Tag: nevin manimala

Enferm Infecc Microbiol Clin. 2021 Jul 10:S0213-005X(21)00205-6. doi: 10.1016/j.eimc.2021.06.009. Online ahead of print.

ABSTRACT

OBJECTIVES: To study the spatio-temporal distribution of cases of invasive pneumococcal disease (IPD) due to serotypes resistant to erythromycin and its relationship with community consumption of macrolides and childhood vaccination coverage.

METHODS: We selected IPD cases in adults over 59 years old, residents in the Community of Madrid (MC), notified in the period 2007-2016. The variables studied were obtained from the Vaccination Information Systems and the Pharmaceutical Service. The cut-off point (minimum inhibitory erythromycin concentration > 0.5 mg/L) of the EUCAST classification was used to define erythromycin resistant serotypes. We used JointPoint to estimate the incidence trends by erythromycin resistant serotypes included in the 13-valent vaccine (STPCV13) and not included in it (STnoPCV13). The association of these incidences with the community consumption of macrolides and vaccination coverage was made using Poisson models. Statistical scanning was used for the detection of temporal-spaces clusters of cases.

RESULTS: 1936 cases were identified, of which 427 erythromycin resistant serotypes were identified. The incidence of all cases due to resistant serotypes was decreasing (AAPC: -5,40%). During the period studied, the incidence of cases due to erythromycin resistant STPCV13 was decreasing with an annual percentage change (APC): -13.8 and was inversely associated with childhood vaccination coverage (IRR 0.641), while that of cases due to erythromycin resistant STnoPCV13 was ascending (APC): 4.5; and was not associated with coverage. 1 cluster was detected by STnoPCV13 and none by STPCV13 after the date of inclusion of the 13-valent in the childhood vaccination calendar.

CONCLUSIONS: The decrease in IPD due to resistant STPCV13 was associated with an increase in childhood vaccination coverage. The presence of clusters due to STnoPCV13 after the date of inclusion of the 13-valent vaccine in the childhood vaccination calendar indicates serotypes replacement. The increase in cases of resistant STnoPCV13 could be related to the replacement of vaccine serotypes in nasopharyngeal colonization, facilitated by the consumption of macrolides still at high levels in MC.

PMID:34256972 | DOI:10.1016/j.eimc.2021.06.009

Curr Probl Diagn Radiol. 2021 Jun 20:S0363-0188(21)00101-8. doi: 10.1067/j.cpradiol.2021.06.003. Online ahead of print.

ABSTRACT

RATIONALE AND OBJECTIVES: The purpose of this manuscript is to elucidate the prevalence, characteristics, outcomes, and perceptions of Alliance of Directors and Vice Chairs of Education in Radiology (ADVICER) members on Clinician Educator Leadership Pathway (CELP) tracks in diagnostic and interventional radiology residency programs in the United States.

MATERIALS AND METHODS: IRB exemption was obtained for this study. A 17-question anonymous survey was administered to the ADVICER members, an Association of University Radiologists (AUR) affiliate group, via email once, and then as a reminder 14 days later. Statistical analysis occurred via built-in analytics of the survey vendor, SurveyMonkey.

RESULTS: Thirty five of 72 ADVICER members (48.6%) responded to the survey. 45.7% (16/35) respondents indicated the presence of leadership or specialty pathways in their respective residencies. 28.6% of respondents indicated a CELP (10/35) in their residency programs. 92.0% of respondents endorsed CELP as preparatory for an academic career, and 93.6% endorsed development of a national CELP curriculum.

CONCLUSION: The majority of radiology residency programs do not have a CELP in their training curriculum. ADVICER leaders overwhelmingly support CELP for professional development of the future educational leaders in radiology and endorse the creation of a national CELP curriculum.

PMID:34256976 | DOI:10.1067/j.cpradiol.2021.06.003

Fertil Steril. 2021 Jul 10:S0015-0282(21)00507-0. doi: 10.1016/j.fertnstert.2021.06.013. Online ahead of print.

ABSTRACT

OBJECTIVE: To characterize the interventional clinical trials in infertility and to assess whether trial location or industry sponsorship was associated with trial noncompletion.

DESIGN: Retrospective review of trials registered with ClinicalTrials.gov.

SETTING: None.

PATIENT(S): None.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Descriptive statistics characterizing the attributes of the clinical trials including intervention type, topic, population, completion status, size, location, sponsor, and results. The effects of the sponsor and trial location on trial noncompletion were assessed via logistic regression.

RESULT(S): In total, 505 trials initiated between 2010 and 2020 were included in our analysis. Drug interventions were the most commonly studied (45%); ovarian stimulation trials accounted for 27% of the studies. Live birth was tracked as an outcome by 20% of the studies; 3% of the trials included mental health outcomes. Few trials (15%) enrolled male participants. Only 11% of the trials reported results, and 4% of the trials reported the race or ethnicity of the participants. Most trials (82%) were conducted outside the United States. Overall, 18% of the trials were not completed, most often because of lack of accrual (47%). United States trials had over twice the odds of noncompletion in univariate analysis (odds ratio = 2.48, 95% confidence interval = [1.47, 4.17]); however, this relationship lost significance after adjusting for potential confounders (odds ratio = 0.95, 95% confidence interval = [0.42, 2.14]). Trial sponsorship was not associated with trial noncompletion.

CONCLUSION(S): Infertility trials predominantly investigated drug interventions, particularly ovarian stimulation. Live birth was an infrequent outcome despite its relevance to patients. Clinical trials should aim to address the unmet needs in fertility care and be inclusive of underserved populations affected by infertility.

PMID:34256949 | DOI:10.1016/j.fertnstert.2021.06.013

Clin Ther. 2021 Jul 11:S0149-2918(21)00216-2. doi: 10.1016/j.clinthera.2021.04.020. Online ahead of print.

ABSTRACT

PURPOSE: The goal of this study was to characterize health-related quality of life (HRQOL) among patients diagnosed with early-stage, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer.

METHODS: A multinational (United States, Japan, France, Germany, Italy, Spain, and United Kingdom) study of patients diagnosed with stage I to III HR+/HER2- breast cancer, either receiving adjuvant treatment or under postadjuvant surveillance, was conducted between June and October 2019. Patients were identified by their consulting physician and invited to complete the Functional Assessment of Cancer Therapy-Breast (FACT-B) and the EQ-5D-5L pen and paper questionnaires. EQ-5D-5L index scores were derived by using available country-specific health state value sets, where available, and numerically compared with general population scores derived from published normative and population data. Descriptive summary statistics were reported for FACT-B, Functional Assessment of Cancer Therapy-General (FACT-G) (total and specific subscales), the EQ-5D index scores, and the EQ-VAS scores for each country. Results were stratified according to disease-free treatment status (active adjuvant treatment or postadjuvant surveillance), age (25-44, 45-54, 55-64, or ≥65 years), stage (I, II, or III), and menopausal status at the time of questionnaire completion (pre-/peri-menopausal or postmenopausal).

FINDINGS: Overall, 1110 patients completed the HRQOL questionnaires (mean age, 59 years; 79% active adjuvant treatment, and 21% under surveillance postadjuvant treatment at time of questionnaire administration; 31% stage I, 48% stage II, and 20% stage III at diagnosis). Of these, 1102 completed the FACT-B and 1083 completed the EQ-5D-5L questionnaires. The mean (SD) FACT-B total score was 99.0 (21.9). The mean FACT-G total score was 72.5 (17.8), which was comparable to the published normative score. The mean EQ-5D index and EQ-VAS scores for each country were similar to corresponding population means; EQ-5D index scores ranged from 0.842 (0.098) in Japan to 0.916 (0.109) in France, and EQ-VAS scores from 68.0 (18.4) in Germany to 78.6 (16.4) in the United States. In addition, mean scores were comparable between the active adjuvant treatment and postadjuvant surveillance groups for the FACT-B total (99.4 [22.5] and 97.7 [19.7], respectively), FACT-G total (72.8 [18.3] and 71.3 [16.0]), EQ-5D index score (0.868 [0.135] and 0.869 [0.142]), and EQ-VAS (74.9 [17.2] and 74.4 [16.1]).

IMPLICATIONS: Patient-reported HRQOL among patients with HR+/HER2- early breast cancer who were disease-free was high, with reported scores comparable to normative scores. These results improve our understanding of HRQOL among patients with early disease and may facilitate future studies examining the potential impact of adjuvant treatment and disease recurrence, including metastasis.

PMID:34256965 | DOI:10.1016/j.clinthera.2021.04.020

Pharmazie. 2021 Jul 1;76(7):313-316. doi: 10.1691/ph.2021.1571.

ABSTRACT

Objective: The aim of the study was to evaluate the effect of arachidonic acid cascade inhibitors on body temperature and cognitive functions of rats (spatial memory, learning ability) in the Morris water maze test (MWM) after acute cold injury (CI). Methods: Animals were trained to find an escape platform in the MWM for two consecutive days. On the third day, rats were treated with saline (10 ml/kg), diclofenac sodium (7 mg/kg), etoricoxib (5 mg/kg), darbufelone mesylate (20 mg/kg) or montelukast (1 mg/kg) intragastrically (i.g.), 30 minutes before CI modeling. Air hypothermia with an acute general cooling (AGC) model was used as a kind of CI. Animals were subjected to cooling for 2 hours at -18°C. Body temperature was measured before and after CI modeling. MWM experimental trials tests were carried out after cold exposure. Number of successful trials, escape latency, distance moved, velocity, meander, and behavioral patterns in individual quadrants were recorded. Results: In the control pathology group, a statistically significantly body temperature decrease was observed (p<0.05 compared to the initial value). All of the studied drugs reduced hypothermia severity, but only in the sodium diclofenac group this reduction reached a significant level in comparison with the untreated animals (p<0.01). A tendency to reduce the severity of hypothermia was observed in the group of animals treated by etoricoxib, darbufelone mesylate, and montelukast. In the control pathology group, the number of successful trials was significantly decreased (p<0.01), velocity (p<0.05), and escape latency (p<0.05) were increased compared with intact animals. Diclofenac sodium significantly reduced escape latency (p<0.05) and increased the number of successful trials in comparison with the control pathology group (p<0.01). Montelukast tended to improve, etoricoxib and darbufelone mesylate did not improve cognitive functions of rats with CI. Conclusions: The results experimentally substantiate the possibility of effective pharmacoprophylaxis of CI and its negative effects on cognitive functions while applying arachidonic acid cascade inhibitors, particularly the non-selective COX inhibitor diclofenac sodium.

PMID:34256893 | DOI:10.1691/ph.2021.1571

Prehosp Disaster Med. 2021 Jul 14:1-17. doi: 10.1017/S1049023X21000728. Online ahead of print.

ABSTRACT

INTRODUCTION: In the early phase of the coronavirus disease 2019 (COVID-19) pandemic, United States Emergency Medical Services (EMS) experienced a decrease in calls, and at the same time, an increase in out-of-hospital deaths. This finding led to a concern for the implications of potential delays in care for the obstetric population.

HYPOTHESIS/PROBLEM: This study examines the impact of the pandemic on prehospital care amongst pregnant women.

METHODS: A retrospective observational study was conducted comparing obstetric-related EMS activations in Maryland (USA) during the pandemic (March 10-July 20, 2020) to a pre-pandemic period (March 10-July 20, 2019). Comparative analysis was used to analyze the difference in frequency and acuity of calls between the two periods.

RESULTS: There were fewer obstetric-related EMS encounters during the pandemic compared to the year prior (daily average during the pandemic 12.5 [SD = 3.8] versus 14.6 [SD = 4.1] pre-pandemic; P <.001), although the percent of total female encounters remained unchanged (1.6% in 2020 versus 1.5% in 2019; P = .091). Key indicators of maternal status were not significantly different between the two periods. African-American women represented a disproportionately high percentage of obstetric-related activations (36.2% in 2019 and 34.8% in 2020).

CONCLUSIONS: In this state-wide analysis of EMS calls in Maryland early in the pandemic, no significant differences existed in the utilization of EMS by pregnant women. Prehospital EMS activations amongst pregnant women in Maryland only decreased slightly without an increase in acuity. Of note, over-representation by African-American women compared to population statistics raises concern for broader systemic differences in access to obstetric care.

PMID:34256885 | DOI:10.1017/S1049023X21000728

Hum Genomics. 2021 Jul 13;15(1):44. doi: 10.1186/s40246-021-00342-3.

ABSTRACT

BACKGROUND: Previous research in autism and other neurodevelopmental disorders (NDDs) has indicated an important contribution of protein-coding (coding) de novo variants (DNVs) within specific genes. The role of de novo noncoding variation has been observable as a general increase in genetic burden but has yet to be resolved to individual functional elements. In this study, we assessed whole-genome sequencing data in 2671 families with autism (discovery cohort of 516 families, replication cohort of 2155 families). We focused on DNVs in enhancers with characterized in vivo activity in the brain and identified an excess of DNVs in an enhancer named hs737.

RESULTS: We adapted the fitDNM statistical model to work in noncoding regions and tested enhancers for excess of DNVs in families with autism. We found only one enhancer (hs737) with nominal significance in the discovery (p = 0.0172), replication (p = 2.5 × 10^-3), and combined dataset (p = 1.1 × 10^-4). Each individual with a DNV in hs737 had shared phenotypes including being male, intact cognitive function, and hypotonia or motor delay. Our in vitro assessment of the DNVs showed they all reduce enhancer activity in a neuronal cell line. By epigenomic analyses, we found that hs737 is brain-specific and targets the transcription factor gene EBF3 in human fetal brain. EBF3 is genome-wide significant for coding DNVs in NDDs (missense p = 8.12 × 10^-35, loss-of-function p = 2.26 × 10^-13) and is widely expressed in the body. Through characterization of promoters bound by EBF3 in neuronal cells, we saw enrichment for binding to NDD genes (p = 7.43 × 10^-6, OR = 1.87) involved in gene regulation. Individuals with coding DNVs have greater phenotypic severity (hypotonia, ataxia, and delayed development syndrome [HADDS]) in comparison to individuals with noncoding DNVs that have autism and hypotonia.

CONCLUSIONS: In this study, we identify DNVs in the hs737 enhancer in individuals with autism. Through multiple approaches, we find hs737 targets the gene EBF3 that is genome-wide significant in NDDs. By assessment of noncoding variation and the genes they affect, we are beginning to understand their impact on gene regulatory networks in NDDs.

PMID:34256850 | DOI:10.1186/s40246-021-00342-3

J Pharm Policy Pract. 2021 Jul 13;14(1):60. doi: 10.1186/s40545-021-00346-3.

ABSTRACT

BACKGROUND: Each year, the French independent bulletin Prescrire publishes a list of medicines, “Drugs to avoid”, that should not be used in clinical practice as their risk-to-benefit ratio is unfavourable. This study assessed the market approval, reimbursement and use of these medicines in Australia.

METHODS: The approval status of the medicines included in 2019 Prescrire “Drugs to avoid” list was assessed by searching the Australian Register of Therapeutic Goods website. Funding status was assessed on the Pharmaceutical Benefits Scheme (PBS) website, the Australian public insurance system. Use levels were determined by examining governmental reports on prescribing rates including the Australian Statistics on Medicines (ASM) reports, drug use reports released by the Drug Utilisation Sub Committee (DUSC) and PBS statistics.

RESULTS: Of the 93 medicines included in the Prescrire 2019 “Drug to avoid” list included, 57 (61%) were approved in Australia in 2019 including 9 (16%) that were sold as over-the-counter medicines, 35 (38%) were listed on the PBS, 22 (24%) were registered but not listed on the PBS. Although most of these medicines were used infrequently, 16 (46%) had substantial use despite serious safety concerns. Dipeptidyl peptidase-4 (DPP-4) inhibitors were used by 22% of patients receiving a treatment for diabetes in 2016. More than 50,000 patients received an anti-dementia medicine in 2014, a 19% increase since 2009. Denosumab became the 8th medicine, in terms of total sales, funded by the Australian Government in 2017-2018.

CONCLUSIONS: Prescrire’s assessments provide a reliable external benchmark to assess the current use of medicines in Australia. Sixteen “drugs to avoid”, judged to be more harmful than beneficial based on systematic, independent evidence reviews, are in substantial use in Australia. These results raise serious concerns about the awareness of Australian clinicians of medicine safety and efficacy. Medicines safety has become an Australian National Health Priority. Regulatory and reimbursement agencies should review the marketing and funding status of medicines which have not been shown to provide an efficacy and safety at least similar to alternative therapeutic options.

PMID:34256874 | DOI:10.1186/s40545-021-00346-3

J Ovarian Res. 2021 Jul 13;14(1):93. doi: 10.1186/s13048-021-00842-9.

ABSTRACT

OBJECTIVE: The aim of this meta-analysis was to assess the effectiveness and safety of secondary cytoreductive surgery plus chemotherapy (SCS + CT) in recurrent ovarian cancer (ROC). Our secondary purpose was to analyze whether patients could benefit from complete resection.

METHODS: We searched EMBASE, MEDLINE, the Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials, from inception to April 2021. We used appropriate scales to assess the risk of bias. Data from included studies that reported median PFS or OS were weighted by individual study sample size, and aggregated for meta-analysis. We calculated the pooled proportion of complications within 30 days after surgery.

RESULTS: We identified 13 articles, including three RCTs and ten retrospective cohort studies. A total of 4572 patients were included, of which 916 patients achieved complete resection, and all patients were comparable at baseline. Compared with chemotherapy alone, SCS + CT significantly improved the PFS (HR = 0.54, 95% CI: 0.43-0.67) and OS (HR = 0.60, 95% CI: 0.44-0.81). Contrary to the results of cohort studies, the meta-analysis of RCTs showed that SCS + CT could not bring OS benefits (HR = 0.93, 95% CI: 0.66-1.3). The subgroup analysis showed the prognostic importance of complete resection. Compared with chemotherapy alone, complete resection was associated with longer PFS (HR = 0.53, 95% CI: 0.45-0.61) and OS (HR = 0.56, 95% CI: 0.39-0.81), while incomplete resection had no survival benefit. Additionally, complete resection could maximize survival benefit compared with incomplete resection (HR = 0.56, 95% CI: 0.46-0.69; HR = 0.61, 95% CI: 0.50-0.75). The pooled proportion for complications at 30 days was 21% (95% CI: 0.12-0.30), and there was no statistical difference in chemotherapy toxicity between the two groups.

CONCLUSION: The review indicated that SCS + CT based regimens was correlated with better clinical prognosis for patients with recurrent ovarian cancer, but the interpretation of OS should be cautious. The meta-analysis emphasizes the importance of complete resection, suggesting that the potential benefits of prolonging survival may outweigh the disadvantages of any short-term complications associated with surgery.

PMID:34256813 | DOI:10.1186/s13048-021-00842-9

Genome Biol. 2021 Jul 13;22(1):208. doi: 10.1186/s13059-021-02418-8.

ABSTRACT

One challenge facing omics association studies is the loss of statistical power when adjusting for confounders and multiple testing. The traditional statistical procedure involves fitting a confounder-adjusted regression model for each omics feature, followed by multiple testing correction. Here we show that the traditional procedure is not optimal and present a new approach, 2dFDR, a two-dimensional false discovery rate control procedure, for powerful confounder adjustment in multiple testing. Through extensive evaluation, we demonstrate that 2dFDR is more powerful than the traditional procedure, and in the presence of strong confounding and weak signals, the power improvement could be more than 100%.

PMID:34256818 | DOI:10.1186/s13059-021-02418-8