Nevin Manimala

Neurosciences (Riyadh). 2021 Oct;26(4):331-338. doi: 10.17712/nsj.2021.4.20210063.

ABSTRACT

OBJECTIVES: To perform screening of dysphagia in Montenegrin multiple sclerosis (MS) patients. Dysphagia is often neglected problem in patients with MS.

METHODS: We included 104 patients with relapsing-remitting MS who completed 3 questionnaires: dysphagia in multiple sclerosis (DYMUS), eating assessment tool-10 (EAT-10) and swallowing disturbance questionnaire (SDQ). Our study was performed in the clinic for neurology of the Clinical Center of Montenegro (Podgorica, Montenegro) and Polyclinic Neuron (Bijelo Polje, Montenegro) between November 2020 and December 2020.

RESULTS: Self-reported prevalence of this symptom in our group was simmilar to previously reported results. We did not find correlation between DYMUS and expanded disability status scale (EDSS), as it was reported before. Time spent from disease onset to diagnosis is strongly correlated with reported SDQ results. The population of dysphagia-patients is statistically significantly older compared to the non-dysphagia patients, and statistically higher mean values in this population of our subjects were proven on all 3 questionnaires used.

CONCLUSION: The importance of this issue is not just because it warns of potientially malnutrion in MS patients, but also important factor in therapy choosing algorithm in the era of orally used immunomodulatory drugs.

PMID:34663705 | DOI:10.17712/nsj.2021.4.20210063

Pharmacol Rev. 2021 Oct;73(4):1-32. doi: 10.1124/pharmrev.121.000317.

ABSTRACT

Brain cancer is a formidable challenge for drug development, and drugs derived from many cutting-edge technologies are being tested in clinical trials. We manually characterized 981 clinical trials on brain tumors that were registered in ClinicalTrials.gov from 2010 to 2020. We identified 582 unique therapeutic entities targeting 581 unique drug targets and 557 unique treatment combinations involving drugs. We performed the classification of both the drugs and drug targets based on pharmacological and structural classifications. Our analysis demonstrates a large diversity of agents and targets. Currently, we identified 32 different pharmacological directions for therapies that are based on 42 structural classes of agents. Our analysis shows that kinase inhibitors, chemotherapeutic agents, and cancer vaccines are the three most common classes of agents identified in trials. Agents in clinical trials demonstrated uneven distribution in combination approaches; chemotherapy agents, proteasome inhibitors, and immune modulators frequently appeared in combinations, whereas kinase inhibitors, modified immune effector cells did not as was shown by combination networks and descriptive statistics. This analysis provides an extensive overview of the drug discovery field in brain cancer, shifts that have been happening in recent years, and challenges that are likely to come. SIGNIFICANCE STATEMENT: This review provides comprehensive quantitative analysis and discussion of the brain cancer drug discovery field, including classification of drug, targets, and therapies.

PMID:34663683 | DOI:10.1124/pharmrev.121.000317

Neurol Neuroimmunol Neuroinflamm. 2021 Oct 18;8(6):e1089. doi: 10.1212/NXI.0000000000001089. Print 2021 Nov.

ABSTRACT

BACKGROUND AND OBJECTIVES: Neuromyelitis optica (NMO) is a CNS inflammatory disease that predominantly affects the optic nerves and the spinal cord. It is more frequent in Asian and African populations than in European ones. Data on epidemiology, clinical presentation, additional investigations, and treatment in the African continent are scarce. We aim to (1) collect and analyze published data on neuromyelitis optica spectrum disorder (NMOSD), (2) indicate challenges in the diagnosis and management, and (3) discuss opportunities for future research, education, and policy making, specifically on the African continent.

METHODS: A systematic review was performed in January 2021 with the search terms “Neuromyelitis optica and Africa,” “Devic Disease and Africa,” and “NMOSD and Africa.” We included all study types except case reports, correspondence, or conference abstracts on NMO or NMOSD. Extracted data included study design, country, study period, demographic and clinical characteristics, results of paraclinical investigations, and outcome. Data analysis was performed with descriptive statistics.

RESULTS: We retrieved a total of 79 records, of which 19 were included. Ten of 54 African countries reported a total of 410 cases. Almost half of them were from North African countries. The mean age at diagnosis was 33 years (range 7-88 years), and 75% were female. Transverse myelitis followed by optic neuritis were the most frequent symptoms at the time of presentation. One hundred nineteen patients experienced at least 1 previous relapse, and 106 had a relapsing course after diagnosis. Relapses were treated with IV methylprednisolone. Azathioprine and steroids were used most often as maintenance treatments. Outcomes were rarely described.

DISCUSSION: The majority of studies on NMOSD from the African continent are retrospective, and most countries do not report any data. Our systemic review shows that data derived from patients living in Africa correspond well to what has been previously published in meta-analyses on patients of African ancestry with NMOSD who live outside of Africa, except for a younger age at onset and a lower proportion of females. We advocate for systematic data collection to adequately capture and monitor the burden of NMOSD, for expansion of research efforts and facilities to perform fundamental and clinical research, and for improved access to health care including diagnostics, treatments, and rehabilitation services for people affected by NMOSD in the African continent.

PMID:34663674 | DOI:10.1212/NXI.0000000000001089

BMJ Open. 2021 Oct 18;11(10):e049595. doi: 10.1136/bmjopen-2021-049595.

ABSTRACT

INTRODUCTION: Most individuals newly diagnosed with type 1 diabetes (T1D) have 10%-20% of beta-cell function remaining at the time of diagnosis. Preservation of residual beta-cell function at diagnosis may improve glycaemic control and reduce longer-term complications.Immunotherapy has the potential to preserve endogenous beta-cell function and thereby improve metabolic control even in poorly compliant individuals. We propose to test ustekinumab (STELARA), a targeted and well-tolerated therapy that may halt T-cell and cytokine-mediated destruction of beta-cells in the pancreas at the time of diagnosis.

METHODS AND ANALYSIS: This is a double-blind phase II study to assess the safety and efficacy of ustekinumab in 72 children and adolescents aged 12-18 with new-onset T1D.Participants should have evidence of residual functioning beta-cells (serum C-peptide level >0.2nmol/L in the mixed-meal tolerance test (MMTT) and be positive for at least one islet autoantibody (GAD, IA-2, ZnT8) to be eligible.Participants will be given ustekinumab/placebo subcutaneously at weeks 0, 4 and 12, 20, 28, 36 and 44 in a dose depending on the body weight and will be followed for 12 months after dose 1.MMTTs will be used to measure the efficacy of ustekinumab for preserving C-peptide area under the curve at week 52 compared with placebo. Secondary objectives include further investigations into the efficacy and safety of ustekinumab, patient and parent questionnaires, alternative methods for measuring insulin production and exploratory mechanistic work.

ETHICS AND DISSEMINATION: This trial received research ethics approval from the Wales Research Ethics Committee 3 in September 2018 and began recruiting in December 2018.The results will be disseminated using highly accessed, peer-reviewed medical journals and presented at conferences.

TRIAL REGISTRATION NUMBER: ISRCTN14274380.

PMID:34663658 | DOI:10.1136/bmjopen-2021-049595

BMJ Open. 2021 Oct 18;11(10):e048299. doi: 10.1136/bmjopen-2020-048299.

ABSTRACT

INTRODUCTION: Older adults (age ≥65 years) are pursuing increasingly complex, elective surgeries; and, are at higher risk for intraoperative and postoperative complications. Patients and their caregivers frequently struggle with the postoperative recovery process at home, which may contribute to complications. We aim to identify opportunities to intervene during the preoperative period to improve postoperative outcomes by understanding the preparatory behaviours of older adults and their caregivers before a complex, elective surgery.

METHODS AND ANALYSIS: As a result of the COVID-19 pandemic, we will conduct this study via telephone and videoconferencing. Using a multiphase mixed-methods research design, we will collect data on 10-15 patient-caregiver dyads from a pool of older adults (across a spectrum of cognitive abilities) scheduled for an elective colorectal surgery between 1 July 2020 and 30 May 2021. We will collect quantitative and qualitative data before (T1, T2) and after (T3, T4) surgery. Preoperatively, participants will each complete a cognitive assessment and a semi-structured qualitative interview that focuses on their preparatory behaviours (T1). They will then answer questionnaires about mood, self-efficacy and home environment (T2). Three weeks following hospital discharge, participants will complete another qualitative interview focusing on a comparison of preoperative and postoperative preparedness (T3). Researchers will also collect information about the patient’s medical conditions, the postoperative complications and healthcare utilisation from the patient’s chart 30 days following discharge (T4). We will code and conduct thematic analysis of the qualitative data to identify salient themes. Quantitative data will be analysed using basic descriptive statistics to characterise the participants. We will integrate the qualitative and quantitative findings using results from the quantitative scales to group participants and with use of joint display analysis.

ETHICS AND DISSEMINATION: Ethics approval was obtained from the University of Michigan IRB. Study findings will be disseminated through peer-reviewed journals and presentations at conferences.

PMID:34663655 | DOI:10.1136/bmjopen-2020-048299

BMJ Open. 2021 Oct 18;11(10):e046618. doi: 10.1136/bmjopen-2020-046618.

ABSTRACT

OBJECTIVE: We evaluated the temporal trend in gender ratios of first and last authors in the field of oncological research published in major general medical and oncology journals and examined the gender pattern in coauthorship.

DESIGN: We conducted a retrospective study in PubMed using the R package RISmed. We retrieved original research articles published in four general medical journals and six oncology specialty journals. These journals were selected based on their impact factors and popularity among oncologists. We identified the names of first and last authors from 1 January 2002 to 31 December 2019. The gender of the authors was identified and validated using the Gender API database (https://gender-api.com/).

PRIMARY AND SECONDARY OUTCOME MEASURES: The percentages of first and last authors by gender and the gender ratios (male to female) and temporal trends in gender ratios of first and last authors were determined.

RESULTS: We identified 34 624 research articles, in which 32 452 had the gender of both first and last authors identified. Among these 11 650 (33.6%) had women as the first author and 7908 (22.8%) as the last author, respectively. The proportion of female first and last authors increased from 26.6% and 16.2% in 2002, to 32.9% and 27.5% in 2019, respectively. However, the gender ratio (male to female) of first and last authors decreased by 1.5% and 2.6% per year, respectively, which were statistically significant (first author: incidence rate ratio (IRR) 0.98, 95% CI 0.97 to 1.00; last author: IRR 0.97, 95% CI 0.96 to 0.99). Male first and last authorship was the most common combination. Male-female and female-female pairs increased by 2.0% and 5.0%, respectively (IRR 1.02, 95% CI 1.01 to 1.03 and IRR 1.05, 95% CI 1.04 to 1.06, respectively).

CONCLUSIONS: The continued under-representation of women means that more efforts to address parity for advancement of women in academic oncology are needed.

PMID:34663651 | DOI:10.1136/bmjopen-2020-046618

J Neurol Neurosurg Psychiatry. 2021 Oct 18:jnnp-2021-326602. doi: 10.1136/jnnp-2021-326602. Online ahead of print.

ABSTRACT

OBJECTIVE: This study investigated the longitudinal course of depressive symptom severity over 19 years in former American football players and the influence of concussion history, contact sport participation and physical function on observed trajectories.

METHODS: Former American football players completed a general health questionnaire involving demographic information, medical/psychiatric history, concussion/football history and validated measures of depression and physical function at three time points (2001, 2010 and 2019). Parallel process latent growth curve modelling tested associations between concussion history, years of football participation, and overall and change in physical function on the overall level and trajectory of depressive symptoms.

RESULTS: Among the 333 participants (mean(SD) age, 48.95 (9.37) at enrolment), there was a statistically significant, but small increase in depressive symptom severity from 2001 (48.34 (7.75)) to 2019 (49.77 (9.52)), slope=0.079 (SE=0.11), p=0.007. Those with greater concussion history endorsed greater overall depressive symptom severity, B=1.38 (SE=0.33), p<0.001. Concussion history, B<0.001 (SE=0.02), p=0.997 and years of participation, B<0.001 (SE=0.01), p=0.980, were not associated with rate of change (slope factor) over 19 years. Greater decline in physical function, B=-0.71 (SE=0.16), p<0.001, was predictive of a faster growth rate (ie, steeper increase) of depression symptom endorsement over time.

CONCLUSIONS: Concussion history, not years of participation, was associated with greater depressive symptom severity. Neither factor was predictive of changes over a 19-year period. Decline in physical function was a significant predictor of a steeper trajectory of increased depressive symptoms, independent of concussion effects. This represents one viable target for preventative intervention to mitigate long-term neuropsychiatric difficulties associated with concussion across subsequent decades of life.

PMID:34663623 | DOI:10.1136/jnnp-2021-326602

Cancer Epidemiol Biomarkers Prev. 2021 Oct 18:cebp.0809.2021. doi: 10.1158/1055-9965.EPI-21-0809. Online ahead of print.

ABSTRACT

BACKGROUND: Prolonged sitting and physical inactivity are associated with higher circulating levels of estrogens. It is unknown whether these risk factors are associated with circulating androgens/androgen metabolites, another set of hormones implicated in the etiology of cancers in postmenopausal women.

METHODS: We conducted a cross-sectional analysis of 1,782 postmenopausal women in the Women’s Health Initiative Observational Study. Serum concentrations of 12 androgens/androgen metabolites were quantified using liquid chromatography-tandem mass spectrometry. Physical activity and sitting time were self-reported at baseline. We performed linear regression to estimate geometric means(GMs) of androgen/androgen metabolite concentrations(pmol/L) according to physical activity and sitting time, adjusting for potential confounders and stratified by menopausal hormone therapy(MHT) use.

RESULTS: Physical activity (>15 vs. 0 MET-hour/week) was inversely associated with estrogen-to-androgen ratios among never/former MHT users (adj-GM=37.5 vs. 49.6 unconjugated estrone:androstenedione; 20.2 vs. 30.3 unconjugated estradiol:testosterone; all p-trend<0.03) but was not associated among current MHT users. Prolonged sitting(>10 vs. <5 hours/day) was positively associated with these ratios among both never/former (adj-GM=44.2 vs. 38.3, p-trend=0.10; adj-GM=23.4 vs. 20.2, p-trend=0.17; respectively) and current MHT users (adj-GM=197 vs. 147; 105 vs. 75.5; respectively; all p-trend<0.02) but the associations were statistically significant among current MHT users only. The associations persisted after adjustment for BMI. After adjustment for adrenal androgens, physical activity and sitting were not associated with androgen metabolites.

CONCLUSIONS: Physical activity and sitting were associated with serum estrogen-to-androgen ratios but not androgen metabolites.

IMPACT: This study contributes to our understanding of the link between physical activity, sitting, and cancer risk in postmenopausal women.

PMID:34663616 | DOI:10.1158/1055-9965.EPI-21-0809

Cancer Epidemiol Biomarkers Prev. 2021 Oct 18:cebp.0625.2021. doi: 10.1158/1055-9965.EPI-21-0625. Online ahead of print.

ABSTRACT

BACKGROUND: Human papillomavirus (HPV) vaccine effectiveness (VE) evaluations provide important information for vaccination programs. We established a linkage between statewide central registries in Michigan to estimate HPV VE against in situ and invasive cervical lesions (CIN3+).

METHODS: We linked females in Michigan’s immunization and cancer registries using birth records to establish a cohort of 773,193 women with known vaccination history, of whom 3,838 were diagnosed with CIN3+. Residential address histories from a stratified random sample were used to establish a subcohort of 1,374 women without CIN3+ and 2,900 with CIN3+ among continuous Michigan residents. VE and 95% confidence intervals (CI) were estimated using cohort and case-cohort methods for up-to-date (UTD) vaccination and incomplete vaccination with 1 and 2 doses, and stratified by age at vaccination.

RESULTS: Both analytic approaches demonstrated lower CIN3+ risk with UTD and non-UTD vaccination vs. no vaccination. The cohort analysis yielded VE estimates of 66% (95% CI 60-71%) for UTD, 33% (95% CI 18-46%) for 2 doses-not UTD, and 40% (95% CI 27-50%) for 1 dose. The case-cohort analysis yielded VE estimates of 72% (95% CI 64-79%) for UTD, 39% (95% CI 10-58%) for 2 doses-not UTD, and 48% (95% CI 25-63%) for 1 dose. VE was higher for vaccination at age <20 than {greater than or equal to}20 years.

CONCLUSIONS: The statewide registry linkage found significant VE against CIN3+ with incomplete HPV vaccination, and an even higher VE with UTD vaccination.

IMPACT: Future VE evaluations by number of doses for women vaccinated at younger ages may further clarify dose-related effectiveness.

PMID:34663615 | DOI:10.1158/1055-9965.EPI-21-0625

Ann Geriatr Med Res. 2021 Oct 19. doi: 10.4235/agmr.21.0085. Online ahead of print.

ABSTRACT

OBJECTIVE: To improve the rehabilitation team’s awareness of patient mobility and participation by improving communication between therapists and nurses and conducting patient education.

DESIGN: This study used a non-equivalent control group with a nonsynchronized design. To facilitate communication between therapists and nurses, we used a manual for mobility management to improve the sharing of information on the functional status of patients. We also implemented patient education to improve their awareness of mobility and participation. Finally, we conducted newly devised surveys related to patient functional status and awareness that were applied by therapists and nurses.

RESULTS: The nurses reported significantly lower functional levels of patients compared to those assessed by therapists. After the intervention, the kappa values representing the concordance between therapists and nurses improved to almost perfect agreement for transfer ability (κ=0.836), mobility (κ=0.664), and toileting (κ=1.000). We also observed a statistically significant increase in questionnaire scores with respect to nurses’ awareness (p < 0.05).

CONCLUSION: Improving communication among the rehabilitation team, including nurses through the use of a continuous education program, was effective in promoting the mobility and functional level of patients in the inpatient ward.

PMID:34662935 | DOI:10.4235/agmr.21.0085