Using Reddit as a recruitment strategy for addiction science research.

Reddit is a forum-based social media and message board platform that has been used in the social sciences as a recruitment source of human subject data. In addiction science, Reddit remains a viable but underutilized tool, compared to other websites (e.g., Amazon's Mechanical Turk, Prolific). The purpose of this commentary is to provide a rationale and recommendations for the successful use of Reddit for addiction science researchers interested in adding it as a recruitment tool. We provide an example of how Reddit can be used to target specific populations of interest, such as individuals struggling with depression or alcohol use disorder. Last, we discuss the limitations of Reddit as a research tool and some considerations for future research to help promote effective use of the platform.

CyBorD-DARA in Newly Diagnosed Transplant-Eligible Multiple Myeloma: Results from the 16-BCNI-001/CTRIAL-IE 16-02 Study Show High Rates of MRD Negativity at End of Treatment.

The phase 1b 16-BCNI-001/CTRIAL-IE 16-02 CyBorD-DARA trial investigated the combination of Daratumumab with cyclophosphamide, bortezomib and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM), followed by autologous stem cell transplantation and Daratumumab maintenance. CR/sCR rates were 50% after transplant and 62.5% at end of treatment. The overall percentage of patients achieving complete response or better was 77.8%. Progression-free survival rate at end of maintenance was 81.3% and estimated 2-year overall survival was 88.9%. 37.5% of patients demonstrated sustained MRD negativity to a level of 10-5 from transplant to analysis at EOT. In this phase 1b study, we have shown CyBorD-DARA to be an effective and well-tolerated immunomodulatory agent-free regiment in transplant-eligible NDMM.

Ambient air pollutant concentrations and asthma-related hospital admissions during COVID-19 transport restrictions.

OBJECTIVES: Exposure to air pollution is a known risk factor for asthma exacerbations and hospitalisations. This study aimed to identify if COVID-19 transport restrictions led to improvements in air quality in Dublin and if this had an impact on asthma-related hospital admissions. STUDY DESIGN: This was a population-based retrospective cohort study. METHODS: Daily concentration levels of particulate matter (PM2.5 and PM10) and nitrogen dioxide (NO2) were obtained from the Environmental Protection Agency (EPA). The Hospital In-Patient Enquiry (HIPE) system provided the daily number of asthma-related hospital admissions in Dublin. The figures for 2018-2019 were compared with the period of transport restrictions (from March 2020). RESULTS: During the period of transport restrictions, there was a significant decrease in mean daily concentrations in both PM2.5 (8.9 vs 7.8 µg/m3, P = 0.002) and NO2 (24.0 vs 16.7 µg/m3, P < 0.001). There was also a significant reduction in the mean number of daily asthma admissions (4.5 vs 2.8 admissions, P < 0.001). Only NO2 showed a statistically significant correlation with asthma admissions (r = 0.132, P < 0.001). CONCLUSION: Transport restrictions introduced to mitigate against COVID-19 led to lower pollutant levels and improved air quality. Previously described associations between pollutants and asthma would indicate that these improvements in air quality contributed to the reduction in asthma-related admissions. The complex nature of PM is the likely explanation for the lack of correlation between its concentration and asthma admissions, unlike NO2 whose primary source is vehicular emissions. Public Health needs to advocate for transport policies, which can improve air quality and hence improve human health.

Impact of COVID-19 Lockdown Restrictions: Ambient NO2 and Asthma Hospital Admissions.

Aim The World Health Organization (WHO) declared the COVID-19 pandemic a global health emergency. Many countries of the world, including Ireland, closed their borders and imposed nationwide lockdown. During this period, all major anthropogenic transport activities, which contribute to atmospheric pollution, were restricted. The current study examines the impact of the transport restrictions on ambient nitrogen dioxide (NO2) concentrations and hospital admissions for asthma across Ireland. Methods This is a retrospective population-based cohort study. National ambient air quality monitoring network data were analysed to investigation variations in NO2 concentrations. Asthma hospital admissions data were collected from the HSE Hospital In-patient Enquiry (HIPE) for Cork, Dublin, and Meath. Results During the period of transport restrictions, there were reductions in the annual mean NO2 for Cork, Dublin and Meath (i.e. 12µg/m3 to 11µg/m3 (p = 1); 25µg/m3 to 17µg/m3 (p < 0.001); and 23µg/m3 to 21µg/m3 (p = 1)). Reductions in asthma hospital admissions were also observed. Among the 8,471 patient episodes included in this study, the mean [SD] age at admission was 47.2[22.9] years; 61% were female (n=5,134); mean [SD] length of stay was 4.9[10.9] days. Conclusion The findings of this study provide an opportunity to explore the impact of NO2 emissions for Cork, Dublin and Meath on asthma hospital admissions, in order to improve air quality modelling and policy development of management of asthma.

COVID-19 transport restrictions in Ireland: impact on air quality and respiratory hospital admissions.

AIM: Exposure to poor air quality is a well-established factor for exacerbation of respiratory system diseases (RSDs); whether air pollutants are a cause of the development of RSD, however, remains unclear. This study aimed to examine the relationship between COVID-19 transport restrictions and hospital admissions because of RSD in Dublin city and county for 2020. STUDY DESIGN: This was a retrospective population-based cohort. METHODS: Admission data were collected from the Health Service Executive Hospital In-patient Enquiry. Daily count of hospital admissions with Dublin city and county address with primary diagnosis of RSD was performed. The daily air nitrogen dioxide (NO2) data were obtained from the Environmental Protection Agency (EPA). RESULTS: During the period of transport restrictions, there was a reduction in the annual mean NO2 from 25 µg/m3 to 17 µg/m3 (P < 0.001), and decreases in hospital admissions for RSD were observed. Among the 9934 patient episodes included in this study, the mean age at admission was 61.5 years, 57.8% were female (n = 5744), and mean (standard deviation) length of stay was 7.5 (13.52) days. CONCLUSION: This study, using routinely gathered data, suggests that decreases in ambient NO2 as related to COVID-19 transport restrictions were significantly associated with lower asthma and chronic obstructive pulmonary disease admissions.

Evaluation of the Impact of Magnetic Resonance Imaging with Susceptibility-weighted Imaging for Screening and Surveillance of Radiation-induced Cavernomas in Long-term Survivors of Malignancy.

AIMS: Radiation-induced cavernomas (RIC) are common late toxicities in long-term survivors of malignancy following cerebral irradiation. However, the natural history of RIC is poorly described. We report the first series of long-term surveillance of RIC using modern magnetic resonance imaging (MRI) including highly sensitive susceptibility-weighted imaging (SWI). The aims of this research were to better characterise the natural history of RIC and investigate the utility of MRI-SWI for screening and surveillance. MATERIALS AND METHODS: Eligibility required long-term survivors of malignancy with previous exposure to cerebral irradiation and RIC identified on MRI-SWI surveillance. The number and size of RIC were reported on Baseline MRI-SWI and last Follow-up MRI-SWI. RESULTS: In total, 113 long-term survivors with RIC underwent MRI-SWI surveillance; 109 (96%) were asymptomatic at the time of RIC diagnosis. The median age at cerebral irradiation was 9.3 years; the median radiotherapy dose was 50.4 Gy. The median time from cerebral irradiation to Baseline MRI-SWI was 17.9 years. On Baseline MRI-SWI, RIC multiplicity was present in 89% of patients; 34% had >10 RIC; 65% had RIC ≥4 mm. The median follow-up from Baseline MRI-SWI was 7.3 years. On Follow-up MRI-SWI, 96% of patients had multiple RIC; 62% had >10 RIC; 72% had RIC ≥4 mm. Of the 109 asymptomatic patients at RIC diagnosis, 96% remained free from RIC-related symptoms at 10 years. Only two required neurosurgical intervention for RIC; there was no RIC-related mortality. CONCLUSIONS: RIC are commonly multiple, asymptomatic and typically increase in size and number over time. Our findings suggest that MRI-SWI for screening of RIC is unlikely to influence longer term intervention in asymptomatic cancer survivors. In the absence of neurological symptoms, assessment or monitoring of RIC are insufficient indications for MRI-SWI surveillance for long-term survivors of malignancy with past exposure to cerebral irradiation.

Single-use lidocaine hydrochloride 5 per cent w/v and phenylephrine hydrochloride 0.5 per cent w/v topical spray; can it now be employed as a multi-use atomiser?

OBJECTIVE: This study investigated the risk of contamination of lidocaine hydrochloride 5 per cent w/v and phenylephrine hydrochloride 0.5 per cent w/v topical solution after modification of the application technique. METHODS: This paper reports a prospective basic sciences study involving 22 study samples and 1 control sample of the lidocaine hydrochloride and phenylephrine hydrochloride topical anaesthetic spray. The samples were assessed for microbiological contamination after a single use on patients using a modified application technique. The modification involves keeping the nozzle (actuator) pressed down whilst withdrawing the spray to at least 30 cm (1 ft) from the patient, before releasing the nozzle (actuator) and subsequently reapplying the spray. RESULTS: Three of the 23 samples confirmed bacterial growth in the bottle contents, but there was no growth in any of the samples from the pump. These bacteria are considered to be contaminants. CONCLUSION: There is a potential to use the lidocaine hydrochloride 5 per cent w/v and phenylephrine hydrochloride 0.5 per cent w/v topical solution as a multi-use spray by changing the actuator between patients. This would have significant beneficial cost implications without the attendant infection control risk.

Disability Improvement Is Associated with Less Brain Atrophy Development in Multiple Sclerosis.

BACKGROUND AND PURPOSE: It is unknown whether deceleration of brain atrophy is associated with disability improvement in patients with MS. Our aim was to investigate whether patients with MS with disability improvement develop less brain atrophy compared with those who progress in disability or remain stable. MATERIALS AND METHODS: We followed 980 patients with MS for a mean of 4.8 ± 2.4 years. Subjects were divided into 3 groups: progress in disability (n = 241, 24.6%), disability improvement (n = 101, 10.3%), and stable (n = 638, 65.1%) at follow-up. Disability improvement and progress in disability were defined on the basis of the Expanded Disability Status Scale score change using standardized guidelines. Stable was defined as nonoccurrence of progress in disability or disability improvement. Normalized whole-brain volume was calculated using SIENAX on 3D T1WI, whereas the lateral ventricle was measured using NeuroSTREAM on 2D-T2-FLAIR images. The percentage brain volume change and percentage lateral ventricle volume change were calculated using SIENA and NeuroSTREAM, respectively. Differences among groups were investigated using ANCOVA, adjusted for age at first MR imaging, race, T2 lesion volume, and corresponding baseline structural volume and the Expanded Disability Status Scale. RESULTS: At first MR imaging, there were no differences among progress in disability, disability improvement, and the stable groups in whole-brain volume (P = .71) or lateral ventricle volume (P = .74). During follow-up, patients with disability improvement had the lowest annualized percentage lateral ventricle volume change (1.6% ± 2.7%) followed by patients who were stable (2.1% ± 3.7%) and had progress in disability (4.1% ± 5.5%), respectively (P < .001). The annualized percentage brain volume change values were -0.7% ± 0.7% for disability improvement, -0.8% ± 0.7% for stable, and -1.1% ± 1.1% for progress in disability (P = .001). CONCLUSIONS: Patients with MS who improve in their clinical disability develop less brain atrophy across time compared with those who progress.

Air Quality and Its Association with Cardiovascular and Respiratory Hospital Admissions in Ireland.

Aim Cardiovascular (CVD) and respiratory (RSD) diseases are leading causes of morbidity and mortality in Ireland. Clear links have been demonstrated in the literature between poor air quality and these diseases. This study aimed to use routinely available data to examine the relationship between air quality index for health (AQIH) (Available URL: http://www.epa.ie/air/quality/index/) and hospital admissions due to CVD and RSD in Dublin City and County between 2014 and 2018. Methods Admission data were collected from the HSE Hospital In-Patient Enquiry (HIPE). Daily count of hospital admissions with Dublin city and county address with a primary diagnosis of CVS and RSD was performed. The daily AQIH were obtained from the EPA for Dublin. Results Overall, AQIH distribution was: Good: 96% (1,575/1,642); Fair: 3% (52/1,642); and Poor: 1% (11/1,642). There were significant rises in admissions with change in AQIH (i.e. from good to very poor) for asthma, chronic obstructive airways disease and heart failure. There were also varying significant changes in short-term admission rates (i.e. up to 72 hours) following change in AQIH. Conclusions This study, using routinely gathered data, suggests that in Dublin city, where the AQ is predominantly good, that change in ambient AQ appears to impact admissions with CVD and RSD.

Extensive pneumatosis intestinalis and portal venous gas mimicking mesenteric ischaemia in a patient with SARS-CoV-2.

We present the case of a critically ill 47-year-old man diagnosed with SARS-CoV-2 (COVID-19) who developed extensive pneumatosis intestinalis and portal venous gas in conjunction with an acute abdomen during the recovery phase of his acute lung injury. A non-surgical conservative approach was taken as the definitive surgical procedure; a complete small-bowel resection was deemed to be associated with an unacceptably high long-term morbidity. However, repeat computed tomography four days later showed complete resolution of the original computed tomography findings. Pneumatosis intestinalis from non-ischaemic origins has been described in association with norovirus and cytomegalovirus. To our knowledge, this is the first time that this has been described in COVID-19.

Biopsychosocial factors associated with depression and anxiety in older adults with intellectual disability: results of the wave 3 Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing.

BACKGROUND: Depression and anxiety are amongst the most prevalent mental health disorders in the older population with intellectual disability (ID). There is a paucity of research that pertains to associative biopsychosocial factors for depression and anxiety in this population. The aim of this study is to determine the biopsychosocial factors associated with depression and anxiety in a population of older adults with ID in Ireland. METHODS: The study was part of 'The Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing'. Depressive symptoms were assessed using the Glasgow Depression Scale for people with a Learning Disability. Anxiety symptoms were measured using the Glasgow Anxiety Scale for people with a Learning Disability. The cross-sectional associations of depression and anxiety with biopsychosocial parameters were measured using a variety of self-report and proxy-completed questionnaires. RESULTS: For the study population, 9.97% met the criteria for depression, and 15.12% met the criteria for an anxiety disorder. Participants meeting criteria for depression were more likely to be taking regular mood stabiliser medications and to exhibit aggressive challenging behaviour. Participants meeting criteria for anxiety were more likely to have sleep difficulties and report loneliness. Participants meeting criteria for either/both depression and anxiety were more likely to report loneliness. CONCLUSIONS: This study identified both treatable and modifiable, as well as unmodifiable, biopsychosocial factors associated with depression and/or anxiety in older adults with ID. A longitudinal study follow-up will further develop our knowledge on the causality and direction of associated biopsychosocial factors with depression and anxiety in older adults with ID and better inform management strategies, prevention policies and funding of services.

The preoperative management of Hepatitis C may improve the outcome after total knee arthroplasty.

AIMS: With an ageing population of patients who are infected with hepatitis C virus (HCV), the demand for total knee arthroplasty (TKA) in this high-risk group continues to grow. It has previously been shown that HCV infection predisposes to poor outcomes following TKA. However, there is little information about the outcome of TKA in patients with HCV who have been treated successfully. The purpose of this study was to compare the outcomes of TKA in untreated HCV patients and those with HCV who have been successfully treated and have a serologically confirmed remission. PATIENTS AND METHODS: A retrospective review of all patients diagnosed with HCV who underwent primary TKA between November 2011 and April 2018 was conducted. HCV patients were divided into two groups: 1) those whose HCV was cured (HCV-C); and 2) those in whom it was untreated (HCV-UT). All variables including demographics, HCV infection characteristics, surgical details, and postoperative medical and surgical outcomes were evaluated. There were 64 patients (70 TKAs) in the HCV-C group and 63 patients (71 TKAs) in the HCV-UT cohort. The mean age at the time of surgery was 63.0 years (sd 7.5; 44 to 79) in the HCV-C group and 61.7 years (sd 6.9; 47 to 88) in the HCV-UT group. RESULTS: HCV-UT patients had a significantly longer mean hospital stay (3.4 days vs 2.9 days; p = 0.04), were more likely to be transferred to the intensive care unit (14.1% vs 4.3%; p = 0.04), and were significantly more often discharged to a post-acute care facility (39.4% vs 14.3%; p < 0.01). HCV-UT patients had significantly more postoperative infections (15.5% vs 4.3%; p = 0.03), surgical complications (21.1% vs 7.1%; p = 0.02), and revision TKA (12.7% vs 1.4%; p < 0.01) than HCV-C patients. CONCLUSION: The preoperative treatment of HCV can reduce the risk of complications, including prosthetic joint infection and revision TKA. We recommend that HCV treatment regimens should be integrated into the preoperative optimization protocol for this high-risk group of patients. Cite this article: Bone Joint J 2019;101-B:667-674.

An Under-Recognised Cause of Iatrogenic, Severe Metabolic Acidosis

Case Pyroglutamic acidosis is an uncommonly diagnosed but important cause of a high anion gap metabolic acidosis. Our case report concerns an elderly male admitted to the Intensive Care Unit (ICU) following the acute onset of coma which developed during treatment of a prosthetic joint infection. A diagnosis of pyroglutamic acidosis was ultimately made and later confirmed with laboratory testing. Blood gas analysis revealed a profound high anion gap metabolic acidosis. Treatment Treatment included withdrawal of the precipitating medications, N-acetylcysteine and sodium bicarbonate. Discussion This case highlights an unusual cause of severe metabolic acidosis caused by commonly used medications and readily reversible if recognised. This is of particular relevance in elderly, frail patients as incorrect alternate diagnoses may result in decisions which incorrectly limit critical care therapies.

CyBorD-DARA is potent initial induction for MM and enhances ADCP: initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study.

Daratumumab (DARA) has shown impressive activity in combination with other agents for the treatment of multiple myeloma (MM). We conducted a phase 1b study to assess the safety and preliminary efficacy, as well as potential mechanisms of action, of DARA (16 mg/kg) in combination with a weekly schedule of subcutaneous bortezomib (1.3-1.5 mg/m2), cyclophosphamide (150-300 mg/m2), and dexamethasone (40 mg) (CyBorD DARA) as initial induction before autologous stem cell transplantation (ASCT). Eligible patients were ≤70 years of age with untreated MM requiring treatment and who lacked significant comorbidities. A total of 18 patients were enrolled. Their median age was 56 years (range, 32-66 years), and all patients had Eastern Cooperative Oncology Group performance status ≤1. The International Staging System stages were I, II, and III in 78%, 17%, and 6% of patients, respectively; 28% of patients had high-risk genetic features. There was no dose-limiting toxicity, and the incidence of grade 3 or 4 infection or neutropenia was <10%. On an intention-to-treat basis, 94% achieved ≥very good partial response with ≥complete response in 44% of patients. Among 14 of 15 patients who underwent ASCT and were evaluable for response, all 14 achieved at least very good partial response, with 8 (57%) of 14 achieving complete response. After ASCT, 10 (83%) of 12 patients in whom minimal residual disease analysis was possible were negative at a sensitivity of 10-5 (56% on intention-to-treat/whole study population) according to next-generation sequencing. Flow cytometry analysis of patient samples indicated CyBorD DARA induced activation of macrophage-mediated antibody-dependent cellular phagocytosis. This trial was registered at www.clinicaltrials.gov as #NCT02955810.

A Serial 10-Year Follow-Up Study of Atrophied Brain Lesion Volume and Disability Progression in Patients with Relapsing-Remitting MS.

BACKGROUND AND PURPOSE: Disappearance of T2 lesions into CSF spaces is frequently observed in patients with MS. Our aim was to investigate temporal changes of cumulative atrophied brain T2 lesion volume and 10-year confirmed disability progression. MATERIALS AND METHODS: We studied 176 patients with relapsing-remitting MS who underwent MR imaging at baseline, 6 months, and then yearly for 10 years. Occurrence of new/enlarging T2 lesions, changes in T2 lesion volume, and whole-brain, cortical and ventricle volumes were assessed yearly between baseline and 10 years. Atrophied T2 lesion volume was calculated by combining baseline lesion masks with follow-up CSF partial volume maps. Ten-year confirmed disability progression was confirmed after 48 weeks. ANCOVA detected MR imaging outcome differences in stable (n = 76) and confirmed disability progression (n = 100) groups at different time points; hierarchic regression determined the unique additive variance explained by atrophied T2 lesion volume regarding the association with confirmed disability progression, in addition to other MR imaging metrics. Cox regression investigated the association of early MR imaging outcome changes and time to development of confirmed disability progression. RESULTS: The separation of stable-versus-confirmed disability progression groups became significant even in the first 6 months for atrophied T2 lesion volume (140% difference, Cohen d = 0.54, P = .004) and remained significant across all time points (P ≤ .007). The hierarchic model, including all other MR imaging outcomes during 10 years predicting confirmed disability progression, improved significantly after adding atrophied T2 lesion volume (R 2 = 0.27, R 2 change 0.11, P = .009). In Cox regression, atrophied T2 lesion volume in 0-6 months (hazard ratio = 4.23, P = .04) and 0-12 months (hazard ratio = 2.41, P = .022) was the only significant MR imaging predictor of time to confirmed disability progression. CONCLUSIONS: Atrophied T2 lesion volume is a robust and early marker of disability progression in relapsing-remitting MS.

The association of life events and mental ill health in older adults with intellectual disability: results of the wave 3 Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing.

BACKGROUND: Exposures to life events are associated with emotional, psychological and behavioural problems in those with intellectual disability (ID). Older adults with ID may experience different life events given differences in living circumstances, cognitive decline, greater dependency on others and less autonomy. This study examines the relationship of life events and mental ill health in an older ID population in Ireland. METHODS: The study was part of 'The Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing'. The frequency of life events was assessed using a 20-item checklist, and the level of stress experienced was assessed using a three-point Likert scale measuring the burden of the life event. The associations of life events with factors associated with mental ill health were measured using a variety of self-report and proxy completed questionnaires. RESULTS: For the study population, 88.1% had been exposed to at least one life event in the preceding 12 months and 64.5% to two or more life events. Frequency and burden of life events were significantly higher in individuals living in institutional settings and in individuals with any current psychiatric condition, increased depressive and anxiety symptoms, challenging behaviour and reported poorer self-rated mental and physical health. More life events were significantly associated with new psychiatric diagnoses as well as initiation and increased dosage of mood stabilising, hypnotic and sedative medications. CONCLUSIONS: Life events are significantly associated with mental ill health in the older ID population. Service providers must focus on limiting the exposure to these events and, in situations where they cannot be avoided, should support and manage individuals compassionately and effectively, prioritising their mental and physical well-being.

Brain Atrophy Is Associated with Disability Progression in Patients with MS followed in a Clinical Routine.

BACKGROUND AND PURPOSE: The assessment of brain atrophy in a clinical routine is not performed routinely in multiple sclerosis. Our aim was to determine the feasibility of brain atrophy measurement and its association with disability progression in patients with MS followed in a clinical routine for 5 years. MATERIALS AND METHODS: A total of 1815 subjects, 1514 with MS and 137 with clinically isolated syndrome and 164 healthy individuals, were collected retrospectively. Of 11,794 MR imaging brain scans included in the analysis, 8423 MRIs were performed on a 3T, and 3371 MRIs, on a 1.5T scanner. All patients underwent 3D T1WI and T2-FLAIR examinations at all time points of the study. Whole-brain volume changes were measured by percentage brain volume change/normalized brain volume change using SIENA/SIENAX on 3D T1WI and percentage lateral ventricle volume change using NeuroSTREAM on T2-FLAIR. RESULTS: Percentage brain volume change failed in 36.7% of the subjects; percentage normalized brain volume change, in 19.2%; and percentage lateral ventricle volume change, in 3.3% because of protocol changes, poor scan quality, artifacts, and anatomic variations. Annualized brain volume changes were significantly different between those with MS and healthy individuals for percentage brain volume change (P < .001), percentage normalized brain volume change (P = .002), and percentage lateral ventricle volume change (P = .01). In patients with MS, mixed-effects model analysis showed that disability progression was associated with a 21.9% annualized decrease in percentage brain volume change (P < .001) and normalized brain volume (P = .002) and a 33% increase in lateral ventricle volume (P = .004). CONCLUSIONS: All brain volume measures differentiated MS and healthy individuals and were associated with disability progression, but the lateral ventricle volume assessment was the most feasible.

Impact of Focal White Matter Damage on Localized Subcortical Gray Matter Atrophy in Multiple Sclerosis: A 5-Year Study.

BACKGROUND AND PURPOSE: It is unclear to what extent subcortical gray matter atrophy is a primary process as opposed to a result of focal white matter damage. Correlations between WM damage and atrophy of subcortical gray matter have been observed but may be partly attributable to indirect relationships between co-occurring processes arising from a common cause. Our aim was to cross-sectionally and longitudinally characterize the unique impact of focal WM damage on the atrophy of connected subcortical gray matter regions, beyond what is explainable by global disease progression. MATERIALS AND METHODS: One hundred seventy-six individuals with MS and 47 healthy controls underwent MR imaging at baseline and 5 years later. Atrophy and lesion-based disruption of connected WM tracts were evaluated for 14 subcortical gray matter regions. Hierarchic regressions were applied, predicting regional atrophy from focal WM disruption, controlling for age, sex, disease duration, whole-brain volume, and T2-lesion volume. RESULTS: When we controlled for whole-brain volume and T2-lesion volume, WM tract disruption explained little additional variance of subcortical gray matter atrophy and was a significant predictor for only 3 of 14 regions cross-sectionally (ΔR2 = 0.004) and 5 regions longitudinally (ΔR2 = 0.016). WM tract disruption was a significant predictor for even fewer regions when correcting for multiple comparisons. CONCLUSIONS: WM tract disruption accounts for a small percentage of atrophy in connected subcortical gray matter when controlling for overall disease burden and is not the primary driver in most cases.

Evaluation of Leptomeningeal Contrast Enhancement Using Pre-and Postcontrast Subtraction 3D-FLAIR Imaging in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Leptomeningeal contrast enhancement is found in patients with multiple sclerosis, though reported rates have varied. The use of 3D-fluid-attenuated inversion recovery pre- and postcontrast subtraction imaging may more accurately determine the frequency of leptomeningeal contrast enhancement. The purpose of this study was to investigate the frequency of leptomeningeal contrast enhancement using the pre- and postcontrast subtraction approach and to evaluate 3 different methods of assessing the presence of leptomeningeal contrast enhancement. MATERIALS AND METHODS: We enrolled 258 consecutive patients with MS (212 with relapsing-remitting MS, 32 with secondary-progressive MS, and 14 with clinically isolated syndrome) who underwent both pre- and 10-minute postcontrast 3D-FLAIR sequences after a single dose of gadolinium injection on 3T MR imaging. The analysis included leptomeningeal contrast-enhancement evaluation on 3D-FLAIR postcontrast images in native space (method A), on pre- and postcontrast 3D-FLAIR images in native space (method B), and on pre-/postcontrast 3D-FLAIR coregistered and subtracted images (method C, used as the criterion standard). RESULTS: In total, 51 (19.7%) patients with MS showed the presence of leptomeningeal contrast enhancement using method A; 39 (15.1%), using method B; and 39 (15.1%), using method C (P = .002). Compared with method C as the criterion standard, method A showed 89.8% sensitivity and 92.7% specificity, while method B showed 84.6% sensitivity and 97.3% specificity (P < .001) at the patient level. Reproducibility was the highest using method C (κ agreement, r = 088, P < .001). The mean time to analyze the 3D-FLAIR images was significantly lower with method C compared with methods A and B (P < .001). CONCLUSIONS: 3D-FLAIR postcontrast imaging offers a sensitive method for detecting leptomeningeal contrast enhancement in patients with MS. However, the use of subtraction imaging helped avoid false-positive cases, decreased reading time, and increased the accuracy of leptomeningeal contrast-enhancement foci detection in a clinical routine.

Prevalence and patterns of anti-epileptic medication prescribing in the treatment of epilepsy in older adults with intellectual disabilities.

BACKGROUND: The prevalence of epilepsy is higher in people with intellectual disability (ID) and increases with the degree of ID. Although life expectancy for people with ID is increasing, people with ID coexisting with epilepsy have a higher mortality rate, particularly those who had recent seizures. There have been few observational studies of the prevalence and patterns of anti-epileptic prescribing among older people with ID and epilepsy. The aim of this study was to investigate prevalence and patterns of anti-epileptic prescribing in the treatment of epilepsy in a representative population of older people with ID and epilepsy. METHODS: This was an observational cross-sectional study from wave 1 (2009/2010) of Intellectual Disability Supplement to the Irish Longitudinal Study on Aging, a nationally representative sample of 753 persons with ID aged between 41 and 90 years. Participants and/or proxies recorded medicines used on a regular basis and reported doctor's diagnosis of epilepsy; medication data were available for 736 (98%). Prescribing of anti-epileptic drugs (AEDs) for epilepsy in those with a doctor's diagnosis of epilepsy (N = 205) was the primary exposure of interest for this study. Participant exposure to these AEDs was then categorised into AED monotherapy and polytherapy. Participants/carers reported seizure frequency, when epilepsy was last reviewed and which practitioner reviewed epilepsy. In addition, medications that may lower the seizure threshold that were listed in the Maudsley prescribing guidelines in psychiatry were examined. RESULTS: Of the 736 participants with reported medicines use, 38.9% (n = 287) were exposed to AEDs, and 30.6% (225) had a doctor's diagnosis of epilepsy. Of those with epilepsy (n = 225), 90.9% (n = 205) reported concurrent use of AEDs and epilepsy. Of these 205 participants, 50.3% (n = 103) were exposed to AED polytherapy, and 63 different polytherapy regimes were reported. The most frequently reported AEDs were valproic acid (n = 100, 48.7%), carbamazepine (n = 89, 46.3%) and lamotrigine (n = 57, 27.8%). In total, 13.7% had a concurrent psychotropic, which should be avoided in epilepsy, and 32.6% had a psychotropic where caution is required. Antipsychotics with potential epileptogenic potential accounted for 80% of these medications. Of those with AED polytherapy (n = 103), 29.5% (28) reported being seizure free for the previous 2 years. CONCLUSIONS: Prevalence of epilepsy was high among older people with ID, and half were exposed to two or more AEDs. Despite the use of AED therapy, over half had seizures in the previous 2 years. As the primary goals of optimal AED treatment are to achieve seizure freedom without unacceptable adverse effects, this was not achievable for many older patients with ID and epilepsy. Our findings indicated that people with ID and epilepsy were often exposed to psychotropic medications that may lower the seizure threshold. Regular review of epilepsy and medicines (including medicines that may interact with AEDs or lower the seizure threshold) by multidisciplinary teams working to agreed standards may improve quality of prescribing. Improved exchange of information and coordination of care between specialists and primary care practitioners in line with expert consensus recommendations could bring substantial benefit.