Recombinant human growth hormone (rhGH) improves growth in patients with growth hormone deficiency or idiopathic short stature. Its role in patients with cystic fibrosis (CF) is unclear.
To review ...the effectiveness of rhGH in the treatment of patients with CF.
Medline and the Cochrane Central Register of Controlled Trials were searched from the earliest date through April 2010. Randomized controlled trials, observational studies, systematic reviews/meta-analyses, or case reports were included if rhGH therapy was administered to patients with CF and data on prespecified harms, intermediate outcomes, or final health outcomes were reported. When applicable, end points were pooled by using a random-effects model. The overall body of evidence was graded for each outcome as insufficient, low, moderate, or high.
Ten unique controlled trials (n = 312) and 8 observational studies (n = 58) were included. On quantitative synthesis of controlled trials, several markers of pulmonary function, anthropometrics, and bone mineralization were significantly improved versus control. Results of single-arm observational studies for the aforementioned outcomes were generally supportive of findings in clinical trials. There is insufficient evidence to determine the effect of rhGH on intravenous antibiotic use during therapy, pulmonary exacerbations, health-related quality-of-life, bone consequences, or total mortality, but moderate evidence suggests that rhGH therapy reduces the rate of hospitalization versus control.
rhGH improved almost all intermediate measures of pulmonary function, height, and weight in patients with CF. Improvements in bone mineral content are also promising. However, with the exception of hospitalizations, the benefits on final health outcomes cannot be directly determined at this time.
During percutaneous coronary intervention (PCI), dislodgement of atherothrombotic material from coronary lesions can result in distal embolization, and may lead to increased major adverse ...cardiovascular events (MACE) and mortality. We sought to systematically review the comparative effectiveness of adjunctive devices to remove thrombi or protect against distal embolization in patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI of native vessels.
We conducted a systematic literature search of Medline, the Cochrane Database, and Web of Science (January 1996-March 2011), http://www.clinicaltrials.gov, abstracts from major cardiology meetings, TCTMD, and CardioSource Plus. Two investigators independently screened citations and extracted data from randomized controlled trials (RCTs) that compared the use of adjunctive devices plus PCI to PCI alone, evaluated patients with STEMI, enrolled a population with 95% of target lesion(s) in native vessels, and reported data on at least one pre-specified outcome. Quality was graded as good, fair or poor and the strength of evidence was rated as high, moderate, low or insufficient. Disagreement was resolved through consensus.
37 trials met inclusion criteria. At the maximal duration of follow-up, catheter aspiration devices plus PCI significantly decreased the risk of MACE by 27% compared to PCI alone. Catheter aspiration devices also significantly increased the achievement of ST-segment resolution by 49%, myocardial blush grade of 3 (MBG-3) by 39%, and thrombolysis in myocardial infarction (TIMI) 3 flow by 8%, while reducing the risk of distal embolization by 44%, no reflow by 48% and coronary dissection by 70% versus standard PCI alone. In a majority of trials, the use of catheter aspiration devices increased procedural time upon qualitative assessment.Distal filter embolic protection devices significantly increased the risk of target revascularization by 39% although the use of mechanical thrombectomy or embolic protection devices did not significantly impact other final health outcomes. Distal balloon or any embolic protection device increased the achievement of MBG-3 by 61% and 20% and TIMI3 flow by 11% and 6% but did not significantly impact other intermediate outcomes versus control. Upon qualitative analysis, all device categories, with exception of catheter aspiration devices, appear to significantly prolong procedure time compared to PCI alone while none appear to significantly impact ejection fraction. Many of the final health outcome and adverse event evaluations were underpowered and the safety of devices overall is unclear due to insufficient amounts of data.
In patients with STEMI, for most devices, few RCTs evaluated final health outcomes over a long period of follow-up. Due to insufficient data, the safety of these devices is unclear.
Recent cannabinoid research has a primary focus on developing therapeutics against human diseases. Many studies on cannabinoids indicate important progress for protection against several ...neurodegenerative disorders. Agonists of cannabinoid receptors activate signalling pathways in the brain that are linked to neuronal repair and cell maintenance, and endogenous ligands can also activate neuroprotective responses. These endocannabinoids are bioactive fatty acid amides and esters that are synthesised in the brain and include arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol. Endocannabinoids are released in response to pathogenic events, thus representing a potential compensatory repair mechanism. Enhancing this on-demand action of endocannabinoids is a strategy with which to promote endogenous repair signalling. For such enhancement, considerable work has gone into modulating the availability of endocannabinoids by blocking the processes of their deactivation. The targets include the anandamide-hydrolysing enzyme fatty acid amide hydrolase, the carrier-mediated anandamide transport system and 2-arachidonoyl glycerol-deactivating enzyme monoacylglycerol lipase. The activity of endocannabinoids is terminated through transport and degradation and, accordingly, selective inhibitors of these processes effectively exploit the protective nature of cannabinergic responses. This review highlights recent studies implicating the endocannabinoid system in neuroprotection against different disorders of the CNS.
Abstract Background Plant sterols and stanols are plant steroids with a similar chemical structure and cellular function to human cholesterol, and are recommended as dietary modifiers of serum ...lipids. Plant sterols have a higher degree of absorption than plant stanols, suggesting differential efficacy between the two. Design A meta-analysis of randomized controlled trials was performed to summarize direct comparisons between the effect of plant sterols vs plant stanols on serum lipid levels in healthy patients and patients with hypercholesterolemia. Methods A systematic literature search of MEDLINE, EMBASE, Cochrane CENTRAL, and the Natural Medicines Comprehensive Database was conducted from January 1950 through January 2009. Trials were included in the analysis if they were randomized controlled trials evaluating the effect of plant sterols vs plant stanols in healthy patients or patients with hypercholesterolemia who reported efficacy data on total, low-density lipoprotein, and high-density lipoprotein cholesterols or triglycerides. The weighted mean difference (WMD) of the change from baseline (in mg/dL) with 95% confidence interval was calculated as the difference between the means in the plant sterol and plant stanol groups using a random-effects model. Results Fourteen studies (n=531 patients) met the inclusion criteria. Upon meta-analysis, the results showed that there is no statistically or clinically significant difference between plant sterols and plant stanols in their abilities to modify total cholesterol (WMD −1.11 mg/dL −0.0286 mmol/L, 95% confidence interval CI −4.12 to 1.90, P =0.47), low-density lipoprotein cholesterol (WMD −0.35 mg/dL −0.0091 mmol/L, 95% CI −2.98 to 2.28, P =0.79), high-density lipoprotein cholesterol (WMD −0.28 mg/dL –0.00073 mmol/L, 95% CI −1.18 to 0.62, P =0.54), or triglycerides (WMD −1.80 mg/dL −0.0203 mmol/L, 95% CI −6.80 to 3.21, P =0.48). Conclusions Plant sterols and plant stanols do not have statistically or clinically relevant differing effects on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride levels. The selection of plant sterols vs plant stanols should then be based on potential differences in safety parameters and further study is required to elucidate such differences.
Abstract Almond consumption may be associated with improvements in serum lipid profiles. The aim was to evaluate the influence of almonds on lipid parameters to help define the role of almonds as a ...lipid modulator. MEDLINE, EMBASE, Cochrane CENTRAL, and the Natural Medicines Comprehensive Database were searched through July 2008, with no language restrictions, for randomized controlled trials of almonds in human patients that reported efficacy data on at least one of the following endpoints: total, low-density lipoprotein (LDL), or high-density lipoprotein (HDL) cholesterol, triglycerides, or the LDL:HDL ratio. A manual search of references from primary or review articles was performed to identify additional relevant trials. Five randomized, controlled trials (totaling 142 participants) met all inclusion criteria. Upon meta-analysis, almond consumption ranging from 25 to 168 g/day significantly lowered total cholesterol weighted mean difference –6.95 mg/dL (95% confidence interval CI −13.12 to −0.772) (−0.18 mmol/L 95% CI −0.34 to −0.02) and showed a strong trend toward reducing LDL cholesterol weighted mean difference –5.79 mg/dL (95% CI –11.2 to 0.00) (–0.15 mmol/L 95% CI –0.29 to 0.00). No significant effect on HDL cholesterol, triglycerides, or LDL:HDL ratio was found. No statistical heterogeneity was observed for any analysis ( I2 =0% for all). Review of funnel plots and the Egger's weighted regression statistic P values suggested a low likelihood of publication bias in all analyses ( P >0.25 for all). Almond consumption may decrease total cholesterol and does not significantly affect LDL or HDL cholesterol, triglycerides, or the LDL:HDL ratio. The current body of randomized trials does not support the ingestion of almonds solely for their lipid modifying effects. Both the lipid modulating effects and the safety/tolerability of almonds should be further investigated through the conduction of larger randomized, double-blinded trials of longer duration. Such studies might focus specifically on whether the efficacy of almonds as a lipid modulator varies by dose or comorbidity.
Doc number: 74 Abstract Background: During percutaneous coronary intervention (PCI), dislodgement of atherothrombotic material from coronary lesions can result in distal embolization, and may lead to ...increased major adverse cardiovascular events (MACE) and mortality. We sought to systematically review the comparative effectiveness of adjunctive devices to remove thrombi or protect against distal embolization in patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI of native vessels. Methods: We conducted a systematic literature search of Medline, the Cochrane Database, and Web of Science (January 1996-March 2011), http://www.clinicaltrials.gov , abstracts from major cardiology meetings, TCTMD, and CardioSource Plus. Two investigators independently screened citations and extracted data from randomized controlled trials (RCTs) that compared the use of adjunctive devices plus PCI to PCI alone, evaluated patients with STEMI, enrolled a population with 95% of target lesion(s) in native vessels, and reported data on at least one pre-specified outcome. Quality was graded as good, fair or poor and the strength of evidence was rated as high, moderate, low or insufficient. Disagreement was resolved through consensus. Results: 37 trials met inclusion criteria. At the maximal duration of follow-up, catheter aspiration devices plus PCI significantly decreased the risk of MACE by 27% compared to PCI alone. Catheter aspiration devices also significantly increased the achievement of ST-segment resolution by 49%, myocardial blush grade of 3 (MBG-3) by 39%, and thrombolysis in myocardial infarction (TIMI) 3 flow by 8%, while reducing the risk of distal embolization by 44%, no reflow by 48% and coronary dissection by 70% versus standard PCI alone. In a majority of trials, the use of catheter aspiration devices increased procedural time upon qualitative assessment. Distal filter embolic protection devices significantly increased the risk of target revascularization by 39% although the use of mechanical thrombectomy or embolic protection devices did not significantly impact other final health outcomes. Distal balloon or any embolic protection device increased the achievement of MBG-3 by 61% and 20% and TIMI3 flow by 11% and 6% but did not significantly impact other intermediate outcomes versus control. Upon qualitative analysis, all device categories, with exception of catheter aspiration devices, appear to significantly prolong procedure time compared to PCI alone while none appear to significantly impact ejection fraction. Many of the final health outcome and adverse event evaluations were underpowered and the safety of devices overall is unclear due to insufficient amounts of data. Conclusions: In patients with STEMI, for most devices, few RCTs evaluated final health outcomes over a long period of follow-up. Due to insufficient data, the safety of these devices is unclear.
Many factors contribute to suboptimal diabetes control including insufficiently-intensive treatment and non-adherence to medication and lifestyle. Determining which of these is most relevant for ...individual patients is challenging. Patient engagement techniques may help identify contributors to suboptimal adherence and address barriers (using motivational interviewing) and help facilitate choices among treatment augmentation options (using shared decision-making). These methods have not been used in combination to improve diabetes outcomes.
To evaluate the impact of a telephone-based patient-centered intervention on glycosylated hemoglobin (HbA1c) control for individuals with poorly-controlled diabetes.
Two-arm pragmatic randomized control trial within an explanatory sequential mixed-methods design.
1,400 participants 18-64 years old with poorly-controlled type 2 diabetes.
The intervention was delivered over the telephone by a clinical pharmacist and consisted of a 2-step process that integrated brief negotiated interviewing and shared decision-making to identify patient goals and options for enhancing diabetes management.
The primary outcome was change in HbA1c. Secondary outcomes were medication adherence measures. Outcomes were evaluated using intention-to-treat principles; multiple imputation was used for missing values in the 12-month follow-up. We used information from pharmacist notes to elicit factors to potentially explain the intervention's effectiveness.
Participants had a mean age of 54.7 years (SD:8.3) and baseline HbA1c of 9.4 (SD:1.6). Change in HbA1c from baseline was -0.79 (SD:2.01) in the control arm and -0.75 (SD:1.76) in the intervention arm (difference:+0.04, 95%CI: -0.22, 0.30). There were no significant differences in adherence. In as-treated analyses, the intervention significantly improved diabetes control (-0.48, 95%CI: -0.91, -0.05). Qualitative findings provided several potential explanations for the findings, including insufficiently addressing patient barriers.
A novel telephone-based patient-centered intervention did not improve HbA1c among individuals with poorly-controlled diabetes, though as-treated analyses suggest that the intervention was effective for those who received it.
ClinicalTrials.gov NCT02910089.
IntroductionAdherence to and persistence of medications for chronic diseases remains poor and many interventions to improve medication use have only been modestly effective. Targeting interventions ...to patients who are most likely to benefit should improve their efficiency and clinical impact. This study aims to test the impact of three cost-equivalent pharmacist-led interventions on insulin persistence and glycaemic control among patients with diabetes.Methods and analysisTARGIT-Diabetes (Targeted Adherence Intervention to Reach Glycemic Control with Insulin Therapy for patients with Diabetes) is a randomised controlled trial that will evaluate three different multifaceted pharmacist-outreach strategies for improving long-term insulin use among individuals with diabetes. We will randomise 6000 patients in a large insurer to one of three arms. The arms are designed to deliver an increasingly intensive intervention to a progressively targeted population, identified using predictive analytics. The central component of the intervention in all arms is a tailored telephone consultation with a pharmacist which varies across arms based on the: (A) proportion of patients offered the intervention and (B) intervention intensity, including follow-up frequency and cointerventions such as text reminders and interactions with patients’ providers. The primary outcome is insulin persistence, assessed using pharmacy claims data, and the secondary outcomes are glycaemic control as measured by glycosylated haemoglobin values, healthcare utilisation and healthcare spending.Ethics and disseminationThis protocol has been approved by the Institutional Review Board of Brigham and Women’s Hospital and the Privacy Board of Horizon Blue Cross Blue Shield of New Jersey. We plan to present the results of this trial at national meetings and in manuscripts submitted to peer-reviewed journals.Trial registration numberNCT 02846779.
Patient adherence to antidiabetic medications, especially insulin, remains poor, leading to adverse outcomes and increased costs. Most adherence interventions have only been modestly effective, ...partly because they are not targeted to patients who could benefit most.
To evaluate whether delivering more intensive insulin-adherence interventions only to individuals with type 2 diabetes predicted to benefit most was more effective than delivering a lower-intensity intervention to a larger group of unselected individuals.
This 3-arm pragmatic randomized clinical trial used data from Horizon, the largest health insurer in New Jersey, on 6000 participants 18 years or older with type 2 diabetes who were receiving basal insulin. Patients were excluded if they were insured by Medicaid or Medicare or had fewer than 3 months of continuous enrollment. The study was conducted from July 7, 2016, through October 5, 2017. Analyses were conducted from February 5 to September 24, 2018.
Eligible patients were randomized to 3 arms in a 1:1:1 ratio. Randomization was stratified based on baseline availability of 1 or more glycated hemoglobin A1c (HbA1c) test values. All arms were designed to cost the same, and each cohort received a tailored pharmacist telephone consultation varying based on (1) proportion receiving the intervention and (2) intensity, including follow-up frequency and cointerventions. Arm 1 offered a low-intensity intervention to all patients. Arm 2 offered a moderate-intensity intervention to 60% of patients based on their predicted risk of insulin nonadherence. Arm 3 offered a high-intensity intervention to 40% of patients based on glycemic control and predicted risk of insulin nonadherence.
The primary outcome was insulin persistence. Secondary outcomes were changes in HbA1c level and health care utilization. Outcomes were evaluated in arms 2 and 3 vs arm 1 using claims data, intention-to-treat principles, and multiple imputation for missing values in the 12-month follow-up.
Among 6000 participants, mean (SD) age was 55.9 (11.0) years and 3344 (59.8%) were male. Compared with arm 1, insulin nonpersistence did not differ in arm 2 (relative risk, 0.88; 95% CI, 0.75-1.03) or arm 3 (relative risk, 0.91; 95% CI, 0.77-1.06). Glycemic control was similar in arm 2 and arm 1 (absolute HbA1c level difference, -0.15%; 95% CI, -0.34% to 0.05%) but was better in arm 3 (absolute HbA1c level difference, -0.25%; 95% CI, -0.43% to -0.06%). Total spending and office visits did not differ, but arm 2 (moderate intensity intervention) had more hospitalizations (odds ratio, 1.22; 95% CI, 1.06-1.41) and emergency department visits (odds ratio, 1.38; 95% CI, 1.24-1.53) than did arm 1 (low intensity intervention).
Compared with an untargeted low-intensity intervention, delivering a highly targeted high-intensity intervention did not improve insulin persistence but modestly improved mean glycemic control. A partially targeted moderate-intensity intervention did not change insulin persistence or HbA1c level but was associated with a small increase in hospitalizations.
ClinicalTrials.gov Identifier: NCT02846779.
OBJECTIVE To determine the strength of evidence supporting an accentuated bleeding risk when patients with CHADS2 risk factors (chronic heart failure, hypertension, advanced age, diabetes, and prior ...stroke/transient ischemic attack) receive warfarin. METHODS A systematic literature search of MEDLINE (January 1, 1950, through December 22, 2009) and Cochrane CENTRAL (through December 22, 2009) was conducted to identify studies that reported multivariate results on the association between CHADS2 covariates and risk of bleeding in patients receiving warfarin. Each covariate was evaluated for its association with a specific type of bleeding. Individual evaluations were rated as good, fair, or poor using methods consistent with those recommended by the Agency for Healthcare Research and Quality. The strength of the associations between each CHADS2 covariate and a specific type of bleeding was determined using Grading of Recommendations Assessment, Development and Evaluation criteria as insufficient, very low, low, moderate, or high for the entire body of evidence. RESULTS Forty-one studies were identified, reporting 127 multivariate evaluations of the association between a CHADS2 covariate and bleeding risk. No CHADS2 covariate had a high strength of evidence for association with any bleeding type. For the vast majority of evaluations, the strength of evidence between covariates and bleeding was low. Advanced age was the only covariate that had a moderate strength of evidence for association; this was the strongest independent positive predictor for major bleeding. Similar findings were observed regardless of whether all included studies, or only those evaluating patients with atrial fibrillation, were assessed. CONCLUSION The associations between CHADS2 covariates and increased bleeding risk were weak, with the exception of age. Given the known association of the CHADS2 score and stroke risk, the decision to prescribe warfarin should be driven more by patients' risk of stroke than by the risk of bleeding.
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