Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study.

OBJECTIVES: The aim of this analysis was to characterize transmitted drug resistance (TDR) in Strategic Timing of Antiretroviral Treatment (START) study participants by next-generation sequencing (NGS), a sensitive assay capable of detecting low-frequency variants. METHODS: Stored plasma from participants with entry HIV RNA > 1000 copies/mL were analysed by NGS (Illumina MiSeq). TDR was based on the WHO 2009 surveillance definition with the addition of reverse transcriptase (RT) mutations T215N and E138K, and integrase strand transfer inhibitor (INSTI) surveillance mutations (Stanford HIVdb). Drug resistance mutations (DRMs) detected at three thresholds are reported: > 2%, 5% and 20% of the viral population. RESULTS: Between 2009 and 2013, START enrolled 4684 antiretroviral therapy (ART)-naïve individuals in 35 countries. Baseline NGS data at study entry were available for 2902 participants. Overall prevalence rates of TDR using a detection threshold of 2%/5%/20% were 9.2%/5.6%/3.2% for nucleoside reverse transcriptase inhibitors (NRTIs), 9.2%/6.6%/4.9% for non-NRTIs, 11.4%/5.5%/2.4% for protease inhibitors (PIs) and 3.5%/1.6%/0.1% for INSTI DRMs and varied by geographic region. Using the 2% detection threshold, individual DRMs with the highest prevalence were: PI M46IL (5.5%), RT K103NS (3.5%), RT G190ASE (3.1%), T215ISCDVEN (2.5%), RT M41L (2.2%), RT K219QENR (1.7%) and PI D30N (1.6%). INSTI DRMs were detected almost exclusively below the 20% detection threshold, most commonly Y143H (0.4%), Q148R (0.4%) and T66I (0.4%). CONCLUSIONS: Use of NGS in this study population resulted in the detection of a large proportion of low-level variants which would not have been detected by traditional Sanger sequencing. Global surveillance studies utilizing NGS should provide a more comprehensive assessment of TDR prevalence in different regions of the world.

Digital monitoring and compensation of MDL based on higher-order Poincaré spheres.

We present a digital technique able to monitor and compensate for the mode-dependent losses (MDL) in space-division multiplexing (SDM) transmission systems. The working principle of the technique is based on the analysis of the received signal samples in the higher-order Poincaré spheres (HoPs). When an arbitrary pair of tributaries is represented in the respective HoPs, the effect of the MDL can be modeled as a simple shift of the constellation points in a such sphere. Therefore, the MDL can be estimated by computing those shifts over all the HoPs and the induced signal distortions can be compensated by re-centering all the constellations in the respective HoPs. It should be highlighted that the proposed technique is scalable with an arbitrary number of spatial channels, modulation format agonistic and free of training sequences. The HoPs-based MDL monitoring (compensation) technique allows the MDL estimation (compensation) up to values of ≈ 6 dB. The proposed technique can partially compensate the MDL distortion, making a MDL sensitive algorithm in an insensitive one. When the proposed technique assists a HoPs-based space-demultiplexing algorithm, it provides signal-to-noise ratio (SNR) enhancements of 2, 4 and 8 dB for PM-QPSK, PM-16QAM and PM-64QAM signals, respectively, for the particular case of a SDM-based transmission system with a spatial diversity of 2 and 2 dB of MDL.

Emergence and control of an outbreak of infections due to Panton-Valentine leukocidin positive, ST22 methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit.

Methicillin resistant Staphylococcus aureus (MRSA) infection can cause significant morbidity and mortality in neonates. We investigated a nosocomial MRSA outbreak in a neonatal intensive care unit (NICU), using a novel typing method. Following two fatal cases, in May 2011, a prospective outbreak investigation was conducted, involving neonates, mothers and healthcare workers in a large tertiary NICU in Sydney. MRSA isolates were characterized by antimicrobial susceptibility testing, a multiplex PCR-based reverse line blot (mPCR/RLB) binary typing system and other molecular typing methods. Over 7 months, 14 neonates were colonized with MRSA and six infected: three with superficial lesions and three with life-threatening disease, including the two index cases, who died despite empirical treatment with vancomycin. Isolates from 15 neonates were indistinguishable by RLB typing and identified as a PVL-producing ST22 SCCmec IV MRSA strain, which was resistant to gentamicin and trimethoprim-sulphamethoxazole. The outbreak strain was also isolated from one healthcare worker, one environmental swab and one father, but the source remained obscure. During the same period several different non-multiresistant and multiresistant MRSA strains were isolated from five neonates, five mothers (including two whose infants were colonized with the outbreak strain), one father, three healthcare workers and two environmental swabs. Rapid turnaround time of typing results allowed us to recognize and define the outbreak and implement targeted infection control interventions. PVL-producing ST22 SCCmec IV MRSA appears to be a virulent and highly transmissible pathogen in the NICU, which was difficult to control.

Halting the fuse discharge propagation using optical fiber microwires.

We report and analyze the halting of the fuse effect propagation in optical fiber microwires. The increase of the mode field diameter in the tapered region decreases the optical intensity resulting in the extinction of the fuse effect. This fiber element presents a low insertion loss and can be introduced in the optical network in order to protect the active equipment from the damage caused by the fuse effect.

Seizures in cerebral vein and dural sinus thrombosis.

To describe early symptomatic and late seizures in a cohort of patients with acute cerebral vein and dural sinus thrombosis (CVDST) and to identify their determinants, we performed a prospective registry and follow-up study of CVDST patients admitted to 20 Portuguese hospitals, from June 1995 to June 1998. Of 91 registered patients, 31 (34%) had early symptomatic seizures; 29 (31.9%) as a presenting feature and 2 (2.1%) after admission. Early symptomatic seizures were more frequent in patients with motor and sensory deficits and in those with focal oedema/ischaemic infarcts or haemorrhages on admission CT/MR. On multivariate logistic regression analysis, sensory defects (OR = 7.8; 95% CI = 0.8-74.8) and a parenchymal lesion on admission CT/MR (OR = 3.7, 95% CI = 1.4-9.4) were found to be significant predictors of early symptomatic seizures. Seizures were directly related to acute death in 2 patients. Eight (9.5%) patients had late seizures, which were multiple in 4 (4.8%). Late seizures were more frequent in patients with early symptomatic seizures and with haemorrhage on admission CT/MR. Neither early symptomatic seizures nor late seizures were related to functional prognosis at the last follow-up (median = 1 year). There is a moderate risk of seizure recurrence early in the course and during the first year after CVDST. Seizures can be a cause of acute death, but might not have an independent influence on functional outcome. Pharmacological prevention of seizures after CVDST should probably be limited to patients with early symptomatic seizures and cerebral lesions on admission CT/MR.

Role of pancreatic polypeptide as a market of transplanted insulin-producing fetal pig cells.

Transplantation of insulin-producing fetal pancreatic tissue into diabetic recipients has been shown to normalize blood glucose levels after several months. This time period is required for the growth and maturation of the fetal tissue so insulin levels cannot be used as a marker of graft function while the beta-cell is immature. Therefore, we have examined the use of another pancreatic endocrine hormone, pancreatic polypeptide (PP), to monitor graft function. The cell that produces this hormone has been shown to be the first mature endocrine cell in the fetal pancreas. Fetal pig pancreatic tissue, both in the form of 1 mm3 explants and islet-like cell clusters (ICCs), was transplanted into immunodeficient SCID mice and the levels of PP and insulin were measured in plasma and in the graft for up to 12 weeks. PP was detected in the untransplanted explants (0.58 pmol/mg) and ICCs (0.06 pmol/ICC) and the PP to insulin ratio was 2.7% and 5.8%, respectively. PP (but not porcine C-peptide, a marker of insulin secretion) was detectable in the plasma of SCID mice from 4 days to 3 weeks after transplantation, but not thereafter. The highest values were obtained at 4 days to 1 week. In the grafted tissue PP and insulin were present at all time points and the ratio of PP to insulin was 59%, 87%, 75%, 56%, 7%, 8%, and 7% at 4 days, 1, 2, 3, 6, 9, and 12 weeks, respectively. The decline in PP levels 3 weeks after transplantation was associated with beta-cell development in the graft. PP was also secreted by fetal pig pancreatic explants transplanted into diabetic NOD/SCID mice, with plasma levels measurable in the first week after the tissue was grafted. In immunocompetent BALB/c mice transplanted with the tissue, PP was detectable in plasma for 2 days after transplantation but not at 4 days, when cellular rejection commenced, or thereafter. We conclude that plasma PP levels can be used as a marker of the viability of fetal porcine pancreatic tissue in the first 3 weeks after it is transplanted into mice. These findings may have relevance to fetal pancreatic tissue transplanted into humans if suitable techniques can be developed to separate pig from human PP.

Epidermal growth factor and keratinocyte growth factor differentially regulate epidermal migration, growth, and differentiation.

Various growth factors such as epidermal growth factor and keratinocyte growth factor have been reported to promote wound closure and epidermal regeneration. In the present study epidermis reconstructed on de-epidermized dermis was used to investigate the effects of epidermal growth factor and keratinocyte growth factor on keratinocyte proliferation, migration and differentiation. Our results show that epidermal growth factor supplemented cultures share many of the features which are observed during regeneration of wounded epidermis: a thickening of the entire epidermis, an enhanced rate of proliferation and migration, and an increase in keratin 6, keratin 16, skin-derived antileukoproteinase, involucrin and transglutaminase 1 expression. The increase in transglutaminase 1 protein is accompanied by an increase in the amount of active transglutaminase 1 enzyme. Surprisingly no increase in keratin 17 is observed. Prolonging the culture period for more than two weeks results in rapid senescence and aging of the cultures. In contrast, keratinocyte growth factor supplemented cultures have a tissue architecture that is similar to healthy native epidermis and remains unchanged for at least 4 weeks of air-exposure. The rate of proliferation and the expression of keratins 6, 16 and 17, skin-derived antileukoproteinase, involucrin and transglutaminase 1 is similar to that found in healthy epidermis and furthermore keratinocyte migration does not occur. When the culture medium is supplemented with a combination of keratinocyte growth factor and a low concentration of epidermal growth factor, skin-derived antileukoproteinase, involucrin and keratins 6, 16 and 17 expression is similar to that found in cultures supplemented with keratinocyte growth factor alone and in healthy epidermis. Only high transglutaminase 1 expression remains similar to that observed in cultures supplemented with epidermal growth factor alone. Our results show that the regulation of keratinocyte growth, migration and differentiation depends on the availability of these growth factors. Epidermal growth factor may play a dominant early role in wound healing by stimulating keratinocyte proliferation and migration while keratinocyte growth factor may play a role later in the repair process by stabilizing epidermal turnover and barrier function.

Differentiation of fetal pig endocrine cells after allografting into the thymus gland.

BACKGROUND: The thymus of large animals, such as the pig, is thought to be an appropriate site for transplanting adult islets, which contain numerous beta cells, for the purpose of reversing diabetes. Whether fetal islet-like cell clusters (ICCs), which contain few beta cells, will develop at this site, so that adequate amounts of insulin can be produced, is unknown. METHODS: Between 15,000 and 40,000 ICCs were injected into the thymus gland of six juvenile immunosuppressed pigs, and the animals were killed up to 30 days later. The graft was then examined histologically and comparisons made with untransplanted ICCs and those grafted into the omentum of immunosuppressed pigs. RESULTS: At transplantation, the percentage of cells in the ICCs containing insulin, glucagon, somatostatin, or pancreatic polypeptide was 9+/-1%, 13+/-2%, 9+/-1%, and 3+/-1% respectively. Within 9-30 days of transplantation into the thymus, the percentage of all endocrine cells increased, insulin to 41+/-3%, glucagon to 43+/-6%, somatostatin to 26+/-4%, and pancreatic polypeptide to 9+/-3%. There was co-localization of more than one hormone in some cells. Omental grafts contained a similar percentage of insulin and glucagon-containing cells, but significantly fewer somatostatin and pancreatic polypeptide-containing cells. CONCLUSIONS: Endocrine cells from the fetal pig pancreas will differentiate when transplanted into the thymus gland of the pig, making this a suitable site for grafting ICCs to test their ability to normalize blood glucose levels of diabetic recipients.

Can a clinical classification of stroke predict complications and treatments during hospitalization?

The predictive value of the Oxfordshire Community Stroke Project ischemic stroke classification for acute stroke complications, therapeutic interventions and disability at discharge was investigated in 297 consecutive first-ever acute stroke patients. More than one medical complication (odds ratio, OR = 2.2), fever (OR = 2.5) and dependency (Rankin grade > 2) at discharge (OR = 2.3) were more frequent in intracerebral hemorrhage patients. Fever and urinary tract infections were the most common complications among ischemic stroke patients. Both were more frequent in total anterior circulation infarct (TACI) patients (OR = 11.5 and OR = 3.7). Neurological deterioration was observed in about 10% of TACI and posterior circulation infarct (POCI) patients. Dependency at discharge was more frequent in TACI patients (OR = 10.3). Logistic regression analysis identified ischemic stroke subgroups (OR = 8.4) and medical complications (OR = 3.8) as predictors of poor outcome (Rankin score > or = 4). A clinical classification is useful to predict possible medical and neurological complications in the acute phase, death and dependency at discharge.

Diagnosis of stroke by the nonneurologist. A validation study.

BACKGROUND AND PURPOSE: The first medical contact of an acute stroke victim is often a nonneurologist. Validation of stroke diagnosis made by these medical doctors is poorly known. The present study seeks to validate the stroke diagnoses made by general practitioners (GPs) and hospital emergency service physicians (ESPs). METHODS: Validation through direct interview and examination by a neurologist was performed for diagnoses of stroke made by GPs in patients under their care and doctors working at the emergency departments of 3 hospitals. RESULTS: Validation of the GP diagnosis was confirmed in 44 cases (85%); 3 patients (6%) had transient ischemic attacks and 5 (9%) suffered from noncerebrovascular disorders. Validation of the ESP diagnosis was confirmed in 169 patients (91%); 16 (9%) had a noncerebrovascular diagnosis. Overall, the most frequent conditions misdiagnosed as stroke were neurological in nature (cerebral tumor, 3; subdural hematoma, 1; seizure, 1; benign paroxysmal postural vertigo, 1; peripheral facial palsy, 2; psychiatric condition, 6; and other medical disorders, 7). CONCLUSIONS: In the majority of cases, nonneurologists (either GPs or ESPs) can make a correct diagnosis of acute stroke. Treatment of acute stroke with drugs that do not cause serious side effects can be started before evaluation by a neurologist and CT scan.

Diagnosis of transient ischemic attack by the nonneurologist. A validation study.

BACKGROUND AND PURPOSE: Interobserver reliability of the diagnosis of transient ischemic attack (TIA) is low, and diagnosis of TIA made by nonneurologists is often erroneous. We sought to validate the diagnosis of TIA made by general practitioners (GPs) and by hospital emergency service physicians (emergency MDs). METHODS: A list of 20 neurological symptoms was distributed to 20 GPs and 22 neurologists who graded the compatibility of each symptom with the TIA diagnosis. At least two neurologists validated TIA diagnoses made by GPs for patients under their care or by emergency MDs. RESULTS: Compared with neurologists, GPs considered "confusion" and "unexplained fall" more often compatible with TIA and "lower facial palsy" and "monocular blindness" less often compatible with TIA. Validation of diagnosis by GP was confirmed in 10 patients (19%); 26 patients had strokes, and 16 (31%) had a noncerebrovascular disorder. Validation of diagnosis by emergency MD was confirmed in 4 patients (13%); 10 patients had strokes, and 17 (55%) had noncerebrovascular disorders. The most frequent conditions misdiagnosed as TIAs were transient disturbances of consciousness, mental status, and balance. CONCLUSIONS: The TIA concept is understood differently by neurologists and nonneurologists. GPs and emergency MDs often label minor strokes and several nonvascular transient neurological disturbances as TIAs. Until this misconception of TIA is changed, the term TIA should probably be avoided in the communication between referring physicians and neurologists. If not referred to a neurologist, one third to one half of patients labeled with a diagnosis of TIA will be inappropriately managed.

Headache in intracerebral hematomas.

OBJECTIVES: We sought to describe the frequency and location of headache in intracerebral hematoma (ICH) and to analyze its clinical and CT predictors by means of multivariate analysis. BACKGROUND: Headache is more common in intracerebral hemorrhage than in ischemic stroke, and its frequency varies with hematoma location, but the pathophysiologic mechanisms of headache associated with ICH are not fully known. METHODS: We examined a cohort of 289 patients with ICH during a 14-month period in a university hospital. Clinical, including the presence and location of headache, and CT features were collected by two neurologists. RESULTS: One hundred and sixty-five (57%) patients with ICH had a headache at the onset of their stroke. Headache was more common in cerebellar and lobar hemorrhages than in deep ones (thalamic, caudate, capsuloputaminal, brainstem). Headache was also more common in women, patients younger than 70 years, those who vomited, and those with meningeal signs, a Glasgow Coma Scale score < 10, a hematoma volume > 10 ml or CT evidence of intraventricular or subarachnoid bleeding, moderate to severe hydrocephalus, or transtentorial herniation or midline shift. In multiple logistic regression analysis, only meningeal signs (odds ratio [OR] = 2.3), cerebellar or lobar location (OR = 2.1), transtentorial herniation (OR = 1.8), and female gender (OR = 1.6) were significant predictors of headache at the onset of ICH. CONCLUSIONS: Hematoma location, meningeal signs, and gender are more predictive of headache than hematoma volume, suggesting that headache is more often related to the activation of an anatomically distributed system in susceptible individuals and to subarachnoid bleeding than to intracranial hypertension.

AIDS and cerebrovascular disease.

BACKGROUND: Although neurological complications of human immunodeficiency virus (HIV) infection are common, the presence of cerebrovascular disease (CVD) has been seldom reported. The purpose of this report is to review available data on the association between stroke and acquired immunodeficiency syndrome (AIDS). SUMMARY OF REVIEW: A review of all literature published between mid-1976 and December 1994 was performed through a MEDLINE search with the following key words: AIDS, CVD, human T-cell lymphotropic virus type III, and HIV-1. Only reports of clinical stroke in patients with AIDS or HIV infection and autopsy series with stroke findings were selected. The type of study, population, number of stroke patients, subtype and etiology of stroke, and associated AIDS conditions were described. Six clinical series and 11 autopsy series were found, with a total of 1885 cases with AIDS, AIDS-related complex, and HIV carriers. Forty percent had a neurological complication, but only 1.3% had a stroke syndrome. Ischemic infarcts were more common than intracerebral hemorrhages. Cerebral infarcts were generally due to nonbacterial thrombotic endocarditis or concomitant opportunistic central nervous system infection, and intracerebral hemorrhages were usually associated with thrombocytopenia, primary central nervous system lymphoma, and metastatic Kaposi's sarcoma. Autopsy findings of CVD were generally not related with clinical stroke before death. Data are not available to determine the role of risk factors for AIDS in CVD. CONCLUSIONS: Because of limitations of the available data, it is still not clear whether there is an association between AIDS and stroke. Further studies are needed to better define the epidemiology of CVD in association with AIDS.

Seizures at the onset of subarachnoid haemorrhage.

In a prospective study of 253 patients with subarachnoid haemorrhage, 16 (6.3%) had seizures at the onset of bleeding. None had a previous history of seizures. One was an alcoholic. None had metabolic imbalance. Hemiparesis, Hunt's grade > 3, the amount of subarachnoid blood and the presence of an aneurysm were significantly more frequent in patients with seizures at the onset of subarachnoid haemorrhage. Although rebleeding and mortality or severe disability at discharge were more frequent in these patients, seizures were not a significant predictor of prognosis. One of the survivors with early seizures developed recurrent epileptic seizures 1 year later.

Carotid stenosis associated with atrial fibrillation.

PURPOSE AND SETTING: To describe the prevalence and risk factors for carotid stenosis in TIA/stroke patients with non valvular atrial fibrillation (AF) and to compare clinical and CT characteristics of TIA/stroke in AF patients with and without carotid stenosis. SUBJECTS: 50 TIA/stroke patients with AF who had ultrasound investigation of the extracranial vessels, included in a prospective hospitalar registry. RESULTS: Twenty-two patients had some degree of carotid stenosis, but only 5 had more than 50% stenosis, including one with occlusion. Stenosis was neither more frequent nor more severe on the symptomatic side. Smokers were significantly more frequent in AF patients with > 50% stenosis. Clinical and CT features were quite similar in patients with and without carotid stenosis. CONCLUSION: The association in a TIA/Stroke patient of AF and severe carotid stenosis on the symptomatic side is exceptional. TIA/strokes related to carotid stenosis cannot be identified by their clinical/CT characteristics. Management of these patients must be decided by stratification of risk of recurrence for AF and from carotid stenosis and balance of these risks with that of endarterectomy.

Headache associated with transient ischemic attacks.

Sixty (29%) of 205 consecutive patients with transient ischemic attacks registered in a hospital stroke data base had headache within 72 hours of onset. Headache was significantly more common in nonsmokers (odds ratio = 2.8; 95% confidence interval = 6.7 to 1.2). Headache was infrequent in patients with amaurosis fugax, and was not significantly associated with any other particular clinical presentation of transient ischemic attack. Headache was more common in vertebrobasilar (33%) than in carotid distribution (24%) episodes, and was not rare in transient ischemic attacks presenting as lacunar syndromes (29%). Headache was less frequent in patients whose computerized tomograms showed an infarct appropriate to the symptoms (odds ratio = 0.2; 95% confidence interval = 0.02 to 1.4). A diffuse headache was more common in patients with lacunar events than in patients with cortical attacks (odds ratio = 3.0; 95% confidence interval = 13 to 0.07). No other association was found between headache location and the presumed involved vascular territory. Headache in patients with transient ischemic attacks is poorly related/explained by the clinical characteristics of the ischemic event.

A multivariate study of headache associated with ischemic stroke.

Thirty-four percent of 182 ischemic stroke patients registered during 1 year in a prospective hospital stroke data base complained of headache within a 72-hour interval of stroke onset. Headache was more common in patients under 70 years of age, in nonsmokers, in those with a past history of migraine, and in subjects presenting transient loss of consciousness, nausea/vomiting, or visual field defects. Headache was more frequent in vertebrobasilar (57%) than in carotid (20%) territory strokes, more so in posterior cerebral artery (90%) and cerebellar infarcts (80%), and was infrequent in subcortical infarcts (7%) and lacunes due to single perforator disease (9%). In multiple regression analysis, vertebrobasilar stroke (odds ratio 6.9), lacuanr stroke (odds ratio 0.06), and past history of migraine (odds ratio 6.7) were significant independent predictors of headache, suggesting that ischemic stroke location is the major determinant of stroke-associated headache, most probably related to activation of the trigeminovascular system, whose threshold may be modified by individual susceptibility.

Perimesencephalic and nonperimesencephalic subarachnoid haemorrhages with negative angiograms.

BACKGROUND: van Gijn and co-workers identified "Perimesencephalic haemorrhage" (PM) as distinct, benign, non-aneurysmal subarachnoid haemorrhage. However, there is only one retrospective series of this entity outside the Netherlands. PURPOSE: to confirm (or not) the benign nature of perimesencephalic subarachnoid haemorrhage by evaluating its clinical course and long-term follow-up in a consecutive series of patients admitted to a University Hospital. METHODS: Patients with subarachnoid haemorrhage and negative cerebral angiography admitted between January 1985 and April 1992 were classified according to the distribution of blood on a CT scan performed within 72 hours after onset, in perimesencephalic and non-perimesencephalic haemorrhages. Demographic and clinical data (collected consecutively), complications and long-term follow-up (obtained by chart review and follow-up by mail) were compared in the two groups. RESULTS: Seventy one cases, 36 perimesencephalic and 35 nonperimesencephalic were included. Sex and age distribution were similar in the two groups. A normal examination on admission was the rule in the perimesencephalic group. Only one patient with perimesencephalic haemorrhage had a complication--transient neurological signs during angiography--and there were no deaths or morbidity during follow-up. In the non-perimesencephalic group three patients rebleed, four developed hydrocephalus and two had delayed cerebral ischaemia. Mean duration of follow-up was 27.6 months for the perimesencephalic and 30.8 months for the non-perimesencephalic group. After discharge there was a fatal rebleed in the latter group. Fifteen percent of the subjects (11% of the perimesencephalic group and 20% of the non-perimesencephalic group) retired from work during the follow-up period. Headaches and depression were found in similar percentages (22-25%) in both groups. CONCLUSIONS: This study confirms that perimesencephalic haemorrhage is a distinct entity within the larger group of subarachnoid haemorrhage with negative angiograms, with a good short term and long-term prognosis, and no need for repeated angiographic investigation.

Smoking and aneurysmal subarachnoid haemorrhage: a case-control study.

BACKGROUND: Despite recent advances in the management of subarachnoid haemorrhage, the mortality rate associated with the condition remains high. The identification of risk factors for subarachnoid haemorrhage may lead to the development of interventions aimed at its prevention. METHODS: We compared the prevalence of vascular risk factors using a case-control design in 141 consecutively admitted patients who had suffered a subarachnoid haemorrhage with that in age- and sex-matched subjects registered with a general practitioner in a western suburb of Lisbon. RESULTS: The prevalence of diabetes and hyperlipidaemia did not differ between the groups. Hypertension was 8.3 times more frequent among patients with subarachnoid haemorrhage (95% confidence interval 4.6-16.7) than in the control group, and smoking was four times more frequent (95% confidence interval 2.0-8.6). The association between smoking and subarachnoid haemorrhage persisted after controlling for the presence of hypertension (odds ratio for hypertensive participants = 10.5, 95% confidence interval 1.9-56.4; odds ratio for normotensive participants = 3.7, 95% confidence interval 1.6-10.1) and was independent of both age and sex. CONCLUSION: These results indicate that hypertension and smoking are both involved in the growth or rupture of cerebral aneurysms.