Category: Nevin Manimala

Sud Med Ekspert. 2022;65(4):18-23. doi: 10.17116/sudmed20226504118.

ABSTRACT

The objective of the study is to establish a set of possible causes and patterns that influence the frequency and severity of road traffic accidents with fatalities. The results of the 5-year monitoring analysis of fatal road traffic injuries in Kazan are presented. We analyzed 662 cases. It was established that the main risk group for fatal road accidents includes subjects aged 20-39. The risk group for drivers is 30-39 years old, passengers 20-29 years old, and pedestrians 55-64 years old. Children account for 3% of all traffic fatalities; 80% of them are under 10 years old. Most children (70%) were in the vehicle at the time of the crash, and their parents may not have been using special equipment (car seats and seat belts). We identified the most traumatic months of the year, days of the week and times of the day for drivers, passengers and pedestrians. These patterns can be used for organizational measures to prevent road accidents.

PMID:35947404 | DOI:10.17116/sudmed20226504118

Sud Med Ekspert. 2022;65(4):5-8. doi: 10.17116/sudmed2022650415.

ABSTRACT

The study objective is to improve epidemic control measures in the bureau of forensic medicine by reviewing current local regulatory documents, formulating proposals for their modification, and updating issues related to infectious safety and diagnostic accuracy of infectious diseases. Specific proposals have been provided for modifications of statistical forms for infectious disease recording, regulatory documents, and internal instructions.

PMID:35947401 | DOI:10.17116/sudmed2022650415

JAMA Netw Open. 2022 Aug 1;5(8):e2225973. doi: 10.1001/jamanetworkopen.2022.25973.

ABSTRACT

IMPORTANCE: Of approximately 9 million patients with cancer in China in 2020, more than half were diagnosed with late-stage cancers. Recent regulatory reforms in China have focused on improving the availability of new cancer drugs. However, evidence on the clinical benefits of new cancer therapies authorized in China is not available.

OBJECTIVE: To characterize the clinical benefits of cancer drugs approved in China, as defined by the availability and magnitude of statistically significant overall survival (OS) results.

DESIGN, SETTING, AND PARTICIPANTS: This mixed-methods study comprising a systematic review and cross-sectional analysis identified antineoplastic agents approved in China between January 1, 2005, and December 31, 2020, using publicly available data and regulatory review documents issued by the National Medical Products Administration. The literature published up to June 30, 2021, was reviewed to collect results on end points used in pivotal trials supporting cancer drug approvals.

MAIN OUTCOMES AND MEASURES: The primary outcome measure was a documented statistically significant positive OS difference between a new cancer therapy and a comparator treatment. Secondary outcome measures were the magnitude of OS benefit and other primary efficacy measures in pivotal trials.

RESULTS: Between 2005 and 2020, 78 cancer drugs corresponding to 141 indications were authorized in China, including 20 drugs (25.6%) (for 30 indications) approved in China only. Of all indications, 26 (18.4%) were evaluated in single-arm or dose-optimization trials, most of which were authorized after 2017. By June 30, 2021, 34 drug indications (24.1%) had a documented lack of OS gain. For 68 indications (48.2%) that had documented evidence of OS benefit, the median magnitude of OS improvement was 4.1 (range, 1.0-35.0) months. After a median follow-up of 1.9 (range, 1.0-11.1) years from approval, OS data for 13 indications (9.2%) were either not reported or were still not mature. Fewer than one-third of cancer drug indications approved in China only had documented evidence of OS benefits (9 of 30 [30.0%]), whereas more than one-half of the cancer drug indications also available in the US or Europe had OS benefits (59 of 111 [53.1%]).

CONCLUSIONS AND RELEVANCE: In this study, almost half of cancer drug indications approved in China had demonstrated OS gain. With the increase of cancer drug approvals based on single-arm trials or immature survival data in recent years, these findings highlight the need to routinely monitor the clinical benefits of new cancer therapies in China.

PMID:35947385 | DOI:10.1001/jamanetworkopen.2022.25973

JAMA Surg. 2022 Aug 10. doi: 10.1001/jamasurg.2022.3113. Online ahead of print.

NO ABSTRACT

PMID:35947378 | DOI:10.1001/jamasurg.2022.3113

JAMA Surg. 2022 Aug 10. doi: 10.1001/jamasurg.2022.3110. Online ahead of print.

NO ABSTRACT

PMID:35947376 | DOI:10.1001/jamasurg.2022.3110

JAMA Surg. 2022 Aug 10:e222935. doi: 10.1001/jamasurg.2022.2935. Online ahead of print.

ABSTRACT

IMPORTANCE: Patients with abdominal aortic aneurysm (AAA) can choose open repair or endovascular repair (EVAR). While EVAR is less invasive, it requires lifelong surveillance and more frequent aneurysm-related reinterventions than open repair. A decision aid may help patients receive their preferred type of AAA repair.

OBJECTIVE: To determine the effect of a decision aid on agreement between patient preference for AAA repair type and the repair type they receive.

DESIGN, SETTING, AND PARTICIPANTS: In this cluster randomized trial, 235 patients were randomized at 22 VA vascular surgery clinics. All patients had AAAs greater than 5.0 cm in diameter and were candidates for both open repair and EVAR. Data were collected from August 2017 to December 2020, and data were analyzed from December 2020 to June 2021.

INTERVENTIONS: Presurgical consultation using a decision aid vs usual care.

MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients who had agreement between their preference and their repair type, measured using χ2 analyses, κ statistics, and adjusted odds ratios.

RESULTS: Of 235 included patients, 234 (99.6%) were male, and the mean (SD) age was 73 (5.9) years. A total of 126 patients were enrolled in the decision aid group, and 109 were enrolled in the control group. Within 2 years after enrollment, 192 (81.7%) underwent repair. Patients were similar between the decision aid and control groups by age, sex, aneurysm size, iliac artery involvement, and Charlson Comorbidity Index score. Patients preferred EVAR over open repair in both groups (96 of 122 [79%] in the decision aid group; 81 of 106 [76%] in the control group; P = .60). Patients in the decision aid group were more likely to receive their preferred repair type than patients in the control group (95% agreement [93 of 98] vs 86% agreement [81 of 94]; P = .03), and κ statistics were higher in the decision aid group (κ = 0.78; 95% CI, 0.60-0.95) compared with the control group (κ = 0.53; 95% CI, 0.32-0.74). Adjusted models confirmed this association (odds ratio of agreement in the decision aid group relative to control group, 2.93; 95% CI, 1.10-7.70).

CONCLUSIONS AND RELEVANCE: Patients exposed to a decision aid were more likely to receive their preferred AAA repair type, suggesting that decision aids can help better align patient preferences and treatments in major cardiovascular procedures.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03115346.

PMID:35947375 | DOI:10.1001/jamasurg.2022.2935

JAMA Psychiatry. 2022 Aug 10. doi: 10.1001/jamapsychiatry.2022.2196. Online ahead of print.

ABSTRACT

IMPORTANCE: Past studies have identified associations between brain macrostructure and alcohol use behaviors. However, identifying directional associations between these phenotypes is difficult due to the limitations of observational studies.

OBJECTIVE: To use mendelian randomization (MR) to identify directional associations between brain structure and alcohol use and elucidate the transcriptomic and cellular underpinnings of identified associations.

DESIGN, SETTING, AND PARTICIPANTS: The main source data comprised summary statistics from population-based and case-control genome-wide association studies (GWAS) of neuroimaging, behavioral, and clinical phenotypes (N = 763 874). Using these data, bidirectional and multivariable MR was performed analyzing associations between brain macrostructure and alcohol use. Downstream transcriptome-wide association studies (TWAS) and cell-type enrichment analyses investigated the biology underlying identified associations. The study approach was data driven and did not test any a priori hypotheses. Data were analyzed August 2021 to May 2022.

MAIN OUTCOMES AND MEASURES: Brain structure phenotypes (global cortical thickness [GCT] and global cortical surface area [GCSA] in 33 709 individuals and left-right subcortical volumes in 19 629 individuals) and alcohol use behaviors (alcoholic drinks per week [DPW] in 537 349 individuals, binge drinking frequency in 143 685 individuals, and alcohol use disorder in 8845 individuals vs 20 657 control individuals [total of 29 502]).

RESULTS: The main bidirectional MR analyses were performed in samples totaling 763 874 individuals, among whom more than 94% were of European ancestry, 52% to 54% were female, and the mean cohort ages were 40 to 63 years. Negative associations were identified between genetically predicted GCT and binge drinking (β, -2.52; 95% CI, -4.13 to -0.91) and DPW (β, -0.88; 95% CI, -1.37 to -0.40) at a false discovery rate (FDR) of 0.05. These associations remained significant in multivariable MR models that accounted for neuropsychiatric phenotypes, substance use, trauma, and neurodegeneration. TWAS of GCT and alcohol use behaviors identified 5 genes at the 17q21.31 locus oppositely associated with GCT and binge drinking or DPW (FDR = 0.05). Cell-type enrichment analyses implicated glutamatergic cortical neurons in alcohol use behaviors.

CONCLUSIONS AND RELEVANCE: The findings in this study show that the associations between GCT and alcohol use may reflect a predispositional influence of GCT and that 17q21.31 genes and glutamatergic cortical neurons may play a role in this association. While replication studies are needed, these findings should enhance the understanding of associations between brain structure and alcohol use.

PMID:35947372 | DOI:10.1001/jamapsychiatry.2022.2196

Transl Vis Sci Technol. 2022 Aug 1;11(8):9. doi: 10.1167/tvst.11.8.9.

ABSTRACT

PURPOSE: To explore the relationship between serum uric acid (SUA) and retinochoroidal microcirculation in the Chinese population.

METHODS: This prospective cross-sectional study was conducted among the residents of Guangzhou, southern China. A commercially available optical coherence tomography angiography (OCTA) device was used to obtain the superficial vessel density (SVD) and deep vessel density in the retina and the choriocapillaris flow deficit (CFD) in the macular region. Univariable and multivariable linear regression models were used to assess the association of hyperuricemia and SUA levels with OCTA parameters.

RESULTS: A total of 638 participants with normal SUA and 296 participants with hyperuricemia were included in the study. Parafoveal SVD was significantly reduced among the participants with hyperuricemia compared to participants with normal SUA (P < 0.001), while the parafoveal CFD was higher in hyperuricemic participants than those of normal SUA levels (P = 0.007). After adjusting for potential confounders, greater SUA levels was associated with lower SVD (β = -0.078; P < 0.001) and greater CFD (β = 0.015; P = 0.011). Gender difference analysis indicated that a 10-µmol/L increase in SUA levels among the female participants led to a 0.144 decrease in SVD (P < 0.001), but it was not statistically significant for the male participants (P = 0.653).

CONCLUSIONS: An elevated uric acid level and its fluctuations were independently associated with impaired retinal and choroidal microcirculation using OCTA in the study population. Women appear to be more sensitive to high SUA levels than men.

TRANSLATIONAL RELEVANCE: Elevating uric acid concentration may play a role in the development and progression of cardiovascular diseases through microvascular alteration, as demonstrated by OCTA parameters.

PMID:35947369 | DOI:10.1167/tvst.11.8.9

JAMA Dermatol. 2022 Aug 10. doi: 10.1001/jamadermatol.2022.3142. Online ahead of print.

ABSTRACT

IMPORTANCE: Other than single-center case studies, little is known about generalized pustular psoriasis (GPP) flares.

OBJECTIVE: To assess GPP flares and their treatment, as well as differences between patients with and patients without flares documented in US electronic health records (EHRs).

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included adult patients with GPP (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code L40.1) identified in Optum deidentified EHR data between July 1, 2015, and June 30, 2020. The index GPP diagnosis was the first occurrence in the EHR, with no coded history of GPP for at least 6 months prior. Flare episodes were identified using an algorithm based on diagnosis coding, care setting, type of clinician, GPP disease terms, and flare terms and attributes in the EHR.

MAIN OUTCOMES AND MEASURES: Flare episodes were characterized by the frequency of occurrence per patient, the care setting in which they were identified, the type of specialist managing the episode, associated symptoms, and the type of treatment before, during, and after the episode. Patients were divided into groups based on whether or not they had a flare episode documented in their EHR. Comparisons were made between the groups based on demographic characteristics, comorbidity burden, health care use, and treatments.

RESULTS: Of 1535 patients with GPP (1018 women [66.3%]; mean [SD] age, 53.4 [14.7] years), 271 had 513 flares documented. Compared with patients without flares, patients with flares had a 34% higher mean (SD) Charlson Comorbidity Index score (2.80 [3.11] vs 2.09 [2.52]), were almost 3 times more likely to have inpatient visits (119 of 271 [44%] vs 194 of 1264 [15%]), were more than twice as likely to have emergency department (ED) visits (126 of 271 [47%] vs 299 of 1264 [24%]), and had higher use of almost all treatment classes. Flares were identified in outpatient (271 of 513 [53%]), inpatient (186 of 513 [36%]), and ED (48 of 513 [9%]) settings. The most common treatments during flares were topical corticosteroids (35% of episodes [178 of 513]), opioids (21% [106 of 513]), other oral treatments, (eg, methotrexate, cyclosporine, tacrolimus; 13% [67 of 513]), and oral corticosteroids (11% [54 of 513]). Almost one-fourth of flare episodes (24% [122 of 513]) had no dermatologic treatment 30 days before, during, or 30 days after a flare episode.

CONCLUSIONS AND RELEVANCE: This cohort study suggests that there is significant unmet need for the treatment of GPP and its flares, as evidenced by patients seeking treatment in inpatient and ED settings, as well as the lack of advanced treatments.

PMID:35947363 | DOI:10.1001/jamadermatol.2022.3142

Clin Pharmacokinet. 2022 Aug 10. doi: 10.1007/s40262-022-01161-y. Online ahead of print.

ABSTRACT

BACKGROUND: The combination of polymyxins, meropenem, and sulbactam demonstrated efficacy against multi-drug-resistant bacillus Acinetobacter baumannii. These three antibiotics are commonly used against major blood, skin, lung, and heart muscle infections.

OBJECTIVE: The objective of this study was to predict drug disposition and extrapolate the efficacy in these tissues using a physiologically based pharmacokinetic modeling approach that linked drug exposures to their target pharmacodynamic indices associated with antimicrobial activities against A. baumannii.

METHODS: An adult physiologically based pharmacokinetic model was developed for meropenem, colistin, and sulbactam and scaled to pediatrics accounting for both renal and non-renal clearances. The model reliability was evaluated by comparing simulated plasma and tissue drug exposures to observed data. Target pharmacodynamic indices were used to evaluate whether pediatric and adult dosing regimens provided sufficient coverage.

RESULTS: The modeled plasma drug exposures in adults and pediatric patients were consistent with reported literature data. The mean fold errors for meropenem, colistin, and sulbactam were in the range of 0.710-1.37, 0.981-1.47, and 0.647-1.39, respectively. Simulated exposures in the blood, skin, lung, and heart were consistent with reported penetration rates. In a virtual pediatric population aged from 2 to < 18 years, the interpretive breakpoints were achieved in 85-90% of subjects for their targeted pharmacodynamic indices after administration of pediatric dosing regimens consisting of 30 mg/kg of meropenem, and 40 mg/kg of sulbactam three times daily as a 3-h or continuous infusion and 5 mg/kg/day of colistin base activity.

CONCLUSIONS: The physiologically based pharmacokinetic modeling supports pediatric dosing regimens of meropenem/colistin/sulbactam in a co-administration setting against infections in the blood, lung, skin, and heart tissues due to A. baumannii.

PMID:35947360 | DOI:10.1007/s40262-022-01161-y