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Biomedical subjects

John Wright

Publications and source records attributed to John Wright.

At least 37 records · Page 2Linked to original sources

Bilateral total knee replacement: staging and pulmonary embolism.

BACKGROUND: When a bilateral total knee replacement is indicated, it is not clear whether it is preferable to operate on both knees during the same hospitalization (simultaneously) or to stage the procedures in two separate hospital stays. A greater risk of pulmonary embolism after simultaneous total knee replacement has been reported by some authors, but little national data are available. METHODS: We reviewed the records of 122,385 United States Medicare enrollees who had had a total knee replacement in 2000. We noted whether they had had a unilateral procedure or two procedures and, if they had had two procedures, whether both had been done during the same hospitalization or whether the operations had been performed during two separate hospital stays. Age, sex, race, residence, Medicaid eligibility (a proxy for low income), and the Charlson comorbidity score were documented for each patient as were the total numbers of total knee replacements performed in the year 2000 by the hospital and the surgeon. The probability of a symptomatic pulmonary embolism developing in the first three months after surgery was calculated for the simultaneous, staged, and unilateral procedures. RESULTS: Simultaneous procedures were much more likely to be performed in high-volume hospitals and by high-volume surgeons than were staged procedures. Men had proportionately more simultaneous procedures than did women. Hospitals in the northeastern United States were the most likely to perform simultaneous procedures. A pulmonary embolism developed in the first three months in 0.81% of the patients who had had a single procedure compared with 1.44% of the patients who had undergone a simultaneous procedure (adjusted hazard ratio 1.81; 95% confidence interval, 1.49, 2.20). CONCLUSIONS: The systematic differences in patient gender, hospital and surgeon volume, and geographic region between those who undergo simultaneous total knee replacements and those who undergo staged procedures should be borne in mind when outcomes are being compared. The adjusted risk of pulmonary embolism is about 80% higher in the three months after a simultaneous procedure than in the three months after a single procedure, which suggests that the sum of the risks associated with the two operations of a staged procedure may equal or exceed the risk of simultaneous total knee replacement.

Aged↗

Extent of followup care after elective total hip replacement.

OBJECTIVE: To estimate the extent of radiographic and orthopedic followup among recipients of total hip replacement (THR), and to identify patients who are less likely to have consistent followup over 6 years postoperatively. METHODS: We studied a population-based sample of 622 patients who received THR in 1995. We developed a multivariate ordinal regression model with the extent of radiographic followup as the dependent variable (none, early, and consistent), adjusting for demographic and preoperative clinical characteristics, and hospital and surgeon volume. RESULTS: Ninety-four (15%) patients indicated that they had no followup radiographs, 269 (43%) had early followup only, and 259 (42%) had consistent followup radiographs over 6 years. Ninety percent of those with consistent followup orthopedic visits also had consistent followup radiographs over 6 years. Multivariate analyses revealed that older patients were less likely to have radiographic followup than younger patients (OR 0.76, 95% CI 0.65, 0.89) per each 5-year increase in age. Subjects with no college education were less likely to have radiographic followup than those with more education (OR 0.58, 95% CI 0.41, 0.83), and those with lower income were less likely to have radiographic followup than those with a higher income (OR 0.50, 95% CI 0.27, 0.92). CONCLUSION: Only 42% of THR recipients reported consistent radiographic followup. Older patients, patients with lower income, and those with lower education level were less likely to have consistent radiographic followup over 6 years after THR. These population groups can serve as targets for interventions to improve followup after elective THR.

Aged↗

Phase I clinical trial of the farnesyltransferase inhibitor BMS-214662 administered as a weekly 24 h continuous intravenous infusion in patients with advanced solid tumors.

PURPOSE: BMS-214662 is a novel farnesyltransferase (FT) inhibitor that has shown promising suggestions of single agent activity in patients with advanced solid tumors when administered as a 1 h intravenous (i.v.) infusion every 3 weeks. The degree of FT inhibition in peripheral blood mononuclear cells (PBMCs) was greatest at the end of the infusion and rapidly reversed as the concentration of the drug in the plasma decayed. A second phase I trial of BMS-214662 administered as a weekly 24 h i.v. infusion was initiated to determine if the duration of maximum FT inhibition could be significantly extended by prolonging the infusion time and increasing the frequency of administration. PATIENTS AND METHODS: Infusion of BMS-214662 was prolonged from 2, 4, 8, 16, 24 h in single patient cohorts and repeated weekly for 3 out of 4 weeks. The initial dose was 56 mg/m(2). When the infusion duration reached 24 h, the dose was escalated at a constant multiples of 1.4 in single patient cohorts until the occurrence of toxicity greater than grade 1, upon which groups of at least three patients were evaluated at each dose level. The plasma pharmacokinetics and FT inhibition in PBMCs were measured in all patients at the prospective maximum tolerated dose. RESULTS: Nineteen patients participated in the study (11 males/8 females) and the weekly dose was increased to a maximum of 300 mg/m(2) given as a 24 h i.v. infusion. Drug-related toxicity greater than grade 1 first occurred at 300 mg/m(2), with two patients experiencing dose-limiting toxicity. One patient developed a grade 3 hyponatremia and another developed reversible grade 3 diarrhea, grade 2 renal toxicity, and grade 3 transaminitis. A 275 mg/m(2) dose was then evaluated, where one of the three patients treated experienced reversible grade 4 renal toxicity and grade 3 diarrhea. In view of the identical renal toxicity at 275 mg/m(2) in another study and limited drug availability, there was no further accrual to this dose level and the study was closed. No evidence of antitumor activity was observed. The plasma pharmacokinetics of BMS-214662 was linear with high interpatient variability. In the three patients evaluated at the 275 mg/m(2) dose level, the maximum inhibition of FT activity in PBMCs was 47+/-23% of the baseline. CONCLUSION: Administering BMS-214662 as a weekly 24 h continuous i.v. infusion permitted a considerably greater dose intensity to be delivered as compared to a single 1 h infusion given once every 3 weeks. The more prolonged infusion schedule resulted in a much lower degree of maximum FT inhibition in PBMCs than achieved with the 1 h infusion, although the duration of enzyme inhibition was longer, consistent with the lower peak plasma concentration of the drug provided by comparably tolerated doses when given as a 24 h infusion. Similarly, delivering the drug with increased dose intensity permitted by this weekly administration schedule did not appear to enhance its therapeutic benefit, at least in this phase I trial. Continued development of BMS-214662 may depend upon the potential for using it in combination with other anticancer drugs.

Adult↗

A phase II study of perifosine in androgen independent prostate cancer.

OBJECTIVES: Perifosine is an alkylphospholipid that has exhibited broad antineoplastic activity in preclinical studies. The primary objective of this study was to determine the clinical efficacy of this agent in the treatment of androgen-independent prostate cancer (AIPC) using PSA and clinical criteria. PATIENTS AND METHODS: Nineteen patients with progressive, metastatic AIPC were treated with oral perifosine. Cycles were 28 days in length. A loading dose of 900 mg was given on day 1 of cycle 1 followed by a maintenance dose of 150 mg daily for the next 20 days. A loading dose of 600 mg was administered on the first day of subsequent cycles by the maintenance dose of 150 mg daily for the next 20 days. Pharmacokinetic measurements were made throughout the course of the study. Circulating epithelial cells were collected via leukapheresis on day 0, 3, and 28. RESULTS: Median patient age was 67 years and median PSA was 180 ng/mL (range: 19-904 ng/ml). Grade 1-2 fatigue and gastrointestinal toxicities were common. Pharmacokinetic studies showed an average minimum concentration at steady-state of approximately 4059 ng/ml which correlated well with previous studies. Median time to progression was four weeks. There were no radiographic responses or PSA declines of 50% or greater related to perifosine. CONCLUSIONS: Treatment with perifosine was complicated by fatigue and gastrointestinal toxicity. No significant clinical activity against prostate cancer was observed. This agent does not merit further study in the setting of monotherapy in this population.

Aged↗

Phase I trial of tipifarnib in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs: a North American Brain Tumor Consortium Study.

PURPOSE: To determine the maximum-tolerated dose (MTD), toxicities, and clinical effect of tipifarnib, a farnesyltransferase (FTase) inhibitor, in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs (EIAEDs). This study compares the pharmacokinetics and pharmacodynamics of tipifarnib at MTD in patients on and off EIAEDs. PATIENTS AND METHODS: Recurrent malignant glioma patients were treated with tipifarnib using an interpatient dose-escalation scheme. Pharmacokinetics and pharmacodynamics were assessed. RESULTS: Twenty-three assessable patients taking EIAEDs received tipifarnib in escalating doses from 300 to 700 mg bid for 21 of 28 days. The dose-limiting toxicity was rash, and the MTD was 600 mg bid. There were significant differences in pharmacokinetic parameters at 300 mg bid between patients on and not on EIAEDs. When patients on EIAEDs and not on EIAEDs were treated at MTD (600 and 300 mg bid, respectively), the area under the plasma concentration-time curve (AUC)(0-12 hours) was approximately two-fold lower in patients on EIAEDs. Farnesyltransferase inhibition was noted at all tipifarnib dose levels, as measured in peripheral-blood mononuclear cells (PBMC). CONCLUSION: Toxicities and pharmacokinetics differ significantly when comparing patients on or off EIAEDs. EIAEDs significantly decreased the maximum concentration, AUC(0-12 hours), and predose trough concentrations of tipifarnib. Even in the presence of EIAEDs, the levels of tipifarnib were still sufficient to potently inhibit FTase activity in patient PBMCs. The relevance of these important findings to clinical activity will be determined in ongoing studies with larger numbers of patients.

Administration, Oral↗

South Asians and epilepsy: exploring health experiences, needs and beliefs of communities in the north of England.

PURPOSE: To examine the beliefs and experiences of South Asians with epilepsy and the extent of provision of appropriate information and accessible services for them by health professionals. METHODS: Qualitative interviews with 30 South Asians with epilepsy, 16 carers and 10 health professionals. In addition, two focus groups were held with 16 South Asians without epilepsy recruited from community centers. The interview sample was divided by religious groupings (Hindus, Sikhs and Muslims). Fieldwork was conducted in Bradford and Leeds (England). RESULTS: Beliefs that epilepsy is caused by spirit possession (Muslims) or attributable to sins committed in a past life (Sikhs and Hindus) were reported as being widely held among South Asians living both in the UK and the Indian subcontinent, although few informants themselves subscribed to such views. Compliance with conventional medication was high; however, those who experienced seizures most often were most likely to turn to traditional South Asian therapies. Most informants used both treatments simultaneously. The main issues regarding the provision of services were: lack of appropriate information and advice; language and communication barriers; problems in interaction with health professionals. Also discussed were the potential merits of attending support groups. Greatest dissatisfaction was expressed in relation to primary care, whereas the highest praise was reserved for specialist epilepsy nurses. CONCLUSIONS: Our findings show both similarities and differences between participants' experiences, where gender, age or other aspects of personal biography can be as important as religion, culture or country of origin. Furthermore, the impact of being diagnosed with epilepsy can be exacerbated by structural impediments to accessing information and appropriate services.

Adolescent↗

Experimental inoculation of European red foxes with recombinant vaccinia virus expressing zona pellucida C proteins.

The antifertility potential of zona pellucida proteins was tested in European red foxes by immunizing females with recombinant vaccinia viruses that express zona pellucida subunit C proteins. The fox zona pellucida C (fZPC) protein was newly identified and isolated as a cDNA clone from fox ovary RNA. Eighteen European foxes were inoculated with the recombinant vaccinia viruses or with wildtype vaccinia virus (wtVV) and their clinical, virological and immune responses evaluated. Following intradermal inoculation with wtVV or recombinant vaccinia virus expressing fox zona pellucida C (rVV-fZPC), or after peroral administration with recombinant vaccinia virus expressing the porcine zona pellucida C protein (rVV-pZPC) clinical signs of disease were not observed. Five out of six foxes developed antibodies to wtVV proteins. However, none of 12 foxes (six inoculated intradermally with rVV-fZPC, six perorally with rVV-pZPC) reacted in immunoblots with the transgenic fZPC or pZPC, respectively. Infectious wtVV, rVV-fZPC or rVV-pZPC was not isolated from mucosal secretions of any of the foxes whereas viral DNA was present in oral swabs of 3/18 foxes as determined by PCR. Hematological parameters remained mostly unchanged. Histopathological changes were not observed in the ovaries of rVV-fZPC or wtVV inoculated foxes. The data indicate that inoculation of foxes with cell culture infectious wtVV, rVV-fZPC or rVV-pZPC did not result in production of infectious progeny virus in vivo. For this reason transgene expression may have been insufficient to induce adequate immune responses against the transgenic proteins.

Animals↗

A phase II trial with pharmacodynamic endpoints of the proteasome inhibitor bortezomib in patients with metastatic colorectal cancer.

PURPOSE: To evaluate the effects of the proteasome inhibitor bortezomib on tumor growth in patients with advanced colorectal cancer, and to explore the relationship between correlative studies and clinical outcome. DESIGN: Bortezomib (1.3 mg/m(2)) was administered i.v. on days 1, 4, 8, and 11 of a 21-day cycle. Tumor response was assessed after every two cycles. Tumor biopsies were done prior to treatment and on day 9 of the first treatment cycle. Biopsies were examined for Ser(32/36)-IkappaB, Ser(276)-nuclear factor kappaB (NFkappaB), hypoxia-inducible factor-1alpha (HIF-1alpha), carbonic anhydrase IX (CAIX), p53, and microvessel density using immunohistochemistry. RESULTS: Nineteen patients received 42 cycles (range 1-4) of bortezomib. No objective response was seen; three patients had stable disease at cycle 2, two patients had progressive disease after cycle 1, and 11 patients had progressive disease at cycle 2. Of the three patients with stable disease, one had progressive disease after cycle 4, and two were withdrawn due to toxicity. The median time to progression was 5.1 weeks (95% confidence interval, 5.1-11.1 weeks). There was a significant increase in the expression of HIF-1alpha relative to its transcriptional target CAIX following bortezomib, and a similar effect was also observed in a companion study using a human tumor xenograft model. Expression of p53, Ser(276)-NFkappaB, and Ser(32/36)-IkappaB was unchanged. CONCLUSION: Single agent bortezomib is inactive in metastatic colorectal cancer. Using this regimen, there was no detectable effect on NFkappaB, but a significant accumulation of HIF-1alpha was seen relative to CAIX. This suggests that proteasome inhibition alters the response to tumor hypoxia, and further investigation of this effect is indicated.

Aged↗

Institutionalizing policy-level health impact assessment in Europe: is coupling health impact assessment with strategic environmental assessment the next step forward?

European Union (EU) Member States are interested in using health impact assessment (HIA) as a means of safeguarding their obligations to protect human health under the 1997 Treaty of Amsterdam. However, several have encountered difficulties institutionalizing HIA with the policy-making process. As a consequence, the World Health Organization (WHO) Regional Office for Europe has suggested coupling HIA with strategic environmental assessment (SEA). Traditionally, the incorporation of HIA into other forms of impact assessment has been resisted, for fear of losing its focus on health issues to environmental concerns, and compromising its social model of health with the introduction of biophysical indicators. But can these fears be substantiated? In this paper, we investigate the grounds for such concerns by reviewing the relevant policy documents and departmental guidelines of four non-European countries that have considered the use of integrated assessment. We found that the case for associating HIA with SEA in Europe is strong, and offers potential solutions to problems of screening, theoretical framework, causal pathways and ready entry to the policy process. Coupling HIA with SEA may thus be the next step forward in a longer journey towards institutionalizing HIA as an independent policy-linked device.

Australia↗

Phase I study of the farnesyltransferase inhibitor BMS-214662 given weekly in patients with solid tumors.

PURPOSE: A phase I trial of BMS-214662, a selective farnesyltransferase inhibitor with significant preclinical antitumor activity in which drug was given as a weekly 1-hour infusion for four of six weeks, was conducted to evaluate the tolerability, pharmacokinetics, and pharmacodynamic effect on farnesyltransferase activity in peripheral blood mononuclear cells. EXPERIMENTAL DESIGN: BMS-214662 was given to 27 patients with solid tumors at 10 escalating dose levels (28-220 mg/m(2)) allowing intrapatient dose escalation; pharmacokinetics and pharmacodynamics were done at the first seven dose levels. RESULTS: Grade 4 neutropenia (four patients) was the most common dose-limiting toxicity followed by aminotransferase elevation (grade 3 alanine aminotransferase and grade 4 aspartate aminotransferase) and grade 3 dehydration. Most frequent toxicities were neutropenia in 11 (14%), anemia in 15 (19%), fatigue in 9 (12%), and nausea and diarrhea in 6 (8%) of courses, respectively. One minor response lasting 18 weeks in a patient with non-small cell lung cancer, serum calcitonin level reduction accompanied by disease stabilization in two of four patients with medullary thyroid carcinoma, and stable disease in 16 of 25 evaluable patients was seen. No correlation was observed between dose and C(max), total body clearance (mean, 26.15 +/- 10.88 L per hour per m(2)), volume of distribution at steady state (mean, 39.51 +/- 17.91 L/m(2)), or half-life (mean, 2.63 +/- 1.81 hours); a moderate correlation existed between dose given and systemic drug exposure (AUC). Substantial inhibition of peripheral blood mononuclear cell farnesyltransferase activity but near complete recovery by 24 hours was seen. CONCLUSION: BMS-214667 was well tolerated as a weekly 1-hour i.v. infusion for four of six weeks with evidence of pharmacodynamic effect. The study was terminated before maximum tolerated dose was reached. Alternative schedules of drug administration might result in improved pharmacodynamic profile.

Adolescent↗

Chemoresistance to depsipeptide FK228 [(E)-(1S,4S,10S,21R)-7-[(Z)-ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,22-pentanone] is mediated by reversible MDR1 induction in human cancer cell lines.

Histone acetylation status, an epigenetic determinant of gene transcription, is controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). The potent HDAC inhibitor FK228 [(E)-(1S,4S,10S,21R)-7-[(Z)-ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,22-pentanone] is a substrate for multidrug resistance protein (MDR1) and multidrug resistance-associated protein 1 (MRP1), both of which mediate FK228 resistance. To determine the mechanisms underlying acquired FK228 resistance, we developed four FK228-resistant cell lines from HCT-15, IGROV1, MCF7, and K562 cells by stepwise increases in FK228 exposure. Parent and resistant cells were characterized using a 70-oligomer cDNA microarray, real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and cytotoxicity assays. At both mRNA and protein levels, MDR1, but not MRP1 or other potential resistance genes, was strongly up-regulated in all resistant cell lines. HAT or HDAC activities were unaffected in resistant cells, consistent with a lack of cross-resistance to HDAC inhibitors that are not MDR1 substrates. FK228 was found to reversibly induce MDR1 expression by HDAC inhibition and subsequent histone hyperacetylation at the MDR1 promoter, as shown by real-time RT-PCR, Western blot, and chromatin immunoprecipitation. This study reveals a significant role of histone acetylation in MDR1 transcription, which seems to mediate FK228 resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Phase I study of BMS-214662, a farnesyl transferase inhibitor in patients with acute leukemias and high-risk myelodysplastic syndromes.

PURPOSE: To investigate the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of BMS-214662, a farnesyl transferase (FTase) inhibitor, in patients with acute leukemias and high-risk myelodysplastic syndromes (MDS). PATIENTS AND METHODS: Patients with relapsed or refractory acute leukemias or MDS, or previously untreated but poor candidates for chemotherapy, were included in this phase I study with a 3 + 3 dose escalation design. BMS-214662 was administered as a 1-hour bolus once weekly at doses of 42 to 157 mg/m2. Once the MTD was identified, the schedule was changed to a 24-hour continuous infusion once weekly (starting dose, 300 mg/m2). RESULTS: Thirty patients were treated at a dose of 42 (n = 1), 56 (n = 3), 84 (n = 3), 118 (n = 13), 157 (n = 6) or 300 mg/m2 (n = 4). DLT occurred in 3 patients at 157 mg/m2, including nausea, vomiting, diarrhea, hypokalemia and cardiovascular problems. No DLT occurred with 24-hour continuous infusion. MTD with a 1-hour infusion was 118 mg/m2, with no MTD identified with the 24-hour infusion. Plasma concentrations of BMS-214662 correlated with the dose. Inhibition of FTase activity of approximately 60% occurred after the infusion with recovery to near baseline after 24 hours. Five patients had evidence of antileukemia activity, including two with complete remission with incomplete platelet recovery, one with hematologic improvement, and two with morphologic leukemia-free state. CONCLUSION: BMS-214662 is well tolerated at doses of up to 118 mg/m2 as a 1-hour infusion. The toxicity profile and efficacy may be improved with prolonged exposure. Further investigation of this agent in leukemia is warranted.

Acute Disease↗

Participation in health impact assessment: objectives, methods and core values.

Health impact assessment (HIA) is a multidisciplinary aid to decision-making that assesses the impact of policy on public health and on health inequalities. Its purpose is to assist decision-makers to maximize health gains and to reduce inequalities. The 1999 Gothenburg Consensus Paper (GCP) provides researchers with a rationale for establishing community participation as a core value of HIA. According to the GCP, participation in HIA empowers people within the decision-making process and redresses the democratic deficit between government and society. Participation in HIA generates a sense that health and decision-making is community-owned, and the personal experiences of citizens become integral to the formulation of policy. However, the participatory and empowering dimensions of HIA may prove difficult to operationalize. In this review of the participation strategies adopted in key applications of HIA in the United Kingdom, we found that HIA's aim of influencing decision-making creates tension between its participatory and knowledge-gathering dimensions. Accordingly, researchers have decreased the participatory dimension of HIA by reducing the importance attached to the community's experience of empowerment, ownership and democracy, while enlarging its knowledge-gathering dimension by giving pre-eminence to "expert" and "research-generated" evidence. Recent applications of HIA offer a serviceable rationale for participation as a means of information gathering and it is no longer tenable to uphold HIA as a means of empowering communities and advancing the aims of participatory democracy.

Community Health Planning↗

Factors predicting functional and radiographic outcomes after arthroscopic partial meniscectomy: a review of the literature.

We reviewed articles examining the associations between factors identifiable before or during arthroscopic partial meniscectomy (APM) and functional and radiographic outcomes. We assessed the magnitude of effect and statistical significance of associations between predictor variables and outcomes within each study. We then qualitatively synthesized these observations across multiple studies. Twenty-five studies met our criteria for inclusion. Eight of the studies had a prospective design. There were no randomized, controlled trials. The studies had important methodological limitations. Greater size of meniscal resection and female gender showed the strongest and most consistent associations with greater radiographic evidence of osteoarthritis across multiple studies. Greater articular cartilage degeneration assessed at surgery, greater size of meniscal resection, greater laxity of the anterior cruciate ligament, and prior surgery on the index knee were the strongest predictors of worse functional outcomes. Patients with worse preoperative health status (SF-36 score <60), Workers' Compensation, and pending litigation had worse functional outcomes, but these factors were examined in only 1 study. There was consistently no significant difference in radiographic or functional outcome between medial or lateral meniscal injury. Clinicians should incorporate these predictors of outcome into their conversations with patients regarding the advantages and drawbacks of APM.

Female↗

Impact of marital and psychological distress on therapeutic alliance in couples undergoing couple therapy.

In this study, we describe the psychometric properties of the Couple Therapy Alliance Scale--revised (CTAS-r) and investigates the impact of marital and psychiatric distress on alliance. Seventy-nine couples in therapy completed a French version of the Dyadic Adjustment Scale and of the Psychiatric Symptoms Index at session one, and a French version of the CTAS-r at session three. Results indicate that the French version of the CTAS-r has adequate psychometric properties, although the subscales of the instrument are highly intercorrelated. Furthermore, marital adjustment predicts alliance scores, whereas psychiatric symptoms do not. Finally, male marital adjustment and female psychiatric symptoms are lower in couples where spouses have divergent perceptions of the alliance. Future research directions are discussed.

Adaptation, Psychological↗

Evidence of cultural hybridity in responses to epilepsy among Pakistani muslims living in the UK.

OBJECTIVES: To examine how people from Bradford's Pakistani Muslim community experience living with epilepsy. Specifically, the paper addresses social interactions and negotiations with care providers and considers how different understandings of epilepsy are integrated. METHODS: Interviews were conducted with a sample of Bradford's Pakistani Muslim community (n = 20). Interviews were analysed to identify themes and significant areas of shared concern. RESULTS: This paper identifies popular, professional and folk sectors contributing to an individual's 'health system'. Where sectors overlap, zones of hybridity are created: that is, a person might simultaneously seek help from a doctor and from a religious healer, or might offer explanations for seizures that include neurological and spiritual components. DISCUSSION: While there are many similarities between the experiences of these minority ethnic community members and published work on the lived experience of epilepsy in other communities, there are also important differences that service providers need to recognize and respond to. Differences include forms of cultural expression and specific language needs. Improving communication between professionals and persons with epilepsy needs to be prioritized.

Access to Information↗

Clinical correlates and repetition of self-harming behaviors among female adolescent victims of sexual abuse.

This study investigated self-harming behaviors in 149 female adolescent victims of sexual abuse, first, by determining the rates of nine types of self-mutilating behavior at intake and nine months later and, second, by investigating comorbidity of clinical correlates associated with these behaviors. The adolescents were divided into three groups according to level of self-mutilating behavior and then compared on symptom self-reports; 62.1% of the adolescents engaged in at least one self-mutilating behavior. A graded relation was observed between level of self-mutilating behavior and rate, and total number of clinical disorders. At nine month follow-up, one in four teenagers still reported a moderate or high level of self-harm. The need for systematic assessment and intervention of self-mutilating behaviors is discussed.

Adolescent↗