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Dye Chromoendoscopy Outperforms High-Definition White Light Endoscopy in Dysplasia Detection for Patients With Inflammatory Bowel Disease: An Updated Meta-Analysis of Randomized Controlled Trials.
Mohamed, MFH, Marino, D, Elfert, K, Beran, A, Nayfeh, T, Abdallah, MA, Sultan, S, Shah, SA
The American journal of gastroenterology. 2024;(4):719-726
Abstract
INTRODUCTION Whether dye spray chromoendoscopy (DCE) adds value in surveillance colonoscopy with high-definition (HD) scopes remains controversial. This updated meta-analysis compares dysplasia detection using DCE and high-definition white light endoscopy (HD-WLE) in patients with inflammatory bowel disease (IBD) undergoing surveillance colonoscopy. METHODS A comprehensive search was performed for randomized controlled trials (RCT) comparing HD-WLE and DCE in patients with IBD. The primary outcome was to compare the proportion of patients with at least 1 dysplastic lesion detected by DCE vs HD-WLE. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using the random-effects model, with I2 > 60% indicating substantial heterogeneity. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of evidence (CoE). RESULTS Six RCT involving 978 patients were analyzed (DCE = 479 vs HD-WLE = 499 patients). DCE detected significantly more patients with dysplasia than HD-WLE (18.8% vs 9.4%), OR 1.94 (95% CI 1.21-3.11, I2 = 28%, P = 0.006, high CoE). This remained significant after excluding 2 RCT published as abstracts. A sensitivity analysis excluding a noninferiority RCT with a single experienced operator eliminated the results' heterogeneity, OR 2.46 (95% CI 1.56-3.90, I2 = 0%). Although high-grade dysplasia detection was numerically higher in the DCE group (2.8% vs 1.1%), the difference was statistically insignificant, OR 2.21 (95% CI 0.64-7.62, I2 = 0%, low CoE). DISCUSSION Our updated meta-analysis supports DCE as a superior strategy in overall dysplasia detection in IBD, even with HD scopes. When expertise is available, DCE should be considered for surveillance colonoscopy in patients with high-risk IBD, with the acknowledgment that virtual chromoendoscopy shows equivalence in recent studies. Further multicenter trials with multiple endoscopists with varying expertise levels and longer-term outcome data showing a reduction in cancer or cancer-related death are needed.
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Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review and Network Meta-analysis for the American College of Physicians.
Drake, T, Landsteiner, A, Langsetmo, L, MacDonald, R, Anthony, M, Kalinowski, C, Ullman, K, Billington, CJ, Kaka, A, Sultan, S, et al
Annals of internal medicine. 2024
Abstract
BACKGROUND Newer diabetes medications may have beneficial effects on mortality, cardiovascular outcomes, and renal outcomes. PURPOSE To evaluate the effectiveness, comparative effectiveness, and harms of sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP1) agonists, dipeptidyl peptidase-4 (DPP4) inhibitors, and long-acting insulins as monotherapy or combination therapy in adults with type 2 diabetes mellitus (T2DM). DATA SOURCES MEDLINE and EMBASE for randomized controlled trials (RCTs) published from 2010 through January 2023. STUDY SELECTION RCTs lasting at least 52 weeks that included at least 500 adults with T2DM receiving eligible medications and reported any outcomes of interest. DATA EXTRACTION Data were abstracted by 1 reviewer and verified by a second. Independent, dual assessments of risk of bias and certainty of evidence (CoE) were done. DATA SYNTHESIS A total of 130 publications from 84 RCTs were identified. CoE was appraised using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria for direct, indirect, and network meta-analysis (NMA); the highest CoE was reported. Compared with usual care, SGLT2 inhibitors and GLP1 agonists reduce all-cause mortality (high CoE) and major adverse cardiovascular events (MACE) (moderate to high CoE), SGLT2 inhibitors reduce progression of chronic kidney disease (CKD) and heart failure hospitalizations and GLP1 agonists reduce stroke (high CoE), and SGLT2 inhibitors reduce serious adverse events and severe hypoglycemia (high CoE). The threshold for minimally important differences, which was predefined with the American College of Physicians Clinical Guidelines Committee, was not met for these outcomes. Compared with usual care, insulin, tirzepatide, and DPP4 inhibitors do not reduce all-cause mortality (low to high CoE). Compared with insulin, SGLT2 inhibitors and GLP1 agonists reduce all-cause mortality (low to moderate CoE). Compared with DPP4 inhibitors, GLP1 agonists reduce all-cause mortality (moderate CoE). Compared with DPP4 inhibitors and sulfonylurea (SU), SGLT2 inhibitors reduce MACE (moderate to high CoE). Compared with SU and insulin, SGLT2 inhibitors and GLP1 agonists reduce severe hypoglycemia (low to high CoE). LIMITATIONS Infrequent direct comparisons between drugs of interest; sparse data for NMA on most outcomes; possible incoherence due to differences in baseline patient characteristics and usual care; insufficient data on predefined subgroups, including demographic subgroups, patients with prior cardiovascular disease, and treatment-naive persons. CONCLUSION In adults with T2DM, SGLT2 inhibitors and GLP1 agonists (but not DPP4 inhibitors, insulin, or tirzepatide) reduce all-cause mortality and MACE compared with usual care. SGLT2 inhibitors reduce CKD progression and heart failure hospitalization and GLP1 agonists reduce stroke compared with usual care. Serious adverse events and severe hypoglycemia are less frequent with SGLT2 inhibitors and GLP1 agonists than with insulin or SU. PRIMARY FUNDING SOURCE American College of Physicians. (PROSPERO CRD42022322129).
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Cost-Effectiveness of Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review of Cost-Effectiveness Studies for the American College of Physicians.
Schousboe, JT, Landsteiner, A, Drake, T, Sultan, S, Langsetmo, L, Kaka, A, Anthony, M, Billington, CJ, Kalinowski, C, Ullman, K, et al
Annals of internal medicine. 2024
Abstract
BACKGROUND In the United States, costs of antidiabetes medications exceed $327 billion. PURPOSE To systematically review cost-effectiveness analyses (CEAs) of newer antidiabetes medications for type 2 diabetes. DATA SOURCES Bibliographic databases from 1 January 2010 through 13 July 2023, limited to English. STUDY SELECTION Nonindustry-funded CEAs, done from a U.S. perspective that estimated cost per quality-adjusted life-year (QALY) gained for newer antidiabetic medications. Two reviewers screened the literature; disagreements were resolved with a third reviewer. DATA EXTRACTION Cost-effectiveness analyses were reviewed for treatment comparisons, model inputs, and outcomes. Risk of bias (RoB) of the CEAs was assessed using Drummond criteria and certainty of evidence (CoE) was assessed using GRADE (Grading of Recommendations Assessment, Development, and Evaluations). Certainty of evidence was determined using cost per QALY thresholds predetermined by the American College of Physicians Clinical Guidelines Committee; low (>$150 000), intermediate ($50 to $150 000), or high (<$50 000) value per QALY compared with the alternative. DATA SYNTHESIS Nine CEAs were eligible (2 low, 1 high, and 6 some concerns RoB), evaluating glucagon-like peptide-1 agonists (GLP1a), dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucose-dependent insulinotropic peptide agonist (GIP/GLP1a), and insulin. Comparators were metformin, sulfonylureas, neutral protamine Hagedorn (NPH) insulin, and others. Compared with metformin, GLP1a and SGLT2i are low value as first-line therapy (high CoE) but may be of intermediate value when added to metformin or background therapy compared with adding nothing (low CoE). Insulin analogues may be similarly effective but more expensive than NPH insulin (low CoE). The GIP/GLP1a value is uncertain (insufficient CoE). LIMITATIONS Cost-effectiveness analyses varied in methodological approach, assumptions, and drug comparisons. Risk of bias and GRADE method for CEAs are not well established. CONCLUSION Glucagon-like peptide-1 agonists and SGLT2i are of low value as first-line therapy but may be of intermediate value when added to metformin or other background therapy compared with adding nothing. Other drugs and comparisons are of low or uncertain value. Results are sensitive to drug effectiveness and cost assumptions. PRIMARY FUNDING SOURCE American College of Physicians. (PROSPERO CRD42022382315).
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4.
A Comprehensive Review: Epidemiological Strategies, Catheterization and Biomarkers used as a Bioweapon in Diagnosis and Management of Cardio Vascular Diseases.
Abbas, A, Raza, A, Ullah, M, Hendi, AA, Akbar, F, Khan, SU, Zaman, U, Saeed, S, Ur Rehman, K, Sultan, S, et al
Current problems in cardiology. 2023;(7):101661
Abstract
Coronary artery disease (CAD) is a serious health problem that causes a considerable number of mortality in a number of affluent nations throughout the world. The estimated death encountered in many developed countries includes including Pakistan, reached 111,367 and accounted for 9.87% of all deaths, despite the mortality rate being around 7.2 million deaths per year, or 12% of all estimated deaths accounted annually around the globe, with improved health systems. Atherosclerosis progressing causes the coronary arteries to become partially or completely blocked, which results in CAD. Additionally, smoking, diabetes mellitus, homocystinuria, hypertension, obesity, hyperlipidemia, and psychological stress are risk factors for CAD. The symptoms of CAD include angina which is described as a burning, pain or discomfort in the chest, nausea, weakness, shortness of breath, lightheadedness, and pain or discomfort in the arms or shoulders. Atherosclerosis and thrombosis are the 2 pathophysiological pathways most frequently involved in acute coronary syndrome (ACS). Asymptomatic plaque disruption, plaque bleeding, symptomatic coronary blockage, and myocardial infarction are the prognoses for CAD. In this review, we will focus on medicated therapy which is being employed for the relief of angina linked with CAD including antiplatelet medicines, nitrates, calcium antagonists, blockers, catheterization, and the frequency of recanalized infarct-related arteries in patients with acute anterior wall myocardial infarction (AWMI). Furthermore, we have also enlightened the importance of biomarkers that are helpful in the diagnosis and management of CAD.
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Reducing the Threshold of Primary Prevention of Cardiovascular Disease to 10% Over 10 Years: The Implications of Altered Intensity "Statin" Therapy Guidance.
Sultan, S, Khan, SU, Holden, K, Hendi, AA, Saeed, S, Abbas, A, Zaman, U, Naeem, S, Rehman, KU
Current problems in cardiology. 2023;(2):101486
Abstract
Cardiovascular disease (CVD) is a significant noncommunicable disease associated with high long-term mortality. In addition to more effective secondary therapies, the primary prevention of CVD has developed markedly in the past several years. This study aims to investigate the evidence and impact of reducing the threshold for primary CVD risk management to 10% over 10 years with "statin" therapy. To conduct research a systematic review utilizing 5 electronic database searches was completed for studies, analyzing the clinical effect of reducing the threshold of CVD risk to 10% over 10 years for primary prevention with statin therapy. The study included six (6) trials. Statin therapy was allocated to 31,018 participants. The mean age was 61 years and the mean follow-up was 4.6 years. The mean relative reduction in total cholesterol was 19% (from an average of), low-density lipoprotein cholesterol was 28.3% (from mmol/L to mmol/L) and triglycerides were 14.8% (from mmol/L to mmol/L). High-density lipoprotein cholesterol was observed to increase by a mean of 3.3% (from mmol/L to mmol/L). When examining all-cause mortality, statin therapy was associated with a 12% relative risk reduction compared with control, where overall rates were reduced from 1.4% to 1. % There is a 30% risk reduction in general major coronary events (from to %). There is a 19% risk reduction in general major cerebrovascular events with the statin group. While there is undoubtedly statistical evidence that supports the observation of the effectiveness of statin therapy for primary prevention, there is a risk that many hundreds of patients need to be treated to avoid a single adverse clinical outcome.
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Gastrointestinal Endoscopy in Patients with Coronavirus Disease 2019: Indications, Findings, and Safety.
Sultan, S
Gastroenterology clinics of North America. 2023;(1):157-172
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Abstract
The coronavirus disease 2019 (COVID-19) pandemic has changed the practice of gastroenterology and how we perform endoscopy. As with any new or emerging pathogen, early in the pandemic, there was limited evidence and understanding of disease transmission, limited testing capability, and resource constraints, especially availability of personal protective equipment (PPE). As the COVID-19 pandemic progressed, enhanced protocols with particular emphasis on assessing the risk status of patients and proper use of PPE have been incorporated into routine patient care. The COVID-19 pandemic has taught us important lessons for the future of gastroenterology and endoscopy.
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Youth Culturally adapted Manual Assisted Problem Solving Training (YCMAP) in Pakistani adolescent with a history of self-harm: protocol for multicentre clinical and cost-effectiveness randomised controlled trial.
Husain, N, Tofique, S, Chaudhry, IB, Kiran, T, Taylor, P, Williams, C, Memon, R, Aggarwal, S, Alvi, MH, Ananiadou, S, et al
BMJ open. 2022;(5):e056301
Abstract
INTRODUCTION Suicide is a global health concern. Sociocultural factors have an impact on self-harm and suicide rates. In Pakistan, both self-harm and suicide are considered as criminal offence's and are condemned on both religious and social grounds. The proposed intervention 'Youth Culturally Adapted Manual Assisted Problem Solving Training (YCMAP)' is based on principles of problem-solving and cognitive-behavioural therapy. YCMAP is a brief, culturally relevant, scalable intervention that can be implemented in routine clinical practice if found to be effective. METHOD AND ANALYSIS A multicentre rater blind randomised controlled trial to evaluate the clinical and cost-effectiveness of YCMAP including a sample of 652 participants, aged 12-18 years, presenting to general physicians/clinicians, emergency room after self harm or self referrals. We will test the effectiveness of 8-10 individual sessions of YCMAP delivered over 3 months compared with treatment as usual. Primary outcome measure is repetition of self-harm at 12 months. The seconday outcomes include reduction in suicidal ideation, hopelessness and distress and improvement in health related quality of life. Assessments will be completed at baseline, 3, 6, 9 and 12 months postrandomisation. The nested qualitative component will explore perceptions about management of self-harm and suicide prevention among adolescents and investigate participants' experiences with YCMAP. The study will be guided by the theory of change approach to ensure that the whole trial is centred around needs of the end beneficiaries as key stakeholders in the process. ETHICS AND DISSEMINATION Ethics approval has been obtained from the Ethics Committee of University of Manchester, the National Bioethics Committee in Pakistan. The findings of this study will be disseminated through community workshops, social media, conference presentations and peer-reviewed journals. TRIAL REGISTRATION NUMBER NCT04131179.
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AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Diarrhea.
Lembo, A, Sultan, S, Chang, L, Heidelbaugh, JJ, Smalley, W, Verne, GN
Gastroenterology. 2022;(1):137-151
Abstract
BACKGROUND & AIMS Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder associated with significant disease burden. This American Gastroenterological Association Guideline is intended to support practitioners in decisions about the use of medications for the pharmacological management of IBS with predominant diarrhea (IBS-D) and is an update of a prior technical review and guideline. METHODS The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The technical review panel prioritized clinical questions and outcomes according to their importance for clinicians and patients and conducted an evidence review of the following agents: eluxadoline, rifaximin, alosetron, loperamide, tricyclic antidepressants, selective serotonin reuptake inhibitors, and antispasmodics. The guideline panel reviewed the evidence and used the Evidence-to-Decision Framework to develop recommendations. CONCLUSIONS The panel agreed on 8 recommendations for the management of patients with IBS-D. The panel made conditional recommendations for eluxadoline, rifaximin, alosetron, (moderate certainty), loperamide (very low certainty), tricyclic antidepressants, and anstispasmodics (low certainty). The panel made a conditional recommendation against the use of selective serotonin reuptake inhibitors (low certainty).
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AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Constipation.
Chang, L, Sultan, S, Lembo, A, Verne, GN, Smalley, W, Heidelbaugh, JJ
Gastroenterology. 2022;(1):118-136
Abstract
BACKGROUND & AIMS Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction associated with significant disease burden. This American Gastroenterological Association guideline is intended to support practitioners in decisions about the use of medications for the pharmacological management of IBS-C and is an update of a prior technical review and guideline. METHODS The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The technical review panel prioritized clinical questions and outcomes according to their importance for clinicians and patients and conducted an evidence review of the following agents: tenapanor, plecanatide, linaclotide, tegaserod, lubiprostone, polyethylene glycol laxatives, tricyclic antidepressants, selective serotonin reuptake inhibitors, and antispasmodics. The Guideline Panel reviewed the evidence and used the Evidence-to-Decision Framework to develop recommendations. CONCLUSIONS The panel agreed on 9 recommendations for the management of patients with IBS-C. The panel made a strong recommendation for linaclotide (high certainty) and conditional recommendations for tenapanor, plecanatide, tegaserod, and lubiprostone (moderate certainty), polyethylene glycol laxatives, tricyclic antidepressants, and antispasmodics (low certainty). The panel made a conditional recommendation against the use of selective serotonin reuptake inhibitors (low certainty).
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Association Of Bone Mineral Profile With Restless Leg Syndrome In Patients With End Stage Renal Disease.
Sultan, S, Nasir, K, Qureshi, R, Dhrolia, M, Ahmad, A
Journal of Ayub Medical College, Abbottabad : JAMC. 2022;(3):S660-S664
Abstract
BACKGROUND Restless leg syndrome (RLS) is one of the problem hemodialysis patients may encounter. This study was done to find out the association of restless legs syndrome (RLS) in end stage renal disease patients with serum calcium, phosphorus and parathyroid hormone levels. METHODS This cross-sectional observational study was done at The Kidney Centre, postgraduate Training Institute Karachi, Pakistan from Jan to June 2020. One hundred and twelve patients on three per week hemodialysis for more than three months at our hemodialysis centre were face to face interviewed as per International Restless Legs Syndrome Study Group criteria (IRLSSG) for the presence of RLS symptoms. Their demographic data and laboratory values were recorded from history chart and computer records. The bone mineral profile in this study includes serum calcium (corrected for albumin), serum phosphate levels and serum intact Parathyroid hormone (iPTH) levels. Statistical analyses were done by using SPSS-21. RESULTS In our study, 38.4% patients had RLS. Serum phosphorus levels were significantly higher in patients with RLS as compared to those who didn't have RLS. No significant association of serum calcium and Parathyroid hormone (PTH) levels with RLS was found. CONCLUSION There is a high prevalence of RLS in ESRD patients as compared to general population. Serum phosphorus levels need to be observed and corrected along with maintenance of calcium and PTH levels to improve symptoms of RLS in these patients.