Effectiveness of helmets in preventing severe injuries in a setting with poorly enforced quality standards

Helmets save lives, yet many countries do not have laws about their quality assessment or how they should be worn. We assessed the effectiveness of helmet use in preventing injuries in such a setting. The data were extracted from a large road traffic injury surveillance study in Karachi, Pakistan. We assessed the association of wearing helmets with several injury outcomes including deaths, injury severity (via New Injury Severity Score, NISS ≥ 9) and moderate or severe injury (via Abbreviated Injury Score, AIS ≥ 2) to head, face, or other regions of the body. The data about helmet use was available for about 109,210 riders injured between January 2007 and December 2013. Only 6% of riders wore helmets, whereas this proportion was less than one percent in pillion riders and women. The rates were also lower among those aged 18 years or younger (1%) and those aged 18 to 25 years (4%). About 2% of riders died; 34% had an injury to the head region, 30% to face, 1% to chest, 5% to abdominal, 46% to extremities, and 61% to external body regions. Likelihood of dying was low among helmet users (adjusted odds ratio [aOR] = 0.37, 95% confidence interval [CI] = 0.28 to 0.50). Helmets reduced the likelihood of moderate to severe injuries to the head (aOR = 0.68, 95% CI = 0.58 to 0.80) but not to the face region (aOR = 1.37, 95%CI = 1.17 to 1.62). Helmet users also had severer injuries in other body regions except for chest injuries. Helmets prevented deaths and severe head injuries but had limited effectiveness in preventing facial injuries in this setting with poor helmet use standards. More work is needed to understand the helmet wearing and rider behaviours in helmet users in this setting

Association of depression with treatment outcomes in Type 2 Diabetes Mellitus: A cross-sectional study from Karachi, Pakistan

Background: To assess the associations of depression with glycemic control and compliance to self-care activities in adult Patients with Type 2 Diabetes Mellitus. Methods: This cross-sectional study was conducted at a tertiary-care hospital in Karachi (Aga Khan University Hospital). Equal numbers of depressed and non-depressed Patients were consecutively recruited from the diabetic clinic. Information on demographic and clinical characteristics was collected in face-to-face interviews and from medical records. Hospital Anxiety Depression Scale (HADS) was used to measure depression. Associations of depressed status (HADS \u3e= 8) with poor glycemic control (Hemoglobin A1c level \u3e= 7%) and compliance to self-care activities were assessed by logistic regression analyses. Results: A total of 286 Patients were included in this study with a male-female ratio of 1.2:1. Mean age was 52 years and in 64.7% of them, the duration of diabetes was more than 3 years. Depressed Patients were more likely to be female (adjusted odds ratio [OR] = 1.88, 95% confidence interval [95% CI] = 1.07-3.31), had a family history of diabetes (OR = 2.64, 95% CI = 1.26-5.55), and poor glycemic control (OR = 5.57, 95% CI = 2.88-10.76) compared with non-depressed Patients. Depression was also associated with low compliance to self-care activities such as taking dose as advised (OR = 0.32, 95% CI = 0.14-0.73), dietary restrictions (OR = 0.45, 95% CI = 0.26-0.79) and foot care (OR = 0.38, 95% CI = 0.18-0.83). Conclusions: Adult Patients with Type 2 Diabetes who have depression were more likely to have poor glycemic control and lower compliance to self-care activities, and they might need particular attention during follow-up visits

School-based injury outcomes in children from a low-income setting: results from the pilot injury surveillance in Rawalpindi city, Pakistan

Background School-based injuries account for one in five unintentional childhood injuries. Little is known about the epidemiology of school-based injuries in low-income settings. The objective of our study was to compare emergency department (ED) outcomes of the school-based injuries with respect to age, sex, and injury mechanisms in a Pakistani urban setting. Findings A pilot injury surveillance study was conducted at the EDs of three major tertiary-care hospitals of Rawalpindi city from July 2007 to June 2008 and included children of less than 15 years injured at school. The World Health Organization’s questionnaire for injury surveillance was used. There were 923 school injury cases. Mean age of children involved was 8.3 years (SD ± 3.3) with male female ratio 2.9:1. Most injuries occurred while playing 85.6% (n = 789); of which the most common mechanism was falls (n = 797, 86.4%). Nineteen of twenty cases were directly discharged home from the ED (N = 861). Compared to ED discharged cases, injury characteristics overrepresented in hospital admitted cases (n = 46) were age 10–14 years (65.2% vs. 40.9%, p = 0.005), male (88.6% vs. 25.9%), involved in educational activities (39.1% vs. 5.3%), injured from fire/heat (37.8% vs. 0.6%), had burns (39.5% vs. 0.9%) and head injuries (27.9% vs. 6.4%). Conclusion Falls while playing are the commonest injury mechanism in school-based injuries reported in our ED sample. School officials need to prevent these injuries. Studying injury hazards present in school environment in Pakistan might facilitate developing specific prevention strategies

Peripheral Blood Cell-Stratified Subgroups of Inflamed Depression.

BACKGROUND: Depression has been associated with increased inflammatory proteins, but changes in circulating immune cells are less well defined. METHODS: We used multiparametric flow cytometry to count 14 subsets of peripheral blood cells in 206 depression cases and 77 age- and sex-matched controls (N = 283). We used univariate and multivariate analyses to investigate the immunophenotypes associated with depression and depression severity. RESULTS: Depression cases, compared with controls, had significantly increased immune cell counts, especially neutrophils, CD4+ T cells, and monocytes, and increased inflammatory proteins (C-reactive protein and interleukin-6). Within-group analysis of cases demonstrated significant associations between the severity of depressive symptoms and increased myeloid and CD4+ T-cell counts. Depression cases were partitioned into 2 subgroups by forced binary clustering of cell counts: the inflamed depression subgroup (n = 81 out of 206; 39%) had increased monocyte, CD4+, and neutrophil counts; increased C-reactive protein and interleukin-6; and more severe depression than the uninflamed majority of cases. Relaxing the presumption of a binary classification, data-driven analysis identified 4 subgroups of depression cases, 2 of which (n = 38 and n = 100; 67% collectively) were associated with increased inflammatory proteins and more severe depression but differed in terms of myeloid and lymphoid cell counts. Results were robust to potentially confounding effects of age, sex, body mass index, recent infection, and tobacco use. CONCLUSIONS: Peripheral immune cell counts were used to distinguish inflamed and uninflamed subgroups of depression and to indicate that there may be mechanistically distinct subgroups of inflamed depression.This work was supported by the Wellcome Trust [104025]. M Lynall was supported by a fellowship and grant from Addenbrooke’s Charitable Trust, Cambridge and a fellowship from the Medical Research Council (MR/S006257/1). M. R. Clatworthy is supported by the NIHR Cambridge Biomedical Research Centre (Transplant and Regenerative Medicine), NIHR Blood and Transplant Research Unit, MRC New Investigator Research Grant, MR/N024907/1; Arthritis Research UK Cure Challenge Research Grant, 21777), and an NIHR Research Professorship (RP-2017-08-ST2-002). E. T. Bullmore and C. M. Pariante are each supported by a NIHR Senior Investigator award. This work was also supported by the NIHR Cambridge Biomedical Research Centre (Mental Health) and the Cambridge NIHR BRC Cell Phenotyping Hub, as well as the NIHR BRC at the South London and Maudsley NHS Foundation Trust and King's College London, London

Dead on arrival in a low-income country: results from a multicenter study in Pakistan

BACKGROUND: This study assessed the characteristics of dead on arrival (DOA) patients in Pakistan. METHODS: Data about the DOA patients were extracted from Pakistan National Emergency Department Surveillance study (Pak-NEDS). This study recruited all ED patients presenting to seven tertiary care hospitals during a four-month period between November 2010 and March 2011. This study included patients who were declared dead-on-arrival by the ED physician. RESULTS: A total of 1,557 DOA patients (7 per 1,000 visits) were included in the Pak-NEDS. Men accounted for two-thirds (64%) of DOA patients. Those aged 20-49 years accounted for about 46% of DOA patients. Nine percent (n = 72) of patients were brought by ambulance, and most patients presented at a public hospital (80%). About 11% of DOA patients had an injury. Factors significantly associated (p \u3c 0.05) with ambulance use were men (adjusted odds ratio [aOR] = 2.72), brought to a private hospital (OR = 2.74), and being injured (aOR = 1.89). Cardiopulmonary resuscitation (CPR) was performed on 6% (n = 42) of patients who received treatment. Those brought to a private hospital were more likely to receive CPR (aOR = 2.81). CONCLUSION: This study noted a higher burden of DOA patients in Pakistan compared to other resourceful settings (about 1 to 2 per 1,000 visits). A large proportion of patients belonging to productive age groups, and the low prevalence of ambulance and CPR use, indicate a need for improving the prehospital care and basic life support training in pakistan

Differences in police, ambulance, and emergency department reporting of traffic injuries on Karachi-Hala road, Pakistan

<p>Abstract</p> <p>Background</p> <p>Research undertaken in developing countries has assessed discrepancies in police reporting of Road Traffic Injury (RTI) for urban settings only. The objective of this study was to assess differences in RTI reporting across police, ambulance, and hospital Emergency Department (ED) datasets on an interurban road section in Pakistan.</p> <p>Methods</p> <p>The study setting was the 196-km long Karachi-Hala road section. RTIs reported to the police, Edhi Ambulance Service (EAS), and five hospital EDs in Karachi during 2008 (Jan to Dec) were compared in terms of road user involved (pedestrians, motorcyclists, four-wheeled vehicle occupants) and outcome (died or injured). Further, records from these data were matched to assess ascertainment of traffic injuries and deaths by the three datasets.</p> <p>Results</p> <p>A total of 143 RTIs were reported to the police, 531 to EAS, and 661 to hospital EDs. Fatality per hundred traffic injuries was twice as high in police records (19 per 100 RTIs) than in ambulance (10 per 100 RTIs) and hospital ED records (9 per 100 RTIs). Pedestrian and motorcyclist involvement per hundred traffic injuries was lower in police records (8 per 100 RTIs) than in ambulance (17 per 100 RTIs) and hospital ED records (43 per 100 RTIs). Of the 119 deaths independently identified after matching, police recorded 22.6%, EAS 46.2%, and hospital ED 50.4%. Similarly, police data accounted for 10.6%, EAS 43.5%, and hospital ED 54.9% of the 1 095 independently identified injured patients.</p> <p>Conclusions</p> <p>Police reporting, particularly of non-fatal RTIs and those involving vulnerable road users, should be improved in Pakistan.</p

Brain-behaviour modes of covariation in healthy and clinically depressed young people

Abstract: Understanding how variations in dimensions of psychometrics, IQ and demographics relate to changes in brain connectivity during the critical developmental period of adolescence and early adulthood is a major challenge. This has particular relevance for mental health disorders where a failure to understand these links might hinder the development of better diagnostic approaches and therapeutics. Here, we investigated this question in 306 adolescents and young adults (14–24 y, 25 clinically depressed) using a multivariate statistical framework, based on canonical correlation analysis (CCA). By linking individual functional brain connectivity profiles to self-report questionnaires, IQ and demographic data we identified two distinct modes of covariation. The first mode mapped onto an externalization/internalization axis and showed a strong association with sex. The second mode mapped onto a well-being/distress axis independent of sex. Interestingly, both modes showed an association with age. Crucially, the changes in functional brain connectivity associated with changes in these phenotypes showed marked developmental effects. The findings point to a role for the default mode, frontoparietal and limbic networks in psychopathology and depression

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice.

Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer's disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer's disease and other tau-mediated neurodegenerative diseases.Funded by a grant from the Wellcome Trust (Grant number: 104025/Z/14/Z), and by the NIHR Oxford Health Biomedical Research Centre

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer’s disease and other tau-mediated neurodegenerative diseases

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction:Plasma biomarkers for Alzheimer’s disease (AD) diagnosis/stratification are a“Holy Grail” of AD research and intensively sought; however, there are no well-established plasmamarkers.Methods:A hypothesis-led plasma biomarker search was conducted in the context of internationalmulticenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL;259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.Results:Ten analytes showed significant intergroup differences. Logistic regression identified five(FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD andCTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI(AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Twoanalytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).Discussion:Plasma markers of inflammation and complement dysregulation support diagnosis andoutcome prediction in AD and MCI. Further replication is needed before clinical translatio