Tag: nevin manimala

JAMA Netw Open. 2022 Sep 1;5(9):e2230367. doi: 10.1001/jamanetworkopen.2022.30367.

ABSTRACT

IMPORTANCE: Insufficient treatment response and resulting chronicity constitute a major problem in depressive disorders. Remission rates range as low as 15% to 40% and treatment-resistant depression (TRD) is associated with low-grade inflammation, suggesting anti-inflammatory interventions as a rational treatment strategy. Minocycline, which inhibits microglial activation, represents a promising repurposing candidate in the treatment of TRD.

OBJECTIVE: To determine whether 6 weeks of minocycline as add-on to antidepressant treatment as usual can significantly reduce depressive symptoms in patients with TRD.

DESIGN, SETTING, AND PARTICIPANTS: The study was conducted in Germany and designed as a multicenter double-blind randomized clinical trial (RCT) of 200 mg/d minocycline treatment over a course of 6 weeks with a 6-month follow-up. Participants were recruited from January 2016 to August 2020 at 9 university hospitals that served as study sites. Key inclusion criteria were a diagnosis of major depressive disorder (according to Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] criteria), severity of depressive symptoms on the Hamilton Depression Rating Scale (HAMD-17) greater than or equal to 16 points, aged 18 to 75 years, body mass index 18 to 40, Clinical Global Impression Scale (CGI-S) greater than or equal to 4, failure to adequately respond to an initial antidepressant standard medication as per Massachusetts General Hospital Antidepressant Treatment History Questionnaire, and stable medication for at least 2 weeks. A total of 258 patients were screened, of whom 173 were randomized and 168 were included into the intention-to-treat population. Statistical analysis was performed from April to November 2020.

INTERVENTIONS: Participants were randomized (1:1) to receive adjunct minocycline (200 mg/d) or placebo for 6 weeks.

MAIN OUTCOMES AND MEASURES: Primary outcome measure was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 6 analyzed by intention-to-treat mixed model repeated measures. Secondary outcome measures were response, remission, and various other clinical rating scales.

RESULTS: Of 173 eligible and randomized participants (84 randomized to minocycline and 89 randomized to placebo), 168 formed the intention-to-treat sample (79 [47.0%] were women, 89 [53.0%] were men, 159 [94.6%] were White, 9 [6.4%] were of other race and ethnicity, including Asian and unknown ethnicity), with 81 in the minocycline group and 87 in the placebo group. The mean (SD) age was 46.1 (13.1) years, and the mean (SD) MADRS score at baseline was 26.5 (5.0). There was no difference in rates of completion between the minocycline (83.3% [70 of 81]) and the placebo group (83.1% [74 of 87]). Minocycline treatment did not alter the course of depression severity compared with placebo as assessed by a decrease in MADRS scores over 6 weeks of treatment (1.46 [-1.04 to 3.96], P = .25). Minocycline treatment also exhibited no statistically significant effect on secondary outcomes.

CONCLUSIONS AND RELEVANCE: In this large randomized clinical trial with minocycline at a dose of 200 mg/d added to antidepressant treatment as usual for 6 weeks, minocycline was well tolerated but not superior to placebo in reducing depressive symptoms in patients with TRD. The results of this RCT emphasize the unmet need for therapeutic approaches and predictive biomarkers in TRD.

TRIAL REGISTRATION: EU Clinical Trials Register Number: EudraCT 2015-001456-29.

PMID:36103181 | DOI:10.1001/jamanetworkopen.2022.30367

JAMA Surg. 2022 Sep 14. doi: 10.1001/jamasurg.2022.4245. Online ahead of print.

ABSTRACT

IMPORTANCE: Same-day home recovery (SHR) is now the standard of care for many major surgical procedures and has the potential to become standard practice for benign foregut procedures (eg, hiatal hernia repair, fundoplication, and Heller myotomy).

OBJECTIVE: To determine whether SHR for patients undergoing benign foregut surgery is feasible, safe, and effective.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study took place across 19 medical centers within an integrated health care system in northern California from January 2019 through September 2021. Participants included consecutive patients undergoing elective benign foregut surgery.

EXPOSURES: Standardized SHR program.

MAIN OUTCOMES AND MEASURES: The primary end point was the rate of SHR. The secondary end points were 7-day and 30-day rates of postoperative emergency department visits, hospital readmissions, and reoperations.

RESULTS: Of 1248 patients who underwent benign foregut surgery from January 2017 through September 2021, 558 were patients before implementation of the SHR program and 690 were patients postimplementation. The mean age of patients was 60 years, and 759 (59%) were female. The preimplementation SHR rate was 64 of 558 patients (11.5%) in 2018 and increased to 82 of 113 patients (72.6%) by 2021 (94/350 [26.9%] in 2019 and 112/227 [49.3%] in 2020; P < .001). There were no statistical differences in the 7-day and 30-day rates of postoperative emergency visits, hospital readmissions, and reoperations or 30-day mortality in the SHR vs non-SHR groups in the postimplementation era.

CONCLUSIONS AND RELEVANCE: In this study, implementation of a regional SHR program among patients undergoing elective benign foregut surgery was feasible, safe, and effective. The changes in perioperative care require comprehensive patient education and full multidisciplinary support. An SHR program for benign foregut procedures has the potential to improve patient care and cost-effectiveness in care delivery.

PMID:36103170 | DOI:10.1001/jamasurg.2022.4245

JAMA Dermatol. 2022 Sep 14. doi: 10.1001/jamadermatol.2022.3745. Online ahead of print.

ABSTRACT

IMPORTANCE: With worldwide emergence of recalcitrant and resistant dermatophytosis, itraconazole is increasingly being used as the first-line drug for treatment of tinea corporis/cruris (TCC). Apparent inadequacy with low doses has led to empirical use of higher doses and antifungal combinations.

OBJECTIVE: To compare cure rates, treatment durations, safety profiles, and relapse rates of itraconazole 100, 200, and 400 mg/d for the treatment of TCC.

DESIGN, SETTING, AND PARTICIPANTS: This double-blind randomized clinical trial included adult patients with treatment-naive TCC involving at least 5% body surface area. Patients were recruited from the dermatology outpatient department of a tertiary care hospital in New Delhi, India between March 1, 2020, and August 31, 2021.

INTERVENTIONS: Patients were randomized to 1 of the 3 treatment groups. Biweekly blinded assessments were performed until cure or treatment failure. Posttreatment follow-up of at least 8 weeks was conducted to detect relapses.

MAIN OUTCOME AND MEASURES: Cure rates, treatment durations, safety profiles, and relapse rates were assessed. Secondary outcomes included comparison of rapidity of clinical response and cost-effectiveness between groups.

RESULTS: Of the 149 patients assessed, the mean (SD) age was 34.3 (12.2) years, 69 patients (46.4%) were women, and 80 patients (53.6%) were men. The difference in cure rate between the 100- and 200-mg groups was statistically nonsignificant (hazard ratio [HR], 1.44; 95% CI, 0.91-2.30; P = .12), while the difference between the 100- and 400-mg groups (HR, 2.87; 95% CI, 1.78-4.62; P < .001) and between the 200- and 400-mg groups (HR, 1.99; 95% CI, 1.28-3.09; P = .002) was statistically significant. Mean (SD) treatment durations were statistically significantly different between the 100- and 400-mg groups (7.7 [4.7] weeks vs 5.2 [2.6] weeks; P = .03) and between the 200- and 400-mg groups (7.2 [3.8] weeks vs 5.2 [2.6] weeks; P = .004), but the difference between the 100- and 200-mg groups was not statistically significant. A total of 55 patients (47.4%) relapsed after treatment. Relapse rates were comparable across groups. No patient discontinued treatment due to adverse effects. Treatment with the 200-mg dose incurred a 63% higher cost and 400 mg a 120% higher cost over 100 mg in achieving cure.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, high overall efficacy was observed among the 3 itraconazole doses for treatment of TCC, but with prolonged treatment durations and considerable relapse rates. Treatment with the 200- and 100-mg doses did not differ significantly in efficacy or treatment durations, while 400 mg scored over the other 2 on these outcomes. Considerable additional cost is incurred in achieving cure with the 200- and 400-mg doses.

TRIAL REGISTRATION: Clinical Trials Registry of India Identifier: CTRI/2020/03/024326.

PMID:36103158 | DOI:10.1001/jamadermatol.2022.3745

JAMA Dermatol. 2022 Sep 14. doi: 10.1001/jamadermatol.2022.3682. Online ahead of print.

ABSTRACT

IMPORTANCE: Psoriasis, psoriatic arthritis, and inflammatory bowel disease, ie, Crohn disease and ulcerative colitis, are chronic systemic immune-mediated disorders affecting an increasing proportion of adults and children worldwide. Observational studies have suggested an association between inflammatory bowel disease and psoriasis and vice versa. So far, however, it remains unclear whether and in which direction causal relationships exist.

OBJECTIVE: To investigate the association between inflammatory bowel disease, particularly Crohn disease and ulcerative colitis, and psoriasis or psoriatic arthritis.

DESIGN, SETTING, AND PARTICIPANTS: A bidirectional 2-sample mendelian randomization study was conducted using summary statistics from genome-wide association studies including up to 463 372 European individuals. Total and direct effects were derived performing an iterative radial and robust inverse-variance weighted method within the univariable and multivariable mendelian randomization setting, respectively. Causal estimates were verified using a validation inflammatory bowel disease sample, a series of pleiotropy-robust mendelian randomization methods, and sensitivity analyses based on a PhenoScanner search in conjunction with network analysis. Data analysis was performed from April to May 2022.

MAIN OUTCOMES AND MEASURES: Inflammatory bowel disease, Crohn disease, ulcerative colitis, psoriasis, and psoriatic arthritis were used as both exposures and outcomes.

RESULTS: The European samples included 12 882 cases of inflammatory bowel disease and 5621 cases of psoriasis. The proportion of women ranged between 48% and 56%. Genetically predicted inflammatory bowel disease was associated with higher risk of psoriasis (pooled odds ratio [OR], 1.10; 95% CI, 1.05-1.15; P < .001) and psoriatic arthritis (pooled OR, 1.10; 95% CI, 1.04-1.18; P = .003). In contrast with ulcerative colitis, the Crohn disease subentity was associated with psoriasis (OR, 1.16; 95% CI, 1.12-1.20; P < .001) and psoriatic arthritis (OR, 1.13; 95% CI, 1.06-1.20; P < .001). Regarding the reverse directions, no notable associations could be found.

CONCLUSIONS AND RELEVANCE: Findings of this mendelian randomization study support a causal effect between inflammatory bowel disease and psoriasis as well as psoriatic arthritis, but not vice versa. It seems that especially Crohn disease and not ulcerative colitis is responsible for the causal effect of inflammatory bowel disease on both psoriasis outcomes. These findings have implications for the management of inflammatory bowel disease and psoriasis in clinical practice.

PMID:36103169 | DOI:10.1001/jamadermatol.2022.3682

Endocr Connect. 2022 Sep 1:EC-22-0187. doi: 10.1530/EC-22-0187. Online ahead of print.

ABSTRACT

PURPOSE: We aimed to assess the factors influencing the development of diabetes insipidus after transsphenoidal surgery for pituitary adenomas.

METHODS: A retrospective analysis was conducted on the clinical data of patients with pituitary adenomas who underwent transsphenoidal surgery. The predictors of postoperative diabetes insipidus were determined using statistical analysis.

RESULTS: Of the 415 patients who underwent microscopic transsphenoidal surgery for pituitary adenomas, 196 experienced postoperative diabetes insipidus. The sinking depth of the diaphragma sellae and the difference between the preoperative and postoperative pituitary stalk deviation angles in the diabetes insipidus group were greater than those in the non-diabetes insipidus group. Logistic regression analysis showed that the risk of diabetes insipidus after transsphenoidal surgery was higher in patients with a larger difference in their pituitary stalk deviation angles (odds ratio [OR] = 2.407, 95% confidence interval [CI] = 1.335-4.342; P = 0.004).

CONCLUSION: The difference in the pituitary stalk deviation angle could predict the onset of diabetes insipidus after transsphenoidal surgery for pituitary adenomas.

PMID:36103145 | DOI:10.1530/EC-22-0187

Cardiovasc Drugs Ther. 2022 Sep 14. doi: 10.1007/s10557-022-07379-z. Online ahead of print.

ABSTRACT

BACKGROUND: It is widely accepted that omega-3 fatty acids are beneficial in the prevention of cardiovascular disease, but many large randomized controlled trial studies and meta-analyses have come to different conclusions. The evidence for omega-3 fatty acids supplementation to prevent cardiovascular disease remains insufficient. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of several types of omega-3 fatty acids supplements.

METHODS: We comprehensively searched the online database and found 15 RCTs. The primary efficacy outcomes included major cardiovascular events, myocardial infarction, heart failure, atrial fibrillation, stroke, cardiovascular death, and all-cause death. The safety endpoints included gastrointestinal problems, bleeding-related disorders, and cancer. Subgroup analysis was conducted according to the main characteristics of the population, and the dose-response relationship of omega-3 fatty acids was evaluated by meta-regression. All results were calculated by the random effect model. Statistical heterogeneity was assessed using chi-square tests and quantified using I-square statistics.

RESULTS: The incidence of major cardiovascular events (RR 0.95, 95%CI 0.91 to 0.99, P = 0.026), myocardial infarction (RR 0.90, 95%CI 0.83 to 0.98; P = 0.021), and cardiovascular death (RR 0.94, 95%CI 0.88 to 0.99; P = 0.028) was reduced in the omega-3 fatty acid group compared with the control group. An increased risk of atrial fibrillation (RR 1.25, 95%CI 1.10 to 1.41; P = 0.000) was observed in patients in the omega-3 fatty acid group. No statistical differences were observed between the two groups in heart failure, stroke, and all-cause death. For safety endpoints, there were no statistically significant differences between the two groups in gastrointestinal problems, bleeding-related disorders, and cancer. Subgroup analysis showed that the cardiovascular benefit of omega-3 fatty acids was primarily attributable to the prescription of EPA ethyl ester. Omega-3 fatty acids may reduce the risk of major cardiovascular events in patients with cardiovascular disease or risk factors, and reduce the risk of myocardial infarction in patients without cardiovascular disease; however, they may increase the risk of stroke in patients with myocardial infarction. In addition, prescription omega-3 acid ethyl ester has a good safety profile, and prescription EPA ethyl ester has a high risk of bleeding.

CONCLUSION: Moderate evidence showed that the use of omega-3 fatty acids may reduce the risk of major cardiovascular events, myocardial infarction, and cardiovascular death. Compared to other types of omega-3 fatty acids supplements, we support the use of prescription EPA ethyl ester formulations for the prevention of cardiovascular disease, but the potential risk of atrial fibrillation and bleeding cannot be ignored. It is important to note that omega-3 fatty acids should be applied with caution in patients with previous myocardial infarction, which may increase the risk of stroke. Finally, omega-3 fatty acids are relatively safe and in general do not increase gastrointestinal problems, bleeding-related disorders, or cancer, but attention needs to be paid to the risk of bleeding with prescription EPA ethyl ester formulations.

PMID:36103100 | DOI:10.1007/s10557-022-07379-z

Int J Implant Dent. 2022 Sep 14;8(1):37. doi: 10.1186/s40729-022-00437-z.

ABSTRACT

PURPOSE: To histologically examine early bone formation around transmucosal implants and to evaluate the influence of surface characteristics on early peri-implant bone healing using a miniature pig model. For this, commercially available dental implants with a rough zirconia (YTZP) surface were compared to surface-modified Ti control implants at 4 and 8 weeks after placement.

METHODS: Immediately following the extraction of six mandibular premolars, 20 two-piece, tissue-level, screw-shaped YTZP implants (Patent™ Standard Zirconia Implant ø4.1 × 11 mm) with a modified rough blasted before sintering surface were inserted in four adult miniature pigs. In addition, four titanium (Ti) tissue-level implants (Straumann^® Standard RN ø4.1 × 10 mm Roxolid^®) with a moderate surface (SLActive^®), one per animal, were placed as control implants. A histological analysis was performed on the hard tissues after 4 and 8 weeks of transmucosal healing.

RESULTS: The results show a high rate of osseointegration of the test YTZP dental implants at 4 and 8 weeks following insertion. At 4 weeks, a bone-to-implant contact ratio (BIC) of 73.7% (SD ± 16.8) for the test implants (n = 10) and 58.5% for the first control implant was achieved. The second control implant had to be excluded from analysis. At 8 weeks, a BIC of 82.4% (SD ± 16.9) for the test implants (n = 9) and 93.6% (SD ± 9.1) (n = 2) for the control implant was achieved. No statistical difference was observed comparing 4 and 8 weeks YTZP data (p = 0.126).

CONCLUSIONS: The results indicate a predictable osseointegration of immediate zirconia implants with a modified YTZP implant surface and a high degree of BIC present at 4 weeks following insertion. After 8 weeks of healing both the zirconia implants and the Ti implants show a BIC indicating full osseointegration. Further studies involving a larger sample size with more time points are needed to confirm these results.

PMID:36103094 | DOI:10.1186/s40729-022-00437-z

Bull Math Biol. 2022 Sep 14;84(10):118. doi: 10.1007/s11538-022-01072-w.

ABSTRACT

Phylogenetic trees describe relationships between extant species, but beyond that their shape and their relative branch lengths can provide information on broader evolutionary processes of speciation and extinction. However, currently many of the most widely used macro-evolutionary models make predictions about the shapes of phylogenetic trees that differ considerably from what is observed in empirical phylogenies. Here, we propose a flexible and biologically plausible macroevolutionary model for phylogenetic trees where times to speciation or extinction events are drawn from a Coxian phase-type (PH) distribution. First, we show that different choices of parameters in our model lead to a range of tree balances as measured by Aldous’ [Formula: see text] statistic. In particular, we demonstrate that it is possible to find parameters that correspond well to empirical tree balance. Next, we provide a natural extension of the [Formula: see text] statistic to sets of trees. This extension produces less biased estimates of [Formula: see text] compared to using the median [Formula: see text] values from individual trees. Furthermore, we derive a likelihood expression for the probability of observing an edge-weighted tree under a model with speciation but no extinction. Finally, we illustrate the application of our model by performing both absolute and relative goodness-of-fit tests for two large empirical phylogenies (squamates and angiosperms) that compare models with Coxian PH distributed times to speciation with models that assume exponential or Weibull distributed waiting times. In our numerical analysis, we found that, in most cases, models assuming a Coxian PH distribution provided the best fit.

PMID:36103093 | DOI:10.1007/s11538-022-01072-w

Intern Emerg Med. 2022 Sep 14. doi: 10.1007/s11739-022-03081-y. Online ahead of print.

ABSTRACT

COVID-19 has rapidly evolved since it was first discovered in December 2019. We aimed to retrospectively review our experience with COVID-19 infection across 2020-2022, focusing on differences in laboratory markers at presentation. Consecutive adult patients admitted to hospital with confirmed COVID-19 infection were retrospectively reviewed across three periods (29/3/2020-29/9/2020, 16/8/2021-13/10/2021 and 1/1/2022-31/1/2022), correlating with the lineages B.1.338, Delta (B.1.617.2) and Omicron (B.1.1.159), respectively. Laboratory findings of the first requested blood test within 24 h of presentation were recorded and correlated with patient outcome. The primary outcome was requirement for oxygen therapy at any point. Inflammatory markers, namely serum ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP) were significantly lower on presentation during 2022 compared to 2021, corresponding to a milder disease course. More than 80% of 2022 patients had received 2 or more vaccine doses and fully vaccinated patients displayed significantly lower inflammatory markers at presentation. Using 2022 data, a multivariate prediction model was constructed to predict for oxygen requirement, with c-statistic 0.86. Patients in 2022, corresponding with the Omicron variant, displayed a milder disease course, even in hospitalised patients, with the majority not requiring oxygen and lower inflammatory markers. We constructed a simple-to-use risk prediction model with c-statistic 0.86 which may identify individuals who can be safely managed as outpatients in the era of highly transmissible variants.

PMID:36103084 | DOI:10.1007/s11739-022-03081-y

Environ Sci Pollut Res Int. 2022 Sep 14. doi: 10.1007/s11356-022-22985-y. Online ahead of print.

ABSTRACT

Exposure to arsenic (As) from a diet of contaminated rice is a widespread problem and a serious concern in several parts of the world. There is a need to develop sustainable, effective, and reliable strategies to reduce As accumulation in rice. Our goal was to develop and test a simple crop rotation method of alternating rice with the As hyperaccumulator plant, Chinese brake fern (Pteris vitatta L.), to reduce As concentrations in rice grains. A greenhouse column study was performed for 2 years using As-contaminated rice paddy soil from West Bengal. Rice was grown under flooded conditions and irrigated with As-contaminated water to simulate field conditions. Chinese brake fern was grown between two rice cycles in experimental columns, while control columns were left unplanted. Our results show that at the end of two cycles, there was a statistically significant decrease in soil As concentrations in the treatment columns compared to the control columns. After one rotation with the fern, there was a significant decline in As concentrations in rice grains in treatment plants and a concomitant decline in both noncarcinogenic and carcinogenic health risks. Our results indicate that there could be substantial benefit in implementing this simple crop rotation model to help lower human health risks from As exposure via rice ingestion.

PMID:36103075 | DOI:10.1007/s11356-022-22985-y