Archives
Meta-Analysis: Acute adverse effects of therapeutic psilocybin doses in treating depression and anxiety – JAMA Netw Open
7 May, 2024 | 15:29h | UTCThis meta-analysis examined the acute adverse effects of psilocybin when used in therapeutic doses for treating depression and anxiety. The study analyzed data from six randomized, double-blind clinical trials involving a total of 528 participants. Significant adverse effects identified included headaches, nausea, anxiety, dizziness, and elevated blood pressure, compared to controls. No significant risks of paranoia or transient thought disorder were associated with psilocybin use. Overall, the adverse effects were tolerable and typically resolved within 48 hours, although the study calls for further research into their management.
Reference (link to free full-text):
RCT: Effects of combined time-restricted eating and high-intensity functional training on body composition and cardiometabolic health in women with obesity – PLOS One
7 May, 2024 | 15:28h | UTCThis randomized clinical trial investigated the effects of time-restricted eating (TRE) and high-intensity functional training (HIFT), both separately and in combination, on body composition and cardiometabolic health in inactive women with obesity. Sixty-four participants were assigned to three groups: TRE alone, HIFT alone, and both TRE and HIFT (TRE-HIFT). Over 12 weeks, the TRE-HIFT group showed the most significant improvements in waist and hip circumference, fat mass, total cholesterol, triglyceride levels, insulin sensitivity, and blood glucose levels compared to the other groups. Weight and BMI reductions were also more substantial in the TRE-HIFT group than in the HIFT-only group. Furthermore, while all groups exhibited improvements, those combining both interventions experienced more pronounced changes in cardiometabolic parameters, suggesting the potential of integrated lifestyle interventions for enhancing health outcomes in this population.
Reference (link to free full-text):
RCT: Oral and topical minoxidil equally effective for male hair loss treatment – JAMA Dermatol
7 May, 2024 | 15:26h | UTCThis study examines the effectiveness, safety, and tolerability of oral minoxidil compared to topical minoxidil in treating male androgenetic alopecia. Conducted as a double-blind, placebo-controlled randomized clinical trial, 90 men aged 18 to 55 with varying degrees of hair loss were recruited and followed for 24 weeks. Participants were divided into two groups: one receiving oral minoxidil 5 mg daily and the other using topical minoxidil 5% twice daily. The primary endpoint was the change in terminal hair density in both the frontal and vertex regions. Results showed that oral minoxidil did not outperform topical minoxidil in terms of increasing hair density on the frontal scalp, though it did show a slight superiority on the vertex area. Common side effects for the oral minoxidil group included hypertrichosis and headaches. Overall, oral minoxidil demonstrated similar efficacy to its topical counterpart and offers an alternative for patients preferring oral treatment or those intolerant to topical formulations.
Reference (link to abstract – $ for full-text):
Review: Acute and complicated inflammatory pericarditis – Mayo Clin Proc
6 May, 2024 | 18:03h | UTCThe article provides a comprehensive review of current approaches to the diagnosis and management of inflammatory pericardial disease, with a particular focus on acute and complicated cases of pericarditis. Here’s a summary tailored for a medical audience:
Key Points:
1 – Epidemiology and Presentation:
– Acute pericarditis is relatively common, particularly among younger populations.
– It can be effectively managed in most cases but poses a significant risk of recurrence and morbidity if not properly treated.
– Presentations can vary, with chest pain being a predominant symptom, which improves upon leaning forward and worsens in the supine position.
2 – Diagnostic Evaluation:
– Diagnosis hinges on a combination of clinical signs (e.g., chest pain, pericardial rub), ECG changes, imaging findings, and laboratory markers (elevated CRP and white blood cell count).
– Multimodality imaging plays a critical role in diagnosis and management, including echocardiography, CT, and MRI to evaluate pericardial effusion and inflammation.
3 – Management Strategies:
– The treatment landscape has evolved with the introduction of targeted anti-inflammatory therapies and a more systematic approach to care.
– Management includes NSAIDs as first-line therapy, colchicine to reduce recurrence rates, and corticosteroids for severe cases. Recent advancements include the use of interleukin-1 receptor blockers for complicated cases.
– Pericardiectomy may be considered in chronic or recurrent cases that are refractory to medical management.
4 – Future Directions:
– Ongoing research is directed at improving diagnostic accuracy through advanced imaging techniques and refining treatment protocols to minimize recurrence and manage complicated cases effectively.
– The integration of novel biological agents and personalized medicine approaches is anticipated to enhance outcomes for patients with pericardial disease.
This article emphasizes the importance of a protocol-driven approach to the initial care, the use of targeted therapeutics based on individual patient profiles, and the integration of care pathways to manage acute and complicated pericarditis effectively.
Reference (link to free full-text):
Malik, A. A., Lloyd, J. W., Anavekar, N. S., & Luis, S. A. (2024). Acute and Complicated Inflammatory Pericarditis: A Guide to Contemporary Practice. Mayo Clinic Proceedings, 99(5), 795-811. https://doi.org/10.1016/j.mayocp.2024.01.012
RCT: No significant benefit of adjuvant prednisone for patients with cystic fibrosis with exacerbations unresponsive to antibiotics – Eur Respir J
6 May, 2024 | 06:32h | UTCThis randomized, double-blind, placebo-controlled trial investigated the effectiveness of adjuvant oral prednisone in enhancing lung function recovery in patients with cystic fibrosis (CF) experiencing pulmonary exacerbations (PExs) unresponsive to initial intravenous (IV) antibiotic treatment. The study involved 173 participants, with 76 not achieving more than 90% of their baseline forced expiratory volume in one second (ppFEV1) by Day 7 of antibiotic treatment and subsequently randomized to receive either oral prednisone (1 mg·kg−1 twice daily, up to 60 mg/day) or placebo for an additional 7 days. Results showed that 50% of the prednisone group and 39% of the placebo group recovered over 90% of their baseline ppFEV1 by Day 14. However, the difference was not statistically significant (11% difference; 95% CI -11, 34%; p=0.34). Additionally, prednisone did not significantly prolong the time to the next exacerbation compared to placebo. This study concludes that adjuvant oral prednisone does not significantly improve lung function recovery or delay subsequent exacerbations in CF patients not responding to initial antibiotic therapy.
Reference (link to abstract – $ for full-text):
RCT: Azithromycin fails to prevent moderate or severe chronic lung disease in preterm infants – Lancet Respir Med
6 May, 2024 | 06:28h | UTCThis randomized, placebo-controlled trial evaluated the effectiveness of azithromycin in preventing chronic lung disease (CLD) in preterm infants born at less than 30 weeks’ gestation across 28 UK neonatal intensive care units. A total of 799 infants were randomized to receive either intravenous azithromycin or a placebo. The primary outcome measured was survival without moderate or severe CLD at 36 weeks postmenstrual age. Results showed no significant difference between the azithromycin group (42% survival without CLD) and the placebo group (45% survival without CLD), with an adjusted odds ratio of 0.84 (95% CI 0.55–1.29, p=0.43). Pulmonary Ureaplasma spp colonization did not affect the treatment outcome. Given the lack of efficacy and the presence of several serious adverse events in the azithromycin group, the study concluded that azithromycin should not be recommended for preventing CLD in this population.
Reference (link to free full-text):
Cohort Study: Extending colonoscopy intervals to 15 years seems feasible in after a negative initial test in individuals without family history of CRC – JAMA Oncol
6 May, 2024 | 06:25h | UTCThis cohort study analyzed Swedish register-based data, examining colorectal cancer (CRC) diagnoses and CRC-specific mortality. The study included 110,074 individuals with a negative first colonoscopy (exposed group) and 1,981,332 matched controls, from 1990 to 2018. Participants were aged 45 to 69 at initial screening and were followed for up to 29 years.
During the follow-up, 484 new CRC cases and 112 CRC-specific deaths occurred in the exposed group. The study found significantly lower risks of CRC and CRC-specific death in the exposed group compared to controls over 15 years. The data suggest extending the screening interval from 10 to 15 years could miss only 2 CRC cases and prevent 1 CRC-specific death per 1,000 individuals while potentially reducing unnecessary colonoscopies.
The findings suggest that for individuals with no family history of CRC and a negative initial screening, the standard 10-year colonoscopy interval could safely be extended to 15 years. This adjustment could decrease the number of invasive procedures without significantly impacting cancer incidence and mortality, optimizing resource allocation and reducing patient burden.
Reference (link to abstract – $ for full-text):
Randomized Crossover Trial: Prophylactic recombinant ADAMTS13 prevents acute events in congenital thrombotic thrombocytopenic purpura – N Engl J Med
6 May, 2024 | 06:22h | UTCThis study evaluates the efficacy and safety of recombinant ADAMTS13 compared to standard plasma-derived therapy in managing congenital thrombotic thrombocytopenic purpura (TTP). In a phase 3, open-label, crossover trial involving 48 patients, each participant underwent two 6-month prophylaxis periods, receiving either recombinant ADAMTS13 or standard therapy, followed by a switch to the alternate treatment. Results indicate that recombinant ADAMTS13 prevented acute TTP events during prophylaxis, with no events recorded, versus one event under standard therapy. Furthermore, recombinant ADAMTS13 was associated with significantly lower rates of thrombocytopenia and adverse events compared to standard therapy. The treatment increased ADAMTS13 activity to approximately 100% of normal levels, with no development of neutralizing antibodies. Overall, recombinant ADAMTS13 was found to be safe and more effective than standard therapy in preventing TTP events and manifestations.
Reference (link to abstract – $ for full-text):
Systematic Review: Prophylactic antivirals significantly reduce CMV disease and mortality in organ transplant recipients – Cochrane Library
6 May, 2024 | 06:18h | UTCStudy Design and Population:
This systematic review and randomized controlled trial assessed the benefits and harms of antiviral medications in preventing cytomegalovirus (CMV) disease among solid organ transplant recipients. The analysis included 41 studies with a total of 5,054 participants. The reviewed studies compared various antiviral drugs, such as aciclovir, ganciclovir, and valaciclovir, against placebos or no treatment, and examined different dosing regimens.
Main Findings:
The findings revealed that prophylaxis with aciclovir, ganciclovir, or valaciclovir significantly reduces the risk of developing CMV disease, with risk ratios (RRs) indicating strong effectiveness (RR 0.42, 95% CI 0.34-0.52 for CMV disease prevention). The treatments also lowered all-cause mortality (RR 0.63, 95% CI 0.43-0.92) and CMV infection rates (RR 0.61, 95% CI 0.48-0.77). Additionally, ganciclovir was found to be more effective than aciclovir in preventing CMV disease (RR 0.37, 95% CI 0.23-0.60). The extended duration of prophylaxis appeared to offer additional benefits compared to shorter courses.
Implications for Practice:
The results support the routine use of antiviral prophylaxis in both CMV-positive recipients and CMV-negative recipients receiving organs from CMV-positive donors. These findings are crucial for clinical practice, indicating that maintaining or implementing antiviral prophylaxis can significantly decrease the incidence of CMV disease and related mortality in this high-risk population. Further studies are recommended to explore optimal dosing and duration strategies, especially among different organ transplant groups and varying immunosuppressive regimes.
Reference (link to abstract – $ for full-text):
SCCM/IDSA Updated guidelines for evaluating new fever in adult ICU patients – Crit Care Med
5 May, 2024 | 15:12h | UTCThe 2023 revision of the guidelines for assessing new-onset fever in adult ICU patients stresses rigorous diagnostic processes using the GRADE methodology. These guidelines, developed without industry funding, offer 12 recommendations and nine best-practice statements focused primarily on the accurate measurement of core body temperature and initial diagnostic evaluations geared towards identifying potential infectious causes. Central temperature monitoring is recommended when possible; otherwise, oral or rectal measurements are preferred. The utility of imaging studies and rapid diagnostic tests is highlighted, along with the selective use of biomarkers to guide the cessation of antimicrobial therapy. The guidelines underscore that most recommendations are based on weak evidence, thus highlighting the need for continued research in diagnostic methodologies and fever management in the ICU setting.
Reference (link to free full-text):
M-A: Effects of long-term salt substitution on cardiovascular mortality and events – Ann Intern Med
5 May, 2024 | 15:10h | UTCThis systematic review and meta-analysis assessed the impact of long-term salt substitution on cardiovascular outcomes by analyzing data from 16 randomized controlled trials (RCTs). The primary investigation focused on mortality, major cardiovascular events (MACE), and adverse events with a study period of six months or longer. Key findings include a potential reduction in all-cause mortality (rate ratio [RR] of 0.88) and cardiovascular mortality (RR of 0.83), based on low-certainty evidence from studies predominantly conducted in China or Taiwan among older adults or those at higher cardiovascular risk. Results also indicated a slight reduction in MACE (RR of 0.85) with very low certainty. Evidence suggests no significant increase in serious adverse events. Limitations include the dominance of a single large RCT and limited generalizability of results to Western populations. The study concludes that while salt substitution could reduce mortality, the effects on cardiovascular events remain uncertain, with more robust evidence needed for broader demographic applicability.
Reference (link to abstract – $ for full-text):
Prospective Validation Study: High accuracy of PECARN rules in reducing unnecessary CT scans in pediatric blunt trauma – Lancet Child Adolesc Health
5 May, 2024 | 15:08h | UTCStudy Design and Population:
This multicenter prospective validation study tested the Pediatric Emergency Care Applied Research Network (PECARN) prediction rules aimed at reducing unnecessary CT scans for children presenting with blunt abdominal or minor head trauma. Over a nearly five-year period, children and adolescents under 18 from six U.S. emergency departments in cities including Sacramento, Dallas, and Los Angeles were enrolled. Exclusion criteria included pregnancy, pre-existing neurological disorders, penetrating trauma, injuries older than 24 hours, prior CT or MRI scans, or suspicion of non-accidental trauma.
Main Findings:
A total of 7,542 children with blunt abdominal trauma and 19,999 with minor head trauma were enrolled. The intra-abdominal injury rule demonstrated a sensitivity and negative predictive value (NPV) of 100%, confirming its reliability in detecting injuries requiring acute intervention. For head traumas, the sensitivity varied slightly with age; 100% for children under 2 years and 98.8% for those aged 2 years and older, with an NPV of 100% in both groups. Only two cases in the older cohort were misclassified, neither requiring neurosurgery.
Implications for Practice:
The validation of PECARN rules with high sensitivity and NPV supports their use as a safe guideline to minimize unnecessary CT scans in pediatric trauma cases, thereby promoting efficient use of resources and reducing exposure to radiation in children. These results suggest that implementation of these rules should be considered in emergency pediatric care to improve outcomes and healthcare efficiency.
Reference (link to abstract – $ for full-text):
RCT: Adding Ibrutinib to immunochemotherapy and autologous stem-cell transplantation improves PFS in young mantle cell lymphoma patients but increases toxicity – The Lancet
5 May, 2024 | 15:02h | UTCStudy Design and Population:
This study is a three-arm, randomized, open-label, phase 3 superiority trial named TRIANGLE, conducted across 165 centers in Europe and Israel. It aimed to compare the effectiveness of adding ibrutinib to standard immunochemotherapy, both with and without autologous stem-cell transplantation (ASCT), in 870 previously untreated mantle cell lymphoma patients aged 18-65 years, suitable for ASCT.
Main Findings:
After a median follow-up of 31 months, the arm with ibrutinib added to immunochemotherapy followed by ASCT (group A+I) demonstrated a 3-year failure-free survival rate of 88% compared to 72% in the standard immunochemotherapy plus ASCT group (group A). This indicates a significant improvement (hazard ratio 0.52; p=0.0008). Conversely, the efficacy of ASCT in the presence of ibrutinib (group A+I vs. group I, ibrutinib without ASCT) remains under analysis. Adverse events were more frequent and severe post-ASCT, particularly concerning hematological complications and infections.
Implications for Practice:
The results suggest that adding ibrutinib to first-line immunochemotherapy regimens significantly enhances clinical outcomes in younger patients with mantle cell lymphoma. However, the increased toxicity observed warrants careful patient monitoring, especially following ASCT. Further research is needed to evaluate the necessity and timing of ASCT in regimens containing ibrutinib.
Reference (link to free full-text):
RCT: Early patching proves more effective than extended optical treatment in pediatric amblyopia management – The Lancet
5 May, 2024 | 15:00h | UTCStudy Design and Population:
The EuPatch study was a multicenter, randomized controlled trial conducted across 30 hospitals in multiple European countries, including the UK, Greece, Austria, Germany, and Switzerland. It targeted children aged 3–8 years diagnosed with amblyopia due to anisometropia, strabismus, or both, with an interocular difference ≥0.30 logMAR in best corrected visual acuity (BCVA). Participants were divided into two groups: one underwent 18 weeks of glasses use before patching (Extended Optical Treatment, EOT), and the other just 3 weeks (early patching), each supplemented with an intensive patching regimen.
Main Findings:
Out of the 334 initially randomized participants, 317 were analyzed for the primary outcome. The early patching group demonstrated a significantly higher success rate, achieving ≤0.20 logMAR interocular difference in BCVA in 67% of cases compared to 54% in the EOT group after 12 weeks of patching (p=0.019). The median follow-up times were 42 weeks for the EOT group and 27 weeks for the early patching group, with dropout rates of 14% and 6%, respectively.
Implications for Practice:
The findings suggest that early patching is superior to EOT in the management of amblyopia in children, presenting a viable option for enhancing treatment effectiveness. This study supports the potential personalization of amblyopia treatments based on the quicker onset of patching. These results could influence future guidelines and clinical practices in pediatric ophthalmology.
Reference (link to free full-text):
Systematic Review: Daratumumab enhances survival in newly diagnosed multiple myeloma patients ineligible for transplant – Cochrane Library
4 May, 2024 | 13:46h | UTCStudy Design and Population:
This Cochrane review evaluates four open-label, two-arm randomized controlled trials involving 1,783 adults with newly diagnosed multiple myeloma ineligible for autologous stem cell transplant. The studies were conducted globally, mainly in middle- and high-income countries, with participants aged between 69 to 74 years. Adding Daratumumab, a CD38-targeting monoclonal antibody, to standard antineoplastic therapy was compared to standard antineoplastic therapy alone.
Main Findings:
Daratumumab significantly improved overall survival with a hazard ratio of 0.64 and increased progression-free survival with a hazard ratio of 0.48, based on moderate-certainty evidence from the studies. Quality of life showed a slight improvement, although the evidence was of low certainty. Treatment-related serious adverse events were more common in the daratumumab group, with a risk ratio of 1.18. However, there was no significant increase in adverse events of CTCAE grade ≥3, except for a higher risk of infections.
Implications for Practice:
The addition of daratumumab to standard antineoplastic therapy offers a potential benefit in overall survival and disease progression control for patients with multiple myeloma who are ineligible for transplant. These benefits must be weighed against the increased risk of serious adverse events and infections. Future studies could provide further insights, particularly into the long-term quality of life and management of side effects.
Reference (link to abstract – $ for full-text):
Systematic Review: Effects of ACE inhibitors and ARBs on kidney and cardiovascular outcomes in diabetic patients – Cochrane Library
4 May, 2024 | 13:32h | UTCStudy Design and Population:
This systematic review and meta-analysis evaluated the effectiveness of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in managing cardiovascular and kidney outcomes in adults with diabetes and kidney disease. It included data from 109 randomized controlled trials totaling 28,341 participants, comparing the impact of ACEi and ARBs, either alone or in combination, against each other, placebo, or no treatment.
Main Findings:
The analysis revealed that ACEi may reduce the risk of kidney failure (RR 0.61, 95% CI 0.39 to 0.94) but generally has little effect on all-cause mortality and cardiovascular death compared to placebo, with low certainty of evidence. Similarly, ARBs showed potential in preventing kidney failure (RR 0.82, 95% CI 0.72 to 0.94) and the progression from microalbuminuria to macroalbuminuria. The effects on cardiovascular outcomes remained uncertain and showed minimal difference compared to placebo or no treatment.
Implications for Practice:
While ACEi and ARBs may aid in preventing kidney failure in patients with diabetic kidney disease, their broader impacts on mortality and cardiovascular health remain uncertain. This underscores the necessity for further rigorous research to verify these findings and better determine the optimal therapeutic strategies. Clinicians should weigh these results against individual patient profiles considering the overall low certainty of the evidence.
Reference (link to abstract – $ for full-text):
Systematic Review: Comparing antibiotic treatment vs. appendectomy for the initial treatment of uncomplicated appendicitis – Cochrane Library
4 May, 2024 | 13:09h | UTCStudy Design and Population:
This Cochrane review analyzed 13 randomized controlled trials involving 3,358 participants to compare the efficacy of antibiotic treatment versus appendectomy in managing uncomplicated acute appendicitis. The included studies predominantly involved adult participants and utilized broad-spectrum antibiotics, with interventions ranging from open to predominantly laparoscopic appendectomy. Data collection spanned from hospital admission to up to seven years, with studies conducted across various global regions, including Asia, Europe, and North America.
Main Findings:
The primary outcomes revealed that antibiotic treatment might slightly increase the risk of unsuccessful treatment with 76 additional unsuccessful cases per 1,000 individuals compared to surgery, though these results did not reach clinical significance. Antibiotics reduced wound infections but possibly increased the average hospital stay by half a day. About 30.7% of participants treated with antibiotics required an appendectomy within one year. Secondary outcomes showed very uncertain evidence on antibiotics’ effect on intra-abdominal abscess or reoperation rates, and a slight increase in negative appendectomy rates was observed.
Implications for Practice:
The findings suggest that while antibiotics could serve as an initial treatment to avoid surgery in two-thirds of cases annually, a significant portion may still require surgical intervention. This information is crucial for clinicians in making informed treatment decisions, particularly considering patient preferences and the risk of surgery. Further research is needed to explore long-term outcomes and identify patient subgroups that may benefit most from either treatment.
Reference (link to abstract – $ for full-text):
RCT: Acute impact of provoked anger on endothelial health in healthy adults – J Am Heart Assoc
4 May, 2024 | 13:00h | UTCThis study explored the immediate effects of negative emotions on vascular endothelial health in a sample of 280 healthy adults. Participants were assigned to recall tasks that induced feelings of anger, anxiety, sadness, or a neutral emotional state, followed by assessments of endothelial health. The primary measure, endothelium-dependent vasodilation (reactive hyperemia index), significantly deteriorated in the anger group compared to the neutral condition (mean change: 0.20±0.67 vs. 0.50±0.60; P=0.007). Anxiety and sadness did not significantly affect this measure. Additionally, there were no significant changes in endothelial cell-derived microparticles or endothelial progenitor cells across all conditions. The findings indicate that short-term anger provocation can impair endothelial function, suggesting a specific pathway by which anger could increase cardiovascular disease risk.
Reference (link to free full-text):
M-A: Psilocybin significantly reduces depression symptoms across diverse populations – The BMJ
4 May, 2024 | 12:51h | UTCStudy Design and Population:
This systematic review and meta-analysis synthesized data from randomized trials assessing the efficacy of psilocybin as a treatment for depression in adults. Researchers utilized five electronic databases for published literature and four databases for unpublished and international studies. The analysis included 436 participants, aged 36 to 60 years, from seven randomized trials, with both genders represented and varying comorbidities such as cancer.
Main Findings:
The meta-analysis revealed a significant reduction in depression scores among participants treated with psilocybin, with a Hedges’ g value of 1.64, indicating a large effect size. Notably, the improvement was more pronounced among those with secondary depression and those assessed using self-report depression scales. Subgroup analyses and metaregression also highlighted that older age and previous use of psychedelics correlated with greater symptom improvement. Despite the robust findings, high heterogeneity and a risk of small study bias led to a low certainty of evidence.
Implications for Practice:
The findings support psilocybin’s potential as an effective antidepressant, particularly among specific subgroups such as those with secondary depression. However, the presence of high heterogeneity and small study biases suggests that further research is needed to explore the impact of expectancy effects, moderating factors, and treatment modalities. Clinicians should consider these elements when discussing psilocybin as a treatment option with patients, and further high-quality studies are necessary to solidify its role in clinical practice.
Reference (link to free full-text):
ACP Guidelines for the pharmacologic management of type 2 diabetes in adults – Ann Intern Med
3 May, 2024 | 14:05h | UTCThe American College of Physicians (ACP) has issued an updated guideline focusing on the pharmacological management of type 2 diabetes. This guideline reviews the efficacy and safety of new medications, including GLP-1 agonists, SGLT-2 inhibitors, and others, emphasizing a systematic evaluation using the GRADE methodology. Key recommendations advise the integration of SGLT-2 inhibitors or GLP-1 agonists with metformin and lifestyle changes for better glycemic control and reduction in mortality and major cardiovascular events. Conversely, the use of DPP-4 inhibitors in similar therapeutic contexts is not recommended due to insufficient evidence of benefit. This guideline targets healthcare providers managing nonpregnant adults with type 2 diabetes.
Reference (link to free full-text):
ACP cost-effectiveness analysis: Newer antidiabetic medications in type 2 diabetes – Ann Intern Med
3 May, 2024 | 13:57h | UTCThis systematic review evaluates the cost-effectiveness of newer antidiabetic medications for type 2 diabetes from U.S. clinical and economic perspectives. Analyzing non-industry funded cost-effectiveness analyses (CEAs) using GRADE and Drummond criteria, the study identifies varying cost per quality-adjusted life-year (QALY) values for medications such as GLP1a and SGLT2i. It concludes that while GLP1a and SGLT2i offer low value as primary therapies due to high costs, they may present intermediate value as adjunct treatments to metformin. The study highlights the methodological variability in CEAs and the influence of drug cost and effectiveness assumptions on outcomes. The results suggest cautious interpretation in clinical decision-making due to varied evidence quality and cost-effectiveness profiles among the reviewed medications.
Reference (link to free full-text):
ACP Meta-Analysis: Comparative efficacy of newer antidiabetic agents in type 2 diabetes management – Ann Intern Med
3 May, 2024 | 13:49h | UTCThis systematic review and network meta-analysis evaluates the effectiveness and safety of modern antidiabetic drugs in managing type 2 diabetes mellitus. The study analyzed 130 publications from 84 randomized controlled trials, using GRADE criteria for evidence assessment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) agonists demonstrated significant reductions in all-cause mortality and major adverse cardiovascular events when compared to usual care, with SGLT2 inhibitors also showing benefits in reducing chronic kidney disease progression and hospitalizations due to heart failure. In contrast, dipeptidyl peptidase-4 (DPP4) inhibitors, insulin, and tirzepatide showed no significant mortality benefits. The study identified limitations including sparse direct drug comparisons and inadequate data for certain patient subgroups. Overall, SGLT2 inhibitors and GLP1 agonists were associated with fewer serious adverse events and severe hypoglycemia compared to insulin and sulfonylureas.
Reference (link to free full-text):
Review: Key findings from the Women’s Health Initiative studies on postmenopausal interventions – JAMA
3 May, 2024 | 13:34h | UTCThe Women’s Health Initiative (WHI) studied the impact of various interventions on postmenopausal women aged 50-79, using data from 161,808 participants between 1993 and 2018. The findings suggest that hormone therapy, specifically with conjugated equine estrogens and medroxyprogesterone acetate, does not reduce the risk of cardiovascular diseases, dementia, or other chronic conditions in postmenopausal women. It is, however, effective for managing severe menopausal symptoms when initiated before age 60 in women without contraindications. The trials also concluded that universal supplementation of calcium and vitamin D does not effectively prevent fractures and should be limited to those not meeting dietary intake recommendations. Furthermore, a low-fat diet rich in fruits, vegetables, and grains did not reduce the incidence of breast or colorectal cancer, though it may decrease breast cancer mortality rates, indicating the need for further investigation.
Reference (link to free full-text for a limited period):
Clinical Trial Follow-up: Antenatal corticosteroids not associated with adverse neurodevelopmental outcomes in late preterm births – JAMA
2 May, 2024 | 23:25h | UTCStudy Design and Population:
This research involved a prospective follow-up study of a multicenter randomized clinical trial, specifically focusing on children aged 6 years or older whose birthing parents were enrolled in the Antenatal Late Preterm Steroids (ALPS) trial. The trial initially examined the impact of administering 12 milligrams of intramuscular betamethasone, given twice 24 hours apart, on late preterm infants (34-36 completed weeks). The follow-up study involved 949 children from 13 centers in the Maternal-Fetal Medicine Units (MFMU) Network, assessed for neurodevelopmental outcomes.
Main Findings:
The primary outcome measured was the General Conceptual Ability score less than 85 on the Differential Ability Scales, 2nd Edition (DAS-II). Results showed no statistically significant differences between the betamethasone group (17.1%) and the placebo group (18.5%) in achieving this score. Secondary outcomes related to motor function and social responsiveness also showed no significant differences between the groups. Sensitivity analyses further confirmed these findings, suggesting that the administration of betamethasone did not adversely affect neurodevelopmental outcomes at age 6 or older.
Implications for Practice:
These findings support the continued use of antenatal corticosteroids for improving short-term neonatal respiratory outcomes in late preterm deliveries without concern for long-term neurodevelopmental harm. Clinicians can consider these results reassuring, as the study effectively dispels earlier concerns about potential negative long-term effects related to neurodevelopment from antenatal steroid use in late preterm infants.
Reference (link to abstract – $ for full-text):
RCT: Xanomeline-trospium reduces psychosis symptoms in patients with schizophrenia – JAMA Psychiatry
2 May, 2024 | 23:24h | UTCStudy Design and Population:
This study, titled EMERGENT-3 (NCT04738123), is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial conducted to evaluate the efficacy and safety of xanomeline-trospium chloride in adults with schizophrenia experiencing acute psychosis. It involved 256 participants across 30 inpatient sites in the US and Ukraine, with the study period running from April 1, 2021, to December 7, 2022. Data analysis occurred from February to June 2023.
Main Findings:
The primary outcome was the change from baseline to week 5 in the Positive and Negative Syndrome Scale (PANSS) total score. Xanomeline-trospium significantly reduced the PANSS total score compared to placebo, with a least squares mean difference of -8.4 and a Cohen’s d effect size of 0.60. The most common adverse events were gastrointestinal, mild to moderate in intensity, and generally transient. Safety and tolerability profiles were favorable, with similar discontinuation rates due to adverse events between the xanomeline-trospium and placebo groups.
Implications for Practice:
The results of EMERGENT-3, alongside the consistent findings from earlier phases of the trial, affirm xanomeline-trospium’s potential as a novel class of antipsychotic medication. Its mechanism of action, which does not involve D2 dopamine receptor blocking, offers a promising alternative to traditional antipsychotics, particularly for patients who may benefit from different therapeutic approaches due to issues with current treatments.
Commentary on X:
Xanomeline-trospium is efficacious & well tolerated in people with schizophrenia experiencing acute psychosis, finds EMERGENT-3 trial, and supports potential of xanomeline-trospium to be first in a putative new class of antipsychotic medications. https://t.co/ioBCKOgvQa pic.twitter.com/CDmYEgYN2O
— JAMA Psychiatry (@JAMAPsych) May 1, 2024
Reference (link to free full-text):