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Biomedical subjects

Kevin Kelly

Publications and source records attributed to Kevin Kelly.

14 recordsLinked to original sources

Sudden unexpected death in epilepsy: a search for risk factors.

Sudden unexpected death in epilepsy (SUDEP) is the commonest cause of seizure-related mortality in people with refractory epilepsy. Of the 6140 patients registered with the Epilepsy Unit at the Western Infirmary in Glasgow between 1982 and 2005, 529 had died, 62 (11.7%) of whom succumbed to SUDEP. All but 2 deaths occurred at home; 3 were witnessed. Two living controls were matched with each SUDEP case for year of birth, gender, and syndromic classification. Mean duration of epilepsy was significantly longer in cases compared with controls (P=0.001). More people succumbing to SUDEP had had a seizure within the previous year (P=0.007). There were no significant associations between SUDEP and a history of generalized tonic-clonic seizures, drug polytherapy, and current use of carbamazepine. There is an urgent need for a large-scale, prospective, international, community-based study of SUDEP to explore more closely the risk factors to plan preventive strategies.

Adolescent↗

Pharmacological outcomes in older people with newly diagnosed epilepsy.

BACKGROUND: Old age is the most common time in life to develop epilepsy. Despite this, there are few published data exploring pharmacological outcomes in this population. METHODS: We analyzed outcomes in 117 older patients (median age, 73; range, 65-92) for whom localization-related epilepsy was newly diagnosed and treatment begun at a single center over a 20-year period. RESULTS: Seventy-three (62%) patients became seizure-free for at least 12 months on their first AED, with 30 (26%) failing to respond and 14 (12%) not tolerating the treatment. Following pharmacological manipulation, 93 (79%) patients attained remission, 87 (93%) on monotherapy and 6 (7%) on duotherapy. No individual AED was more likely to confer seizure freedom than any other. Patients attaining remission were more likely to have had fewer pretreatment seizures (P=0.0078) than those who did not obtain full seizure control. CONCLUSION: The prognosis in epilepsy may be better in older than younger people, perhaps reflecting lower lesional epileptogenicity and genetic predisposition.

Age Factors↗

Mortality in adults with newly diagnosed and chronic epilepsy: a retrospective comparative study.

BACKGROUND: People with epilepsy are at increased risk of premature death compared with the general population. Many clinicians are unsure whether and when this issue should be broached with their patients. We analysed mortality in patients with newly diagnosed and chronic epilepsy over a 20-year period. METHODS: Patients who attended the epilepsy service at the Western Infirmary in Glasgow, UK between 1981 and 2001, with newly diagnosed epilepsy (n=890) or referred after receiving unsuccessful treatment elsewhere (n=2689) were included in the study. Mortality data were obtained from the General Registrar Office for Scotland. Causes of death were ascertained from death certificates and primary care and health authority records. The two patient cohorts were compared with age-matched and sex-matched Scottish comparison groups. Standardised mortality ratios (SMR) were calculated for each epilepsy type, 10-year age band, and cause of death category. FINDINGS: Newly diagnosed patients had a 42% increase in mortality (SMR 1.42, 95% CI 1.16-1.72) compared with the comparison group. Increased mortality was recorded in those who had not responded to treatment, with no increase in risk observed in patients who were seizure free. In the chronic epilepsy cohort, there was more than double the expected number of deaths (2.05, 1.83-2.26). The incidence of sudden unexpected death in epilepsy was 1.08 and 2.46 per 1000 patient-years in patients with newly diagnosed and chronic epilepsy, respectively. The greatest excess in mortality was reported in patients younger than 30 years. INTERPRETATION: Mortality risks and preventive strategies should be discussed with patients with epilepsy when treatment fails or is refused despite recurrent seizures.

Adult↗

The influence of birth weight and genetic factors on lipid levels: a study in adult twins.

Twins can be used to investigate the biological basis for observed associations between birth weight and later disease risk, as they experience in utero growth restriction compared with singletons, which can differ in magnitude within twin pairs despite partial or total genetic identity. In the present study, sixty monozygotic and seventy-one dizygotic same-sex twin pairs aged 19-50 years and eighty-nine singleton controls matched for age, gestational age, sex, maternal age and parity were recruited from an obstetric database. Associations between fasting lipid levels and birth weight were assessed by linear regression with adjustment for possible confounding factors. Twins were significantly lighter at birth but were not significantly different in adult height, weight or lipid levels from the singleton controls. There was a significant inverse association between birth weight and both total and LDL-cholesterol levels among singleton controls (-0.53 mmol/l per kg (95 % CI -0.97, -0.09), P = 0.02 and -0.39 mmol/l per kg (95 % CI -0.76, -0.02), P = 0.04, respectively), but there was no significant association between birth weight and lipid levels in either unpaired or within-pair analysis of twins. The results suggest that the in utero growth restriction and early catch-up growth experienced by twins does not increase the risk of an atherogenic lipid profile in adult life.

Adult↗

Thoracic microendoscopic discectomy: a human cadaver study.

STUDY DESIGN: Feasibility analysis of percutaneous posterolateral thoracic microendoscopic discectomy in a human cadaver model. OBJECTIVE: To describe a new, minimally invasive, posterolateral approach to the thoracic spine for the treatment of disc herniations. SUMMARY OF BACKGROUND: Thoracoscopic discectomy offers surgeons direct ventral access to thoracic disc herniations but requires entry into the chest. Many surgeons favor a posterolateral approach to the thoracic spine, thereby avoiding morbidity associated with entry into the thoracic cavity. By adapting minimal access surgical techniques to the thoracic spine, effective treatment of thoracic disc herniations should be possible and may help expedite recovery. METHODS: Two cadaveric human torsos were used. Using simple adaptations of our standard lumbar microendoscopic discectomy technique, endoscopic discectomies were performed throughout the mid and lower thoracic spine. Operative time was recorded. The extent of the discectomy as well as the extent of bony removal was evaluated using computed tomography myelography. RESULTS: Nine discectomies were performed in two cadaveric specimens, from T5-T6-T9-T10. Operative times ranged from 46 to 77 minutes (mean 60 minutes). The procedure required removing 3.4 mm (+/-1.9 mm) of the ipsilateral facet, which amounted to 35.4% (+/-17.5%) of the facet complex. Canal decompression averaged 73.5% (+/-7.9%). CONCLUSIONS: Thoracic microendoscopic discectomy allows for a posterolateral approach to thoracic disc herniation without entry into the chest cavity that consistently gives access to the majority of the canal while requiring only a minimal amount of bone removal. This technique provides an approach angle similar to that obtained with other posterolateral discectomy techniques while limiting the morbidity associated with exposure.

Arthroscopy↗

Minimally invasive microendoscopy-assisted transforaminal lumbar interbody fusion with instrumentation.

OBJECT: The authors have developed a novel technique for percutaneous fusion in which standard microendoscopic discectomy is modified. Based on data obtained in their cadaveric studies they considered that this minimally invasive interbody fusion could be safely implemented clinically. The authors describe their initial experience with a microendoscopic transforaminal lumbar interbody fusion (METLIF) technique, with regard to safety in the placement of percutaneous instrumentation, perioperative morbidity, and early postoperative results. METHODS: The METLIF procedure was performed unilaterally in 20 patients with single-level lumbar spondylolisthesis or pure mechanical back pain with endoscopic assistance, hemilaminectomy, unilateral facetectomy, and microdiscectomy. Two interbody grafts were placed via the lateral exposure of the disc space. Bilateral percutaneous pedicle screws were then inserted. Compared with patients who had undergone single-level posterior LIF at the same institutions, intraoperative blood loss, hospital length of stay (LOS), and postoperative narcotic agent use were significantly lower in the METLIF group. The mean LOS for the percutaneous fusion group was 3.4 days (5.1 days in those who underwent PLIF; p < 0.02). There have been no procedure-related complications in this series to date. CONCLUSIONS: The METLIF technique provided an option for percutaneous interbody fusion similar to that in open surgery while minimizing destruction to adjacent tissues. This technique was safe and exhibited a trend toward decreased intraoperative blood loss, postoperative pain, total narcotic use, and the risk of transfusion.

Adult↗

Asthma prevalence and morbidity among rural Iowa schoolchildren.

BACKGROUND: There are conflicting findings about the prevalence of asthma among farm and nonfarm children. OBJECTIVES: We sought to estimate asthma prevalence and morbidity and determine differences between farm and nonfarm children. METHODS: The study population consisted of all children aged 6 to 14 years enrolled in 10 school districts in 2 noncontiguous rural Iowa counties from 2000 through 2002. The mailed parental screening questionnaire included the International Study of Asthma and Allergies in Childhood core questionnaire, items from the Functional Severity Index, and items on physician diagnosis and medication and urgent care use. RESULTS: The response rate was 86.6%. The 12-month prevalence of wheeze was 19.1%. Self-reported physician diagnosis of asthma was reported by 13.4%. On multivariable analysis controlling for age, sex, and county, children who lived on farms were less likely than those who lived in town to have ever wheezed (odds ratio, 0.71; 95% CI, 0.58-0.87) or to have wheezed during the past year (odds ratio, 0.77; 95% CI, 0.60-0.98). However, this protective association with farming was only observed in one of the study counties. Among those who wheezed, farm and nonfarm children were equally likely to have been given a diagnosis of asthma and had comparable morbidity. CONCLUSION: By using a standardized questionnaire with a high response rate in this large, rural, population-based study, asthma prevalence rivaled that in large Midwestern cities. Unmeasured risk factors might account for the apparent protective effect in Keokuk County. These findings cast doubt on a protective effect of rural life for the development of childhood asthma.

Adolescent↗

Pharmacological outcomes in people with mental retardation and epilepsy.

The aim of this study was to examine prospective outcomes in mentally retarded people with epilepsy seen for the first time during 1998 until the end of 2001. Two hundred and fourteen patients (120 men, 94 women, aged 11-70 years [median 34 years]) were referred over this 4-year period. Median duration of follow-up was 18 months (range, 13-36 months). Seventeen (8%) had nonepileptic attacks only, 10 of whom were being treated with antiepileptic drugs (AEDs). The remaining 197 (92%) patients had epilepsy, the majority (n=151, 77%) presenting with focal seizures. A total of 22 patients were started on AED treatment, with seizure freedom for at least a year being achieved in 10 (45%). AED manipulation was undertaken in a further 136 patients, resulting in 59 (43%) becoming seizure-free. No relationship was found between extent of mental retardation and seizure control. There was no deterioration in mean caregiver scores rating sleep, appetite, alertness, and behavior. These findings suggest that AED therapy can result in seizure freedom in more than 40% of mentally retarded people with epilepsy without producing unacceptable toxicity.

Adolescent↗

Levetiracetam for people with mental retardation and refractory epilepsy.

Levetiracetam (LEV) is a novel antiepileptic drug (AED) with efficacy against a wide range of seizures types. The aim of this observational study was to assess its effectiveness in patients with mental retardation and refractory epilepsy. Sixty-four patients were started on adjunctive LEV after a 3-month baseline. LEV was initially dosed at 250 mg daily and increased by 250 mg every 2 weeks thereafter according to clinical response. Caregivers rated the patient's sleep, appetite, alertness, and behavior as poor (1), reasonable (2), or good (3) at each clinic visit. Patients were reviewed until one of four endpoints was reached: seizure freedom for at least 6 months, > or = 50% reduction in seizure frequency (responder) over a 6-month period, <50% reduction in seizure frequency (marginal effect) over a 6-month period, or LEV withdrawal due to lack of efficacy, adverse effects, or both. Twenty-four (38%) patients became seizure-free, 10 of whom were controlled on LEV 250 mg twice daily. An additional 18 (28%) patients were classified as responders, and 8 (12%) reported only marginal benefit from adjunctive LEV. Fourteen (22%) patients discontinued LEV (6 worsening seizures, 1 lack of efficacy, 7 adverse effects). Caregivers rated combined sleep, appetite, alertness, and behavior scores as "improved" at the end of follow-up (P<0.001). LEV improved seizure control in the majority of patients with mental retardation and may also have enhanced their quality of life.

Adolescent↗

Microfluidic devices fabricated in poly(methyl methacrylate) using hot-embossing with integrated sampling capillary and fiber optics for fluorescence detection.

High-aspect-ratio microstructures have been prepared using hot-embossing techniques in poly(methyl methacrylate) (PMMA) from Ni-based molding dies prepared using LIGA (Lithographie, Galvanoformung, Abformung). Due to the small amount of mask undercutting associated with X-ray lithography and the high energy X-ray beam used during photoresist patterning, deep structures with sharp and smooth sidewalls have been prepared. The Ni-electroforms produced devices with minimal replication errors using hot-embossing at a turn around time of approximately 5 min per device. In addition, several different polymers (with different glass transition temperatures) could be effectively molded with these Ni-electroforms and many devices (>300) molded with the same master without any noticeable degradation. The PMMA devices consisted of deep and narrow channels for insertion of a capillary for the automated electrokinetic loading of sample into the microfluidic device and also, a pair of optical fibers for shuttling laser light to the detection zone and collecting the resulting emission for fluorescence analysis. Electrophoretic separations of double-stranded DNA ladders Phi X174 digested with Hae III) were performed with fluorescence detection accomplished using near-IR excitation. It was found that the narrow width of the channels did not contribute significantly to electrophoretic zone broadening and the plate numbers generated in the extended length separation channel allowed sorting of the 271/281 base pair fragments associated with this sizing ladder when electrophoresed in methylcellulose entangled polymer solutions. The dual fiber detector produced sub-attomole detection limits with the entire detector, including laser source, electronics and photon transducer, situated in a single box measuring 3'' x 10" x 14".

Dinitrobenzenes↗

Fatal respiratory failure associated with treatment of prostate cancer using docetaxel and estramustine.

Chemotherapy that targets microtubular trafficking induces responses in most patients with prostate cancer. One regimen under investigation is the combination of docetaxel and estramustine. We report on 2 patients with androgen-independent disease who received continuous weekly docetaxel and estramustine and who died of irreversible respiratory failure. The clinical, pathologic, and radiographic data support drug toxicity as the likely etiology. Inclusive of these patients, only 17 cases (10 fatal) of acute pulmonary toxicity using docetaxel have been reported, despite its wide use. We recommend that patients receiving weekly docetaxel, with or without estramustine, have frequent treatment breaks and be evaluated with computed tomography of the chest every 8 weeks.

Aged↗

Topiramate in patients with learning disability and refractory epilepsy.

PURPOSE: Management of seizures in learning disabled people is challenging. This prospective study explored the efficacy and tolerability of adjunctive topiramate (TPM) in patients with learning disability and refractory epilepsy attending a single centre. METHODS: Sixty-four patients (36 men, 28 women, aged 16-65 years) were begun on adjunctive TPM after a 3-month prospective baseline on unchanged medication. Efficacy end points were reached when a consistent response was achieved over a 6-month period at optimal TPM dosing. These were seizure freedom or > or =50% seizure reduction (responder). Appetite, behaviour, alertness, and sleep were assessed by caregivers throughout the study. RESULTS: Sixteen (25%) patients became seizure free with adjunctive TPM. There were 29 (45%) responders. A further 10 (16%) patients experiencing a more modest improvement in seizure control continued on treatment at the behest of their family and/or caregivers. TPM was discontinued in the remaining nine (14%) patients, mainly because of side effects. Final TPM doses and plasma concentrations varied widely among the efficacy outcome groups. Many patients responding well to adjunctive TPM did so on < or =200 mg daily. Mean carer scores did not worsen with TPM therapy. CONCLUSIONS: TPM was effective as add-on therapy in learning-disabled people with difficult-to-control epilepsy. Seizure freedom is a realistic goal in this population.

Adolescent↗

A DSM-IV-referenced screening instrument for preschool children: the Early Childhood Inventory-4.

OBJECTIVE: To examine the validity of the Early Childhood Inventory-4 (ECI-4), a parent and teacher rating scale designed to screen for DSM-IV emotional and behavioral disorders. METHOD: The convergent, divergent, and discriminant validity and clinical utility of the ECI-4 was studied in a sample of 224 consecutive referrals (3-6-year-old children) to a child psychiatric outpatient clinic. RESULTS: The ECI-4 demonstrated adequate criterion validity for the most common disorders (attention-deficit/hyperactivity disorder, oppositional defiant disorder, pervasive developmental disorder) when compared with data-based psychiatric diagnoses and correlated well with relevant scales of the Child Behavior Checklist, Teacher's Report Form, and Inattention/Overactivity With Aggression (IOWA) Conners. CONCLUSION: The ECI-4 appears to be a useful screening measure for certain disorders in clinically referred children, but continued research is needed to determine its value in other settings (e.g., school and community), and its validity with other measurement methodologies.

Affective Symptoms↗