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Objective: This longitudinal pilot study aimed to evaluate the feasibility, safety and potential benefits of Platelet-Rich Plasma injections into the lumbar intervertebral discs in patients with low back pain and degenerative intervertebral monodiscopathy, assessing potential efficacy on disability., Design: Longitudinal pilot study., Methods: Six participants with chronic low back pain and lumbar degenerative intervertebral disc (monodiscopathy) disease underwent 1 Platelet-Rich Plasma injection, with a 1-year follow-up. Platelet-Rich Plasma injections were administered into the lumbar intervertebral disc, and outcomes were measured using the Roland Morris Disability Questionnaire, numeric rating scale for pain, Tampa scale for kinesiophobia and lumbar flexion range. Magnetic resonance imaging analysis assessed disc changes., Results: No adverse events were reported. At the end of the 1-year follow-up, half of the patients showed significant improvements in disability scores at 1 year, while 3 of the 6 patients had no change. Magnetic resonance imaging revealed no significant disc changes., Conclusion: Platelet-Rich Plasma injections show promise for some patients with low back pain and degenerative intervertebral discopathy patients. However, caution is warranted due to study limitations, including small sample size and lack of a control group. Further research is needed to define Platelet-Rich Plasma therapy protocols., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s).)

Objectives: In Sindh Province, Pakistan, confirmed Crimean-Congo haemorrhagic fever (CCHF) increased from zero in 2008 to 16 in 2015-2016. To counter this increase, in 2016, we initiated structured CCHF surveillance to improve estimates of risk factors for CCHF in Sindh and to identify potential interventions., Methods: Beginning in 2016, all referral hospitals in Sindh reported all CCHF cases to surveillance agents. We used laboratory-confirmed cases from CCHF surveillance from 2016 to 2020 to compute incidence rates and in a case-control study to quantify risk factors for CCHF., Results: For the 5 years, CCHF incidence was 4.2 per million for the Sindh capital, Karachi, (68 cases) and 0.4 per million elsewhere. Each year, the onset of new cases peaked during the 13 days during and after the 3-day Eid-al-Adha festival, when Muslims sacrificed livestock, accounting for 38% of cases. In Karachi, livestock for Eid were purchased at a seasonal livestock market that concentrated up to 700,000 livestock. CCHF cases were most common (44%) among the general population that had visited livestock markets (odds ratio = 102)., Conclusions: Urban CCHF in Sindh province is associated with the general public's exposure to livestock markets in addition to high-risk occupations., Competing Interests: Declarations of Competing Interest The authors of the manuscript entitled ‘Risk factors of Crimean-Congo haemorrhagic fever in Sindh Province, Pakistan’ have no competing interests to declare., (Published by Elsevier Ltd.)

Background: The management of chronic pain may involve an array of tools, including radiofrequency thermocoagulation (Rf-Tc) of sensory nerve terminals. Like many other invasive procedures, Rf-Tc can generate anxiety in a lot of patients, either during the expectation of the procedure or in the course of it. Virtual reality hypnosis (VRH) is a promising tool for managing anxiety and pain in several situations, but its anxiolytic property has not been investigated in participants with chronic pain and going through a Rf-Tc procedure., Objectives: The goal of this study was to evaluate the effectiveness of VRH for reducing self-assessed anxiety in participants with chronic pain, when received in preparation for Rf-Tc., Materials and Methods: This prospective, controlled trial was conducted in the Interdisciplinary Algology Centre of the University Hospital of Liège (Belgium). Participants were assigned to two groups: VRH or control (usual care). Assessment was carried-out at 4 time points: T0 (one week before Rf-Tc); T1 (pre-intervention, on the day of Rf-Tc); T2 (immediately after the VRH intervention outside of the Rf-Tc room); and T3 (right after Rf-Tc). Medical, sociodemographic data, anxiety trait and immersive tendencies were collected at T0. Anxiety state and pain intensity were assessed at each time points. Satisfaction was examined at T3., Results: Forty-two participants were quasi-randomly assigned to the VRH or control group. No statistically significant interaction group by time was observed regarding all measured variables, including primary endpoint. However, a significant effect of time was found for anxiety and pain when considering both groups together, toward a progressive reduction., Conclusion: In the context of our study, there appears to be no significant effect of VRH at reducing anxiety in participants with chronic pain undergoing Rf-Tc. Anxiety decreases along the procedure, while pain is attenuated by the local anesthetic infiltration of the Rf site. Our results suggest that the presence of a caregiver throughout the procedure might explain the progressive decrease in anxiety. Future randomized controlled trials are needed to precisely study the effectiveness of the VRH tool, and the possibility of using it as a complementary approach for anxiety during invasive procedures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Safy, Rousseaux, Faymonville, Libbrecht, Fontaine, Raaf, Staquet, Tasset, Bonhomme, Vanhaudenhuyse and Bicego.)

Purpose: Evaluating the short- and long-term efficacy of a continuous ten day suprascapular nerve block combined with daily multidisciplinary rehabilitation on shoulder range of motion (ROM), pain, and function in patients with refractory adhesive capsulitis (AC)., Methods: In this retrospective cohort study, patients admitted to a specialized pain clinic for refractory AC for more than 6 months underwent continuous suprascapular nerve blockade for ten days and received 2 hours of physiotherapy and occupational therapy daily. Standardized assessments were performed at baseline, at days three, six, ten, 30, 90, and 180, and included active and passive ROM measurements, the visual analog scale (VAS) for pain and the disabilities of the arm, shoulder and hand (DASH) questionnaire to assess pain, disability, and quality of life. Improvements over time were assessed using ANOVAs., Results: Thirty-two patients were followed (age: 52 ± 8 years, 25 females, mean symptoms duration of two years). There was a significant improvement in ROM for all amplitudes at day ten (short-term; range: 20-35°, p < 0.001) and at day 180 (long-term; range: 18-47°, p < 0.001). The pain and disability scores significantly reduced by day 180 (mean VAS reduction: 2.6 units, p < 0.001; mean DASH reduction: 9.5 points, p < 0.001)., Conclusion: Continuous SSNB combined with intensive multidisciplinary rehabilitation represents an efficient therapeutic option for patients with chronic AC who did not respond to conventional treatments., (© 2023. The Author(s) under exclusive licence to SICOT aisbl.)

Background: Following reports of an outbreak of HIV infection among children in Larkana District, Pakistan, an international team investigated the extent and cause of the outbreak between April and June 2019., Aims: To investigate the incidence of HIV among children in Larkana District, Pakistan and describe the distribution of cases by time, place and person., Methods: Self-referred persons were tested for HIV using the national testing protocol. Local epidemiology of HIV was reviewed to generate hypotheses. An infection prevention and control (IPC) team conducted site visits and reviewed IPC practices., Results: Between 25 April and 27 June 2019, a total of 30 191 persons were tested for HIV in Larkana District, and 876 of them tested positive. Of those who tested positive, 719 (82%) were children aged <15 years. Traditional skin piercing procedures and transmission from high-risk populations to children were ruled out during the investigation. Informative interviews with parents or guardians of a convenience sample of 211 children aged <15 years showed that 99% of children had an injection or infusion for medical treatment within the past 12 months. Our investigation identified lack of HIV prevalence data for the general population including tuberculosis patients and those who attended antenatal care services., Conclusions: Investigations indicate that unsafe healthcare practices in formal and informal healthcare settings as the most likely cause of the 2019 outbreak of HIV infection in Larkana, Pakistan. Measures should be taken to improve IPC practices at the facility level, especially in pediatric and antenatal care clinics., (Copyright: © Authors 2024; Licensee: World Health Organization. EMHJ is an open access journal. All papers published in EMHJ are available under the Creative Commons Attribution Non-Commercial ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

When assessing multiple exposures in epidemiologic studies, epidemiologists often use multivariable regression models with main effects only to control for confounding. This method can mask the true effects of individual exposures, potentially leading to wrong conclusions. We revisited a simple, practical, and often overlooked approach to untangle effects of the exposures of interest, in which the combinations of all levels of the exposures of interest are recoded into a single, multicategory variable. One category, usually the absence of all exposures of interest, is selected as the common reference group (CRG). All other categories representing individual and joint exposures are then compared to the CRG using indicator variables in a regression model or in a 2×2 contingency table analysis. Using real data examples, we showed that using the CRG analysis results in estimates of individual and joint effects that are mutually comparable and free of each other's confounding effects, yielding a clear, accurate, intuitive, and simple summarization of epidemiologic study findings involving multiple exposures of interest., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: A qualitative evaluation study of the prematurely terminated PrEgabalin Lidocaine Capsaicin Neuropathic Pain (PELICAN) study was performed. The PELICAN study aimed to examine pain management for localized neuropathic pain (LNP), as epidemiological figures have shown a high percentage of LNP patients in Belgium. The study compared systemic and topical medications according to pain relief, adverse effects, and several measures of quality of life., Objective: Achieving better study patient recruitment through qualitative research. To investigate and determine the causes of the observed recruitment problems in the PELICAN study, pain centers involved in the study as well as nonrecruiting pain centers were included. Furthermore, it aimed to highlight the positive and negative lessons learned from the conducted study and the number of obstacles the team had to overcome., Methods: A qualitative study, using a mixed methods approach, was performed. Multiple pain centers in Belgium completed an online survey, after which a structured interview was conducted to elaborate the responses in more detail. The broad topics of these meetings were feedback about the study, reviewing survey answers, and actions undertaken to enhance recruitment., Results: Different factors contributed to the low recruitment rate in the PELICAN study, such as limited and late referral from the general practitioners to the Belgian pain centers, insufficient internal referrals from nonpain specialists, lack of specific expertise on LNP in some centers, scarcity of staff, limited reimbursement to administer complex analgesic schemes, overestimation of the patient population, and the reluctance of patients to participate in pain research. Additionally, shortcomings in the implemented study design and the need for more logistical investments were identified., Conclusion: The findings of the qualitative study demonstrate the need for further, more varied LNP research in Belgium, not limited to pharmacological studies. It also sheds important light on the recruitment obstacles that may be faced during these studies. Future studies could support this research by offering better proposals for feasibility and recruitment, for instance, by designing and conducting a compelling pilot study or applying social media during the recruitment phase. Clinical Trials . This trial is registered with NCT03348735. EUDRACT number 2018-003617-17., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Guy H. Hans et al.)

Background: From April to June 2019, a total of 909 new HIV infections were identified in Larkana, Pakistan; 86% was children younger than 15 years. To identify the possible transmission links in this outbreak, a case-control study was conducted in June 2019., Methods: For cases, we selected a systematic random sample of 100 HIV-positive children from the screening list. We chose 2 age-matched and sex-matched controls from the neighborhood of each HIV-positive case. All selected children were tested using the World Health Organization-approved rapid diagnosis test algorithm. We interviewed the parents of each selected child about previous exposures to parenteral treatment and compared exposures of case and control children using conditional logistic regression., Results: The ages of the selected children ranged from 1 month to 10 years. More than 90% of both HIV+ and HIV- children had received outpatient health care from MBBS-qualified private physicians. Eighty-three percent of HIV+ children versus 46% of HIV- children had received health care from one private physician [adjusted odds ratio (aOR) = 29, 95% confidence interval (95% CI): 10 to 79]. Intravenous infusions during the last outpatient visit were reported by 29% of case versus 7% of controls (aOR 57, 95% CI: 2.9 to >1000), whereas no case children and 17% of control children had received only intramuscular injections (aOR 0, 95% CI: 0 to 41). Among cases, 94% had been given infusions through a drip set compared with 85% of control children (aOR = 7.7, 95% CI: 2.3 to 26). Infusions had been administered with reused IV drip sets in 70% of cases compared with 8% of controls (aOR = 197, 95% CI: 16 to 2400)., Discussion: Private physicians reusing intravenous drip sets to treat outpatients seen in private practice were responsible for this HIV epidemic. Mapping and regulation of private practitioners were suggested., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Field epidemiology training programs (FETPs) have trained field epidemiologists who strengthen global capacities for surveillance and response to public health threats. We describe how FETP residents and graduates have contributed to COVID-19 preparedness and response globally., Methods: We conducted a cross-sectional survey of FETPs between March 13 and April 15, 2020 to understand how FETP residents or graduates were contributing to COVID-19 response activities. The survey tool was structured around the eight Pillars of the World Health Organization's (WHO) Strategic Preparedness and Response Plan for COVID-19. We used descriptive statistics to summarize quantitative results and content analysis for qualitative data., Results: Among 88 invited programs, 65 (74%) responded and indicated that FETP residents and graduates have engaged in the COVID-19 response across all six WHO regions. Response efforts focused on country-level coordination (98%), surveillance, rapid response teams, case investigations (97%), activities at points of entry (92%), and risk communication and community engagement (82%). Descriptions of FETP contributions to COVID-19 preparedness and response are categorized into seven main themes: conducting epidemiological activities, managing logistics and coordination, leading risk communication efforts, providing guidance, supporting surveillance activities, training and developing the workforce, and holding leadership positions., Conclusions: Our findings demonstrate the value of FETPs in responding to public health threats like COVID-19. This program provides critical assistance to countries' COVID-19 response efforts but also enhances epidemiologic workforce capacity, public health emergency infrastructure and helps ensure global health security as prescribed in the WHO's International Health Regulations., (© 2022. The Author(s).)

Background: In chronic pain, it seems that the effect of cognitive-behavioral therapy (CBT) is boosted when it is combined with hypnosis. The aim of this study was to assess the efficacy of self-hypnosis combined with self-care (i.e., a type of CBT) compared to music/self-care, self-care and psychoeducation/CBT and to evaluate their long-term effects., Methods: An open label randomized clinical trial enrolled patients with chronic pain and was carried out at the University Hospital of Liège (Belgium). Patients were randomized into four groups: self-hypnosis/self-care, music/self-care, self-care, psychoeducation/CBT (7 monthly sessions of 2 hours). Two follow-up sessions were delivered at 6- and 12-month. Levels of pain, fatigue intensity, anxiety, depression, insomnia severity, disability, health locus of control, mental and physical quality of life and attitudes (control, disability, harm, emotion, medical cure, medication, solicitude) towards pain were assessed before and after the treatments, and at follow-up., Results: 203 patients were randomized: 52 in self-hypnosis/self-care, 59 in music/self-care, 47 in self-care, and 45 in psychoeducation/CBT. No group effect was found. A significant time effect was showed. Directly after the treatment, all groups decreased in pain attitudes and physical quality of life. Perceived control increased. At 6-month, all patients kept their levels of physical quality of life and perceived control, and showed decrease in pain intensity, harm, emotion and medical cure. At 12-month, scores that had change previously remained ameliorated, a decrease in insomnia severity and an increase in internal locus of control were observed., Conclusions: The present findings are encouraging as they display long-term beneficial effects of complementary biopsychosocial-based treatments in chronic pain. It seems that patients continued to apply the learnt strategies as improvements were observed one year after the treatments had ended., Competing Interests: The authors have declared that no competing interests exist.

The World Health Organization monitoring and evaluation framework for the International Health Regulations (IHR, 2005) describes the targets for the Joint External Evaluation (JEE) indicators. For workforce development, the JEE defines the optimal target for attaining and complying with the IHR (2005) as 1 trained field epidemiologist (or equivalent) per 200,000 population. We explain the derivation and use of the current field epidemiology workforce development target and identify the limitations and lessons learned in applying it to various countries' public health systems. This article also proposes a way forward for improvements and implementation of this workforce development target.

More than ever, competent field epidemiologists are needed worldwide. As known, new, and resurgent communicable diseases increase their global impact, the International Health Regulations and the Global Health Security Agenda call for sufficient field epidemiologic capacity in every country to rapidly detect, respond to, and contain public health emergencies, thereby ensuring global health security. To build this capacity, for >35 years the US Centers for Disease Control and Prevention has worked with countries around the globe to develop Field Epidemiology Training Programs (FETPs). FETP trainees conduct surveillance activities and outbreak investigations in service to ministry of health programs to prevent and control infectious diseases of global health importance such as polio, cholera, tuberculosis, HIV/AIDS, malaria, and emerging zoonotic infectious diseases. FETP graduates often rise to positions of leadership to direct such programs. By training competent epidemiologists to manage public health events locally and support public health systems nationally, health security is enhanced globally.

Previous observational studies have reported protective effects of hand-washing in reducing upper respiratory infections, little is known about the associations between hand-washing and good hygienic habits and seasonal influenza infection. We conducted a case-control study to test whether the risk of influenza transmission associated with self-reported hand-washing and unhealthy hygienic habits among residents in Fujian Province, southeastern China.Laboratory confirmed seasonal influenza cases were consecutively included in the study as case-patients (n = 100). For each case, we selected 1 control person matched for age and city of residence. Telephone interview was used to collect information on hand-washing and hygienic habits. The associations were analyzed using conditional logistic regression. Compared with the poorest hand-washing score of 0 to 3, odds ratios of influenza infection decreased progressively from 0.26 to 0.029 as hand-washing score increased from 4 to the maximum of 9 (P < 0.001). Compared with the poorest hygienic habit score of 0 to 2, odds ratios of influenza infection decreased from 0.10 to 0.015 with improving score of hygienic habits (P < 0.001). Independent protective factors against influenza infection included good hygienic habits, higher hand-washing score, providing soap or hand cleaner beside the hand-washing basin, and receiving influenza vaccine. Regular hand-washing and good hygienic habits were associated with a reduced risk of influenza infection. These findings support the general recommendation for nonpharmaceutical interventions against influenza.

Background: There has been a high mortality and morbidity rate of critical and fatal patients from hand, foot and mouth disease (HFMD) in China in recent. Causes for development of critical and fatal disease remain unclear., Methods: We performed a case-control study to assess the association between use of drugs and development of critical disease and death from HFMD., Results: We found that glucocorticoids treatment was associated with a greater incidence of severe HFMD, whereas andrographolides treatment was associated with a protective effect when they are used for treatment within 48 hours after onset or before being diagnosed as critical., Conclusions: We recommend that glucocorticoids should not be used for mild HFMD and andrographolides should undergo clinical trials for treatment of enterovirus 71 infections.

We investigated a cluster of five cases of severe pneumonia from one village in Yunnan Province, China. We searched for severe pneumonia in the village and hospitals. We interviewed patients and family members about exposures. We tested acute and convalescent sera for antigen and antibody of severe acute respiratory syndrome, avian influenza, and plague. The only common exposure of the five patients was riding together in the enclosed cab of a truck for 1.5 hours while taking the first patient to the hospital. Seroconversion to plague F1 antigen confirmed plague in three survivors. Unfamiliarity of clinicians with plague and lack of sputum examination, blood culture, or postmortem examination delayed the diagnosis. No plague cases occurred among family and village contacts and health care workers. High infectivity in this cluster was limited to a crowded, poorly ventilated truck.

Background: In February 2009, a high school student was diagnosed with sputum-smear positive pulmonary tuberculosis (TB). One year later, 2 other students in the same grade developed sputum-smear positive TB., Methods: We used tuberculin skin testing (TST), chest radiography, sputum smear, and symptomatology for case identification. We defined latent TB infection (LTBI) as a TST induration of 15 mm or larger, probable TB as a chest radiograph indicative of TB plus productive cough/hemoptysis for at least 2 weeks or TST induration of 15 mm or larger, and confirmed TB as 2 or more positive sputum smears or 1 positive sputum smear plus a chest radiograph indicative of TB., Results: Of students in the same grade as the primary case-student, 26% (122/476) had LTBI and 4.8% (23/476) had probable/confirmed TB. Of teachers, 43% (18/42) had LTBI and none had probable/confirmed TB. Sharing a classroom with the primary case-student increased risk for LTBI (rate ratio = 2.5; 95% CI: 1.9-3.4) and probable/confirmed TB (rate ratio = 17, 95% CI: 7.8-39). Of students with LTBI in February 2009 who refused prophylaxis, 50% (11/22) had probable/confirmed TB in April 2010., Conclusions: This TB outbreak was likely started by delayed diagnosis of TB in the case-student and was facilitated by lack of post-exposure chemoprophylaxis. Post-exposure prophylaxis is strongly recommended for all TST-positive students.

In response to several influenza A(H1N1)pdm09 infections that developed in passengers after they traveled on the same 2 flights from New York, New York, USA, to Hong Kong, China, to Fuzhou, China, we assessed transmission of influenza A(H1N1)pdm09 virus on these flights. We defined a case of infection as onset of fever and respiratory symptoms and detection of virus by PCR in a passenger or crew member of either flight. Illness developed only in passengers who traveled on the New York to Hong Kong flight. We compared exposures of 9 case-passengers with those of 32 asymptomatic control-passengers. None of the 9 case-passengers, compared with 47% (15/32) of control-passengers, wore a face mask for the entire flight (odds ratio 0, 95% CI 0-0.71). The source case-passenger was not identified. Wearing a face mask was a protective factor against influenza infection. We recommend a more comprehensive intervention study to accurately estimate this effect.

Background: Clusters of sudden unexplained death (SUD) in Yunnan Province, China, have been linked to eating Trogia venenata mushrooms. We evaluated the toxic effect of this mushroom on mice., Methods: We prepared extracts of fresh T. venenata and Laccaria vinaceoavellanea mushrooms collected from the environs of a village that had SUD. We randomly allocated mice into treatment groups and administered mushroom extracts at doses ranging from 500 to 3500 mg/kg and water (control) via a gavage needle. We observed mice for mortality for 7 days after a 3500 mg/kg dose and for 24 hours after doses from 500 to 3000 mg/kg. We determined biochemical markers from serum two hours after a 2000 mg/kg dose., Results: Ten mice fed T. venenata extract (3500 mg/kg) died by five hours whereas all control mice (L. vinaceoavellanea extract and water) survived the seven-day observation period. All mice died by five hours after exposure to single doses of T. venenata extract ranging from 1500 to 3000 mg/kg, while the four mice exposed to a 500 mg/kg dose all survived. Mice fed 2000 mg/kg of T. venenata extract developed profound hypoglycemia (median= 0.66 mmol/L) two hours after exposure., Discussion: Hypoglycemia and death within hours of exposure, a pattern unique among mushroom toxicity, characterize T. venenata poisoning.

Introduction: Since the late 1970's, time-space clusters of sudden unexplained death (SUD) in northwest Yunnan, China have alarmed the public and health authorities. From 2006-2009, we initiated enhanced surveillance for SUD to identify a cause, and we warned villagers to avoid eating unfamiliar mushrooms., Methods: We established surveillance for SUD, defined as follows: sudden onset of serious, unexplained physical impairment followed by death in <24 hours. A mild case was onset of any illness in a member of the family or close socially related group of a SUD victim within 1 week of a SUD. We interviewed witnesses of SUD and mild case-persons to identify exposures to potentially toxic substances. We tested blood from mild cases, villagers, and for standard biochemical, enzyme, and electrolyte markers of disease., Results: We identified 33 SUD, a 73% decline from 2002-2005, distributed among 21 villages of 11 counties. We found a previously undescribed mushroom, Trogia venenata, was eaten by 5 of 7 families with SUD clusters compared to 0 of 31 other control-families from the same villages. In T. venenata-exposed persons SUD was characterized by sudden loss of consciousness during normal activities. This mushroom grew nearby 75% of 61 villages that had time-space SUD clusters from 1975 to 2009 compared to 17% of 18 villages with only single SUD (p<0.001, Fisher's exact test)., Discussion: Epidemiologic data has implicated T. venenata as a probable cause of clusters of SUD in northwestern Yunnan Province. Warnings to villagers about eating this mushroom should continue.

Introduction: Between October 1 and December 10, 2006, Bao'an, China had a 5-fold increase in acute rotavirus gastroenteritis (ARGE) cases compared with the same time in 2005. To identify the risk factors for ARGE during this outbreak, we conducted a case-control study among children ≤ 24 months old from the most heavily affected area., Methods: We defined an ARGE case as diarrhea, with group A rotavirus antigen detected from fecal samples by the enzyme-linked immunosorbent assay test. In the case-control study, 86 confirmed ARGE cases were identified. We enrolled 98 healthy control children matched by age. We administered questionnaires about exposures through telephone interviews., Results: Of 8 general exposure types, we identified the following as being associated with ARGE: visiting outpatient services of hospital X, odds ratio (OR) = 7.1 (95% confidence interval [CI], 2.2-26); contact with other children with diarrhea, OR = 2.1 (95% CI, 1.1-3.7); and hand-washing before eating, OR = 0.48 (95% CI, 0.27-0.82). After improvements in the outpatient department of hospital X, ARGE incidence in the community during the ARGE transmission season (October through December) decreased from 4.3/10000 in 2006 to 1.4/10000 in 2009., Conclusions: Outpatient services in hospital X may have contributed to the transmission of ARGE and improvements in infection control practices in this setting were associated a marked decrease incidence of ARGE in this community.

Background: Glucocorticoids increase the risk of developing critical disease from viral infections. However, primary care practitioners in China use them as antipyretics, potentially exposing hundreds of millions to this risk., Methods: We enrolled all patients with confirmed pandemic influenza A (pH1N1) virus infection aged ≥3 years with available medical records at 4 Shenyang City hospitals from 20 October to 30 November 2009. A critical patient was any confirmed, hospitalized pH1N1 patient who developed ≥1 of the following: death, respiratory failure, septic shock, failure or insufficiency of ≥2 nonpulmonary organs, mechanical ventilation, or ICU admission. In a retrospective cohort study, we evaluated the risk of developing critical illness in relation to early (≤72 hours of influenza-like illness [ILI] onset) glucocorticoids treatment., Results: Of the 83 hospitalized case-patients, 46% developed critical illness, 17% died, and 37% recovered and were discharged. Critically ill and other patients did not differ by underlying conditions and severity, median temperature at first clinic visit, and other measured risk factors. Of 17 patients who received early glucocorticoid treatment, 71% subsequently developed critical disease compared with 39% of 66 patients who received late (>72 hours) or no glucocorticoid treatment (RR(M-H) = 1.8, 95% CI = 1.2-2.8, after adjusting for 2 summary variables; ie, presence of underlying diseases and presence of underlying risk factors). Proportional hazards modeling showed that use of glucocorticoids tripled the hazard of developing critical disease (hazard ratio [HR] = 2.9, 95% CI = 1.3-6.2, after adjusting for the same summary variables)., Conclusions: Early use of parenteral glucocorticoids therapy for fever reduction and pneumonia prevention increases the risk for critical disease or death from pH1N1 infection. We recommend that guidelines on glucocorticoid use be established and enforced.

Purpose: The production and administration of drugs used intrathecally requires special care to prevent contamination with neurotoxic agents. In 2007, we investigated a widespread outbreak of paraplegia and paraparesis among Chinese patients who received intrathecal drugs to identify the presumed contaminant and its source to prevent further cases., Patients and Methods: We defined a case as onset from January 1 to October 31, 2007, of bilateral flaccid paraparesis or paraplegia or retention and incontinence of stool or urine, in a patient receiving intrathecal drugs. Using a retrospective cohort approach, we selected 12 hospitals from all hospitals that had reported cases. In these hospitals, we identified all 448 patients (including 107 cases) who received intrathecal chemotherapy or chemoprophylaxis in 2007. We calculated attack rates and Mantel-Haenszel adjusted risk ratios for intrathecal drug type and lot., Results: All 12 hospitals used intrathecal methotrexate or cytarabine produced by one pharmaceutical plant. Only two lots of each drug were associated with cases. Lot-specific attack rates ranged from 42% to 100% (risk ratio, ∞; lower confidence bounds, 1.8 to 7.3). Vincristine production had immediately preceded production of the implicated lots on the same equipment. By using ultra performance liquid chromatography, we detected vincristine (0.28 to 18 μg) in unused vials from implicated lots of methotrexate and cytarabine., Conclusion: Trace amounts of vincristine that contaminated intrathecal drugs caused a large outbreak of severe neurologic damage. Vincristine and other neurotoxic drugs should not be produced on any equipment that is also used for producing drugs that are to be administered intrathecally.

Background: Hygiene and social distancing are recommended control measures for hand, foot, and mouth disease (HFMD) and herpangina. However, empirical data to support this recommendation are limited., Methods: During an outbreak of HFMD and herpangina due to infection by the human enterovirus 71, we defined a case as a vesicular papular rash on the hands, feet, buttocks, or oral mucosa and onset from April 30 to June 26, 2008. We selected 176 HFMD and herpangina case-children and a stratified random sample of 201 asymptomatic control-children; frequency matched according to residency status. We administered a questionnaire to the parents about their children's exposures and hygienic behaviors., Results: Risk factors for HFMD and herpangina included playing with neighborhood children (odds ratio [OR]: 11 [95% confidence interval (CI): 6.2-17]), visiting an outpatient clinic for another reason ≤ 1 week before onset (OR: 20 [95% CI: 5.0-88]), and community exposures to crowded places (OR: 7.3 [95% CI: 4.1-13]). By using a score summarizing responses to 4 hand-washing questions, we found that 50% of the case-children and 2.5% of control-children had a poor score of 1 to 3, whereas 12% of the case-children and 78% of control-children had a good score of ≥ 7 (OR: 0.00069 [95% CI: 0.0022-0.022]) after we adjusted for residency, age, and community exposures by using logistic regression., Conclusions: Hand-washing by preschool-aged children and their caregivers had a significant protective effect against community-acquired HFMD and herpangina from the human enterovirus 71 infection.

Background: Human enterovirus 71 (HEV71) causes outbreaks of life-threatening diseases throughout the world. The genesis of these severe diseases is unknown., Methods: During an outbreak of HEV71 infection, we investigated risk factors for critical illness. We developed a modified pediatric index of mortality (mPIM) incorporating heart rate, temperature, white blood cell count, respiratory rate, chest infiltrates, skin color, reflexes, responsiveness, and mobility. We calculated the mPIM for 103 patients (22 deaths) using complete scoring criteria in the medical record. In a case-control study, we compared cases (mPIM > or =10 or death) with controls (mPIM = 0-9) by drugs received within 96 hours after onset of fever, initial temperature, age, and nutritional anthropometry., Results: About 66% (68/103) of the patients with an mPIM score (28 cases and 40 controls) had data on initial exposures. About 50% of the 28 cases and 18% of the 40 controls received an injection to treat fever during the first 96 hours after onset (Odds ratio [OR] = 7.0, 95% confidence interval [CI]: 1.8-28). Injections containing exclusively glucocorticoids (OR = 4.8, 95% CI: 1.2-21) or pyrazolones (OR = 4.1, 95% CI: 0.91-19, P = 0.047) were risk factors for severe HEV71 infection. About 25% of cases and 5% of controls received both drugs parenterally while 7% of cases and 30% of controls received neither (OR = 21, 95% CI: 1.8-305). Conversely, cases and controls had identical average initial temperature, and did not differ significantly by age, sex, nutritional measurements, use of other drugs, or timeliness of medical care received., Conclusion: Fever treatment with glucocorticoids and/or pyrazolones is a risk factor for life-threatening HEV71 infection.

Background: We investigated an outbreak of gluteal abscesses following intramuscular (IM) injections given at a clinic in rural China to identify the causative agent, source, and method of exposure., Methods: We defined a case as an abscess that appeared at the site of an injection given since June 1, 2006. We compared case rates by injection route, medication, and diluents. We reviewed injection practices, and cultured abscesses and environmental sites for mycobacteria., Results: From October through December 2006, 5.8% (n=35) of 604 persons who had received injections at the clinic developed a case. All 35 cases occurred in 184 patients (attack rate=19.0%) who had received IM injections with various drugs that had been mixed with normal saline (NS); risk ratio=infinity; p<0.0001. No cases occurred in the absence of NS exposure. We identified Mycobacterium abscessus from eight abscesses and from the clinic water supply, and observed the inappropriate reuse of a 16-gauge needle left in the rubber septum of 100 ml multiple-dose bottles of NS in the clinic. Fourteen percent (n=527) of the 3887 registered residents of this village had been treated with IM drugs over a three-month period, often for minor illnesses., Conclusions: This outbreak of M. abscessus occurred from exposure to extrinsically contaminated NS through improper injection practices. Frequent treatment of minor illnesses with IM injections of antibiotics was likely an important contributing factor to the size of this outbreak.

Unlabelled: Warfarin dosing algorithms do not account for genetic mutations that can affect anticoagulation response. We retrospectively assessed to what extent the VKORC1 variant genotype would alter the likelihood of being a hyperresponder or hyporesponder to warfarin in patients undergoing total joint arthroplasty. We used the international normalized ratio (INR) on the third postoperative day of 3.0 or greater to define warfarin hyperresponders and 1.07 or less to define hyporesponders. A control group of normal responders was identified. From a cohort of 1125 patients receiving warfarin thromboprophylaxis, we identified 30 free of predisposing factors that could affect warfarin response: 10 hyperresponders, eight hyporesponders, and 12 normal responders. Homozygous carriers of the VKORC1 mutant AA genotype were more likely (compared with carriers of GA or GG genotypes) to be hyperresponders (odds ratio, 7.5; 95% confidence interval, 1.04-54.1). Homozygous carriers of the GG (normal) genotype were more likely (compared with carriers of AA or GA genotypes) to be hyporesponders (odds ratio, 9; 95% confidence interval, 1.14-71). Preoperative screening for the VKORC-1 genotype could identify patients with a greater potential for being a hyperresponder or hyporesponder to warfarin. This may allow an adjusted pharmacogenetic-based warfarin dose to optimize anticoagulation, reducing postoperative risks of bleeding and thrombosis or embolism., Level of Evidence: Level III, diagnostic study.

Background: Nitric oxide regulates bone turnover by osteoblasts and osteoclasts. Nitric oxide production is impaired by the T-786C eNOS single nucleotide polymorphism, with a substitution of the nucleotide thymine by cytosine at a locus 786 base pairs upstream of the eNOS gene. This leads to vasoconstriction, platelet aggregation, reduced angiogenesis, and reduced bone formation, all of which may be associated with osteonecrosis of the hip. We studied relationships between the T-786C eNOS polymorphism and idiopathic and secondary necrosis of the head of the femur in order to better understand the pathophysiology of osteonecrosis., Methods: With use of polymerase chain reaction methodology, the T-786C eNOS polymorphism was compared in ninety-five patients with femoral head necrosis (including thirty-six nonsmokers with idiopathic necrosis and fifty-nine patients with secondary necrosis) and seventy-two healthy normal adult controls., Results: Homozygosity for the mutant eNOS allele (TT) was present in eight (22%) of thirty-six patients with idiopathic osteonecrosis as compared with one (3%) of thirty-six race, gender, and age-matched controls; heterozygosity (TC) was present in nineteen patients (53%) as compared with ten controls (28%); and the wild-type normal genotype (CC) was present in nine patients (25%) as compared with twenty-five controls (69%) (p = 0.0004). Logistic regression revealed that the T-786C eNOS mutant allele was positively associated with idiopathic osteonecrosis of the femoral head (odds ratio, 6.0; 95% confidence interval, 2.51 to 14.4). The fifty-nine patients with secondary osteonecrosis did not differ from fifty-two race, gender, and age-matched controls in terms of the distribution of the T-786C eNOS polymorphism (p = 0.19) or in terms of mutant allele frequency (30% compared with 21%; p = 0.15). The thirty-six patients with idiopathic osteonecrosis differed from the fifty-nine patients with secondary osteonecrosis in that they were more likely to have mutant eNOS genotypes (p = 0.033) and to have a higher mutant T allele frequency (49% compared with 30%; p = 0.009)., Conclusions: The T-786C eNOS polymorphism and resultant reduction of nitric oxide production is associated with, and may contribute to, the pathogenesis of idiopathic osteonecrosis of the femoral head., Level of Evidence: Prognostic Level III. See Instructions to Authors for a complete description of levels of evidence.

Buerger's disease (BD) etiologies are poorly understood. Beyond smoking cessation, medical-surgical treatments have limited success. We hypothesized that mutations associated with arterial vasospasm (stromelysin-1 5A/6A, eNOS T-786C) and C677T-A1298C methylene tetrahydrofolate reductase (MTHFR) interacted with cigarette-cannabis smoking, reducing vasodilatory nitric oxide (NO), promoting arterial spasm-thrombosis. Of 21 smoking BD patients (14 men [2 siblings], 7 women; 20 white, 1 African-American), compared to 21 age-gender-race matched healthy controls, 5A/6A stromelysin- 1 homozygosity was present in 7 of 21 (33%) BD cases versus 5 of 21 (24%) controls (risk ratio 1.4; 95% confidence interval [CI] 0.5-3.7), and eNOS T-786C homozygosity was present in 3 of 21 (14%) BD cases versus 1 of 21 (5%) controls (risk ratio 3.0; 95% CI 0.3-26.6). C677T MTHFR homozygosity or compound C677T-A1298C heterozygosity was present in 7 of 21 cases (33%) versus 11 of 21 controls (52%) (risk ratio 0.6; 95% CI 0.3-1.3). In 18 patients who stopped and 3 who continued smoking, all stromelysin-1 5A/6A and/or eNOS heterozygotes-homozygotes, superficial phlebitis, lower limb gangrenous ulcers, and intractable ischemic rest pain with arterial occlusion progressed despite conventional medical therapy, threatening amputation. In 15 patients, to increase vasodilatory NO via endothelial NO synthase, l-arginine (15 g/day) was given, along with folic acid (5 mg), vitamin B6 (100 mg), and B12 (2000 mg/day) to optimize homocysteine metabolism and reduce asymmetric dimethylarginine, a NO synthase inhibitor. Unexpectedly quickly and strikingly, within 8 weeks to 8 months receiving l-arginine-folic acid, 11 of 15 treated patients improved with uniform pain reduction, ulcer healing, and in 5, full recovery of previously absent peripheral pulses. In smokers homo/heterozygous for stromelysin-1 5A/6A and eNOS T-786C mutations, we speculate that the development and severity of BD are related to a gene-environment vasospastic interaction with reduced NO-mediated vasodilatation. Increasing NO production by l-arginine while optimizing homocysteine metabolism by folic acid-B6-B12 may have therapeutic benefit. Further blinded, placebo-controlled studies are needed to determine whether our observations can be generalized to larger BD cohorts.

Objective: To determine the risk factors involved in the typhoon episodes and to put forward and evaluate the intervention measures., Methods: We defined a confirmed injury case as: 'a person with fall,scalpel and stab, collision, drowning, injuries and trauma due to flying debris and building collapse, asphyxiation due to entrapment in collapsed buildings by typhoon from 0 am,August 12 to 6 pm, August 14 2004' and a death case as: 'a person with fall, scalpel and stab, collision, drowning, injuries and trauma due to flying debris and building collapse, asphyxiation due to entrapment in collapsed buildings by typhoon from 0 am, August 12 to 12 am, August 18 2004'. We investigated all hospitalized injured cases in ten hospitals and telephoned to those who were not hospitalized and the cases of death. We did case-control study with 1 pair versus 2 cases. 74 cases were selected in ten hospitals. The controls were neighbors of the controls matched by occupation, sex, village, and within 5 years of age without injury in this typhoon. We asked the cases and the controls on their alertness regarding typhoon and what actions taken when typhoon arrived., Results: There were 392 injury cases in all ten hospitals and 50 death cases. The attack rate of injury was 27.3 per 100 000. The fatal rate was 11.3% with the death rate 3.1 per 100 000. We investigated 209 injury cases and 31 death cases. The number of cases who were injured from 1 to 6 hours before typhoon landing accounted for 64.6% (155) of all cases. The peak of epidemic curve was 4 hours before the landing of typhoon. Data on the analysis of 74 cases and 148 controls revealed that 42% (31) of the cases were outside their homes before and during typhoon compared to 15% (22) of the controls (OR = 3.9, 95% CI: 1.9-7.7). Compared with 20% (30) control persons (OR = 17,95% CI: 4.2-68). 28% (21) cases did not receive the alert of typhoon before it arrived compared with 18% (27) control persons (OR = 3.3, 95% CI:1.3-8.6). 53% (39) of the cases did not pay attention to the alert of typhoon before typhoon arrived., Conclusion: Staying outdoor, not receiving or did not take seriously about the alert of typhoon seemed to be the risk factors of injury by the typhoon episode, suggesting that the government should increase the emergency preparedness and to raise the awareness on risks associated with typhoon.

Objective: To identify the epidemiological and clinical features of unexpected sudden cardiac deaths (SUD) in Yunnan., Methods: Choosing the old SUD cases from Xiangyun, Heqing, Nanjian and Dayao counties and using the standardized verbal autopsy Form, we interviewed the family members of the cases, witnesses and doctors as well as reviewing their medical files to get relative information., Results: We identified 116 SUDs in 21 villages from 1984 to 2004. The village-specific annually standardized incidence rates were ranged from 0.2/1000 to 8.9/1000 (median = 0.8/1000). 66% and 29% of the SUDs occurred in July and August respectively. The incidence rates of SUD were higher (1.6/1000, chi(2) = 16, P < 0.01) in 10 - 39 year-olds, and higher in females than in males (RR = 1.6, 95% CI: 1.1 - 2.3). Seventy percent of SUD occurred in families having clustering nature and 60% of the additional cases in the family were occurred within 24 hours (median = 20 hours) after the first SUD identified in the family. SUD occurred in 23 families followed the first affected family in a village during the same season. In these 23 families, 61% of the first SUD occurred within 8 days after the first SUD in the first affected family. 68% and 66% of the SUDs did not have any complaints or signs during the last 3 weeks or from 3 weeks to 2 days prior to the onset of the disease. 63% of the SUDs had cardiac symptoms within the last 2 days prior to the onset with major symptoms as dizziness, nausea, faintness, unconsciousness, weakness and palpitation. The median duration from acute onset to death was 2 hours., Conclusions: The extreme time-space clustering of SUD in families and in villages suggested that the risk factors occurred in specific time and location. Familial clustered SUD cases had common exposure pattern. Sudden onset of acute cardiac symptoms often followed by sudden death. Epidemiological study on new cases was necessary to identify risk factors and to develop hypothesis for causation. In July 2005, we instituted a special SUD surveillance system for all the affected counties together with 10 counties which had no reported cases.

We investigated a cluster of 5 plague cases; the patients included 4 with severe pharyngitis and submandibular lymphadenitis. These 4 case-patients had eaten raw camel liver. Yersinia pestis was isolated from bone marrow of the camel and from jirds (Meriones libycus) and fleas (Xenopsylla cheopis) captured at the camel corral.

Epizootics of encephalitis in El Salvador killed 203 equines between November 2001 and April 2003. During an investigation of the outbreaks, 18 (25%) of 73 serum samples collected from stablemates of deceased animals in 2003 had antibodies to West Nile virus. Ten of these infections were confirmed by plaque reduction neutralization tests, suggesting West Nile virus has extended its range and spread to Central America.

A multi-site study to assess the accuracy and performance of the biplex Invader assay for genotyping five polymorphisms implicated in venous thrombosis was carried out in seven laboratories. Genotyping results obtained using the Invader biplex assay were compared to those obtained from a reference method, either allele-specific polymerase chain reaction (AS-PCR), restriction fragment length polymorphism (PCR-RFLP) or PCR-mass spectrometry. Results were compared for five loci associated with venous thrombosis: Factor V Leiden, Factor II (prothrombin) G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, and plasminogen activator inhibitor (PAI-1) 4G/5G. Of a total of 1448 genotypes tested in this study, there were 22 samples that gave different results between the Invader biplex assay and the PCR-based methods. On further testing, 21 were determined to be correctly genotyped by the Invader Assay and only a single discrepancy was resolved in favor of the PCR-based assays. The compiled results demonstrate that the Invader biplex assay provides results more than 99.9% concordant with standard PCR-based techniques and is a rapid and highly accurate alternative to target amplification-based methods.

The K121Q polymorphism of the glycoprotein PC-1 gene was recently reported to associate with insulin resistance (IR) in an all-Caucasian, Sicilian population. Given black-white differences in plasma insulin and IR, we compared the prevalence of the KK, KQ, and QQ genotypes and their associations with insulin and IR in 2 large, biracial pediatric samples: 1 hospital-based (n = 301, 137 blacks and 164 whites) and 1 school-based (n = 639, 344 blacks and 295 whites). The Q allele frequencies in the hospital-based and school-based cohorts in black children were 0.80 and 0.77 and in the white children, 0.15 and 0.13. The K allele frequencies in the hospital-based and school-based cohorts in black children were 0.20 and 0.23 and in the white children, 0.85 and 0.87. Differences in allelic frequencies were highly significant (chi square test, P <.0001) for both the hospital-based cohort and the school-based cohort. Both cohorts were in Hardy-Weinberg equilibrium. Within race, after covariance adjusting for age and body mass index (BMI), there were no significant differences (P >/=.10) among the 3 PC-1 genotypes for insulin, glucose, or homeostasis model assessment (HOMA) IR. After covariance adjusting for age and BMI, black girls had higher insulin (P =.0007) and higher HOMA IR (P =.0002) than white girls. The K121Q polymorphism was not associated with insulin, glucose, or HOMA IR measures in black or white children. However, the QQ genotype was population-specific, encompassing most black children versus 1% to 3% of white children. As such, K121Q genotyping should be useful in epidemiology, population genetics, and forensic anthropology.

In a consecutive case series, cross-sectional study of 401 women referred for hyperlipidemia therapy, (110 [27%] on estrogen replacement therapy [ERT]), we assessed whether ERT-mediated thrombophilia and heritable thrombophilia (20210 G-->A prothrombin gene [PTG], Factor V Leiden gene mutation [FV]) interacted as risk factors for atherothrombotic cardiovascular disease (ATCVD). Thirty-eight percent of women (152/401) had > or = 1 ATCVD event, 57 (14%) had > or = 2 ATCVD events. Fifteen women (3.7%) were PTG heterozygotes, 24 (6.0%) were FV heterozygotes, (there was 1 double heterozygote [0.25%]); 363 (91%) were wild-type normal for both genes. Of the 152 women with > or = 1 ATCVD event, 21 (14%) had > or = 1 thrombophilic gene mutation, versus 17/249 (7%) without events (X(2) = 5.4, P =.02). In women on ERT and with both genes wild-type normal, 23 of 96 (24%) had > or = 1 ATCVD event versus 8 of 14 (57%) on ERT and with > or = 1 thrombophilic mutation, X(2) = 6.6, P =.01. By stepwise logistic regression, in 401 women (152 with > or = 1 ATCVD event, 249 no events), positive explanatory variables for ATCVD included FV and/or PTG (risk odds ratio, 2.59, 95% confidence interval [CI] 1.26 to 5.36, P =.01) and a PTG*ERT interaction term (risk odds ratio, 2.27, 95% CI 1.36 to 3.79, P =.0017). After deleting 23 FV heterozygotes and 14 PTG heterozygotes and 1 double heterozygote from the 401 women, ERT was protective against ATCVD events, with a risk odds ratio of 0.50 and 95% CI of 0.29 to 0.87 P =.014. PTG and FV may increase risk for ATCVD, particularly in the presence of ERT, whereas ERT may be protective against ATCVD when PTG and FV are absent., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Background and Purpose: Intracerebral hemorrhage (ICH) has a 30-day mortality rate of 40% to 50% and lacks a proven treatment. We report a preplanned, midpoint analysis of the first population-based, case-control study that examines both genetic and environmental risk factors of ICH., Methods: We prospectively identified cases of hemorrhagic stroke at all 16 hospitals in the Greater Cincinnati/Northern Kentucky region. All cases underwent medical record and neuroimaging review. Cases enrolled in the direct interview and genetic sampling arm of the study were matched to population-based control subjects by age, race, and sex. Multivariable logistic regression was performed to identify significant independent risk factors., Results: We enrolled 188 cases of ICH (67 lobar, 121 nonlobar) and 366 control subjects in the direct interview arm of the study. Significant independent risk factors for lobar ICH included the presence of an apolipoprotein E2 or E4 allele, frequent alcohol use, prior stroke, and first-degree relative with ICH. Significant independent risk factors for nonlobar ICH were hypertension, prior stroke, and first-degree relative with ICH. An increasing level of education was associated with a decreased risk of nonlobar ICH. The attributable risk of apolipoprotein E2 or E4 for lobar ICH was 29%, and the attributable risk of hypertension for nonlobar ICH was 54%., Conclusions: There is significant epidemiological evidence that the pathophysiology of ICH varies by location. We estimate that a third of all cases of lobar ICH are attributable to possession of an apolipoprotein E4 or E2 allele and that half of all cases of nonlobar ICH are attributable to hypertension.

Background and Purpose: Subarachnoid hemorrhage (SAH) caused by ruptured intracranial aneurysm affects approximately 16 000 Americans annually, and almost 40% of affected patients die within 30 days despite the best current therapy. Prevention of SAH is therefore of paramount importance. We present a preliminary analysis of risk factors for SAH from our population-based, case-control study., Methods: Cases were prospectively collected and matched 2:1 by age, race, and gender to controls using random digit dialing. Personal risk factor history, family history, neuroimaging data, and genetic samples were obtained. Univariate and bivariate analyses were performed and population-attributable risks estimated. Multivariable analysis was performed using conditional logistic regression., Results: Between June 1997 and February 2000, 107 cases and 197 controls were enrolled. In bivariate analyses, a large proportion of population-attributable risk for SAH could be explained by modifiable risk factors: smoking, hypertension, and heavy alcohol use. In multivariable analysis, current cigarette smoking, history of hypertension, frequent alcohol use, lower body mass index, and a family history of a relative with SAH or intracranial aneurysm were found to be significant, independent risk factors for SAH., Conclusion: Our data confirm previous reports that SAH clusters within some families independent of environmental risk factors, suggesting that SAH has a significant genetic component. Yet, even among families at increased risk of SAH, smoking cessation, treatment of hypertension, and reduced alcohol intake may substantially decrease SAH risk. The independent associations with heavy alcohol use and low body mass index with SAH may be confounded by smoking and require further study.