clinical case involving a patient with exacerbated asthma, subcutaneous emphysema, spontaneous pneumomediastinum (SPM), and pneumorrhachis. Case study: The patient was an 18-year-old male with asthma since childhood who only relied on salbutamol to control his asthma symptoms. Results: The patient suddenly experienced dyspnea, chest tightness, and paroxysmal coughing, which prompted him to visit the emergency department. Upon arrival, subcutaneous emphysema was detected on the face, neck, thorax, and left forearm. Chest X-ray showed air in the mediastinum, neck, left supraclavicular region, and chest, all of which were verified by a computed tomography scan that also revealed air in the epidural region. At the hospital, his treatment focused on preventing asthma exacerbation and managing associated symptoms. Conclusion: When a patient has asthma exacerbation that is accompanied by SPM and extensive emphysema, the presence of epidural pneumorrhachis should not be overlooked.

Sliding scale insulin for non-critically ill hospitalised adults with diabetes mellitus.

BACKGROUND: Diabetes mellitus is a metabolic disorder resulting from a defect in insulin secretion, function, or both. Hyperglycaemia in non-critically ill hospitalised people is associated with poor clinical outcomes (infections, prolonged hospital stay, poor wound healing, higher morbidity and mortality). In the hospital setting people diagnosed with diabetes receive insulin therapy as part of their treatment in order to achieve metabolic control. However, insulin therapy can be provided by different strategies (sliding scale insulin (SSI), basal-bolus insulin, and other modalities). Sliding scale insulin is currently the most commonly used method, however there is uncertainty about which strategy provides the best patient outcomes. OBJECTIVES: To assess the effects of SSI for non-critically ill hospitalised adults with diabetes mellitus. SEARCH METHODS: We identified eligible trials by searching MEDLINE, Embase, LILACS, and the Cochrane Library. We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov trial registers. The date of the last search for all databases was December 2017. We also examined reference lists of identified randomised controlled trials (RCTs) and systematic reviews, and contacted trial authors. SELECTION CRITERIA: We included RCTs comparing SSI with other strategies for glycaemic control in non-critically ill hospitalised adult participants of any sex with diabetes mellitus. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, assessed trials for risk of bias, and evaluated the overall certainty of evidence utilising the GRADE instrument. We synthesised data using a random-effects model meta-analysis with 95% prediction intervals, if possible, or descriptive analysis, as appropriate. MAIN RESULTS: Of 720 records screened, we included eight trials that randomised 1048 participants with type 2 diabetes (387 SSI participants and 615 participants in comparator groups were available for final analysis). We included non-critically ill medical and surgical adults with the diagnosis of diabetes mellitus. The mean follow-up time was measured by the mean length of hospital stay and ranged between five and 24 days. The mean age of participants was 44.5 years to 71 years.Overall, we judged the risk of bias on the trial level as unclear for selection bias, high for outcome-related performance and detection bias with regard to hypoglycaemic episodes, other adverse events, and mean glucose levels, and low for all-cause mortality and length of hospital stay. Attrition bias was low for all outcome measures.Six trials compared SSI with a basal-bolus insulin scheme, three of which investigating 64% of all participants in this category also applying an SSI approach in the bolus comparator part. One trial had a basal insulin-only comparator arm, and the remaining trial used continuous insulin infusion as the comparator. For our main comparison of SSI versus basal-bolus insulin, the results were as follows. Four trials reported mortality data. One out of 268 participants in the SSI group (0.3%) compared with two out of 334 participants in the basal-bolus group (0.6%) died (low-certainty evidence). Severe hypoglycaemic episodes, defined as blood glucose levels below 40 mg/dL (2.2 mmol/L), showed a risk ratio (RR) of 0.22, 95% confidence interval (CI) 0.05 to 1.00; P = 0.05; 5 trials; 667 participants; very low-certainty evidence. The 95% prediction interval ranged between 0.02 and 2.57. All nine severe hypoglycaemic episodes were observed among the 369 participants on basal-bolus insulin (2.4%). The mean length of hospital stay was 0.5 days longer for the SSI group, 95% CI -0.5 to 1.4; P = 0.32; 6 trials; 717 participants; very low-certainty evidence. The 95% prediction interval ranged between -1.7 days and 2.7 days. Adverse events other than hypoglycaemic episodes, such as postoperative infections, showed a RR of 1.16, 95% CI 0.25 to 5.37; P = 0.85; 3 trials; 481 participants; very low-certainty evidence. The mean blood glucose levels ranged across basal-bolus groups from 156 mg/dL (8.7 mmol/L) to 221 mg/dL (12.3 mmol/L). The mean blood glucose level in the SSI groups was 14.8 mg/dL (0.8 mmol/L) higher (95% CI 7.8 (0.4) to 21.8 (1.2); P < 0.001; 6 trials; 717 participants; low-certainty evidence). The 95% prediction interval ranged between -3.6 mg/dL (-0.2 mmol/L) and 33.2 mg/dL (1.8 mmol/L). No trial reported on diabetes-related mortality or socioeconomic effects. AUTHORS' CONCLUSIONS: We are uncertain which insulin strategy (SSI or basal-bolus insulin) is best for non-critically hospitalised adults with diabetes mellitus. A basal-bolus insulin strategy in these patients might result in better short-term glycaemic control but could increase the risk for severe hypoglycaemic episodes. The certainty of the body of evidence comparing SSI with basal-bolus insulin was low to very low and needs to be improved by adequately performed, well-powered RCTs in different hospital environments with well-educated medical staff using identical short-acting insulins in both intervention and comparator arms to compare the rigid SSI approach with flexible insulin application strategies.

Prevalence of respiratory viruses in wheezing children not older than 24 months of age.

INTRODUCTION: Wheezing in children not older than 24 months of age is a frequent event, and viruses are usually the causative agents. The aim of the study was to estimate the prevalence of respiratory viruses in wheezing children who were not older than 24 months of age and who had no history of asthma. METHODS: Fifty-five Mexican children were included in an analytical cross-sectional study. Nasal secretions were obtained by using sterile rayon-tipped applicators to identify the virus by polymerase chain reaction or reverse transcription-polymerase chain reaction: adenovirus, bocavirus, human rhinovirus, influenza virus type A, human metapneumovirus, parainfluenza, rhinovirus, and respiratory syncytial virus. The prevalence of viral etiology was estimated by dividing the frequency of the identified virus by the number of participants. Ninety-five percent confidence intervals for proportions were calculated. RESULTS: Most of the patients were male (35/55, 63.6%). The average time of evolution of wheezing episode was 3 days. The third part of enrolled population were receiving antibiotics. Respiratory viruses were detected in 33 (60%; 95% CI: 46.8-71.9%) out of 55 cases, and viral coinfection was detected in five cases (9.1%; 95% CI: 3.5-19.9%). Human metapneumovirus was the most frequently identified virus (23.6%), followed by bocavirus (14.5%), respiratory syncytial virus and rhinovirus (12.7% each), and to a lesser extent influenza virus type A and parainfluenza. Rhinovirus was the predominant virus in outpatient children (28.6%). In the inpatient emergency room and inhalotherapy room, human metapneumovirus predominated (41.2 and 16.1%, respectively). CONCLUSION: bocavirus and human metapneumovirus were the most frequently identified viruses in Mexican children who were < 2 years of age, suffered from wheezing, and had no history of asthma.

[Risk factors associated to diffuse gastric cancer and intestinal histological patterns in an adult population from Western Mexico]. / Factores de riesgo asociados a adenocarcinoma gástrico de patrones histológicos de tipo intestinal y difuso en población adulta del occidente de México.

INTRODUCTION: Gastric cancer (GC) is the third leading cause of cancer death worldwide, and is divided histologically in diffuse gastric cancer (DGC) and intestinal gastric cancer (IGC). Multiple risk factors have been associated with GC in different populations. The objective was to analyze the risk factors associated to DGC and IGC in a population from the western region of Mexico. MATERIAL AND METHODS: The DGC (n = 27) and IGC (n = 26) cases, each matched by age and sex with a control group, were analyzed. Diet and lifestyle data were obtained by a questionnaire. Statistical analysis was performed with the software SPSSv18. The association of risk was calculated in odds ratio (OR); a value of p < 0.05 was considered significant. RESULTS: In the DGC group, the factors with significant OR values were: consumption of pork OR: 3.4 (1.11-10.4; p =0.032), smoking OR: 4.7 (1.5-15.0; p =0.007), green vegetables OR: 0.16 (0.03-0.83; p =0.029) and fruit OR: 0.28 (0.08-0.88; p =0.029). In the IGC group, the consumption of canned sardines was a significant risk factor OR: 4.07 (1.25-13.24; p =0.019). CONCLUSIONS: This work is the first to analyze the risk factors associated with GC in a population from western Mexico.

Subcutaneous rapid-acting insulin analogues for diabetic ketoacidosis.

BACKGROUND: Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of uncontrolled diabetes that mainly occurs in individuals with autoimmune type 1 diabetes, but it is not uncommon in some people with type 2 diabetes. The treatment of DKA is traditionally accomplished by the administration of intravenous infusion of regular insulin that is initiated in the emergency department and continued in an intensive care unit or a high-dependency unit environment. It is unclear whether people with DKA should be treated with other treatment modalities such as subcutaneous rapid-acting insulin analogues. OBJECTIVES: To assess the effects of subcutaneous rapid-acting insulin analogues for the treatment of diabetic ketoacidosis. SEARCH METHODS: We identified eligible trials by searching MEDLINE, PubMed, EMBASE, LILACS, CINAHL, and the Cochrane Library. We searched the trials registers WHO ICTRP Search Portal and ClinicalTrials.gov. The date of last search for all databases was 27 October 2015. We also examined reference lists of included randomised controlled trials (RCTs) and systematic reviews, and contacted trial authors. SELECTION CRITERIA: We included trials if they were RCTs comparing subcutaneous rapid-acting insulin analogues versus standard intravenous infusion in participants with DKA of any age or sex with type 1 or type 2 diabetes, and in pregnant women. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, assessed studies for risk of bias, and evaluated overall study quality utilising the GRADE instrument. We assessed the statistical heterogeneity of included studies by visually inspecting forest plots and quantifying the diversity using the I² statistic. We synthesised data using random-effects model meta-analysis or descriptive analysis, as appropriate. MAIN RESULTS: Five trials randomised 201 participants (110 participants to subcutaneous rapid-acting insulin analogues and 91 to intravenous regular insulin). The criteria for DKA were consistent with the American Diabetes Association criteria for mild or moderate DKA. The underlying cause of DKA was mostly poor compliance with diabetes therapy. Most trials did not report on type of diabetes. Younger diabetic participants and children were underrepresented in our included trials (one trial only). Four trials evaluated the effects of the rapid-acting insulin analogue lispro, and one the effects of the rapid-acting insulin analogue aspart. The mean follow-up period as measured by mean hospital stay ranged between two and seven days. Overall, risk of bias of the evaluated trials was unclear in many domains and high for performance bias for the outcome measure time to resolution of DKA.No deaths were reported in the included trials (186 participants; 3 trials; moderate- (insulin lispro) to low-quality evidence (insulin aspart)). There was very low-quality evidence to evaluate the effects of subcutaneous insulin lispro versus intravenous regular insulin on the time to resolution of DKA: mean difference (MD) 0.2 h (95% CI -1.7 to 2.1); P = 0.81; 90 participants; 2 trials. In one trial involving children with DKA, the time to reach a glucose level of 250 mg/dL was similar between insulin lispro and intravenous regular insulin. There was very low-quality evidence to evaluate the effects of subcutaneous insulin aspart versus intravenous regular insulin on the time to resolution of DKA: MD -1 h (95% CI -3.2 to 1.2); P = 0.36; 30 participants; 1 trial. There was low-quality evidence to evaluate the effects of subcutaneous rapid-acting insulin analogues versus intravenous regular insulin on hypoglycaemic episodes: 6 of 80 insulin lispro-treated participants compared with 9 of 76 regular insulin-treated participants reported hypoglycaemic events; risk ratio (RR) 0.59 (95% CI 0.23 to 1.52); P = 0.28; 156 participants; 4 trials. For insulin aspart compared with regular insulin, RR for hypoglycaemic episodes was 1.00 (95% CI 0.07 to 14.55); P = 1.0; 30 participants; 1 trial; low-quality evidence. Socioeconomic effects as measured by length of mean hospital stay for insulin lispro compared with regular insulin showed a MD of -0.4 days (95% CI -1 to 0.2); P = 0.22; 90 participants; 2 trials; low-quality evidence and for insulin aspart compared with regular insulin 1.1 days (95% CI -3.3 to 1.1); P = 0.32; low-quality evidence. Data on morbidity were limited, but no specific events were reported for the comparison of insulin lispro with regular insulin. No trial reported on adverse events other than hypoglycaemic episodes, and no trial investigated patient satisfaction. AUTHORS' CONCLUSIONS: Our review, which provided mainly data on adults, suggests on the basis of mostly low- to very low-quality evidence that there are neither advantages nor disadvantages when comparing the effects of subcutaneous rapid-acting insulin analogues versus intravenous regular insulin for treating mild or moderate DKA.

Viral coinfection in acute respiratory infection in Mexican children treated by the emergency service: A cross-sectional study.

BACKGROUND: Acute respiratory infections (ARIs) cause illness. Children under five years of age are highly vulnerable to these infections. Viral coinfection or multiple viral infection is a variable that can have a significant impact on the evolution of these diseases. METHODS: This cross-sectional study was carried out in Mexican children (under five years of age) who had an ARI and who were treated by an emergency service in a hospital in Guadalajara, Jalisco, Mexico. The viral etiology, as well as the presence of multiple viral infections, was determined. A structured questionnaire was used to obtain demographic and clinical information. Odds ratio (OR) was calculated, and univariate and multivariate analyses using logistic regression were performed. RESULTS: In the study population, metapneumovirus (hMPV) was the most frequent virus (22%), followed by adenovirus (hAD) (16%), respiratory syncytial virus (RSV) (14%), rhinovirus (hRV) (12%), bocavirus (hBoV) (9%), influenza virus (IF) (7%), and parainfluenza (PIF) (4%). The frequency of viral coinfections was 31.62%, and multiple logistic regression analysis revealed that hMPV, RSV, PIF, and hBoV were independently associated with multiple viral infection. No difference was found in the clinical manifestation of children with simple and multiple infections. Simple hMPV infection was associated with patients who presented with severe ARI. Using a multivariate analysis, we found that overcrowding is associated with coinfection when the viral etiology was hRV (OR = 2.56, 95% confidence interval (CI) 1.07 to 6.13), IF (OR = 2.56, 95% CI 1.07 to 6.13), PIF (OR = 2.96, 95% CI 1.15 to 7.65), hAD (OR = 2.56, 95% CI 1.07 to 6.13), and hBoV (OR = 2.9, 95% CI 1.14 to 7.34). CONCLUSIONS: Viral coinfections are frequent in children requiring treatment by an emergency service. However, the severity of ARI is similar to that of children with a simple infection. The hMPV is common and may confer a significant disease burden in the Mexican population. Finally, overcrowding is a housing characteristic that favors the development of coinfections.

Heparin versus placebo for non-ST elevation acute coronary syndromes.

BACKGROUND: Non-ST elevation acute coronary syndromes (NSTEACS) represent a spectrum of disease including unstable angina and non-ST segment myocardial infarction (NSTEMI). Despite treatment with aspirin, beta-blockers and nitroglycerin, unstable angina/NSTEMI is still associated with significant morbidity and mortality. Although evidence suggests that low molecular weight heparin (LMWH) is more efficacious compared to unfractionated heparin (UFH), there is limited data to support the role of heparins as a drug class in the treatment of NSTEACS. This is an update of a review last published in 2008. OBJECTIVES: To determine the effect of heparins (UFH and LMWH) compared with placebo for the treatment of patients with non-ST elevation acute coronary syndromes (unstable angina or NSTEMI). SEARCH METHODS: For this update the Cochrane Heart Group Trials Search Co-ordinator searched the Cochrane Central Register of Controlled Trials on The Cochrane Library (2013, Issue 12), MEDLINE (OVID, 1946 to January week 1 2014), EMBASE (OVID, 1947 to 2014 week 02), CINAHL (1937 to 15 January 2014) and LILACS (1982 to 15 January 2014). We applied no language restrictions. SELECTION CRITERIA: Randomized controlled trials of parenteral UFH or LMWH versus placebo in people with non-ST elevation acute coronary syndromes (unstable angina or NSTEMI). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed quality of studies and independently extracted data. MAIN RESULTS: There were no new included studies for this update. Eight studies (3118 participants) were included in this review. We found no evidence for difference in overall mortality between the groups treated with heparin and placebo (risk ratio (RR) = 0.84, 95% confidence interval (CI) 0.36 to 1.98). Heparins compared with placebo, reduced the occurrence of myocardial infarction in patients with unstable angina and NSTEMI (RR = 0.40, 95% CI 0.25 to 0.63, number needed to benefit (NNTB) = 33). There was a trend towards more major bleeds in the heparin studies compared to control studies (RR = 2.05, 95% CI 0.91 to 4.60). From a limited data set, there appeared to be no difference between patients treated with heparins compared to control in the occurrence of thrombocytopenia (RR = 0.20, 95% CI 0.01 to 4.24). Assessment of overall risk of bias in these studies was limited as most of the studies did not give sufficient detail to allow assessment of potential risk of bias. AUTHORS' CONCLUSIONS: Compared with placebo, patients treated with heparins had a similar risk of mortality, revascularization, recurrent angina, and thrombocytopenia. However, those treated with heparins had a decreased risk of myocardial infarction and a higher incidence of minor bleeding. Overall, the evidence assessed in this review was classified as low quality according to the GRADE approach. The results presented in this review must therefore be interpreted with caution.