Nevin Manimala

J Clin Epidemiol. 2021 Mar 25:S0895-4356(21)00095-0. doi: 10.1016/j.jclinepi.2021.03.019. Online ahead of print.

ABSTRACT

OBJECTIVE: To conduct a bibliometric analysis using a large sample of overviews of systematic reviews (OoSRs) and reveal research trends and areas of interest about these studies.

STUDY DESIGN AND SETTING: We searched MEDLINE, Scopus and Cochrane Database of Systematic Reviews from 1/1/2000 to 15/10/2020. We used Scopus meta-data and two authors recorded supplementary information independently. We summarized the data using frequencies with percentages.

RESULTS: A total of 1558 studies were considered eligible for analysis. We found that the publications have been increasing yearly and their nomenclature was not uniform (the most frequent label in the title was “overview of systematic reviews”). The largest number of papers and the most cited ones were published by corresponding authors from the UK. The publications were distributed across 737 scholarly journals and many of them were published in the field of complementary/alternative medicine, psychiatry/psychology, nutrition/dietetics, and pediatrics. The co-authorship analysis revealed collaborations among countries. The most common clinical conditions were depression, diabetes, cancer, dementia, pain, cardiovascular disease, stroke, obesity, and schizophrenia.

CONCLUSION: OoSRs have recently become a popular approach of evidence synthesis. International collaborations between overview authors from countries with increased research productivity and countries with less research activity should be encouraged.

PMID:33775811 | DOI:10.1016/j.jclinepi.2021.03.019

Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 25:110308. doi: 10.1016/j.pnpbp.2021.110308. Online ahead of print.

ABSTRACT

This study examined the changes in the mental health state of college students with and without mental disorder background, during successive time cuts of the Argentina’s lengthy mandatory quarantine, while adjusting for quarantine duration, sex, age, suicidal behavior history, loneliness, and region of residence. We used a longitudinal design (N = 1615, 26% with mental disorder history). Successive samplings were performed from three days before quarantine start and across quarantine phases of up to 103-days duration. Follow-up was one month later. Sex (woman) and age (younger) were significant predictors of worse mental health only in college students without mental disorder background. Having any suicidal behavior background significantly predicted worse mental health in college students both with and without mental disorder history. Loneliness and region of residence were not statistically significant. In the between-groups comparisons, college students having mental disorder background had worse mental health than those without such a background. However, in the within-subject comparisons, no statistically significant changes occurred across time in the mental health of college students having mental disorder history. Conversely, significant changes occurred in those without such a background, but only when the interaction between time and quarantine duration was considered. Worsening mental health occurred during the most heavily restrictive quarantine phases, while some of the remissions occurred during the longest, but less restrictive ones.

PMID:33775744 | DOI:10.1016/j.pnpbp.2021.110308

Radiother Oncol. 2021 Mar 25:S0167-8140(21)06160-0. doi: 10.1016/j.radonc.2021.03.023. Online ahead of print.

ABSTRACT

AIM: To assess radiation response using γH2AX assay in surgical specimens from glioblastoma (GB) patients and their corresponding primary gliosphere culture. To test the hypothesis that gliospheres (stem cell enriched) are more resistant than specimens (bulky cell dominated) but that the interpatient heterogeneity is similar.

MATERIAL AND METHODS: Ten pairs of specimens and corresponding gliospheres derived from patients with IDH-wildtype GB were studied. Specimens and gliospheres were irradiated with graded doses and after 24 h the number of residual γH2AX foci was counted.

RESULTS: Gliospheres showed a higher Nestin expression than specimens and exhibited two different phenotypes: free floating (n=7) and attached (n=3). Slope analysis revealed an interpatient heterogeneity with values between 0.15 and 1.30 residual γH2AX foci/ Gy. Free-floating spheres were more resistant than their parental specimens (median slope 0.13 foci/ Gy versus 0.53) as well as than the attached spheres (2.14). The slopes of free floating spheres did not correlate with their corresponding specimens while a trend for a positive correlation was found for the attached spheres and the respective specimens. Association with MGMT did not reach statistical significance.

CONCLUSION: Consistent with the clinical phenotype and our previous experiments, GB specimens show low radiation sensitivity. Stem-cell enriched free-floating gliospheres were more resistant than specimens supporting the concept of radioresistance in stem cell-like cells. The lack of correlation between specimens and their respective gliosphere cultures needs validation and may have a profound impact on future translational studies using γH2AX as a potential biomarker for personalized radiation therapy.

PMID:33775712 | DOI:10.1016/j.radonc.2021.03.023

Cancer Lett. 2021 Mar 25:S0304-3835(21)00133-6. doi: 10.1016/j.canlet.2021.03.022. Online ahead of print.

ABSTRACT

The development of a new generation of tyrosine kinase inhibitors (TKIs) has improved the treatment response in lung adenocarcinomas. However, acquired resistance often occurs due to new epidermal growth factor receptor (EGFR) mutations. In particular, the C797S mutation confers drug resistance to T790M-targeting EGFR TKIs. To address C797S resistance, a promising therapeutic avenue is combination therapy that targets both total EGFR and acquired mutations to increase drug efficacy. We showed that combining vorinostat, a histone deacetylase inhibitor (HDACi), with brigatinib, a TKI, enhanced antitumor effects in primary culture and cell lines of lung adenocarcinomas harboring EGFR L858R/T790 M/C797S mutations (EGFR-3M). While EGFR phosphorylation was decreased by brigatinib, vorinostat reduced total EGFR-3M (L858R/T790 M/C797S) proteins through STUB1-mediated ubiquitination and degradation. STUB1 preferably ubiquitinated other EGFR mutants and facilitated protein turnover compared to EGFR-WT. The association between EGFR and STUB1 required the functional chaperone-binding domain of STUB1 and was further enhanced by vorinostat. Finally, STUB1 levels modulated EGFR downstream functions. Low STUB1 expression was associated with significantly poorer overall survival than high STUB1 expression in patients harboring mutant EGFR. Vorinostat combined with brigatinib significantly improved EGFR-TKI sensitivity to EGFR C797S by inducing EGFR-dependent cell death and may be a promising therapy in treating C797S-resistant lung adenocarcinomas.

PMID:33775711 | DOI:10.1016/j.canlet.2021.03.022

J Infect. 2021 Mar 25:S0163-4453(21)00151-1. doi: 10.1016/j.jinf.2021.03.019. Online ahead of print.

ABSTRACT

BACKGROUND: Screening for SARS-CoV-2 antibodies is under way in some key worker groups; how this adds to self-reported COVID-19 illness is unclear. In this study, we investigate the association between self-reported belief of COVID-19 illness and seropositivity.

METHODS: Cross-sectional study of three key worker streams comprising (A) Police and Fire & Rescue (2 sites) (B) healthcare workers (1 site) and (C) healthcare workers with previously positive PCR result (5 sites). We collected self-reported signs and symptoms of COVID-19 and compared this with serology results from two SARS-CoV-2 immunoassays (Roche Elecsys® and EUROIMMUN).

RESULTS: Between 01 and 26 June, we recruited 2847 individuals (Stream A: 1,247, Stream B: 1,546 and Stream C: 154). Among those without previous positive PCR tests, 687/2,579 (26%) reported belief they had had COVID-19, having experienced compatible symptoms; however, only 208 (30.3%) of these were seropositive on both immunoassays. Both immunoassays had high sensitivities relative to previous PCR positivity (>93%); there was also limited decline in antibody titres up to 110 days post symptom onset. Symptomatic but seronegative individuals had differing symptom profiles and shorter illnesses than seropositive individuals.

CONCLUSION: Non-COVID19 respiratory illness may have been mistaken for COVID-19 during the outbreak; laboratory testing is more specific than self-reported key worker beliefs in ascertaining past COVID-19 disease.

PMID:33775704 | DOI:10.1016/j.jinf.2021.03.019

Clin Chim Acta. 2021 Mar 25:S0009-8981(21)00097-8. doi: 10.1016/j.cca.2021.03.014. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The present study aims to correlate the severity of post-stroke depression (PSD) and serum ceramide concentration.

MATERIALS AND METHODS: In this two-center case-control study, we prospectively collected clinical and demographical information from age and gender-matched 51 PSD patients, 56 non-post-stroke depression (Non-PSD) patients, and 39 patients with major depression (MD) to perform the suitable biochemical analysis to bring a correlation in causing depression in patients soon after the stroke. The ROC curve method was used to evaluate ceramide’s diagnostic efficacy in all three groups of patients. A follow-up analysis was also conducted based on PSD severity to associate serum ceramide levels and neuropsychiatric symptoms. The severity of the patient’s depressive symptoms was assessed by using the self-rating depression scale (SDS).

RESULTS: In comparison between PSD and MD patients, three serum ceramide species were found to be significantly different. Compared with Non-PSD patients, PSD patients had significantly higher levels of all the four serum ceramides, and increasing levels ofC16:0, C18:0(VS MD) and C16: 0(VS Non-PSD) serve as a diagnostic tool and an independent risk factor in all three categories of patients. Moreover, the follow-up analysis results showed that, as the treatment progressed, the differences in the 3 serum ceramide species were statistically significant.

CONCLUSION: There was a stage-specific association between serum ceramides and PSD, and the potential pathophysiological mechanism has to be investigated in future research.

PMID:33775701 | DOI:10.1016/j.cca.2021.03.014

Am J Obstet Gynecol. 2021 Mar 24:S0002-9378(21)00187-3. doi: 10.1016/j.ajog.2021.03.023. Online ahead of print.

ABSTRACT

BACKGROUND: Pregnant and lactating women were excluded from initial COVID-19 vaccine trials; thus, data to guide vaccine decision-making are lacking.

OBJECTIVES: To evaluate the immunogenicity and reactogenicity of COVID-19 mRNA vaccination in pregnant and lactating women compared to: (1) non-pregnant controls and (2) natural COVID-19 infection in pregnancy.

STUDY DESIGN: 131 reproductive-age vaccine recipients (84 pregnant, 31 lactating, and 16 non-pregnant) were enrolled in a prospective cohort study at two academic medical centers. Titers of SARS-CoV-2 Spike and RBD IgG, IgA and IgM were quantified in participant sera (N=131) and breastmilk (N=31) at baseline, second vaccine dose, 2-6 weeks post second vaccine, and at delivery by Luminex. Umbilical cord sera (N=10) titers were assessed at delivery. Titers were compared to those of pregnant women 4-12 weeks from natural infection (N=37) by ELISA. A pseudovirus neutralization assay was used to quantify neutralizing antibody titers for the subset of women who delivered during the study period. Post-vaccination symptoms were assessed via questionnaire. Kruskal-Wallis tests and a mixed effects model, with correction for multiple comparisons, were used to assess differences between groups.

RESULTS: Vaccine-induced antibody titers were equivalent in pregnant and lactating compared to non-pregnant women (median [IQR] 5.59 [4.68-5.89] pregnant, 5.74 [5.06-6.22] lactating, 5.62 [4.77-5.98] non-pregnant, p = 0.24). All titers were significantly higher than those induced by SARS-CoV-2 infection during pregnancy (p < 0.0001). Vaccine-generated antibodies were present in all umbilical cord blood and breastmilk samples. Neutralizing antibody titers were lower in umbilical cord compared to maternal sera, although this finding did not achieve statistical significance (median [IQR] 104.7 [61.2-188.2] maternal sera, 52.3 [11.7-69.6] cord sera, p=0.05). The second vaccine dose (boost dose) increased SARS-CoV-2-specific IgG, but not IgA, in maternal blood and breastmilk. No differences were noted in reactogenicity across the groups.

CONCLUSIONS: COVID-19 mRNA vaccines generated robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in non-pregnant women. Vaccine-induced immune responses were significantly greater than the response to natural infection. Immune transfer to neonates occurred via placenta and breastmilk.

PMID:33775692 | DOI:10.1016/j.ajog.2021.03.023

J Ayub Med Coll Abbottabad. 2021 Jan-Mar;33(1):82-88.

ABSTRACT

BACKGROUND: Feedback is an essential component of the clinical skills development of dental students. The clinical training is a complex integration of knowledge, psychomotor skills, behaviour and clinical communication skills under stress for both instructor and student. This study aimed to investigate the perceptions of undergraduate dental students and their instructors on the quality of clinical feedback.

METHODS: The current cross-sectional observational study was conducted at the Department of Operative Dentistry and Endodontics, Riphah International University, Islamabad from August to December 2019. A self-administered questionnaire was used to collect responses from final year undergraduate dental students and faculty. The questionnaire comprised of 13 items, subdivided into six categories, targeting the various aspects of clinical feedback. SPSS 23 was utilized to analyse the data. Descriptive statistics were tabulated and data was analysed using the Mann-Whitney test (p<0.05) for differences between the two cohorts.

RESULTS: The mean age of the 64 students who responded was 24±0.8 years. Students’ male to female ratio was 1:1.56, while for the 18 instructors the ratio was 1:1. Good agreement between the students and instructors was shown for items related to personal dignity and empathy. Moderate agreement was found for items covering the domains of time, understanding, comfort level, professionalism, and self-assessment. The disagreement was observed for the items associated with conflicting feedback, conflict satisfaction, and effective communication.

CONCLUSIONS: Incongruousness existed between the dental students and instructors, about the quality of clinical feedback provided to the dental students. Communication between the instructors and learners must be promoted to increase the level of understanding of the feedback given by the clinical instructors.

PMID:33774960

J Ayub Med Coll Abbottabad. 2021 Jan-Mar;33(1):54-59.

ABSTRACT

BACKGROUND: Recently the Coronavirus pandemic presented with different manifestations in different parts of the world, both on clinical examinations and on imaging. CT Scanning (CT Scan) chest is used for detailed evaluation of the different characteristic patterns determining the depth of disease. The study is aimed to assess the variations in spectrum of Covid-19 CT findings and relating severity (CT Severity Score) with the Clinical Symptoms in Bahawal Victoria Hospital, Bahawalpur.

METHODS: In this cross-sectional study, patients referred to radiology department from outdoor for COVID screening were included from 1st May to 30th June 2020. Mean age range of patients was calculated, while presenting complaints and co-morbidities were tabulated in frequencies and percentages after analysis. Severity of symptoms and CT findings were correlated with biochemical and haematological tests.

RESULTS: Patients’ age range from 25 to 85 years with 62% males and 38% females. Statistically no significant difference was observed in CTSS on gender basis. As sensitivity of RT PCR is about 70%, negative cases cannot be considered disease free and this is seen in this study as CT findings suggestive of COVID are seen in these patients. Using 40-point CT-SS, 11 patients had a score of >19 with severe diseases, while 14 patients had common disease with a score range of 11-18 and 35 patients had <10 score with mild or no symptoms.

CONCLUSIONS: In this study, a spectrum of patchy ground glass opacities, bilateral peripheral predominantly lower lung consolidations were observed. Quantitative analysis of inflammatory process as occurring in lungs in Coronavirus Disease 2019, using 40-point CTSS scoring on Imaging could provide a timely and objective approach towards identifying patients requiring intensive care and hospitalisation.

PMID:33774955

J Ayub Med Coll Abbottabad. 2021 Jan-Mar;33(1):49-53.

ABSTRACT

BACKGROUND: Combination of DAAs, Sofosbuvir and Ribavirin has been known as an effective treatment for HCV genotype 3. The aim of our study is to assess the efficacy of Sofosbuvir and Ribavirin in relapsed HCV genotype 3 patients.

METHODS: A cross-sectional retrospective analysis of hospital records between January 2015 and December 2016. Data was taken of only those patients who were followed for one year. A total of 193 cases were included in this study who were HCV genotype 3 relapsers and out of these 28 patients failed to be followed. Data was entered and analysed in IBM SPSS software package 23.

RESULTS: Out of the total 193 cases, 74.1% of cases achieved RVR at 4 weeks of therapy. ETR was achieved by 91.2% cases, while 8.8% of cases were non-responders. There was statistical significance in gender achieving ETR with a p-value of .008. 84.5% of cases achieved SVR-12. Statistical significance was noted between haemoglobin levels at presentation and 4 weeks follow-up with a p-value <0.005, and also between 4 weeks and 12 weeks follow-up with a p-value <0.005. Statistical significance was also found between age and PCR at 4 weeks (p-value of .002), age and PCR at 24 weeks (p-value of .051) and between ALT levels and PCR at 4, 12 and 24 weeks follow up (p-value <0.005). At 1-year follow-up, 79.3% of cases achieved a negative PCR, 28 patients failed to be followed, 6.2% of cases had a positive PCR. 5.5% of cases of the total 163 SVR cases had a relapse at 1 year.

CONCLUSIONS: HCV genotype 3 patients can benefit from Sofosbuvir and Ribavirin. With the SVR of more than 80%, this combination is cost-effective and safe. Treatment duration should be dependent on RVR and viral load at 4 weeks follow-up.

PMID:33774954