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S Mandalia

Publications and source records attributed to S Mandalia.

71 records · Page 4Linked to original sources
PubMed1994

The resource implications and service outcomes of genetic services in the context of DNA technology.

The use of DNA technology has transformed genetic counselling services for single gene disorders. For conditions such as Duchenne muscular dystrophy and cystic fibrosis, both of which cause severe morbidity and premature death, DNA tests mean that individuals can be told with greater certainty whether they are carriers of a genetic trait and of the likelihood of their having a child affected by the disorder. This paper presents the findings of an evaluation of the resource implications and service outcomes of genetic services in the context of DNA technology (DNA services). Results are based on data collected over a 4-year period from three large genetics centres throughout the United Kingdom. Our conclusions are that for the conditions for which they are commonly used, and as a regionally based service, DNA services are effective and relatively inexpensive. For severe conditions, and for neurological disorders, although tests will not alter family size plans the demand for tests during pregnancy will be high and the results will have a significant impact on individuals' decisions regarding the continuation of their pregnancies. For conditions of variable severity, those that start late in life or are amenable to treatment, the demand for tests is likely to be low. In comparison with the general population we found a greater existence of psychological side effects amongst counsellees. These effects were linked to individuals having a close relative, usually a child, already affected by a disorder rather than being a consequence of the genetic counselling process.

Adult↗
PubMed1994

The influence of genetic counselling in the era of DNA testing on knowledge, reproductive intentions and psychological wellbeing.

Subjects of reproductive age at risk of having an affected child with a severe single gene disorder such as Duchenne muscular dystrophy (DMD) or cystic fibrosis (CF) were surveyed to ascertain: their views on genetic counselling and antenatal testing; their knowledge of their risk of having an affected child; and their psychological wellbeing. Questionnaires were posted to 209 individuals at 130 addresses; a 65% response rate was achieved. The majority of those surveyed were under 40 years of age (91%), half of them had received genetic counselling only once and for 47% the first encounter was after the diagnosis of their affected child. Most patients expressed their intention to use prenatal testing. However, less than 50% of those counselled knew their risk of having an affected child. Knowledge of risk was associated with the type of disease in the family (p < 0.001) (inheritance of DMD was poorly understood by relevant subjects) and was positively associated with the participant's level of education (p < 0.05). We did not detect a significant association between the number of intended children and the risk of having an affected child. In terms of family relations, genetic counselling appears to be beneficial for the nuclear family, the couple and their children, but some counselees reported a deterioration in relations with other relatives. The results indicate that couples at risk of having a child with a severe genetic disorder value the counselling provided, but many of them do not remember important facts in relation to their risk status.

Adolescent↗
PubMed1994

Metabolic determinants of the course of coronary artery disease in men.

We examined associations between metabolic variables and changes in coronary artery disease (CAD) in the St. Thomas' Atherosclerosis Regression Study (STARS). The course of CAD over 3 years was measured continually by quantitative coronary angiography, i.e., as the per patient change in the mean absolute width of coronary segments (delta MAWS). The decrease in MAWS (progression of CAD) was significantly correlated with in-trial plasma concentrations of cholesterol (P = 0.002), low-density lipoprotein (LDL) cholesterol (P = 0.001), apolipoprotein B (apoB) (P = 0.008), and lipoprotein(a) [Lp(a)] (P = 0.004); no significant associations were found with high-density lipoprotein (HDL) cholesterol, apoA-I, vitamin E, thyroid hormones, fibrinogen, von Willebrand factor, or post-load plasma glucose and insulin concentrations. By multiple regression analysis, LDL cholesterol was the best predictor of delta MAWS, the adjusted model explaining 22% of the variance (P = 0.04). Thus, in men with symptomatic CAD the most important metabolic predictor of change in CAD is plasma LDL cholesterol, there being no advantage in measuring other variables, in particular, apoB or Lp(a).

Adult↗
PubMed1994

Patients who consult with tiredness: frequency of consultation, perceived causes of tiredness and its association with psychological distress.

BACKGROUND: Few prospective studies have been carried out in primary care on patients presenting with tiredness. AIM: A study was undertaken to describe patients whose main complaint was fatigue or of being "tired all the time'. METHOD: Over one year, doctors in four practices in Lancashire, Mid-Glamorgan, Suffolk and Surrey recruited 220 patients aged 16 years or more presenting with fatigue, and matched them with a comparison group from their lists. The general health questionnaire, a fatigue questionnaire and an attribution questionnaire were used to measure outcomes over six months. General practice records of consultations were also examined. RESULTS: Patients consulting for tiredness attended the doctor significantly more frequently than the comparison group both in the six months before and after entering the study. The frequency of attending could not be related to the duration or severity of fatigue alone. The majority consulting with tiredness scored highly on the general health questionnaire but so also did patients with equivalent fatigue scores in the comparison group. The correlation between fatigue and general health questionnaire scores was close for those patients who still had high fatigue scores six months later than it was for patients on entry to the study. Six months following study entry 61% of patients perceived the cause of the tiredness to be physical, while 57% of doctors viewed the problem as psychological. A small number of patients changed their views during the six months follow up from physical to psychological attributions. CONCLUSION: Patients consulting for tiredness are likely to report symptoms of psychological distress and attend more frequently than other patients. They tend to view the problem as physical while their doctors view the problem as psychological. Having established that there is no physical problem, doctors may need to focus more on sharing ideas and explanations when patients complain of being "tired all the time'.

Adolescent↗
PubMed1993

Patients with fatigue in general practice: a prospective study.

OBJECTIVE: To describe the characteristics of patients attending their general practitioners and complaining of fatigue or being "tired all the time." DESIGN: Prospective study of cohort aged 16 years and older with follow up at two weeks and by questionnaires at two and six months. SUBJECTS: 220 patients (164 women) with mean age 43 years and an age-sex matched comparison group. SETTINGS: Doctors and patients in four practices in Lancashire, Mid Glamorgan, Suffolk, and Surrey. MAIN OUTCOME MEASURES: General clinical data, results from standard group of laboratory tests, fatigue questionnaire, and 12 item general health questionnaire. RESULTS: Over twice as many patients with fatigue had high scores on the health questionnaire compared with the comparison group (156 (75%) v 69 (34%)). Results of laboratory tests were abnormal and contributed to the diagnosis in 19 patients. 59 out of 102 patients who responded had high fatigue scores six months later. Patients with persistent fatigue were more likely to have a history of anxiety or depression and to have had fatigue for more than three months on entry to the study. CONCLUSIONS: Women are particularly at risk of fatigue. The outcome is better if patients have had symptoms for three months or less or there is no history of emotional illness.

Adolescent↗
PubMed1993

Comparison of attendance and emergency admission patterns at accident and emergency departments in and out of London.

OBJECTIVE: To compare the sociodemographic characteristics, diagnoses, and mode of referral of people and emergency admissions between an accident and emergency department in inner London and one in a town outside London. DESIGN: Standardised questionnaire completed prospectively over two weeks by field-workers in each accident and emergency department. SETTING: Accident and emergency departments in an inner London teaching hospital and an associated teaching hospital outside London. SUBJECTS: 3039 adults newly attending the departments, 1476 in inner London and 1563 outside London. MAIN OUTCOME MEASURES: Sociodemographic characteristics, diagnosis, mode of referral, and whether the patient was admitted. RESULTS: General practitioner referrals accounted for similar proportions of the adult attendances (12% in inner London, 15% outside London). People attending at the inner London department were more likely to be tourists or long distance commuters (12% (179/1476) v 6% (95/1563)), single (43% (643) v 32% (505)), to live alone (24% (360) v 14% (225)), to have moved recently (13% (194) v 7% (107)), or to be homeless (3.3% (48) v 0.6% (10)). Broad clinical groupings of patients were similar in both departments. 291 people were admitted in inner London and 284 outside London. The proportions admitted from each sociodemographic group were similar in the two hospitals. CONCLUSION: Differences in sociodemographic characteristics were more important than general practice referral patterns in determining the differences in people attending at accident and emergency departments inside and outside London. Many of these characteristics are likely to be found in other inner city populations. A strategy to improve acute care in inner London should take account of the needs of these sociodemographically different groups.

Adult↗
PubMed1993

Independent associations between plasma lipoprotein subfraction levels and the course of coronary artery disease in the St. Thomas' Atherosclerosis Regression Study (STARS).

Associations between plasma lipoprotein subfractions and changes in coronary artery diseases (CAD) were examined in 74 men who completed the St. Thomas' Atherosclerosis Regression Study (STARS). Plasma lipoproteins were isolated by stepwise, preparative ultracentrifugation at repeated intervals during the 38-month trial. Paired coronary angiograms were quantitatively analyzed by a computerized method. In univariate linear regression analysis, changes in mean absolute width (delta MAWS) and minimum absolute with (delta MinAWS) of coronary segments were significantly correlated with in-trial concentrations of cholesterol in intermediate-density lipoprotein ([IDL] d = 1.006 to 1.019 kg/L), low-density lipoprotein ([LDL2] d = 1.019 to 1.040 kg/L; LDL3, d = 1.040 to 1.063 kg/L), and high-density lipoprotein ([HDL3] d = 1.125 to 1.210 kg/L) subfractions; no significant associations were found with other lipoproteins. IDL, LDL3, and HDL3 cholesterol were then selected for multiple linear regression analysis because these variables were not co-correlated and because they attained a significance of P less than or equal to .1 in univariate regression. In this analysis, only LDL3 cholesterol level was a significant negative predictor (P < .05) of both delta MAWS and delta MinAWS; a positive association between delta MinAWS and HDL3 cholesterol level just failed to reach conventional statistical significance (P = .066). Correlations between changes in coronary luminal dimensions and LDL3 cholesterol level were independent of age, smoking, weight, and blood pressure. Most patients showing regression of coronary atherosclerosis had an LDL3 cholesterol level of less than 1.8 mmol/L. The findings suggest that LDL3 is the plasma lipoprotein subfraction that exerts the single most powerful effect on the course of CAD in middle-aged men with hypercholesterolemia.

Analysis of Variance↗
PubMed1993

Purchasing services for end stage renal failure: the potential and limitations of existing information sources.

Renal replacement therapy services already consume considerable health service resources and, as patient stock levels rise and unmet need continues to be identified, the pressure to spend more on renal services will increase. Purchasers of services must decide how to respond to these pressures, and a clear assessment of need and the effectiveness and efficiency of services are key issues when contracts are being developed for such services. This paper reports an examination of the quality and potential of information currently available from routine data sources to support the contracting process. The results expose gaps in current knowledge and identify areas for future research. Locally, purchasers should consider surveying their population to identify the incidence of renal disease, including the reasons for any unmet need. Nationally, research is required to investigate the following: the relationship between ethnicity and the development of renal disease; the criteria for allocating patients to the alternative treatment modalities; and the treatments in terms of their costs and cost-effectiveness.

Age Factors↗
PubMed1992

A methodology for simulating the impact of DNA-probe services on the outcomes of pregnancies.

For certain single-gene disorders, DNA probes allow individuals to make more informed decisions about family size and the outcomes of pregnancies. They may also have important psychological effects. We present a method of assessing their impact on the outcomes of pregnancy. We conclude that the traditional approach, which focuses solely on the potential of prenatal diagnostic services to reduce affected births, is limited. It neglects the potential of such services to promote an increase in unaffected births by reducing the number of unnecessary terminations.

DNA Probes↗
PubMed1992

DNA probe technology: implications for service planning in Britain.

For certain genetic conditions DNA testing identifies carriers and determines the risk status of foetuses, thus helping parents to make more informed prenatal decisions. Data, collected from three genetic centres in England and Wales from August 1986 to July 1990, are used to describe trends in demand for DNA testing, the impact of DNA tests on carrier risk assessment, and the use of DNA tests in relation to pregnancy outcome. Altogether the data include 23,388 subjects and 681 pregnancies in 8738 families divided into five cohorts by year of entry and referral. The most frequent gene disorders referred to the genetic centres are currently being tested or will soon be tested. For these disorders the initial high level of activity has declined and may have reached steady state. Demand for DNA services is high for cystic fibrosis and Duchenne muscular dystrophy, intermediate for Huntington's disease, and low for adult polycystic kidney disease, phenylketonuria and tuberous sclerosis. Based on these findings we suggest that demand for DNA tests will be high in serious, untreatable and slow progressing conditions with early onset; intermediate for conditions affecting intellect and neurological integrity with later onset; and low for treatable, late-onset conditions, or those for which there is evidence of heterogeneity, and variable penetrance. It would be helpful to assess the extent to which this view of demand is confirmed when the new disorders being DNA tested are considered and for the pattern of activity of DNA testing for some types of cancer. Since no DNA centre could offer a fully comprehensive testing service, it is recommended that a structure is created to audit overall activity, assist in policy formulation, and influence supraregional service organisation, in order that the spread of DNA services be planned as effectively as possible. This structure would facilitate monitoring of the evolution of contract specifications agreed by commissioners and providers on a regional basis.

Adolescent↗
PubMed1991

Audit from preschool developmental surveillance of vision, hearing, and language referrals.

Referrals from preschool medical examinations were followed up for two years to assess attendance rate, waiting time for appointment, appropriateness of the referral, the diagnosis and management of the condition. Altogether 184 children were referrals for ophthalmology, 285 for audiology, and 195 for speech therapy. The median waiting time for an appointment was 46 days in ophthalmology, 175 days in audiology, and 83 days in speech therapy. The poorest attendance rate was identified in speech therapy (75%). Approximately 60% of examined children had a justified referral to ophthalmology and 20% had a clear defect. Over half the children in audiology (55%) had an altered impedance or hearing impairment. Of those with a hearing problem kept under review only half improved spontaneously. In speech therapy 80% of those assessed had a language problem. Many health problems were detected for which parents were unaware or did not use the service. Parental awareness alone will not uncover the sizable level of lingual and sensorial problems in inner city areas. This audit identified specific deficiencies in the provision of services and a number of organisational changes are suggested to improve their effectiveness.

Age Factors↗
PubMed1989

An acceptable exercise test to study microalbuminuria in type 1 diabetes.

A modified test for studying the response of urinary albumin excretion (UAV) to exercise in diabetic patients is described. It is designed to produce a standardized increase in pulse rate (by 90-110%) rather than a standardized workload. Thirty-three normotensive Type 1 diabetic patients with normal pre-exercise UAV (less than 10 micrograms min-1) on the day of the test were compared with 25 non-diabetic subjects matched for age and sex. The patients developed a significantly greater increase in the median UAV (p less than 0.05) and systolic blood pressure (p less than 0.01) during exercise, despite the use of lower workloads (p less than 0.05). During exercise, the albumin excretion in the patients was not related to their heart rate, blood pressure, workload or fall in blood glucose; nor was it related to duration of diabetes, glycosylated haemoglobin or insulin dose. An exercise UAV greater than 15 micrograms min-1 was found in 10 of the 33 patients; it was significantly correlated (p less than 0.01) with the frequency of previous overnight microalbuminuria (greater than 10 micrograms min-1), and was associated with a greater progression of microalbuminuria (p less than 0.05) over a mean period of 24 months. Retinol-binding protein excretion rate was also measured as an indicator of proximal tubular function and did not increase in either group.

Adult↗
PubMedDate not supplied

Case-control study of sexually transmitted diseases as cofactors for HIV-1 transmission.

The aim of the study was to investigate the association between infection with HIV-1 infection and a history of other sexually transmitted diseases (STD). We were able to match 1295 HIV-1 infected patients who attended St Mary's Hospital between 1985 and 1991 with 1273 seronegative controls on gender, sexual orientation, injecting drug use and age at time of test. The cases were 3 times more likely to have a history of ever having had another STD than the controls: multivariate conditional logistic regression showed that, after controlling for sexual behaviour, for known sexual contact with an HIV infected individual or AIDS patient or with a resident from a high HIV prevalence area, area of residence and for year of test, a history of gonorrhoea, syphilis, hepatitis B, genital herpes or genital warts were all significantly associated with HIV-1 seropositive status. These findings reinforce the need for HIV containment strategies to be promoted in conjunction with containment programmes for others STDs.

Adult↗
PubMedDate not supplied

Efficacy of a nelfinavir- and nevirapine-containing salvage regimen.

PURPOSE: In this study, our purpose was to assess the efficacy of nelfinavir- and nevirapine-containing salvage regimens in nonnucleoside reverse transcriptase inhibitor (NNRTI)-naive patients virologically failing a protease inhibitor (PI)-based combination. METHOD: A retrospective case note review of all patients virologically failing their PI-based combination who were switched to a regimen containing both nelfinavir (1 g t.d.s.) and nevirapine (200 mg b.d.). CD4 cell counts and viral loads were monitored. Genotypic analysis was performed using RT-PCR sequencing. RESULTS: Nineteen patients commenced a salvage regimen containing nelfinavir and nevirapine. Five patients also changed at least one nucleoside reverse transcriptase inhibitor (NRTI), although in one case this represented recycling. Thirty-eight percent (6/16) of patients achieved a viral load below the level of detection (BLD; <200 copies/mL; complete responders [CR]), 3 achieved <20 copies/mL. Five patients achieved > or =1 log drop (partial responders [PR]) that was not sustained over follow-up, and five failed to respond to therapy (nonresponders [NR]). CRs tended to have wild-type NNRTI and PI sequences relative to PRs and NRs. CONCLUSION: In heavily pretreated patients, a nelfinavir-and nevirapine-containing salvage regimen resulted in a virological response in 38% of patients that was sustained in 31% over 63 weeks.

Adult↗
PubMedDate not supplied

Sequencing to NRTI plus NNRTI-only combinations after virological failure of protease inhibitor-based combination HIV-1 therapy.

PURPOSE: To examine the success of sequencing to nucleoside reverse transcriptase inhibitor (NRTI) plus nonnucleoside reverse transcriptase inhibitor (NNRTI)-only combinations after virological failure of protease inhibitor (PI)-based combinations in NNRTI-naïve individuals. METHOD: This was an observational cohort study. RESULTS: 171 patients were identified. The group was highly antiretroviral therapy-experienced with median cumulative NRTI and PI durations prior to change of 53 months and 21 months, respectively. The median CD4 count and viral load (VL) prior to change were 228 cells/mm(3) and 24500 copies/mL. Overall, 37.4% had a VL below the limit of detection (50 copies/mL) at 12 months (intention-to-treat analysis). Markers associated with success at 12 months were efavirenz (EFV) use, the use of three NRTI+NNRTI combinations, and abacavir (ABC) use. In multivariate analysis, use of EFV remained highly significant (relative hazard of virological success of nevirapine [NVP] vs. EFV = 0.39; p =.003), while ABC use became nonsignificant. A benefit from the use of three NRTI + NNRTI regimens was observed. CONCLUSION: NRTI plus NNRTI-only combinations performed poorly, however the superior outcomes of patients treated with EFV are consistent with findings in cohort studies. The suggestion of benefit in patients receiving three NRTIs in addition to either NVP or EFV deserves further study in randomized trials.

Adult↗