Low-intensity repetitive transcranial magnetic stimulation is safe and well tolerated by people living with MS - outcomes of the phase I randomised controlled trial (TAURUS).

Background: Low-intensity repetitive transcranial magnetic stimulation (rTMS), delivered as a daily intermittent theta burst stimulation (iTBS) for four consecutive weeks, increased the number of new oligodendrocytes in the adult mouse brain. Therefore, rTMS holds potential as a remyelinating intervention for people with multiple sclerosis (MS). Objective: Primarily to determine the safety and tolerability of our rTMS protocol in people with MS. Secondary objectives include feasibility, blinding and an exploration of changes in magnetic resonance imaging (MRI) metrics, patient-reported outcome measures (PROMs) and cognitive or motor performance. Methods: A randomised (2:1), placebo controlled, single blind, parallel group, phase 1 trial of 20 rTMS sessions (600 iTBS pulses per hemisphere; 25% maximum stimulator output), delivered over 4-5 weeks. Twenty participants were randomly assigned to 'sham' (n = 7) or active rTMS (n = 13), with the coil positioned at 90° or 0°, respectively. Results: Five adverse events (AEs) including one serious AE reported. None were related to treatment. Protocol compliance was high (85%) and blinding successful. Within participant MRI metrics, PROMs and cognitive or motor performance were unchanged over time. Conclusion: Twenty sessions of rTMS is safe and well tolerated in a small group of people with MS. The study protocol and procedures are feasible. Improvement of sham is warranted before further investigating safety and efficacy.

Instruments measuring change in cognitive function in multiple sclerosis: A systematic review.

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating/neurodegenerative disease associated with change in cognitive function (CF) over time. This systematic review aims to describe the instruments used to measure change in CF over time in people with MS (PwMS). METHODS: PubMed, OVID, Web of Science, and Scopus databases were searched in English until May 2021. Articles were included if they had at least 100 participants and at least a 1-year interval between baseline and last follow-up measurement of CF. Results were quantitatively synthesized, presented in tables and risk of bias was assessed with the Newcastle-Ottawa Scale. RESULTS: Fifty-seven articles met the inclusion criteria (41,623 PwMS and 1105 controls). An intervention (drug/rehabilitation) was assessed in 22 articles. In the studies that used a test battery, Visual and verbal learning and memory were the most frequently measured domains, but when studies that used test battery or a single test are combined, Information processing speed was the most measured. The Symbol Digit Modalities Test (SDMT) was the most frequently used test as a single test and in a test battery combined. Most studied assessed "change in CF" as cognitive decline defined as 1 or more tests measured as ≥ 1.5 SD from the study control or normative mean in a test battery at baseline and follow-up. Meta-analysis of change in SDMT scores with seven articles indicated a nonstatistically significant -0.03 (95% CI -0.14, 0.09) decrease in mean SDMT score per year. CONCLUSION: This study highlights the slow rate of measured change in cognition in PwMS and emphasizes the lack of a gold standard test and consistency in measuring cognitive change at the population level. More sensitive testing utilizing multiple domains and longer follow-up may define subgroups where CF change follows different trajectories thus allowing targeted interventions to directly support those where CF is at greatest risk of becoming a clinically meaningful issue.

Psychological impacts of COVID-19 pandemic on individuals living with multiple sclerosis: A rapid systematic review.

INTRODUCTION: The global spread of COVID-19 has raised concerns about its possible impact on mental health. People living with multiple sclerosis (PwMS) are considered potentially vulnerable to the mental health effects of the pandemic, as they may be subject to increased social isolation. AIM: To systematically review the current evidence on the impact of the COVID-19 pandemic on mental health outcomes among PwMS. METHOD: We searched four major databases (Medline, EMBASE, PsychInfo and Scopus) and the WHO Global Health COVID-19 research database. We included peer-reviewed primary research studies using validated health-related quality of life (HRQOL) and psychometric screening tools to evaluate mental health outcomes among PwMS during the COVID-19 pandemic. Studies reporting data on the prevalence of mental health disorders, severity of psychological symptoms and contributing demographic and clinical factors for PwMS during the COVID-19 pandemic were included. RESULTS: Our initial search yielded 268 records; 19 studies (13 cross-sectional, 6 longitudinal) were included. Most were conducted during a peak in the pandemic in the host country via an online platform. The main mental health outcomes were depression, anxiety, stress, sleep quality and HRQOL. The included studies used a variety of outcome assessment tools and study designs. The prevalence of mental health issues such as depression, anxiety and stress were high among PwMS during the pandemic. In addition, compared to control populations, PwMS experienced more severe symptoms of depression and stress during the COVID-19 outbreak. However, results from longitudinal studies demonstrate that the severity of mental health symptoms among PwMS during the pandemic were not significantly different compared with the pre-pandemic period. CONCLUSION: Although mental health issues such as anxiety and depression were common among PwMS during the pandemic, current evidence suggests that mental health among PwMS has not been significantly affected by pandemic-related restrictive measures. Instead, the observed differences may be the result of pre-pandemic differences in prevalence and severity. Where possible, future studies should seek to address the methodological issues identified in the included studies to ensure that data collected during the pandemic can be synthesized into recommendations for policy and practice.

Reliability and Validity of a Life Course Passive Smoke Exposure Questionnaire in an Australian Cohort From Childhood to Adulthood.

OBJECTIVES: Life course exposure to passive smoke may predict health, but there are few validated measures. We tested the reliability and validity of a retrospective life course passive smoking questionnaire. METHODS: Participants from the third follow-up of the Childhood Determinants of Adult Health study (2014-2019, ages 36-49 years) retrospectively reported mother/father/other household member smoking when living at home during childhood, including duration (years) and smoking location (never/sometimes/always inside house). The severity of exposure index (SEI; sum of mother/father/other years smoked multiplied by smoking location), cumulative years of exposure (CYE; sum of mother/father/other years), and total household smokers (THS) were derived. The reliability of retrospective passive smoking reports was examined with intraclass correlation coefficients (ICCs) using household smoking reported 34 years earlier in 1985 by participants when aged 7-15 years. Construct validity was examined by correlating retrospective passive smoking with participants' smoking in adulthood and lung function in childhood and adulthood. RESULTS: Among 2082 participants (mean±standard deviation [SD], 45.0±2.5 years; 55.2% females), THS ranged from 0 to 5 (mean± SD, 0.9±1.0), CYE ranged from 0 to 106 (mean±SD, 10.5±13.9), and SEI ranged from 0 to 318 (mean±SD, 24.4±36.0). Retrospective measures showed moderate agreement with total household smokers reported in childhood (ICC, 0.58 to 0.62). The retrospective measures were weakly but significantly (p<0.05) correlated with participants' smoking (r=0.13 to 0.15) and lung function (r= -0.05 to -0.06). CONCLUSIONS: The retrospective passive smoking questionnaire showed reasonable reliability and validity. This measure may be useful for epidemiological studies.

Maternal smoking during pregnancy: Trends and determinants in the conception to community study.

BACKGROUND: Despite earlier declines, maternal smoking during pregnancy continues to be a public health problem. We examined trends and factors associated with maternal smoking during and between pregnancy over six years. METHODS: Participants were 27 532 pregnant women in Tasmanian public hospitals whose smoking status was gathered by midwives during perinatal care between July 2008 and June 2014. Generalized linear modeling was used to examine the trends in prevalence of maternal smoking over time and factors associated with change in smoking status both within and between pregnancies. RESULTS: Smoking during pregnancy decreased from 25.9% in 2008 to 16.4% in 2014 (57.9% decline). Multivariable regression analysis suggested that maternal alcohol consumption during pregnancy, living in a highly socioeconomically disadvantaged area, and being an Aboriginal or Torres Strait Islander significantly increased the risk of maternal smoking during pregnancy. Being older, married, or in a de facto relationship, and intending to breastfeed were associated with reduced risk of smoking during pregnancy. Between index (first birth recorded in data set) and last pregnancy, 35.1% of smokers quit, but 5.1% of nonsmokers started smoking. Only 8.1% of mothers who smoked during the first half of pregnancy quit by the second half. CONCLUSIONS: Maternal smoking during pregnancy is decreasing. To sustain the decline, preventive efforts must address the role of social determinants of health (eg, mothers who drink alcohol, live in highly disadvantaged areas, are younger and single) among women who smoke during pregnancy.

Maternal Smoking in Pregnancy and Child's Hospital Use up to 5 Years of Age in a Data Linkage Birth Cohort.

OBJECTIVES: To examine if exposure to maternal smoking during pregnancy is associated with emergency department (ED) presentation and admission through the ED in children up to 5 years after birth. METHODS: Antenatal records of all children up to 5 years of age who were born in Tasmania, Australia, between July 2008 and June 2014 were linked to health service use (ED presentations and hospital admissions). Negative binomial regression was used to estimate the incidence rate ratio (IRR) and 95% confidence intervals (CIs) at ≤1 year and ≤5 years for ED presentations and admissions to the hospital through the ED for any reason and by 9 major disease categories for children exposed versus children not exposed to maternal smoking during pregnancy. Models were adjusted for sex, socioeconomic position, maternal age at birth, and region of residence. Presentations and admissions for poisoning and injuries were used as a negative control. RESULTS: Among 36 630 infants, 21% were exposed to maternal smoking during pregnancy. Exposed children had a 26% higher rate of presentation to the ED (IRRadjusted 1.26; 95% CI 1.23-1.29) and a 45% higher rate of admission (IRRadjusted 1.45; 95% CI 1.39-1.51) at up to 5 years of age. Compared with the negative control, higher presentation and admission rates were evident in respiratory; eyes, ears, nose, and throat; psychosocial; and infectious disease categories. CONCLUSIONS: Higher health care service use was observed in children exposed to maternal smoking during pregnancy for a range of conditions associated with exposure to smoking. The findings reinforce the need to reduce smoking among people in their childbearing years.

The reach and limits of the US President's Emergency Plan for Aids Relief (PEPFAR) funding of Prevention of Mother-to-Child Transmission (PMTCT) of HIV in Nigeria.

WHO advocates the use of comprehensive 4-pronged strategy for PMTCT of HIV. It includes HIV prevention, preventing unintended pregnancies in HIV positive women and follows up treatment and support as well as therapeutic interventions around delivery. This study examines PEPFAR's funding of Nigerian PMTCT, via an analysis of the funded activities of 396 agencies PEPFAR funds to do PMTCT. PEPFAR Sub-partners selected for this study were included because they were funded to do therapeutic intervention around delivery, but significant gaps were identified regarding the other 3 prongs advocated by WHO. Up to 70% were not funded to do any primary prevention. PEPFAR's own reporting does not allow assessment of Sub-partner involvement in preventing unintended pregnancies. Regarding follow up treatment and care, some Sub-partners were not funded at all. PEPFAR is not supporting a comprehensive approach to PMTCT in the way it funds PMTCT in Nigeria.