Category: Nevin Manimala

JAMA Netw Open. 2022 Jun 1;5(6):e2216183. doi: 10.1001/jamanetworkopen.2022.16183.

ABSTRACT

IMPORTANCE: Ensuring patients have access to safe and efficacious medicines in a timely manner is an essential goal for regulatory agencies, one which has particular importance in oncology because of the substantial unmet need for new therapies. The 2 largest regulatory agencies, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have pivotal global roles, and their recommendations and approvals are frequently followed by other national regulators.

OBJECTIVE: To compare market authorization dates for new oncology therapies approved in the US and Europe over the past decade and to examine and contrast the regulatory activities of the FDA and EMA in the approval of new cancer medicines.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study reviewed the FDA and EMA regulatory databases to identify new oncology therapies approved in both the US and Europe from 2010 to 2019, and characterization of the timings of regulatory activities. Statistical analysis was performed from January to April 2022.

MAIN OUTCOMES AND MEASURES: Regulatory approval date, review time, submission of market authorization application, accelerated approval or conditional marketing authorization status and proportion of approvals prior to peer-reviewed publication of pivotal trial results.

RESULTS: In total, 89 new concomitant oncology therapies were approved in the US and Europe from 2010 to 2019. The FDA approved 85 oncology therapies (95%) before European authorization and 4 therapies (5%) after. The median (IQR) delay in market authorization for new oncology therapies in Europe was 241 (150-370) days compared with the US. The median (IQR) review time was 200 (155-277) days for the FDA and 426 (358-480) days for the EMA. Sixty-four new licensing applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA. Thirty-five oncology therapies (39%) were approved by the FDA prior to pivotal study publication, whereas only 8 (9%) by the EMA.

CONCLUSION AND RELEVANCE: In this cross-sectional study, new oncology therapies were approved earlier in the US than Europe. The FDA received licensing applications sooner and had shorter review times. However, more therapies were approved prior to licensing study publication, leaving uncertainty for practitioners regarding clinical utility and safety of newly approved therapies.

PMID:35687337 | DOI:10.1001/jamanetworkopen.2022.16183

JAMA Netw Open. 2022 Jun 1;5(6):e2216393. doi: 10.1001/jamanetworkopen.2022.16393.

ABSTRACT

IMPORTANCE: An adequate system for triaging patients with head trauma in prehospital settings and choosing optimal medical institutions is essential for improving the prognosis of these patients. To our knowledge, there has been no established way to stratify these patients based on their head trauma severity that can be used by ambulance crews at an injury site.

OBJECTIVES: To develop a prehospital triage system to stratify patients with head trauma according to trauma severity by using several machine learning techniques and to evaluate the predictive accuracy of these techniques.

DESIGN, SETTING, AND PARTICIPANTS: This single-center retrospective cohort study was conducted by reviewing the electronic medical records of consecutive patients who were transported to Tokyo Medical and Dental University Hospital in Japan from April 1, 2018, to March 31, 2021. Patients younger than 16 years with cardiopulmonary arrest on arrival or with a significant amount of missing data were excluded.

MAIN OUTCOMES AND MEASURES: Machine learning-based prediction models to detect the presence of traumatic intracranial hemorrhage were constructed. The predictive accuracy of the models was evaluated with the area under the receiver operating curve (ROC-AUC), area under the precision recall curve (PR-AUC), sensitivity, specificity, and other representative statistics.

RESULTS: A total of 2123 patients (1527 male patients [71.9%]; mean [SD] age, 57.6 [19.8] years) with head trauma were enrolled in this study. Traumatic intracranial hemorrhage was detected in 258 patients (12.2%). Among several machine learning algorithms, extreme gradient boosting (XGBoost) achieved the mean (SD) highest ROC-AUC (0.78 [0.02]) and PR-AUC (0.46 [0.01]) in cross-validation studies. In the testing set, the ROC-AUC was 0.80, the sensitivity was 74.0% (95% CI, 59.7%-85.4%), and the specificity was 74.9% (95% CI, 70.2%-79.3%). The prediction model using the National Institute for Health and Care Excellence (NICE) guidelines, which was calculated after consultation with physicians, had a sensitivity of 72.0% (95% CI, 57.5%-83.8%) and a specificity of 73.3% (95% CI, 68.7%-77.7%). The McNemar test revealed no statistically significant differences between the XGBoost algorithm and the NICE guidelines for sensitivity or specificity (P = .80 and P = .55, respectively).

CONCLUSIONS AND RELEVANCE: In this cohort study, the prediction model achieved a comparatively accurate performance in detecting traumatic intracranial hemorrhage using only the simple pretransportation information from the patient. Further validation with a prospective multicenter data set is needed.

PMID:35687335 | DOI:10.1001/jamanetworkopen.2022.16393

Minerva Cardiol Angiol. 2022 Jun 10. doi: 10.23736/S2724-5683.22.05998-1. Online ahead of print.

ABSTRACT

BACKGROUND: Valvular heart disease (VHD) requires optimized outpatient management that is generally considered to be best delivered by a dedicated, multidisciplinary team (Heart Valve Clinic, HVC). Although HVC is promoted by clinical guidelines and organized in many centers, real world outcome assessments are limited. Thus, we evaluated the performance, clinical and management outcomes during a 6-year experience with an original HVC model.

METHODS: By interrogating the local database, 1047 consecutive patients admitted to the HVC from January 2015 to October 2020 were found. Management and mortality were checked for all patients. After 3 years of HVC activity, in order to improve appropriateness and efficiency, access priority criteria were introduced. Thus, the study population was divided in two Period subgroups (before and after access criteria introduction) that were compared.

RESULTS: A total of 1047 consecutive patients admitted to the HVC constituted the study population; 346 patients (33%) were recommended for invasive treatment. After a mean follow up of 25.7 ± 3.1 months, 37 patients (3.5%) died. When comparing study periods, statistically-significant increase inpatients’ complexity and VHD severity was noticed in Period 2, also translating into higher rate of referral to intervention (39.0% vs. 29.4% in Period 1; p = 0.001). Finally, despite higher rate of elderly and frail patients, operative mortality was not jeopardized.

CONCLUSIONS: The present study reports a comprehensive assessment of the characteristics and outcomes achieved through an original HVC model. Standardization of access criteria supports the HVC improvement.

PMID:35687315 | DOI:10.23736/S2724-5683.22.05998-1

Nanoscale. 2022 Jun 10. doi: 10.1039/d2nr01819e. Online ahead of print.

ABSTRACT

Structural analysis of metal clusters confined in nanoporous materials is typically performed by X-ray-driven techniques. Although X-ray analysis has proved its strength in the characterization of metal clusters, it provides averaged structural information. Therefore, we here present an alternative workflow for bringing the characterization of confined metal clusters towards the local scale. This workflow is based on the combination of aberration-corrected transmission electron microscopy (TEM), TEM image simulations, and powder X-ray diffraction (XRD) with advanced statistical techniques. In this manner, we were able to characterize the clustering of Pb atoms in Linde Type A (LTA) zeolites with Pb loadings as low as 5 wt%. Moreover, individual Pb clusters could be directly detected. The proposed methodology thus enables a local-scale characterization of confined metal clusters in zeolites. This is important for further elucidation of the connection between the structure and the physicochemical properties of such systems.

PMID:35687327 | DOI:10.1039/d2nr01819e

Environ Sci Pollut Res Int. 2022 Jun 10. doi: 10.1007/s11356-022-21333-4. Online ahead of print.

ABSTRACT

Colloidal particles can attach the contaminants like heavy metals and radionuclides and act as contaminant carriers to provide a faster movement of pollutants through the interconnecting pores of the porous medium. The electrostatic repulsive force between the negatively charged colloids and the solid surface restricts the transport of the mobile colloids to the larger pores of the porous medium and initiates the size exclusion mechanism. The temporal moment analysis is treated as an effective tool to interpret the solute breakthrough curves for analyzing the statistical behavior of the contaminants. In past literature, the temporal moments have not been incorporated with the breakthrough curves of colloids and colloid-facilitated contaminants for statistical interpretation. In this research study, the temporal variations of concentrations of mobile colloids, solute attached to the mobile colloids, and the dissolved solute are obtained numerically in a fully saturated one-dimensional column considering a continuous source for varying size exclusion and colloid attachment coefficient. Utilizing the simulated spatially varying breakthrough curves, the temporal moments are estimated to calculate the mass recovery, average residence time, and the spreading of mobile colloids and dissolved solutes. The temporal moment analysis suggests that the velocity enhancement for higher size exclusion reduces the average residence time of the mobile colloids and the solute adsorbed to the mobile colloids significantly. The mass recovery of mobile colloids and the solute attached to the mobile colloids increases at a specific depth for higher size exclusion. The estimated second central moment attributes that the solute spreading follows the nonlinear trend for low size exclusion. The peaks of the relative concentration of mobile colloids and solute attached to mobile colloids drastically decrease with an increase in attachment coefficient. The peak of the relative concentration of dissolved contaminant enhances with attachment coefficient. The high second temporal moment of the dissolved contaminant at a higher attachment coefficient indicates the slow interaction of dissolved solute and porous medium and that enables a greater spreading of solute through the interconnecting porous medium. The study suggests that the faster movement of mobile colloids and the solute attached to the mobile colloids at higher exclusion imparts a potential risk of groundwater contamination and thorough statistical interpretation is needful to analyze the behavior of colloids and colloid-facilitated contaminants. The research work does not consider the transient flow field and the effect of the presence of air phase in the partially saturated soil column in the groundwater system.

PMID:35687282 | DOI:10.1007/s11356-022-21333-4

Eur Child Adolesc Psychiatry. 2022 Jun 10. doi: 10.1007/s00787-022-01986-9. Online ahead of print.

ABSTRACT

The clinical validity of the distinction between ADHD and ASD is a longstanding discussion. Recent advances in the realm of data-driven analytic techniques now enable us to formally investigate theories aiming to explain the frequent co-occurrence of these neurodevelopmental conditions. In this study, we probe different theoretical positions by means of a pre-registered integrative approach of novel classification, subgrouping, and taxometric techniques in a representative sample (N = 434), and replicate the results in an independent sample (N = 219) of children (ADHD, ASD, and typically developing) aged 7-14 years. First, Random Forest Classification could predict diagnostic groups based on questionnaire data with limited accuracy-suggesting some remaining overlap in behavioral symptoms between them. Second, community detection identified four distinct groups, but none of them showed a symptom profile clearly related to either ADHD or ASD in neither the original sample nor the replication sample. Third, taxometric analyses showed evidence for a categorical distinction between ASD and typically developing children, a dimensional characterization of the difference between ADHD and typically developing children, and mixed results for the distinction between the diagnostic groups. We present a novel framework of cutting-edge statistical techniques which represent recent advances in both the models and the data used for research in psychiatric nosology. Our results suggest that ASD and ADHD cannot be unambiguously characterized as either two separate clinical entities or opposite ends of a spectrum, and highlight the need to study ADHD and ASD traits in tandem.

PMID:35687205 | DOI:10.1007/s00787-022-01986-9

Surg Endosc. 2022 Jun 10. doi: 10.1007/s00464-022-09349-w. Online ahead of print.

ABSTRACT

BACKGROUND: Resident involvement in the operating room is a vital component of their medical education. Laparoscopic cholecystectomy (LC) represents the paradigmatic minimally invasive training procedure, both due to its prevalence and its different forms of complexity. We aim to evaluate whether the supervised participation of residents as operative surgeons in LC of different degrees of complexity affects postoperative outcomes in a university hospital.

METHODS: This is a retrospective, single-center study that included all consecutive adult (> 18 years old) patients operated for a LC between January 1, 2012 and December 31, 2017. Each surgical procedure was recorded according to the level of complexity that we established in three types of categorization (level 1: elective surgery; level 2: cholecystitis; level 3: biliary instrumentation). Patients were clinically monitored at an outpatient clinic 7 and 30-day postoperative. Postoperative outcomes of patients operated by supervised residents (SR) and trained surgeons (TS) were compared. Postoperative complications were graded according to the Clavien-Dindo classification of surgical complications.

RESULTS: A total of 2331 patients underwent LC during the study period, of whom 1573 patients (67.5%) were operated by SR and 758 patients (32.5%) by TS. There were no significant differences among age, sex, and BMI between patients operated in both groups, with the exception of ASA (P = 0.0001). Intraoperative cholangiography was performed in 100% of the patients, without bile duct injuries. There were no deaths in the 30 postoperative days. The overall complication rate was 5.70% (133 patients), with no significant differences when comparing LC performed by SR and TS (5.09 vs. 6.99%; P = 0.063). The severity rates of complications were similar in both groups (P = 0.379). Patient readmission showed a statistical difference comparing SR vs TS (0.76% vs. 2.2%; P = 0.010). The postoperative complications rate according to the complexity level of LC was not significant in level 1 and 2 for both groups. However in complexity level 3 the TS group experienced a greater rate of complications compared to the SR group (18.12% vs. 9.38%; P = 0.058). In the multivariate analysis, the participation of the residents as operating surgeons was not independently associated with an increased risk of complications (OR 1.22, 95% CI 0.84-1.77; P = 0.275), neither other risk factors like age ≥ 65 years, BMI, complexity level 2-3, or ASA ≥ 3-4. The association of another surgical procedure with the LC was an independent factor of morbidity (OR 3.85, 95% CI 2.54-5.85; P = 0.000).

CONCLUSION: Resident involvement in LC with different degrees of complexity did not affect postoperative outcomes. The participation of a resident as operating surgeon is not an independent risk factor and may be considered ethical, safe, and reliable whenever implemented in the background of a residency-training program with continuous supervision and national accreditation. The sum of other procedures not related to a LC should be taken as a risk factor of morbidity.

PMID:35687252 | DOI:10.1007/s00464-022-09349-w

AIDS Behav. 2022 Jun 10. doi: 10.1007/s10461-022-03736-z. Online ahead of print.

ABSTRACT

HPTN 069/ACTG 5305 was designed to evaluate potential new PrEP regimens that included maraviroc, tenofovir disoproxil fumarate, and/or emtricitabine. The current analyses assessed antiretroviral (ARV) plasma concentrations in relation to sexual behavior in 224 cisgender men who have sex with men and 2 transgender women at risk for HIV. Poisson generalized estimating equations (GEE) regression were used to test for associations between self-reported sexual behavior, sociodemographic, behavioral variables, and study drug levels The median (IQR) age was 30 [25, 37] years old; 48.2% had completed college; 27.4% were Black and 21.7% Latino. At weeks 24 and 48, one third of participants reported condomless anal sex (CAS) in the prior month with more than one partner. CAS was associated with daily ARV drug use (χ² = 12.64, p = 0.002). Older individuals and those with greater education were more likely to ingest ARV drugs daily (χ² = 9.36, p = 0.009 and χ² = 8.63, p = 0.013, respectively), while neither race nor ethnicity was associated with daily ARV drug use. Participants who reported recent condomless anal sex and/or advanced education had higher rates of daily ARV drug use. These data support the need for ongoing adherence counseling in clinical trials of new PrEP modalities.

PMID:35687192 | DOI:10.1007/s10461-022-03736-z

Eur Arch Otorhinolaryngol. 2022 Jun 10. doi: 10.1007/s00405-022-07449-w. Online ahead of print.

ABSTRACT

OBJECTIVE: This study is to compare the hearing outcomes and complications of stapes surgery and cochlear implantation (CI) in patients with far-advanced otosclerosis (FAO).

DATA SOURCES: A comprehensive electronic search of PubMed/MEDLINE, Scopus, Web of science and Cochrane Library was conducted in June 2021 for articles in the literature till this year.

STUDY SELECTION: Studies are published in English language, conducted on human subjects, concerned with comparison of CI and stapes surgery in the management of FAO, not Laboratory study and not Opinion study. The current review followed the guidelines of preferred reporting items for systematic reviews and meta-analysis statement 2009 (PRISMA).

DATA EXTRACTION: Twenty-six studies were included with 334 patients in CI group and 241 patients in stapes surgery group. Comparison between both groups was done in terms of postoperative complications, audiological outcomes, rete of revision surgery and patients’ satisfaction rate.

RESULTS: Postoperative complications rate was significantly lower in CI (13.6%) than stapes surgery (18.6%). CI had a significantly lower rate of revision surgery (8.1%) than stapes surgery (16.4%). CI had a better mean for pure tone average (29.1 dB) than stapedectomy (52.3 dB) while stapes surgery had a higher mean for recognition of monosyllables and disyllables than CI. CI had significantly higher satisfaction rate than stapes surgery.

CONCLUSION: Both Stapes surgery and CI are reliable treatment options for FAO with close success rates. Statistics of CI are greater than stapes surgery and CI has a consistent improvement in audiometric outcomes in comparison to stapes surgery.

PMID:35687184 | DOI:10.1007/s00405-022-07449-w

Med Klin Intensivmed Notfmed. 2022 Jun 10. doi: 10.1007/s00063-022-00929-1. Online ahead of print.

ABSTRACT

BACKGROUND: Agency nursing is used as a form of labour to counter vacant staff positions in hospitals. Stakeholders and nurses might view this critically for different reasons.

AIM: The aim of this study was to evaluate what individual net income nurses in German intensive care units and intermediate care units consider “fair and acceptable” for their work. Furthermore, what influence does salary have on the willingness to change to agency nursing or back to a permanent position.

METHODS: From September-October 2020, an anonymous online survey was performed among nurses of intermediate care units, intensive care units and special care units in German-speaking countries. The results were evaluated using descriptive statistics.

RESULT: Of 1203 participants, 1036 (86%) of those working in Germany could be evaluated. The question about the individual net income was answered by 1032 (99%) participants. The majority of respondents (n = 522) stated that they had an individual net income of 2000-2999 €/month. The higher the level of the net income, the lower the willingness to switch to agency work. The participants in permanent employment only perceive a net income of 3200 €/month (median 3200 €; interquartile range [IQR] 2800-3800 €) as acceptable and fair for their work. In all, 142 agency nurses stated that an individual net income of 3200 €/month (median 3200 €; IQR 3000-3950 €) would be sufficient to move from agency nursing back into permanent employment.

CONCLUSION: The intensive care nurses in this survey consider a salary of 3200 €/month as acceptable and fair for their work. The salary level can be a parameter for the decision to go into agency work, but also to move back to permanent employment. Regardless of the salary, better working conditions were indicated as an essential element in terms of job satisfaction for all respondent groups.

PMID:35687181 | DOI:10.1007/s00063-022-00929-1