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Biomedical subjects

K Stein

Publications and source records attributed to K Stein.

At least 55 records · Page 3Linked to original sources
PubMed1999

rhDNase therapy for the treatment of cystic fibrosis patients with mild to moderate lung disease.

OBJECTIVE: To assess the cost-effectiveness of rhDNase (Pulmozyme(R)) for patients with cystic fibrosis (CF) aged 5 years or more, with mild to moderate lung disease. The review addresses four questions: a) does rhDNase therapy work in the short term?, b) does rhDNase therapy work more effectively in certain groups of patients?, c) does rhDNase therapy work in the long term? and d) what is the cost-effectiveness of rhDNase therapy? METHODS: A structured rapid review with modelling and cost-effectiveness calculations. Electronic searches were carried out to identify randomised controlled trials (RCTs), systematic reviews, epidemiological and economic information. Databases searched included Cochrane Library, Medline, Healthstar, Embase, PreMedline and NHS Economic Evaluation Database (NHS EED). Exclusion criteria were trials of very short duration (14 days or less) and those which looked at CF patients with severe lung disease. Open label extensions providing information on longer term outcomes were included. RESULTS: Nine published RCTs were identified, although only one met the inclusion criteria. This large RCT was of good methodological quality, and shows that treatment with rhDNase over a 6-month period improves lung function, and decreases the risk of respiratory exacerbations. Expert opinion suggests that there are identifiable subgroups of patients showing improvement, little or no change, and deterioration after treatment with rhDNase. However, the best supporting evidence for this comes from a retrospective case series, showing that response to rhDNase is highly variable, and that early improvement was a good predictive marker for long-term benefit. Evidence for the long-term impact of rhDNase is not yet available from any RCTs. A simplified model was therefore developed to estimate the decline in lung function for patients treated with rhDNase, compared with those who were not treated. From this model it appears that the continued use of rhDNase over the lifetime of a CF patient might extend their life expectancy by 2 years. If treatment is limited to a subgroup of patients with moderate lung disease who respond to treatment, the continued use of rhDNase might extend their life expectancy by 7 years. Using the model, the discounted cost per life year gained for all patients is estimated at approximately pound52 500, with a range of between approximately pound25 000-57 000 from sensitivity analysis. For the subgroup of patients, the discounted cost per life year gained is estimated at approximately pound16 000, with a range of between approximately pound18 000-36 600 from sensitivity analysis. CONCLUSIONS: Although there is short-term evidence that the use of rhDNase improves lung function and decreases the risk of respiratory exacerbations, at present there is no evidence from RCTs to indicate whether this effect is sustained over a longer time period, or whether rhDNase is associated with a reduction in mortality. RCTs to date have been of insufficient duration to answer important questions about long term outcomes, particularly the effects of rhDNase on lung function, respiratory exacerbations and mortality. Further long-term research is needed, with economic analysis to evaluate the long term cost-effectiveness of rhDNase. Research is also needed to identify, in advance, which patients would benefit most from this expensive treatment.

Adolescent↗
PubMed1999

Contact between people with learning disability and general practitioners: a cross-sectional case note survey.

BACKGROUND: This paper describes primary care consultation rates in a sample of people with learning disability. The study was carried out as part of a wider survey of primary care for this population group in response to concerns over quality of care and debate between general practitioners (GPs) and the local health authority over the need for additional remuneration for caring for people with learning disability. Estimates of consultation rates in the literature to date are conflicting and we sought to provide local data on the number and type of contacts with the primary care teams to inform this debate. METHOD: A primary care case note review was carried out of 112 people with learning disability aged over 18, identified from an administrative sample of 967 people known to health and social services. Contact rates (with practice nurses or GPs) were calculated and indirectly standardized for age using data from the fourth National Morbidity Survey in General Practice (MSGP4). RESULTS: Standardized consultation ratio in men was 156 (95 per cent confidence interval (CI) 142-172), in women was 111 (95 per cent CI 102-121) and for both sexes was 127 (95 per cent CI 120-135). Average contact rate was 4.6 per person per year. Eighty per cent of contacts were with GPs. Eighteen per cent (95 per cent CI 11-25 per cent) of subjects consulted, on average, more than once every two months. Limited information on underlying cause of learning disability and severity was available. Consultation rates were independent of age and sex, and were not increased in people with Down's syndrome or epilepsy compared with the rest of the sample population. Consultation rates were highest in people living in staffed group homes (p = 0.01). The presence of special arrangements between practices and residential facilities did not appear to increase service contact, but this finding is prone to measurement bias. CONCLUSIONS: Contrary to the findings of previous studies, people with learning disability consult primary care teams more frequently than the general population. However, this should not be taken as supporting calls for additional resources without addressing the effectiveness and appropriateness of health care offered.

Adult↗
PubMed1999

What is the cost utility of screening for hepatitis C virus (HCV) in intravenous drug users?

OBJECTIVES: To model the likely cost utility of the prevalence round of a screening programme for hepatitis C (HCV) in intravenous drug users (IVDUs) in contact with services in the South and West health region of the UK. METHODS: Information on the prevalence of HCV, performance of diagnostic tests, and effectiveness of interferon alpha (IFN alpha) for treatment of chronic hepatitis were brought together with estimates of the costs of service provision. A simple spreadsheet model was used to estimate cost utility (cost/quality adjusted life year (QALY)). Assumptions (including use of ribavirin plus IFN alpha combination therapy) were tested by a one way sensitivity analysis. RESULTS: About 5600 IVDUs live in the region. A combination of enzyme linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) testing has high sensitivity and specificity for detecting HCV. There is excellent evidence that IFN alpha is effective in producing sustained normalisation of liver function and, by inference, eradicating HCV. Evidence for long term benefits comes from modelling studies based on progression of HBV or non-A, non-B hepatitis and is considerably less robust. The cost of the prevalence round of screening in IVDUs would be about 700,000 Pounds and is likely to identify about 1400 people, of whom about 270 would be eligible for treatment and 20 would respond to IFN alpha. This gives a cost/QALY of 9300 Pounds for the screening programme. However, much uncertainty around the estimates used to inform the cost utility calculation limits confidence in the value of screening IVDUs for HCV. Sensitivity analysis shows a range of possible cost utility from 3333 Pounds to 81,438 Pounds. Estimates are particularly sensitive to adherence to liver biopsy and treatment and to discounting of benefits. CONCLUSIONS: Although potentially cost effective, many important uncertainties surround the assumptions used to estimate the long term effectiveness of screening and treatment. There is insufficient evidence to inform policy development and further research is required in this rapidly changing field.

Comorbidity↗
PubMed1999

Measuring desire for death among patients with HIV/AIDS: the schedule of attitudes toward hastened death.

OBJECTIVE: As physician-assisted suicide is debated, a need for standardized measurement of desire for death among medically ill individuals has emerged. The authors present preliminary validation data for a new self-report instrument, the Schedule of Attitudes Toward Hastened Death. METHOD: The participants were 195 patients with HIV/AIDS from two sites: 148 ambulatory patients and 47 patients who had been recently admitted to a facility for end-of-life care. The ambulatory participants completed the 20-item Schedule of Attitudes Toward Hastened Death and several other instruments, including the Beck Depression Inventory and Brief Symptom Inventory. The terminally ill patients also completed the Schedule of Attitudes Toward Hastened Death, along with other measures, and were assessed by clinicians with the Hamilton Depression Rating Scale and the Desire for Death Rating Scale, a global clinician rating of the patient's desire for death. RESULTS: The Schedule of Attitudes Toward Hastened Death demonstrated high reliability. The total score significantly correlated with the clinician rating on the Desire for Death Rating Scale and with ratings of depression and psychological distress. In addition, the Schedule of Attitudes Toward Hastened Death score significantly correlated with pain intensity and physical symptom distress. Factor analysis supported a single factor structure for the instrument. CONCLUSIONS: These results indicate that the Schedule of Attitudes Toward Hastened Death is a reliable, valid measure of desire for death among patients with HIV/AIDS. Further research with this measure may help address many of the unanswered questions emerging from the ongoing debates regarding legalization of assisted suicide.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Is Fatigue a Long-term Side Effect of Breast Cancer Treatment?

BACKGROUND: Fatigue is one of the most common and distressing symptoms experienced by breast cancer survivors. Despite its prevalence, relatively little is known about the characteristics, etiology, or treatment of fatigue in breast cancer survivors. METHODS: This report reviews studies that assessed fatigue in breast cancer patients previously treated with adjuvant radiotherapy, adjuvant chemotherapy, or autologous bone marrow transplantation. RESULTS: A review of the literature suggests that breast cancer patients who undergo adjuvant chemotherapy or autologous bone marrow transplantation experience clinically significant levels of fatigue for months or even years following the completion of active treatment. In contrast, there is little evidence that patients who receive only regional therapy (ie, surgery plus adjuvant radiotherapy) experience clinically significant fatigue as a long-term treatment side effect. CONCLUSIONS: A growing body of evidence indicates that persistent fatigue can be a long-term side effect of certain forms of breast cancer treatment. The challenges for the future will be to determine the etiology of fatigue among breast cancer survivors and to develop interventions that are effective in preventing or reducing fatigue following breast cancer treatment.

Journal Article↗
PubMed1998

A new immunoenzymometric assay for bioactive N-terminal human parathyroid hormone fragments and its application in pharmacokinetic studies in dogs.

Advances in the treatment of clinical disorders of mineral in homeostatis and metabolic bone disease with intact parathyroid hormone 1-84 or one of the biologically active N-terminal fragments require a precise and sensitive measurement in serum. Therefore, a two-site immunoenzymometric assay for the quantitative determination of bioactive hPTH-1-37 (human parathyroid hormone) at picomolar concentrations was developed. Monoclonal antibodies (mAB) against hPTH-1-37 were raised by hybridoma cells in serum-free cell culture. Furthermore, sequence-specific polyclonal antibodies were obtained by immunisation of rabbits using multiple antigenic peptides (MAP) representing the conspicuous regions of the primary structure of hPTH-1-37. The polyclonal and monoclonal antibodies were characterised by epitope mapping. The combination of a monoclonal antibody (13C63/5) recognising hPTH fragment 16-24 with a polyclonal antibody (k2) showing a predominant binding sequence at hPTH-1-5 led to a sandwich assay specific for N-terminally intact and therefore biologically active hPTH. The validated assay ranging from 4 to 1000 pmol/l was applied to pharmacokinetic studies of hPTH-1-37. After s.c. administration of 30 mu g/kg in 5 beagles, the maximum serum concentrations of hPTH-1-37 ranging at 2139 +/- 857 pmol/l were observed 45 min after the injection. Clearance of the peptide calculated from the exponential disappearance curve was 32.0 +/- 9.1 ml/min/kg with a mean t1/2 of 37 +/- 10 min.

Amino Acid Sequence↗
PubMed1997

A comparison of pain report and adequacy of analgesic therapy in ambulatory AIDS patients with and without a history of substance abuse.

Concerns are often raised regarding the credibility of patients' report of pain and this concern is heightened among individuals with AIDS, where many patients have a history of injection drug use. This study compared the pain experience, adequacy of pain management and psychological well-being among patients with AIDS who reported a history of injection drug use (IDU) as their HIV transmission risk factor and patients with other HIV transmission risk factors. Five hundred and sixteen ambulatory AIDS patients participating in a quality of life study completed a series of self-report instruments including the Brief Pain Inventory, the Beck Depression Inventory, the Brief Symptom Inventory, the Functional Living Inventory and the Social Support Questionnaire. Results demonstrated that IDU and non-IDU subjects did not differ significantly in their report of pain prevalence, pain intensity or pain-related functional interference. However, IDU patients were significantly more likely to receive inadequate analgesic medications, reported lower levels of pain relief and a greater degree of psychological distress. There was also no difference in report of pain intensity, pain relief or functional interference among patients who acknowledged continued drug use, those who denied any recent drug use and patients participating in a methadone maintenance program. These data support the validity of AIDS patients' report of pain, at least in research settings, and suggest that undertreatment of pain is not restricted to patients who actively abuse drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Further support for linkage of extreme obesity to the obese gene in a study group of obese children and adolescents.

The role of the obese gene in human obesity is presently unclear. Evidence for linkage of markers flanking the gene to obesity has been found in some but not all studies. We investigated transmission disequilibrium between two highly polymorphic microsatellite markers (D7S504 and D7S1875) flanking the human obese gene (OB) and extreme obesity in a study group of German children and adolescents. Due to the early onset and severity of obesity in the ob/ob mouse we hypothesized that especially children and adolescents with extreme obesity are enriched for possible mutations in the human OB. The analysis of 88 trios (index probands and both parents) for transmission disequilibrium of a haplotype which has previously been determined to be linked to extreme obesity (Reed et al., 1996) revealed a one-sided transmission disequilibrium test (TDT) p-value of 0.039. Post hoc analyses revealed one-sided TDT p-values of 0.015 for the 214 bp allele of D7S1875 (corrected p-value = 0.03) and 0.215 for the 145 bp allele of D7S504 (corrected p-value = 0.43). These findings substantiate the evidence for linkage of extreme obesity to OB.

Adolescent↗
PubMed1997

Counsellors in primary care in Southampton: a questionnaire survey of their qualifications, working arrangements, and casemix.

BACKGROUND: There has been an upsurge of interest in counselling in primary care over the past five years. This has been stimulated by a growing demand for non-drug treatment of emotional disorders and by the extension of reimbursement for the costs of counsellors. Continued calls for careful evaluation have been largely unheeded in the face of heady growth. AIM: To establish the prevalence of counselling services in the 67 general practices in the Southampton and South West Hampshire Health District, and to describe in detail their qualifications, working arrangements, and casemix. METHOD: A questionnaire enquiring about counselling services was sent to all the general practices in the district. A second questionnaire was then posted to all the counsellors identified as working in these practices. RESULTS: Twenty-six (39%) practices employed one or more counsellors. Fundholding practices were four times more likely than non-fundholders to employ a counsellor. Most of the counselling work was short term (4-20 sessions). The most common presenting complaints were relationship problems, depression, anxiety, and bereavement. CONCLUSION: This descriptive study highlights the wide variation in the qualifications and training of counsellors. Until the issue of effectiveness is resolved through further research, the best safeguard of quality is to ensure that counsellors meet the appropriate training standards laid down by the British Association of Counsellors. Monitoring standards is a legitimate task for those commissioning health care who are increasingly responsible for reimbursement of a counsellor's salary. Counsellors who meet appropriate training criteria should be encouraged to pursue accreditation with the British Association of Counsellors. Those who do not meet these criteria should be encouraged to undergo additional training.

Counseling↗
PubMed1996

Rotavirus infection and bradycardia-apnoea-episodes in the neonate.

UNLABELLED: Rotavirus (RV), a common cause of infectious enteritis in young children including neonates, has not been associated with central nervous symptoms in standard textbooks. However, involvement of the CNS has been reported recently in case reports and small series. From 786 neonatal admissions in 1991 we retrospectively analysed the records of 215 inpatient neonates (68 preterm and 147 term infants) who developed diarrhoea during their stay on the neonatal ward and in whom stools were investigated for RV antigen by ELISA. All 215 neonates were continuously monitored for bradycardia-apnoea-episodes (BAE) at least 2 days before and during the entire diarrhoeal period. In neonates with RV antigen in stools (n = 114) we found a higher incidence of BAE compared to neonates with RV negative stools (33% vs 8%, P < 0.001 for bradycardia; 7% vs 0%, P < 0.05 for apnoea). Furthermore, bradycardia episodes of RV positive neonates were more often followed by cyanosis (11 vs 0%, P < 0.05) and intervention was more often necessary (31 vs 14%, P < 0.05) than in the RV negative neonates. CONCLUSION: RV infection was associated with a high incidence of BAE in neonates with diarrhoea during the acute phase of disease suggesting CNS involvement.

Apnea↗
PubMed1996

Somatostatin analogue octreotide and inhibition of tumour growth in metastatic endocrine gastroenteropancreatic tumours.

Antiproliferative treatment of patients with metastatic endocrine gastroenteropancreatic tumours (GEP) is based mainly on chemotherapeutic protocols whereby drug toxicity is a major handicap. Octreotide is the first choice in the control of hormone mediated symptoms. From retrospective and a few prospective studies it has been suggested that octreotide exhibits antiproliferative properties. The prospective German Sandostatin multicentre phase II trial investigated the effects of 200 micrograms octreotide thrice daily for one year on tumour growth and endocrine abnormalities in 103 patients. Octreotide treatment was continued in those patients responding to the drug until tumour progression occurred. In 28 of those with tumour progression during 200 micrograms thrice daily octreotide dose was increased to 500 micrograms thrice daily. The study sample consisted of 52 patients with computed tomography confirmed tumour progression and 13 patients with stable disease before octreotide treatment, whereas no preobservation period was available in 38 patients. Nineteen patients (36.5%) with computed tomography confirmed tumour progression experienced stabilisation of tumour growth lasting for at least three months. Median duration of stable disease was 18 months. At month 12, stable disease continued in 12 patients, declined after 24 months to nine patients, and after 36 months to five patients. Tumour regression has not been seen in this or other subgroups. In the subgroup with stable disease before octreotide, stable disease continued in 53.8% of patients over 12 months. Increase of octreotide dose to 500 micrograms thrice daily did not influence progression seen during the lower dose with the exception of one patient in whom tumour progression changed to stable disease. No association of tumour size response and patients' characteristics could be detected. The results suggest that octreotide inhibits tumour growth in patients with metastasised endocrine GEP tumours. The antiproliferative effect is, at least in some patients, longlasting. Currently, octreotide can only be recommended as an antiproliferative drug if patients with clearly progressive disease show stabilisation after treatment for three to six months.

Adenoma, Islet Cell↗
PubMed1996

Relation between the incidence of invasive cervical cancer and the screening interval: is a five year interval too long?

OBJECTIVE: To examine the incidence of invasive cervical cancer per 100,000 women years at risk and relative risk according to screening history among eligible women aged 25-69 in Southampton and South West Hampshire during the three years after completion of the first round of comprehensive screening. RESULTS: There was a significantly higher incidence of invasive cervical cancer in women who had not been screened during the preceding 0.5-5.5 years than in those who had been screened (relative risk (RR) 2.6; 95% confidence interval (CI) 1.6 to 4.3). Among the latter group of women (with interval cancers) there was a significantly higher incidence in those with a long interval of 3.5-5.5 years since their most recent smear than in those with a short interval of 0.5-3.5 years (RR 2.2; 95% CI 1.3 to 3.8). Among women with non-interval cancers, there was a significantly higher incidence among those who had no cytology record than among those who had been screened but were overdue for a smear (RR 3.0; 95% CI 1.2 to 7.3). When screen detected cancers were excluded from the figures the relative risks for all the comparative groups described above were greater, though the 95% confidence limits were wider because the numbers were smaller. The most pronounced difference in incidence was between symptomatic cancers in women with a short screening interval (5.8 per 100,000 women years at risk) and in women with no cytology record (71.3 per 100,000 years at risk). Most cancers were interval cancers (76%) because of the high screening coverage: 89.2% of eligible women aged 25-69 had been screened during the preceding 0.5-5.5 years. The overall incidence per 100000 women years at risk approached that of interval cancers, and was nearer to that observed in the short than the long interval because 74.7% of women had been screened within 3.5 years. CONCLUSION: The results confirm the effectiveness of screening but suggest that a five year screening interval may be too long, at least during the early rounds of screening.

Adult↗
PubMed1995

Mechanism of repetitive monomorphic ventricular tachycardia.

BACKGROUND: The most common form of idiopathic ventricular tachycardia (VT) is repetitive monomorphic VT (RMVT), which is characterized by frequent ventricular ectopy and salvos of nonsustained VT with intervening sinus rhythm. Unlike most other forms of idiopathic VT, this tachycardia typically occurs at rest and is nonsustained. The mechanism of RMVT is undefined. Because of a common site of origin, the right ventricular outflow tract (RVOT), we hypothesized that RMVT is mechanistically related to paroxysmal sustained, exercise-induced VT, which has been shown to be consistent with cAMP-mediated triggered activity. Therefore, in this study, we sought to identify (1) the mechanism of RMVT at the cellular level by using electropharmacological probes known to activate either stimulatory or inhibitory G proteins and thereby modify intracellular cAMP levels, (2) potential autonomic triggers of RMVT through analysis of heart rate variability, and (3) whether well-characterized somatic activating mutations in the stimulatory G protein, G alpha s, underlie RMVT. METHODS AND RESULTS: Twelve patients with RMVT underwent electrophysiological study. Sustained monomorphic VT was reproducibly initiated and terminated with programmed stimulation and/or isoproterenol infusion in 11 of the 12 patients (the other patient had incessant RMVT). Induction of VT demonstrated cycle length dependence and was facilitated by rapid atrial or ventricular pacing. Termination of VT occurred in response to interventions that either lowered stimulated levels of intracellular cAMP (and thus decreased intracellular Ca2+)--ie, adenosine (12 of 12), vagal maneuvers or edrophonium (8 of 9), and beta-blockade (3 of 5)--or directly decreased the slow-inward calcium current--ie, verapamil (10 of 12). Analysis of heart rate variability during 24-hour ambulatory monitoring in 7 patients showed that the sinus heart rate is increased and accelerates before nonsustained VT (P < .05), whereas high-frequency heart rate variability is unchanged. These findings are consistent with transient increases in sympathetic tone preceding nonsustained VT. Finally, myocardial biopsy samples were obtained from the site of origin of the VT (typically the RVOT) and from the right ventricular apex from 9 patients. Genomic DNA was extracted from each biopsy sample, and three exons of G alpha s in which activating mutations have previously been described were amplified by polymerase chain reaction. All sequences from these regions were found to be identical to that of control. CONCLUSIONS: Although the arrhythmia occurs at rest, the constellation of findings in idiopathic VT that is characterized by RMVT is consistent with the mechanism of cAMP-mediated triggered activity. Therefore, the spectrum of VT resulting from this mechanism includes not only paroxysmal exercise-induced VT but also RMVT.

Adenosine↗