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Biomedical subjects

J Warner

Publications and source records attributed to J Warner.

At least 19 recordsLinked to original sources

Epidemiology, prescribing patterns and resource use associated with overactive bladder in UK primary care.

This study aimed to estimate the incidence and prevalence of overactive bladder (OAB) symptoms in the UK and analyse the use of anticholinergic/antispasmodic medications and other healthcare resources within UK general practice. Patients with a record of urinary frequency, urgency, nocturia, urge incontinence or irritable/unstable bladder between 1987 and 2004 were identified from the General Practice Research Database. Demographic characteristics, referrals, consultations, investigations and prescriptions for medications licensed for use in OAB were identified. Regression analyses were used to identify the factors determining switches between medications, referrals and use of healthcare resources. The overall prevalence of OAB-related symptoms was 3.87 per 1000 persons, with an incidence of 2.79 per 1000 person-years. Among 68,910 patients with OAB symptoms, 19,444 (28.2%) received anticholinergic medication, of whom 14,454 (74.3%) received one drug and 4055 (20.9%) received two medications sequentially. Overall, 59.1% of patients were referred to relevant secondary care specialities, 2.8% underwent urinary tests/investigations in primary care and 0.2% were seen by a continence nurse. Resource use was higher among patients who tried several different medications. In conclusion, this study suggests that OAB may be under-diagnosed in the UK and that current guidelines recommending use of anticholinergic medication, continence nurse consultations and urinary tests/investigations are inadequately followed.

Cholinergic Antagonists↗

Allergic reactions in the community: a questionnaire survey of members of the anaphylaxis campaign.

BACKGROUND: Allergic reactions to food are well recognized in both children and adults, but because of their relative infrequency their typical features may not be readily recognized by patients and their medical care givers who are not allergists. OBJECTIVE: We sought to investigate the circumstances and clinical characteristics of food allergies in adults and children in the community. METHODS: Self-completed questionnaire responses over a 6-month period from 109 members of the Anaphylaxis Campaign, the major British patient resource group for people who have suffered severe allergic reactions. RESULTS: One hundred and nine respondents reported 126 reactions during the study period. Seventy-five were children (under 16 years, median age 6 years at the time of reaction). Predictably more boys than girls were reported to have had reactions but more women reported reactions than men (P<0.05). Although the groups were equally aware of their food allergies the children had undergone diagnostic tests more often (P<0.001). Foods were implicated in 112 (89%) of reports. Restaurants were implicated less often (14%) than in other series, probably reflecting British eating habits. Children with asthma reported more severe reactions than those without asthma (P=0.008), although frequency or severity of recent asthma symptoms was not associated with severity of allergic reaction reported. When available, self-injectable adrenaline was used in 35% of severe reactions and 13% of non-severe reactions (P=0.01). A quarter of adults who received one dose of adrenaline also received a second dose. CONCLUSION: The allergens implicated in this report reflect previous data from similar patient groups in North America. Asthmatic children suffer more severe reactions than non-asthmatic children. It appears that British adults need better access to expert care of their allergies. Even when it is prescribed and available self-injectable adrenaline appears under-used in severe reactions. The incidence of severe but non-fatal allergic reactions in the UK may have been underestimated in the past.

Adolescent↗

A report of a national mutation testing service for the MEN1 gene: clinical presentations and implications for mutation testing.

INTRODUCTION: Mutation testing for the MEN1 gene is a useful method to diagnose and predict individuals who either have or will develop multiple endocrine neoplasia type 1 (MEN 1). Clinical selection criteria to identify patients who should be tested are needed, as mutation analysis is costly and time consuming. This study is a report of an Australian national mutation testing service for the MEN1 gene from referred patients with classical MEN 1 and various MEN 1-like conditions. RESULTS: All 55 MEN1 mutation positive patients had a family history of hyperparathyroidism, had hyperparathyroidism with one other MEN1 related tumour, or had hyperparathyroidism with multiglandular hyperplasia at a young age. We found 42 separate mutations and six recurring mutations from unrelated families, and evidence for a founder effect in five families with the same mutation. DISCUSSION: Our results indicate that mutations in genes other than MEN1 may cause familial isolated hyperparathyroidism and familial isolated pituitary tumours. CONCLUSIONS: We therefore suggest that routine germline MEN1 mutation testing of all cases of "classical" MEN1, familial hyperparathyroidism, and sporadic hyperparathyroidism with one other MEN1 related condition is justified by national testing services. We do not recommend routine sequencing of the promoter region between nucleotides 1234 and 1758 (Genbank accession no. U93237) as we could not detect any sequence variations within this region in any familial or sporadic cases of MEN1 related conditions lacking a MEN1 mutation. We also suggest that testing be considered for patients <30 years old with sporadic hyperparathyroidism and multigland hyperplasia.

Australia↗

Adaptive immunity in melioidosis: a possible role for T cells in determining outcome of infection with Burkholderia pseudomallei.

Melioidosis is a potentially fatal disease caused by the bacterium Burkholderia pseudomallei. Individuals with subclinical melioidosis have no apparent clinical signs or symptoms, and are identified only by positive serology. The present study is the first to investigate cell-mediated immune (CMI) responses following in vitro stimulation with B. pseudomallei antigens in peripheral blood mononuclear cells (PBMC), collected under field conditions in Papua New Guinea (PNG) from individuals with exposure to B. pseudomallei (n = 13). While five had a clinical history of melioidosis (C(+)), the remaining individuals (n = 8) were seropositive, yet healthy with no clinical history of melioidosis (S(+)/C(-)). Proliferation and IFN-gamma production were significantly greater in lymphocyte cultures from S(+)/C(-) individuals compared to C(+) individuals (P < 0.001 and P < 0.05, respectively). These findings demonstrate that compared to C(+) patients, individuals with subclinical melioidosis have a stronger CMI response to B. pseudomallei antigens in vitro. Such a response may be essential for protection against disease progression.

Adolescent↗

Outcomes and lessons from a pilot RCT of a community-based HIV prevention multi-session group intervention for gay men.

This paper presents the first outcome evaluation of multi-session groupwork for HIV prevention among gay men in the UK. This community-based RCT recruited 50 men, of whom 42% were HIV-positive or untested, and 32% reported status unknown or serodiscordant UAI in the previous 12 months. No knowledge, skills, attitudinal or behavioural differences were detected between intervention and control at baseline. At eight weeks, those attending the group reported significant gains over their control in making sexual choices, physical safety, HIV and STI transmission knowledge, and sexual negotiation skills. At 20 weeks, significant differences remained for HIV and STI transmission knowledge and comfort with sexual choices. Although no behavioural differences were detected, the aims of the National Prevention Strategy were met. This pilot RCT is appraised in the light of modest sample size and attrition, and recommendations for establishing behavioural outcomes are presented. This study has demonstrated that high-risk community samples can be recruited to multi-session interventions, and has provided feasibility data for future rigorous evaluation designs.

Adult↗

Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications.

Familial hyperparathyroidism is not uncommon in clinical endocrine practice. It encompasses a spectrum of disorders including multiple endocrine neoplasia types 1 (MEN1) and 2A, hyperparathyroidism-jaw tumour syndrome (HPT-JT), familial hypocalciuric hypercalcaemia (FHH), and familial isolated hyperparathyroidism (FIHP). Distinguishing among the five syndromes is often difficult but has profound implications for the management of patient and family. The availability of specific genetic testing for four of the syndromes has improved diagnostic accuracy and simplified family monitoring in many cases but its current cost and limited accessibility require rationalisation of its use. No gene has yet been associated exclusively with FIHP. FIHP phenotypes have been associated with mutant MEN1 and calcium-sensing receptor (CASR) genotypes and, very recently, with mutation in the newly identified HRPT2 gene. The relative proportions of these are not yet clear. We report results of MEN1, CASR, and HRPT2 genotyping of 22 unrelated subjects with FIHP phenotypes. We found 5 (23%) with MEN1 mutations, four (18%) with CASR mutations, and none with an HRPT2 mutation. All those with mutations had multiglandular hyperparathyroidism. Of the subjects with CASR mutations, none were of the typical FHH phenotype. These findings strongly favour a recommendation for MEN1 and CASR genotyping of patients with multiglandular FIHP, irrespective of urinary calcium excretion. However, it appears that HRPT2 genotyping should be reserved for cases in which other features of the HPT-JT phenotype have occurred in the kindred. Also apparent is the need for further investigation to identify additional genes associated with FIHP.

Australia↗

Spinocerebellar ataxia type 8 in Scotland: genetic and clinical features in seven unrelated cases and a review of published reports.

OBJECTIVES: To establish whether the DNA expansion linked to spinocerebellar ataxia type 8 (SCA 8) is associated with ataxia in Scotland; to clarify the range of associated clinical phenotypes; and to compare the findings with previous reports. METHODS: DNA was screened from 1190 anonymised controls, 137 subjects who had tested negative for Huntington's disease, 176 with schizophrenia, and 173 with undiagnosed ataxia. Five unrelated ataxic patients with the SCA 8 expansion and a sixth identified subsequently had clinical and psychometric assessment; the clinical features were available in a seventh. A systematic search for other reports of SCA 8 was undertaken. RESULTS: Over 98% of SCA 8 CTA/CTG repeat lengths fell between 14 and 40. Repeat lengths over 91 were observed in three healthy controls (0.12%), two patients with suspected Huntington's disease (0.73%), and six ataxic subjects (1.74%; p<0.0005 v healthy controls). Repeat lengths over 100 occurred in five ataxic subjects but in only one control. All seven symptomatic subjects with the SCA 8 expansion had a cerebellar syndrome; four had upper motor neurone signs; and 5/6 assessed had cognitive complaints. There was personality change in two and mood disturbance in three. In published reports, SCA 8 repeat lengths over 91 occurred in approximately 0.5% of the healthy population but were over-represented among ataxic patients (3.4%; p<0.0001). The predominant clinical phenotype was cerebellar, with pyramidal signs in 50%, and neuropsychiatric features in some cases. CONCLUSIONS: SCA 8 expansion is a risk factor for a cerebellar syndrome, often associated with upper motor neurone and neuropsychiatric features. The expansion occurs unexpectedly often in the general population.

Adolescent↗

Homeopathy for dementia.

BACKGROUND: Dementia is a common illness in older people and has major implications for individuals with the disease, their carers and society. A meta-analysis of population based studies in Europe found the prevalence of dementia in individuals over 65 to be 6.4%. Homeopathy (also spelt "homoeopathy") is a popular form of "complementary" or "alternative" treatment. Some studies have found evidence for efficacy of homeopathic treatment for some conditions, but any mechanism of action of the ultra molecular dilutions used in homeopathy is not comprehensible in terms of current scientific concepts. OBJECTIVES: To evaluate the effectiveness and safety profile of homeopathically prepared medications used in treating dementia, as established by randomized controlled trials. SEARCH STRATEGY: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 10 May 2002 using the terms alum*, homeop*, "nat sulph" and "natrum sulphate". This Register contains records from all major medical databases. In addition the reviewers searched CISCOM, AMED and Hom-Inform. Leading homeopathic researchers, practitioners and manufacturers were also contacted. SELECTION CRITERIA: All types of randomized controlled trials with a sample size of more than 20 were considered. DATA COLLECTION AND ANALYSIS: The database searches resulted in one trial being identified. After examining the abstract, a paper copy was obtained and independently assessed for inclusion by RM and JW. MAIN RESULTS: There were no studies that fulfilled the criteria for inclusion and no data to present. REVIEWER'S CONCLUSIONS: In view of the absence of evidence it is not possible to comment on the use of homeopathy in treating dementia. The extent of homeopathic prescribing for people with dementia is not clear and so it is difficult to comment on the importance of conducting trials in this area.

Dementia↗

Tinea capitis in Cleveland: survey of elementary school students.

BACKGROUND: Tinea capitis, a fungal infection of the scalp, is of increasing public health importance, and Trichophyton tonsurans has become the primary causative agent in North America. OBJECTIVES: To determine the prevalence of dermatophyte-positive scalp cultures among elementary schoolchildren in Cleveland, Ohio, describe predisposing factors, and measure the antifungal susceptibility of isolates collected. OBSERVATIONS: A total of 937 children from 8 Cleveland elementary schools were cultured for the presence of dermatophytes; 122 children (13%), all of whom were African American, had dermatophyte-positive cultures of the scalp. Sixty percent of cases were asymptomatic, indicating a carrier state. Race, scaling, and the use of anti-dandruff shampoo were associated with increased likelihood of infection. T tonsurans was the only organism isolated (except 1 Microsporum canis isolate). All isolates were susceptible to fluconazole, griseofulvin, itraconazole, and terbinafine. CONCLUSIONS: T tonsurans was the predominant dermatophyte isolated. Further multicenter studies are needed to confirm the predominance of dermatophyte-positive scalp cultures among African American children and to determine modifiable and preventable risk factors.

Child↗

Supplements of transgenic malt or grain containing (1,3-1,4)-beta-glucanase increase the nutritive value of barley-based broiler diets to that of maize.

1. A diet with addition to normal barley of malt from transgenic barley expressing a protein engineered, thermotolerant Bacillus (1,3-1,4)-beta-glucanase during germination has previously been demonstrated to provide a broiler chicken weight gain comparable to maize diets. It also reduced dramatically the number of birds with adhering sticky droppings, but did not entirely eliminate sticky droppings. One of the objectives of the broiler chicken trials reported here was to determine if higher concentrations of transgenic malt could alleviate the sticky droppings. 2. Another aim was to investigate the feasibility of using mature transgenic grain containing the thermotolerant (1,3-1,4)-beta-glucanase as feed addition and to compare diets containing transgenic grain to a diet with the recommended amount of a commercial beta-glucanase-based product. 3. Inclusion of 75 or 151 g/kg transgenic malt containing 4.7 or 98 mg/kg thermotolerant (1,3-1,4)-beta-glucanase with 545 or 469 g/kg non-transgenic barley instead of maize yielded a weight gain in Cornish Cross broiler chickens indistinguishable from presently used maize diets. The gene encoding the enzyme is expressed in the aleurone with a barley alpha-amylase gene promoter and the enzyme is synthesised with a signal peptide for secretion into the endosperm of the malting grain. 4. Equal weight gain was achieved, when the feed included 39 g/kg transgenic barley grain [containing 66 mg/kg thermotolerant (1,3-1,4)-beta-glucanase] and 581 g/kg non-transgenic barley instead of maize. In this case, the gene encoding the enzyme has been expressed with the D-hordein gene (Hor3-1) promoter during grain maturation. The enzyme is synthesised as a precursor with a signal peptide for transport through the endoplasmic reticulum and targeted into the storage vacuoles. Deposition of the enzyme in the prolamin storage protein bodies of the endosperm protects it from degradation during the programmed cell death of the endosperm in the final stages of grain maturation and provides extraordinary heat stability. The large amount of highly active (1,3-1,4)-beta-glucanase in the mature grain allowed the reduction of the transgenic grain ingredient to 0.2 g/kg diet, thus making the ingredient comparable to that of the trace minerals added to standard diets. 5. A direct comparison using transgenic grain supplement at the level of 1 g/kg of feed with the standard recommended addition of the commercial enzyme preparation Avizyme 1100 at 1 g/kg yielded equal weight gain, feed consumption and feed efficiency in birds fed a barley-based diet. 6. The production of sticky droppings characteristic of broilers fed on barley diets was avoided with all 9 experimental diets and reduced to the level observed with a standard maize diet by supplementation with transgenic barley. 7. The excellent growth and normal survival of the 400 broilers tested on barley diets supplemented with transgenic grain or malt showed the grain and malt not to be toxic. 8. The barley feed with added transgenic grain or malt containing thermotolerant (1,3-1,4)-beta-glucanase provides an environmentally friendly alternative to enzyme additives, as it uses photosynthetic energy for production of the enzyme in the grain and thus avoids use of non-renewable energy for fermentation. The deposition of the enzyme in the protein bodies of the grain in the field makes coating procedures for stabilisation of enzyme activity superfluous. 9. Barley feed with the small amount of transgenic grain as additive to normal barley provides an alternative for broiler feed in areas where grain maize cannot be grown for climatic reasons or because of unsuitable soil and thus has to be imported.

Animal Feed↗

An exploratory study of fetal behavior at 33 and 36 weeks gestational age in hypertensive women.

The relationship between maternal blood pressure (BP) and fetal behaviors as well as differential spontaneous and vibroacoustic elicited fetal behaviors were examined in hypertensive (n = 21) compared to normotensive (n = 22) women at 33 and 36 weeks gestational age (GA). Maternal BP was negatively related to GA at birth and birth weight. On average, fetuses of hypertensive women were born 2 weeks earlier (38 weeks GA) and 340 g lighter. Maternal systolic BP was negatively related to the number of spontaneous body movements observed on ultrasound scan over 20 min and the magnitude of the fetal heart rate (FHR) acceleration elicited by a vibroacoustic stimulus. At 36 weeks GA, vibroacoustic stimulation elicited differential responding with fetuses in the hypertensive compared to the normotensive group having fewer body movements, a lower magnitude of FHR acceleration, and a lack of cardiac-body movement coupled responses. These findings suggest a relationship between maternal BP and fetal behaviors and differential functional development of sensory-motor response systems which need to be characterized in the subgroups of hypertensive disorders observed during pregnancy.

Acoustic Stimulation↗

Ropinirole for the treatment of tremor in early Parkinson's disease.

The effect of Ropinirole on tremor in early Parkinson's disease (PD) was assessed. The results of three multicentre, randomized, double-blind trials comparing ropinirole monotherapy with levodopa, bromocriptine and placebo treatment were analysed retrospectively with respect to improvement of resting tremor and postural/action tremor as measured by items 20 and 21 of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS). Improvements in resting tremor were significantly better with ropinirole than placebo. There were no significant differences between the effect of ropinirole and those of levodopa (L-dopa) or bromocriptine on resting tremor. Postural/action tremor was mild in these early therapy studies, and there were no significant differences between treatment groups. These results suggest that ropinirole monotherapy is effective in treating resting tremor in early PD. On the other hand, response of postural/action tremor to dopaminergic treatment in early PD was not significantly better than to placebo at the dosages used in these trials.

Aged↗

Randomized clinical trials with added rescue medication: some approaches to their analysis and interpretation.

Patients in some randomized clinical trials may start additional non-randomized medication because of an exacerbation of symptoms or insufficient therapeutic effect. Typically this rescue medication reduces the observed treatment effect in intention-to-treat analysis. We discuss methods of analysis which take account of rescue medication in order to achieve a more meaningful comparison of the randomized treatments, focusing on trials with a repeated quantitative outcome. Ignoring all data after rescue is likely to be biased because rescued patients are a highly selected group. Instead we propose using methods based on ranks or multilevel models. The rank-based methods assume that rescued patients have especially bad underlying outcomes. The multilevel regression model relates a patient's outcome to allocated treatment and rescue status at each time, and requires correct modelling of all prognostic factors which predict starting rescue medication and of the covariance between outcomes measured at different times. We also describe sensitivity analyses over a range of possible models for the effect of rescue medication. We illustrate these methods in a trial in Parkinson's disease. It appears that adjustment for rescue medication will not radically alter the randomized treatment comparison unless rescue medication is substantially imbalanced between randomized groups and has a substantial effect on the outcome.

Activities of Daily Living↗