Bilateral intracortical inhibition during unilateral motor preparation and sequence learning.

Motor sequence learning gradually quickens reaction time, suggesting that sequence learning alters motor preparation processes. Interestingly, evidence has shown that preparing sequence movements decreases short intracortical inhibition (SICI) in the contralateral motor cortex (M1), but also that sequence learning alters motor preparation processes in both the contralateral and ipsilateral M1s. Therefore, one possibility is that sequence learning alters the SICI decreases occurring during motor preparation in bilateral M1s. To examine this, two novel hypotheses were tested: unilateral sequence preparation would decrease SICI in bilateral M1s, and sequence learning would alter such bilateral SICI responses. Paired-pulse transcranial magnetic stimulation was delivered over the contralateral and ipsilateral M1s to assess SICI in an index finger muscle during the preparation of sequences initiated by either the right index or little finger. In the absence of sequence learning, SICI decreased in both the contralateral and ipsilateral M1s during the preparation of sequences initiated by the right index finger, suggesting that SICI decreases in bilateral M1s during unilateral motor preparation. As sequence learning progressed, SICI decreased in the contralateral M1 whilst it increased in the ipsilateral M1. Moreover, these bilateral SICI responses were observed at the onset of motor preparation, suggesting that sequence learning altered baseline SICI levels rather than the SICI decreases occurring during motor preparation per se. Altogether, these results suggest that SICI responses in bilateral M1s reflect two motor processes: an acute decrease of inhibition during motor preparation, and a cooperative but bidirectional shift of baseline inhibition levels as sequence learning progresses.

The intracortical excitability changes underlying the enhancing effects of rewards and punishments on motor performance.

Monetary rewards and punishments enhance motor performance and are associated with corticospinal excitability (CSE) increases within the motor cortex (M1) during movement preparation. However, such CSE changes have unclear origins. Based on converging evidence, one possibility is that they stem from increased glutamatergic (GLUTergic) facilitation and/or decreased type A gamma-aminobutyric acid (GABAA)-mediated inhibition within M1. To investigate this, paired-pulse transcranial magnetic stimulation was used over the left M1 to evaluate intracortical facilitation (ICF) and short intracortical inhibition (SICI), indirect assays of GLUTergic activity and GABAA-mediated inhibition, in an index finger muscle during the preparation of sequences initiated by either the right index or little finger. Behaviourally, rewards and punishments enhanced both reaction and movement time. During movement preparation, regardless of rewards or punishments, ICF increased when the index finger initiated sequences, whereas SICI decreased when both the index and little fingers initiated sequences. This finding suggests that GLUTergic activity increases in a finger-specific manner whilst GABAA-mediated inhibition decreases in a finger-unspecific manner during preparation. In parallel, both rewards and punishments non-specifically increased ICF, but only rewards non-specifically decreased SICI as compared to neutral. This suggests that to enhance performance rewards both increase GLUTergic activity and decrease GABAA-mediated inhibition, whereas punishments selectively increase GLUTergic activity. A control experiment revealed that such changes were not observed post-movement as participants processed reward and punishment feedback, indicating they were selective to movement preparation. Collectively, these results map the intracortical excitability changes in M1 by which incentives enhance motor performance.

Latent TB and depressive symptoms in household contacts of persons with active TB.

BACKGROUND: Depression is common among persons with TB and is associated with poor clinical outcomes. However, little is known about the relationship between latent TB infection (LTBI) and depression. We assessed the association between LTBI and depressive symptoms among household contacts (HHCs) of patients receiving TB treatment.METHODS: We enrolled 1,009 HHCs of 307 patients receiving TB treatment in Lima, Peru, during 2016-2018. At enrollment, HHC LTBI status was assessed using the interferon-gamma release assay (IGRA). Depressive symptoms were assessed at baseline and 12 months later using the Patient Health Questionnaire-9 (PHQ-9) with a cut-off of ≥5. We used logistic regression to estimate the odds ratio (OR) for PHQ-9 ≥5, comparing HHCs with and without baseline LTBI.RESULTS: Among 921 HHCs, 374 (41.0%) had LTBI at baseline, and 69 (12.4%) of 567 HHCs had PHQ-9 ≥5. Compared to HHCs without LTBI at enrollment, those with LTBI had almost two times the odds of PHQ-9 ≥5 at follow-up after controlling for potential confounders (adjusted OR 1.93, 95% CI 1.09-3.39); this association was driven by greater severities of depressive symptoms.CONCLUSION: HHCs with LTBI had increased odds of depressive symptoms 1 year later. This population may benefit from mental health screening and interventions integrated into TB programs.

Culture-negative TB: clinical characteristics, risk factors and treatment outcomes.

BACKGROUND: Although culture remains the standard for TB diagnosis, 15-20% of patients diagnosed and treated for TB are culture-negative. We explored clinical characteristics, risk factors and treatment outcomes for culture-negative TB in a Peruvian cohort.METHODS: We recruited 4,500 index TB patients and 10,160 household contacts in Lima, Peru, and enrolled 692 secondary patients diagnosed with TB during follow-up of household contacts. We analyzed smear and culture status, sociodemographic factors, clinical characteristics and TB treatment outcomes to compare culture-negative and positive patients.RESULTS: Of the 4,880 adult patients, 915 (18.8%) were culture-negative. Culture-negative patients were less likely to report symptoms of TB disease and disease of longer duration. A multivariate analysis showed no statistically significant difference in loss to follow-up, treatment failure or recurrence between the culture-negative and -positive groups but a higher rate of death among culture-negative patients with an adjusted OR of 1.65 (95% CI 1.05-2.60). In a multivariate analysis of determinants of culture negativity, older age, substance use and being a secondary case were associated with culture status.CONCLUSIONS: More recognition and awareness of culture-negative TB is key for early and correct diagnosis to reduce transmission and improve treatment outcomes.

Using digital chatbots to close gaps in healthcare access during the COVID-19 pandemic.

INTRODUCTION: Chatbots have emerged as a first link to care in recent years. The COVID-19 pandemic, and consequent health system disruptions, expanded their use. Socios En Salud (SES) introduced chatbots in Peru, which experienced one of the highest excess COVID mortalities in the world. METHODS: SES and the government identified unmet population health needs, which could be amenable to virtual interventions. Chatbots were developed to screen individuals for these conditions; we describe the period of deployment, number of screenings, and number of people who received services. RESULTS: Between April 2020 and May 2021, SES deployed nine ChatBots: four for mental health, two for maternal and child health, and three for chronic diseases: breast cancer, hypertension, diabetes mellitus, and obesity. Mental health services were provided to 42,932 people, 99.99% of those offered services. The other ChatBots reached fewer people. Overall, more than 50% of eligible people accepted chatbot-based services. DISCUSSION: ChatBot use was highest for mental health. Chatbots may increase connections between a vulnerable population and health services; this is likely dependent on several factors, including condition, population, and penetration of smart phones. Future research will be critical to understand user experience and preferences and to ensure that chatbots link vulnerable populations to appropriate, high-quality care.

INTRODUCTION: Les chatbots se sont imposés comme un premier lien aux soins ces dernières années. La pandémie de COVID-19, et les perturbations du système de santé qui en ont résultées, ont élargi leur champ d'application. Socios En Salud (SES) a introduit les chatbots au Pérou, qui a connu l'une des surmortalités dues au COVID les plus élevées au monde. MÉTHODES: SES et le gouvernement ont identifié des besoins non satisfaits en matière de santé de la population, qui pourraient faire l'objet d'interventions virtuelles. Des chatbots ont été développés pour dépister des individus pour ces conditions ; nous décrivons la période de leur déploiement, le nombre de dépistages et le nombre de personnes qui ont reçu ces services. RÉSULTATS: Entre avril 2020 et mai 2021, SES a déployé neuf ChatBots : quatre pour la santé mentale, deux pour la santé maternelle et infantile et trois pour les maladies chroniques, comme le cancer du sein, l'hypertension, le diabète et l'obésité. Des services de santé mentale ont été fournis à 42 932 personnes, soit 99,99% des personnes proposées. Les autres ChatBots ont touché moins de personnes. Dans l'ensemble, plus de 50% des personnes éligibles ont accepté les services proposés par les chatbots. DISCUSSION: L'utilisation des ChatBots était la plus élevée pour la santé mentale. Les chatbots peuvent augmenter les connexions entre une population vulnérable et les services de santé, mais cela dépende de plusieurs facteurs, dont la condition, la type de population et la pénétration des smartphones. Les recherches futures seront essentielles pour comprendre l'expérience et les préférences des utilisateurs et pour s'assurer que les chatbots relient les populations vulnérables vulnérables aux soins appropriés et de qualité.

A structured community engagement strategy to support uptake of TB active case-finding.

BACKGROUND: In Lima, Peru, a mobile TB screening program ("TB Móvil") was implemented in high TB prevalence districts to increase TB screening. Community engagement activities to promote TB Móvil were simultaneously conducted. OBJECTIVE: To describe a structured, theory-driven community engagement strategy to support the uptake of TB Móvil. METHODS: We adapted Popular Opinion Leader (POL), an evidence-based social networking intervention previously used in Peru to promote HIV testing, for TB Móvil. Community health workers, women who run soup kitchens, and motorcycle taxi drivers served as "popular opinion leaders" who disseminated information about TB Móvil in everyday conversations, aided by a multi-media campaign. Performance indicators of POL included the number/characteristics of persons screened; number of multimedia elements; and proportion of persons with abnormal radiographs hearing about TB Móvil before attending. RESULTS: Between February 2019 and January 2020, 63,899 people attended the TB Móvil program at 210 sites; 60.1% were female. The multimedia campaign included 36 videos, 16 audio vignettes, flyers, posters, community murals and "jingles." Among attendees receiving an abnormal chest X-ray suggestive of TB, 48% (6,935/14,563) reported hearing about TB Móvil before attending. CONCLUSIONS: POL promotes the uptake of TB Móvil and should be considered as a strategy for increasing TB screening uptake.

CONTEXTE: À Lima, Pérou, un programme mobile de dépistage de la TB (« TB Móvil ¼) a été mis en place dans les quartiers à forte prévalence de TB afin d'accroître le dépistage de la maladie. Des activités de mobilisation communautaire visant à promouvoir TB Móvil ont été menées en parallèle. L'objectif de ce rapport est de décrire une stratégie structurée de mobilisation communautaire, fondée sur des principes théoriques, afin de soutenir le recours au programme TB Móvil. MÉTHODES: Nous avons adapté à TB Móvil l'intervention factuelle de réseautage social appelée « Popular Opinion Leader (POL; leader d'opinion) ¼, précédemment utilisée au Pérou pour promouvoir le dépistage du VIH. Les agents de santé communautaires, les femmes responsables de la soupe populaire et les chauffeurs de mototaxis étaient des leaders d'opinion. Ils communiquaient des informations sur TB Móvil lors de leurs conversations quotidiennes, qui étaient étayées par une campagne multimédia. Les indicateurs de performance des POL comprenaient le nombre/les caractéristiques des personnes dépistées, le nombre d'éléments multimédias et le pourcentage de personnes avec cliché radiographique anormal qui avaient entendu parler de TB Móvil avant de se faire dépister. RÉSULTATS: Entre février 2019 et janvier 2020, 63 899 personnes ont pris part au programme TB Móvil dans 210 sites ; 60,1% étaient des femmes. La campagne multimédia reposait sur 36 vidéos, 16 vignettes audio, des prospectus, des posters, des peintures murales dans la communauté et des « jingles ¼. Parmi les personnes dont la radiographie pulmonaire était anormale et évocatrice de TB, 48% (6 935/14 563) ont rapporté avoir entendu parler de TB Móvil avant de venir consulter. CONCLUSIONS: L'intervention POL, qui semblait renforcer le recours au programme TB Móvil, peut donc servir d'une stratégie de promotion du dépistage de la TB.

Intact predictive motor sequence learning in autism spectrum disorder.

Atypical motor learning has been suggested to underpin the development of motoric challenges (e.g., handwriting difficulties) in autism. Bayesian accounts of autistic cognition propose a mechanistic explanation for differences in the learning process in autism. Specifically, that autistic individuals overweight incoming, at the expense of prior, information and are thus less likely to (a) build stable expectations of upcoming events and (b) react to statistically surprising events. Although Bayesian accounts have been suggested to explain differences in learning across a range of domains, to date, such accounts have not been extended to motor learning. 28 autistic and 35 non-autistic controls (IQ > 70) completed a computerised task in which they learned sequences of actions. On occasional "surprising" trials, an expected action had to be replaced with an unexpected action. Sequence learning was indexed as the reaction time difference between blocks which featured a predictable sequence and those that did not. Surprise-related slowing was indexed as the reaction time difference between surprising and unsurprising trials. No differences in sequence-learning or surprise-related slowing were observed between the groups. Bayesian statistics provided anecdotal to moderate evidence to support the conclusion that sequence learning and surprise-related slowing were comparable between the two groups. We conclude that individuals with autism do not show atypicalities in response to surprising events in the context of motor sequence-learning. These data demand careful consideration of the way in which Bayesian accounts of autism can (and cannot) be extended to the domain of motor learning.

Uncovering reasons for treatment initiation delays among children with TB in Lima, Peru.

BACKGROUND: Timely diagnosis and treatment of pediatric tuberculosis (TB) is critical to reducing mortality but remains challenging in the absence of adequate diagnostic tools. Even once a TB diagnosis is made, delays in treatment initiation are common, but for reasons that are not well understood.METHODS: To examine reasons for delay post-diagnosis, we conducted semi-structured interviews with Ministry of Health (MoH) physicians and field workers affiliated with a pediatric TB diagnostic study, and caregivers of children aged 0-14 years who were diagnosed with pulmonary TB in Lima, Peru. Interviews were analyzed using systematic comparative and descriptive content analysis.RESULTS: We interviewed five physicians, five field workers and 26 caregivers with children who initiated TB treatment < 7 days after diagnosis (n = 15) or who experienced a delay of ≥7 days (n = 11). Median time in delay from diagnosis to treatment initiation was 26 days (range 7-117). Reasons for delay included: health systems challenges (administrative hurdles, medication stock, clinic hours), burden of care on families and caregiver perceptions of disease severity.CONCLUSION: Reasons for delay in treatment initiation are complex. Interventions to streamline administrative processes and tools to identify and support families at risk for delays in treatment initiation are urgently needed.

Impact of mental disorders on active TB treatment outcomes: a systematic review and meta-analysis.

BACKGROUND: Comorbid mental disorders in patients with TB may exacerbate TB treatment outcomes. We systematically reviewed current evidence on the association between mental disorders and TB outcomes.METHODS: We searched eight databases for studies published from 1990 to 2018 that compared TB treatment outcomes among patients with and without mental disorders. We excluded studies that did not systematically assess mental disorders and studies limited to substance use. We extracted study and patient characteristics and effect measures and performed a meta-analysis using random-effects models to calculate summary odds ratios (ORs) with 95% confidence intervals (CIs).RESULTS: Of 7687 studies identified, 10 were included in the systematic review and nine in the meta-analysis. Measurement of mental disorders and TB outcomes were heterogeneous across studies. The pooled association between mental disorders and any poor outcome, loss to follow-up, and non-adherence were OR 2.13 (95%CI 0.85-5.37), 1.90 (95%CI 0.33-10.91), and 1.60 (95%CI 0.81-3.02), respectively. High statistical heterogeneity was present.CONCLUSION: Our review suggests that mental disorders in TB patients increase the risk of poor TB outcomes, but pooled estimates were imprecise due to small number of eligible studies. Integration of psychological and TB services might improve TB outcomes and progress towards TB elimination.

Integrating tuberculosis and mental health services: global receptivity of national tuberculosis program directors.

A global survey of National Tuberculosis Program (NTP) directors. To assess the perceived mental health needs of persons with tuberculosis (TB), current practices, and receptivity to integrating evidence-based mental and substance use treatment into national TB guidelines. Semi-structured survey of NTP directors from 26 countries of all income levels using a standardized questionnaire. Of the 26 countries, 21 were classified as high incidence and/or burden countries for TB, TB and human immunodeficiency virus coinfection, and/or drug-resistant TB. Two NTPs included routine screening for any mental disorder, four assessed alcohol or drug use, and five had standard protocols for the co-management of disorders. If effective and low-cost integrated care models were available, 17 NTP directors felt that it was highly likely, and five somewhat likely, that their NTPs would integrate mental health treatment into national TB guidelines and services. The main perceived barriers to service integration were limited capacity, not recognizing mental health as a problem, insufficient resources, and TB-related social stigma. NTPs currently do not address mental disorders as part of routine practice. Nevertheless, receptivity is high, which creates a ripe opportunity to integrate the management of TB and mental disorders into the policies and guidelines of NTPs worldwide. .

Community strengthening and mental health system linking after flooding in two informal human settlements in Peru: a model for small-scale disaster response.

BACKGROUND: Mental health is an important factor in responding to natural disasters. Observations of unmet mental health needs motivated the subsequent development of a community-based mental health intervention following one such disaster affecting Peru in 2017. METHODS: Two informal human settlements on the outskirts of Lima were selected for a mental health intervention that included: (1) screening for depression and domestic violence, (2) children's activities to strengthen social and emotional skills and diminish stress, (3) participatory theater activities to support conflict resolution and community resilience, and (4) community health worker (CHW) accompaniment to government health services. RESULTS: A total of 129 people were screened across both conditions, of whom 12/116 (10%) presented with depression and 21/58 (36%) reported domestic violence. 27 unique individuals were identified with at least one problem. Thirteen people (48%) initially accepted CHW accompaniment to government-provided services. CONCLUSIONS: This intervention provides a model for a small-scale response to disasters that can effectively and acceptably identify individuals in need of mental health services and link them to a health system that may otherwise remain inaccessible.

Preparing to launch the 'Thinking Healthy Programme' perinatal depression intervention in Urban Lima, Peru: experiences from the field.

BACKGROUND: An estimated 19-25% of perinatal women in low- and middle-income countries are affected by depression which, untreated, is associated with multiple health problems for mothers and children. Nonetheless, few perinatal women have access to depression care. The Thinking Healthy Programme (THP), promoted by the World Health Organization (WHO), is an evidence-based, non-specialist delivered depression intervention that addresses this care gap. However, the WHO THP manual explains intervention delivery but not the antecedents to implementation. Here, we describe a principled, planned approach leading to the implementation of THP in Lima, Peru by the non-profit organization Socios En Salud with community health workers (CHW) to inform its implementation in other settings. METHODS: The Replicating Effective Programs (REP) framework guided THP implementation, following four phases: (I) pre-conditions; (II) pre-implementation; (III) implementation; and (IV) maintenance and evolution. This paper centers on REP phases I and II, including (1) documented high perinatal depression rates in Peru; (2) designation of perinatal depression as a government priority; (3) THP Implementation Team orientation and training; (4) data collection plan development; (5) public health system coordination; (6) CHW selection and training; and (7) THP launch. RESULTS: Between December 2016 and March 2017, a THP training program was developed and seven CHW were trained to deliver the intervention to 10 perinatal women, the first of whom was enrolled on 17 April 2017. CONCLUSIONS: THP was rapidly implemented by a community-based organization with no prior experience in delivering non-specialist perinatal depression care. The steps followed may inform the implementation of THP in other settings.

Mental disorders and drug/alcohol use in patients commencing extensively drug-resistant tuberculosis treatment.

Mental disorders and alcohol/drug use worsen treatment outcomes for multidrug-resistant tuberculosis (TB), but data are lacking for extensively drug-resistant (XDR) TB. We investigated the association of baseline mental disorders and alcohol/drug use on XDR-TB treatment outcomes in a retrospective study of 53 XDR-TB Peruvian patients during 2010-2012. Logistic regression estimated the odds ratios for unfavourable XDR-TB treatment outcomes. Overall treatment success was 25%. Mental disorders and drug/alcohol use were found in respectively 22.4% and 20.4% of patients; neither were associated with unfavourable treatment outcomes. Future research should explore the relationship between mental health and drug/alcohol use in XDR-TB treatment outcomes.

Les troubles mentaux et la consommation d'alcool/de drogue entravent le résultat du traitement de la tuberculose multirésistante (TB-MDR), mais on manque de données pour la TB ultrarésistante (TB-XDR). Nous avons examiné l'association de troubles mentaux préexistants et de consommation d'alcool/de drogue sur le résultat du traitement de la TB-XDR dans une étude rétrospective de 53 patients péruviens atteints de TB-XDR en 2010­2012. Une régression logistique a estimé les odds ratios de résultat défavorable du traitement de la TB-XDR. Le taux d'ensemble de succès du traitement a été de 25%. Des troubles mentaux et une consommation d'alcool/de drogue ont été constatés chez respectivement 22,4% et 20,4% des patients ; aucun n'a été associé à un résultat défavorable du traitement. Des recherches ultérieures devraient explorer la relation entre santé mentale et consommation de drogue/alcool et leur impact sur le traitement de la TB-XDR.

Los trastornos mentales y el consumo de alcohol y de drogas agravan los desenlaces terapéuticos de la tuberculosis multidrogorresistente (TB-MDR), pero no existen datos en cuanto a la TB extremadamente resistente (TB-XDR). En un estudio retrospectivo en 53 pacientes peruianos que padecieron TB-XDR del 2010 al 2012, se investigó la asociación de la presencia inicial de trastornos mentales y consumo de alcohol o drogas con los desenlaces del tratamiento de la TB-XDR. Mediante un modelo de regresión logística se calcularon los cocientes de posibilidades de desenlaces terapéuticos desfavorables. La tasa global de éxito terapéutico fue de 25%. Se encontró que el 22,4% de los pacientes sufría trastornos mentales y el 20,4% consumía alcohol o drogas; ninguna de estas características se asoció con desenlaces desfavorables del tratamiento. Nuevas investigaciones tendrán que explorar la correlación que existe entre la salud mental y el consumo de alcohol o drogas y los desenlaces terapéuticos de la TB-XDR.

Prevalence of pyrazinamide resistance and Wayne assay performance analysis in a tuberculosis cohort in Lima, Peru.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) regimens often contain pyrazinamide (PZA) even if susceptibility to the drug has not been confirmed. This gap is due to the limited availability and reliability of PZA susceptibility testing. OBJECTIVES: To estimate the prevalence of PZA resistance using the Wayne assay among TB patients in Lima, Peru, to describe characteristics associated with PZA resistance and to compare the performance of Wayne with that of BACTEC™ MGIT™ 960. METHODS: PZA susceptibility using the Wayne assay was tested in patients diagnosed with culture-positive pulmonary TB from September 2009 to August 2012. Factors associated with PZA resistance were evaluated. We compared the performance of the Wayne assay to that of MGIT 960 in a convenience sample. RESULTS: The prevalence of PZA resistance was 6.6% (95%CI 5.8-7.5) among 3277 patients, and 47.7% (95%CI 42.7-52.6) among a subset of 405 MDR-TB patients. In multivariable analysis, MDR-TB (OR 86.0, 95%CI 54.0-136.9) and Latin American-Mediterranean lineage (OR 3.40, 95%CI 2.33-4.96) were associated with PZA resistance. The Wayne assay was in agreement with MGIT 960 in 83.9% of samples (κ 0.66, 95%CI 0.56-0.76). CONCLUSION: PZA resistance was detected using the Wayne assay in nearly half of MDR-TB patients in Lima. This test can inform the selection and composition of regimens, especially those dependent on additional resistance.

Knowledge of tuberculosis and vaccine trial preparedness in Lima, Peru.

SETTING: A safe, effective vaccine would improve tuberculosis (TB) control worldwide. Extensive community engagement will be essential to ensure the interest and participation of populations at highest risk. OBJECTIVE/METHOD: To inform the potential implementation of efficacy studies, we assessed TB knowledge, attitudes towards licensed vaccines and willingness to participate in future TB vaccine efficacy trials among 262 household contacts of 79 recently diagnosed pulmonary TB cases in Lima, Peru. RESULTS: Overall knowledge of TB was low. Only 41.6% of household contacts perceived themselves as being at high risk of acquiring TB. Slightly above half (54.2%) indicated willingness to participate in a TB vaccine trial. After clustered analysis adjusting for homogeneity among families, willingness to enroll was associated with belief that receiving all recommended vaccinations is important (adjusted OR [aOR] 3.28, P = 0.016), desire to know more about TB risk factors and clinical trials (aOR 2.60, P = 0.004), older age (aOR 1.02, P = 0.027) and TB knowledge (aOR 0.05, P = 0.039). CONCLUSION: Barriers to participation in TB vaccine trials exist among individuals at high risk for TB. Targeted education about TB risk factors, TB transmission and education about the clinical trial process will be critical for laying the groundwork for future vaccine trials.

Effect of weekend admission on in-hospital mortality and functional outcomes for patients with acute subarachnoid haemorrhage (SAH).

BACKGROUND: Aneurysmal subarachnoid haemorrhage (aSAH) is an acute cerebrovascular event with high socioeconomic impact as it tends to affect younger patients. The recent NCEPOD study looking into management of aSAH has recommended that neurovascular units in the United Kingdom should aim to secure cerebral aneurysms within 48 h and that delays because of weekend admissions can increase the mortality and morbidity attributed to aSAH. METHOD: We used data from a prospective audit of aSAH patients admitted between January 2009 and December 2011. The baseline demographic and clinical features of the weekend and weekday groups were compared using the chi-squared test and T-test. Cox proportional hazards models (Proc Phreg in SAS) were used to calculate the adjusted overall hazard of in-hospital death associated with admission on weekend, adjusting for age, sex, baseline WFNS grade, type of treatment received and time from scan to treatment. Sliding dichotomy analysis was used to estimate the difference in outcomes after SAH at 3 months in weekend and weekday admissions. RESULTS: Those admitted on weekends had a significantly higher scan to treatment time (83.05 ± 83.4 h vs 40.4 ± 53.4 h, P < 0.0001) and admission to treatment (71.59 ± 79.8 h vs 27.5 ± 44.3 h, P < 0.0001) time. After adjustments for adjusted for relevant covariates weekend admission was statistically significantly associated with excess in-hospital mortality (HR = 2.1, CL [1.13-4.0], P = 0.01). After adjustments for all the baseline covariates, the sliding dichotomy analysis did not show effects of weekend admission on long-term outcomes on the good, intermediate and worst prognostic bands. CONCLUSIONS: This study provides important data showing excess in-hospital mortality of patients with SAH on weekend admissions served by the United Kingdom's National Health Service.; However, there were no effects of weekend admission on long-term outcomes.

Haemoglobin scavenging after subarachnoid haemorrhage.

Rapid and effective clearance of cell-free haemoglobin after subarachnoid haemorrhage (SAH) is important to prevent vasospasm and neurotoxicity and improve long-term outcome. Haemoglobin is avidly bound by haptoglobin, and the complex is cleared by CD163 expressed on the membrane surface of macrophages. We studied the kinetics of haemoglobin and haptoglobin in cerebrospinal fluid after SAH. We show that haemoglobin levels rise gradually after SAH. Haptoglobin levels rise acutely with aneurysmal rupture as a result of injection of blood into the subarachnoid space. Although levels decline as haemoglobin scavenging occurs, complete depletion of haptoglobin does not occur and levels start rising again, indicating saturation of CD163 sites available for haptoglobin-haemoglobin clearance. In a preliminary neuropathological study we demonstrate that meningeal CD163 expression is upregulated after SAH, in keeping with a proinflammatory state. However, loss of CD163 occurs in meningeal areas with overlying blood compared with areas without overlying blood. Becauses ADAM17 is the enzyme responsible for shedding membrane-bound CD163, its inhibition may be a potential therapeutic strategy after SAH.