An adult cystic fibrosis patient presenting with persistent dyspnea: case report

BACKGROUND: Persistent dyspnea is a common finding in the cystic fibrosis patient that typically leads to further work up of an alternative pulmonary etiology. Adult cystic fibrosis patients; however, are growing in numbers and they are living into the ages in which coronary artery disease becomes prevalent. Coronary disease should be included in the consideration of diagnostic possibilities. CASE PRESENTATION: A 52-year-old white male with cystic fibrosis was evaluated for exertional dyspnea associated with vague chest discomfort. Diagnostic testing revealed normal white blood cell, hemoglobin and platelet count, basic metabolic panel, fasting lipid profile, HbA1c, with chest radiograph confirming chronic cystic findings unchanged from prior radiographs and an electrocardiogram that revealed sinus rhythm with left anterior fascicular block. Stress thallium testing demonstrated a reversible anteroseptal perfusion defect with a 55% left ventricular ejection fraction. Heart catheterization found a 99% occlusion of the left anterior descending artery extending into the two diagonal branches, with 100% obstruction of the left anterior descending artery at the trifurcation and 70% lesion affecting the first posterior lateral branch of the circumflex artery. CONCLUSION: This case report represents the first description in the medical literature of a cystic fibrosis patient diagnosed with symptomatic coronary artery disease. Applying a standard clinical practice guide proved useful toward evaluating a differential diagnosis for a cystic fibrosis patient presenting with dyspnea and chest discomfort

Insulin versus oral agents in the management of Cystic Fibrosis Related Diabetes: a case based study

BACKGROUND: Insulin is the recommend therapeutic agent of choice for the management of Cystic Fibrosis Related Diabetes (CFRD), despite only sub-optimal reductions in glycemic control and increased morbidity and mortality reported by centers using this agent. The newer insulin sensitizing agents demonstrated to have anti-inflammatory mechanisms may provide an alternative management option for CFRD. METHODS: A prospective case based therapeutic comparison between insulin, sulfonylurea, metformin and thiazolidinedione was observed over one decade with 20 CFRD patients diagnosed using American Diabetes Association guideline standards. Patients entering the study elected treatment based on risk and benefit information provided for treatment options. Patients receiving organ transplant or requiring combination diabetic medications were excluded from the study. RESULTS: No statistical advantage was achieved regarding overall glycemic control for oral agents over insulin. Additional outcome measures including changes in weight, liver function testing and FEV(1 )were not statistically significant. CONCLUSION: Insulin alone may not be the only therapeutic option in managing CFRD. Oral hypoglycemic agents were equally effective in treating CFRD and may provide an alternative class of agents for patients reluctant in using insulin

Insulin and Oral Agents for Managing Cystic Fibrosis-Related Diabetes

Background: The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/liter (125 mg/deciliter); or symptomatic diabetes for random glucose levels greater than 11.11 mmol/liter (200 mg/deciliter); or glycated hemoglobin levels of at least 6.5%. Objectives: To establish the effectiveness of agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management. Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences. Date of the most recent search of the Group\u27s Cystic Fibrosis Trials Register: 22 July 2013. Selection criteria: Randomized controlled trials comparing all methods of diabetes therapy in people with diagnosed cystic fibrosis-related diabetes. Data collection and analysis: Two authors independently extracted data and assessed the risk of bias in the included studies. Main results: The searches identified 19 studies (28 references). Three studies (107 participants) are included: one comparing insulin with oral repaglinide and no medication (short-term single-center study of seven patients with cystic fibrosis-related diabetes and normal fasting glucose); one comparing insulin with oral repaglinide and placebo (long-term multi-center study with 81 patients, 61 of whom had cystic fibrosis-related diabetes); and one 12-week single-center study comparing the long-acting insulin, glargine to short-term neutral protamine Hagedorn insulin. The long-term trial of insulin and repaglinide demonstrated no significant difference between treatments. In the smaller study comparing insulin and oral repaglinide, there were two incidents of significant hypoglycemia in the insulin group compared to one in the repaglinide group; in the larger study there were five incidents of significant hypoglycemia in the insulin group and six in the repaglinide group. The study comparing glargine to neutral protamine Hagedorn insulin demonstrated a statistically non-significant weight increase in with longer-acting insulin given at bedtime and reported a mean of six hypoglycemia events in the glargine group compared to five events in the neutral protamine Hagedorn insulin group. None of the three included studies were powered to show a significant improvement in lung function. Authors\u27 conclusions: This review has not found any significant conclusive evidence that long-acting insulins, short-acting insulins or oral hypoglycemic agents have a distinct advantage over one another in controlling hyperglycemia or clinical outcomes associated with cystic fibrosis-related diabetes. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes with this impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority. There is no demonstrated advantage yet established for using oral hypoglycemic agents over insulin, and further studies need to be evaluated to establish whether there is clear benefit for using hypoglycemic agents. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should be further investigated to see if there may be a clinical advantage to adding these medications to insulin as adjuvant therapy

Insulin and Oral Agents for Managing Cystic Fibrosis-Related Diabetes

Background: The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/liter (125 mg/deciliter); or oral glucose tolerance tests greater than 11.11 mmol/liter (200 mg/deciliter) at two hours; or symptomatic diabetes for random glucose levels greater than 11.11 mmol/liter (200 mg/deciliter); or glycated hemoglobin levels of at least 6.5%. Objectives: To establish the effectiveness of insulin and oral agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management. Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group\u27s Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences. Date of the most recent search of the Group\u27s Cystic Fibrosis Trials Register: 18 February 2016. Selection criteria: Randomized controlled trials comparing all methods of diabetes therapy in people with diagnosed cystic fibrosis-related diabetes. Data collection and analysis: Two authors independently extracted data and assessed the risk of bias in the included studies. Main results: The searches identified 22 trials (34 references). Four trials (200 participants) are included: one short-term single-center trial (n = 7) comparing insulin with oral repaglinide and no medication in people with cystic fibrosis-related diabetes and normal fasting glucose; one long-term multicenter trial (n = 100, 74 of whom had cystic fibrosis-related diabetes) comparing insulin with oral repaglinide and placebo; one long-term multicenter trial (n = 73) comparing insulin with oral repaglinide; and one 12-week single-center trial (n = 20) comparing the long-acting insulin glargine to short-term neutral protamine Hagedorn insulin. Two trials with data for the comparison of insulin to placebo did not report any significant differences between groups for the primary outcomes of blood glucose levels, lung function and nutritional status. This was also true for the single trial with data for the comparison of repaglinide to placebo. Two trials (one lasting one year and one lasting two years) contributed data for the comparison of insulin versus repaglinide. There were no significant differences for the primary outcomes at any time point, except at one year (in the two-year trial) when the insulin group had significant improvement in z score for body mass index compared to the repaglinide group. The single trial comparing glargine to neutral protamine Hagedorn insulin also did not report any significant differences in the review\u27s primary outcomes. A few cases of hypoglycemia were seen in three out of the four trials (none in the longest trial), but these events resolved without further treatment. There was an unclear risk of bias from randomization and allocation concealment in two of the four included trials as the authors did not report any details; in the remaining two studies details for randomization led to a low risk of bias, but only one had sufficient details on allocation concealment to allow a low risk judgement, the second was unclear. There was a high risk from blinding for all trials (except for the comparison of oral repaglinide versus placebo) due to the nature of the interventions. Complete data for all outcomes were not available from any trial leading to a high risk of reporting bias. The amounts of insulin and repaglinide administered were not comparable and this may lead to bias in the results. None of the included trials were powered to show a significant improvement in lung function. Authors\u27 conclusions: This review has not found any significant conclusive evidence that long-acting insulins, short-acting insulins or oral hypoglycemic agents have a distinct advantage over one another in controlling hyperglycemia or clinical outcomes associated with cystic fibrosis-related diabetes. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes with this impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority. There is no demonstrated advantage yet established for using oral hypoglycemic agents over insulin, and further trials need to be evaluated to establish whether there is clear benefit for using hypoglycemic agents. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should be further investigated to see if there may be a clinical advantage to adding these medications to insulin as adjuvant therapy

Drug Treatments for Managing Cystic Fibrosis-Related Diabetes

Background: The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes (CFRD) has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/L (125 mg/dL); or oral glucose tolerance tests greater than 11.11 mmol/L (200 mg/dL) at two hours; or symptomatic diabetes for random glucose levels greater than 11.11 mmol/L (200 mg/dL); or glycated hemoglobin levels of at least 6.5%. This is an update of a previously published review. Objectives: To establish the effectiveness of insulin and oral agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management. Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group\u27s Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences. Date of most recent register search: 10 September 2020. We searched online trials registries; date of most recent searches: 21 March 2020. Selection criteria: Randomized controlled trials comparing all methods of pharmacological diabetes therapy in people with diagnosed CFRD. Data collection and analysis: Two authors independently extracted data and assessed the risk of bias in the included studies. Authors also used GRADE to assess the quality of the evidence. Main results: The searches identified 29 trials (45 references). Four included trials provide results: one short-term single-center cross-over trial (seven adults) comparing insulin with oral repaglinide and no medication in adults with CFRD and normal fasting glucose; one long-term multicenter trial (61 adults with CFRD) comparing insulin with oral repaglinide and placebo; one long-term multicenter trial (67 adults) comparing insulin with oral repaglinide; and one 12-week single-center cross-over trial (20 adults) comparing the long-acting insulin glargine to short-term neutral protamine Hagedorn insulin. Two ongoing trials of newly approved incretin mimics have been noted for possible future inclusion. Downgrading of the quality of the evidence was mainly due to risks of bias across all domains, but particularly due to concerns surrounding allocation concealment and selective reporting. There were also some concerns due to imprecision from small sample sizes and low event rates. Finally, there may be some bias due to the amounts of insulin and repaglinide given not being comparable. Data from one trial comparing insulin to placebo (39 participants) did not show any difference between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) or nutritional status (low-quality evidence). Similarly, no differences between groups were seen for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or quality of life (QoL). These results were mirrored in the narrative reports for the second trial in this comparison (seven participants). Data from the one-year trial comparing repaglinide to placebo (38 participants), showed no differences between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) and nutritional status (low-quality evidence). Also, no differences were seen between groups for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or QoL. These findings were mirrored in the narrative reports for the second trial (n = 7) in this comparison. Three trials compared insulin to repaglinide (119 participants). Data from one trial (n = 67) showed no difference in blood glucose levels at either 12 months (high-quality evidence) or 24 months; narrative reports from one trial (45 participants) reported no difference between groups, but the second trial (7 participants) reported a beneficial effect of insulin over repaglinide. Two trials (112 participants) found no difference between insulin and repaglinide in lung function or nutritional status (moderate-quality evidence). Two trials (56 participants) reported no difference in the number of hypoglycemic episodes (low-quality evidence). One trial (45 participants) reported no difference between groups in secondary infections and cystic fibrosis QoL. The single trial comparing glargine to neutral protamine Hagedorn insulin did not report directly on the review\u27s primary outcomes, but did report no differences between groups in post-prandial glucose values and weight; neither group reported infectious complications. There was no difference in episodes of hypoglycemia (very low-quality evidence) and while there was no difference reported in QoL, all participants opted to continue treatment with glargine after the trial was completed. Mortality was not reported by any trial in any comparison, but death was not given as a reason for withdrawal in any trial. Authors\u27 conclusions: This review has not found any conclusive evidence that any agent has a distinct advantage over another in controlling hyperglycemia or the clinical outcomes associated with CFRD. Given the treatment burden already experienced by people with cystic fibrosis, oral therapy may be a viable treatment option. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes and its impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority. Specifically, investigators should evaluate adherence to different therapies and also whether there is benefit in using additional hypoglycemic agents as well as the newly approved incretin mimics. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should also be further investigated as adjuvant therapy to insulin

Insulin and Oral Agents for Managing Cystic Fibrosis-Related Diabetes

BACKGROUND: Insulin therapy is recommended by the Cystic Fibrosis Foundation when cystic fibrosis-related diabetes has been diagnosed. Diagnosis is based on an elevated fasting blood glucose level greater than 6.94 mmol/liter (125 mg/deciliter) or symptomatic diabetes for random glucose levels greater than 11.11 mmol/liter (200 mg/deciliter). OBJECTIVES: To examine the evidence that, when treated with agents for managing diabetes, people with cystic fibrosis improve their sugar metabolic control resulting in beneficial impact on lung function and the ability to maintain optimal weight. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.We also handsearched abstracts from pulmonary and North American Cystic Fibrosis Conference symposia.Date of the most recent search of the Group\u27s Trials Register: December 2004. SELECTION CRITERIA: Randomized controlled trials comparing all methods of diabetes therapy for one month or longer in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: No studies were found which were eligible for inclusion in this review. MAIN RESULTS: Six references to four studies were identified by the searches, but none were eligible for inclusion in the review as they were not randomized controlled trials. AUTHORS\u27 CONCLUSIONS: While some cystic fibrosis centers use oral medications to help control diabetes, a condition which complicates the course of cystic fibrosis, insulin therapy is the recommended and most widely used treatment method. Lung function has been reported to improve with the use of insulin, but this has not been correlated to the degree in which sugar metabolism has been affected. While the Cystic Fibrosis Foundation recommends insulin therapy be used in managing diabetes, this systematic review identifies the need for a multicentre randomized controlled trial assessing both the efficacy of insulin or other insulin-releasing or insulin-sensitizing medications and their possible adverse effects in managing cystic fibrosis-related diabetes

Efficacy of Probiotics in the Treatment of Pediatric Atopic Dermatitis: A Meta-Analysis of Randomized Controlled Trials

Background: Several articles describing the efficacy of probiotics in atopic dermatitis (AD) have been published. However, not all studies support a similar outcome. Objective: To determine whether probiotics are efficacious in treating AD and to explore whether type of probiotic used, duration of therapy, patient age, severity of disease, and IgE sensitization are factors in determining efficacy. Methods: For this meta-analysis of randomized controlled trials describing the efficacy of probiotics in AD, a comprehensive search was performed of databases through January 2008. Three reviewers independently evaluated the studies for methodological qualities. All the data were analyzed, and forest plots were evaluated for the overall efficacy of probiotics in AD and the therapeutic benefit to subgroups of selected patient populations. Results: Eleven studies were identified, and data from 10 studies (n = 678) were available to analyze. There was an overall statistically significant difference favoring probiotics compared with placebo in reducing the Scoring of Atopic Dermatitis Severity Index score (mean change from baseline, -3.01; 95% confidence interval, -5.36 to -0.66; P = .01). Children with moderately severe disease were more likely to benefit. Duration of probiotic administration, age, and type of probiotic used did not affect outcome. Conclusion: Data from this meta-analysis suggest a modest role for probiotics in pediatric AD. The effect is seen in moderately severe rather than mild disease

Efficacy of Probiotics in the Treatment of Pediatric Atopic Dermatitis: A Meta-Analysis of Randomized Controlled Trials

Background: Several articles describing the efficacy of probiotics in atopic dermatitis (AD) have been published. However, not all studies support a similar outcome. Objective: To determine whether probiotics are efficacious in treating AD and to explore whether type of probiotic used, duration of therapy, patient age, severity of disease, and IgE sensitization are factors in determining efficacy. Methods: For this meta-analysis of randomized controlled trials describing the efficacy of probiotics in AD, a comprehensive search was performed of databases through January 2008. Three reviewers independently evaluated the studies for methodological qualities. All the data were analyzed, and forest plots were evaluated for the overall efficacy of probiotics in AD and the therapeutic benefit to subgroups of selected patient populations. Results: Eleven studies were identified, and data from 10 studies (n = 678) were available to analyze. There was an overall statistically significant difference favoring probiotics compared with placebo in reducing the Scoring of Atopic Dermatitis Severity Index score (mean change from baseline, -3.01; 95% confidence interval, -5.36 to -0.66; P = .01). Children with moderately severe disease were more likely to benefit. Duration of probiotic administration, age, and type of probiotic used did not affect outcome. Conclusion: Data from this meta-analysis suggest a modest role for probiotics in pediatric AD. The effect is seen in moderately severe rather than mild disease

Mechanisms of Sickle Cell Anemia

Team-based learning (TBL) is a well-defined instructional strategy that allows a single instructor to teach by conducting multiple small groups simultaneously in the same classroom. Learners actively participate in and out of class as they move through three phases: independent study assignments, readiness assurance testing, and group activities that force them to put knowledge into practice. Students prepare in advance by reading an assigned article. Class time is shifted away from learning facts and toward application and integration of information. The instructor retains control of content and acts as both facilitator and content expert. This TBL program is designed to supplement the first-year Molecular Basis of Medicine course covering quaternary protein structure. The session compares the impact of amino acid substation on HbA, HbS, HbF on quaternary structure and function. Protein solubility, role and rate of oxygenation, hemoglobin concentration, and rate of microvascular transient time relative to polymerization reactions are detailed to enhance appreciation as to mechanisms of disease impacted by quaternary structural defects. The TBL session features a readiness assessment test that is first taken individually and then later by teams, an applications worksheet that uses multiple-choice questions to integrate basic knowledge components into medical decision-making tasks, and a summary point review sheet that acts as a study guide for formal examination assessments used throughout the course. Included is a detailed instructor\u27s guide to facilitate use of the materials, all of which are appended to the instructor\u27s guide. No formal studies have been done, but the session has been used multiple times with a pediatric inpatient team made up of multiple levels of learners. Informal feedback has been uniformly positive that the case is realistic, useful, and practical