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Biomedical subjects

T Ashraf

Publications and source records attributed to T Ashraf.

18 recordsLinked to original sources

Is There Potential Clinical Utility in Reporting Variants of Uncertain Significance From Prenatal Sequencing?

OBJECTIVE: Prenatal sequencing of fetuses with abnormalities detected on imaging is expanding globally. Debate continues over whether variants of uncertain significance (VUS) should be reported prenatally, with some recent national position statements opposing this. In England, VUS that fit the fetal phenotype and require little further evidence for upgrade are discussed at multidisciplinary team (MDT) meetings to determine whether to report. We review the VUS reported by one English laboratory that provides prenatal sequencing to half of England. METHOD: The laboratory's database was searched from 01/10/2020 to 30/04/2025 to ascertain all cases where a VUS was reported. Pregnancy outcomes were obtained from local clinical teams to determine whether the VUS status had been resolved. RESULTS: VUS were reported in 41/881 fetuses sequenced. Follow-up data were available for 38/41 cases, of which 23 were subsequently upgraded to likely pathogenic and 1 downgraded to likely benign. The most common reason for upgrade was new information from post-mortem or postnatal review (17/23). CONCLUSION: There is clinical utility in reporting VUS from prenatal sequencing following MDT discussion. Although reporting VUS leaves parents with uncertainty, follow up (including post-mortem when applicable) resolves this in over 50% of cases (79% of cases re-examined pre- or postnatally).

Humans↗

Polyethylene wear in a non-congruous unicompartmental knee replacement: a retrieval analysis.

Polyethylene wear is considered a threat to the long-term survival of unicompartmental knee replacement (UKR). This study aims to determine the linear penetration and volumetric wear associated with a non-congruent commonly used UKR, the St Georg Sled. This prosthesis has a biconvex femoral component which articulates with a flat polyethylene tibial component resulting in point contact. Components were retrieved from the knees of 19 patients undergoing revision for a failed UKR after primary replacement. Linear penetration and volumetric wear was measured using a coordinate measuring machine. Using an un-used implant, a three-dimensional computer model of the surface was generated and compared to the explanted specimen. Most patients had revisions because of disease progression to other compartments rather than specific wear related pathology. The mean linear wear for the sample was 0.89 mm (S.D. 0.59 mm) over an average period of 5.6 years giving the mean linear penetration rate of 0.15 mm/year. The mean volumetric wear was 99.7 mm3 (S.D. 79.3 mm3) over the same period giving a mean annual volumetric wear rate of 17.3 mm3/year. The results in this study indicate that clinically significant wear is not necessarily a feature of this fixed bearing unicompartmental knee replacement. The pattern of wear is consistent with clinical findings and indicates excavation of the polyethylene after implantation but at a slower rate than would be anticipated.

Arthroplasty, Replacement, Knee↗

Evaluation and comparison of coronary heart disease risk factor profiles of children in a country with developing economy.

OBJECTIVE: To define the risk factors (RF) profile and prevalence rates of high risk factors in an urban Pakistani community and compare it to the RF profile and prevalence rates of Pakistan National Health Survey. METHODS: The present study included RF relevant data of 400 house hold children selected by open invitation as a part of Metroville Health Study (MHS), a risk factor modification study which was a cooperation between National Heart Lung Blood institute (NHLBI) USA and National Institute of Cardiovascular Diseases Pakistan. The base line data of 389 girls and 417 boys age 5-17 was included. PMRC data of 5067 and NHANES III survey data of 10,252 US children was used for comparison with MHS. RF analyzed were height weight, SBP, DBP, BMI and serum cholesterol. Comparisons between MHS and PMRC and US were made by using two tailed student t test and of high RF were defined as those exceeding US standards and expressed as percentages. RESULTS: The RF factor profile of urban Metroville children was worse than the national average of PMRC children. Except for diastolic blood pressure in both boys and girls and SBP in PMRC boys, all other RF were less than US children. Prevalence rates were higher in urban Metroville community, i.e., MHS compared to the PMRC which represents national average data. CONCLUSION: RF profile of Pakistani children has been presented and effect of urbanization demonstrated by comparing the PMRC and MHS RF profile. Hypertension in Pakistani children has emerged as a single most important RF requiring urgent prevention.

Adolescent↗

Symmetrical vs asymmetrical total knee replacement--a medium term comparative analysis.

Modifications of established implants can result in deleterious effects, as with the Capitol and the matt coated Exeter hips. In 1991 the Kinemax plus modification of the Kinematic knee was introduced in Bristol, the design changes having been made to reduce patello-femoral complications. We carried out a comparative analysis of the prospective recorded data on a consecutive series of 182 total knee replacements (95 Kinematic and 87 Kinemax plus knees) performed between 1991 and 1993. The same instrumentation and surgical technique was used. Since the design had introduced a broader trochlear, offset patella and had changed from an asymmetrical to a symmetrical femoral component, particular attention was paid to tracking and range of movement. All patients were reviewed at 5 years using the Bristol knee score and radiographs. There was no difference in the overall score (both prosthesis scoring 85-86) but the Kinemax plus group with a symmetrical trochlear had a significantly greater improvement in the range of movement (14 degrees as opposed to 4 degrees; P<0.05). In addition, secondary intervention for mal-tracking was significantly less in the Kinemax group. No deleterious effect of the changed geometry was observed. It is concluded that the introduction of a symmetrical femoral component with an offset patella reduced patello-femoral complications without detectable disadvantages.

Aged↗

Efficacy of CVD risk factor modification in a lower-middle class community in Pakistan: the Metroville Health Study.

The Metroville Health Study aimed to reduce consumption of total cooking fats by 33%, salt by 25% and replace ghee with vegetable oil in a lower middle class urban community in Pakistan. Households (n=403) were randomly assigned to Intervention and Control groups. A baseline screening collected data on CVD risk factors, knowledge and attitudes and household consumption of cooking fats and salt. Intervention households received information about CVD and regular visits by social workers who measured cooking fats and salt and counselled cooks on the goals of intervention. Two years later, 291 households were re-screened. Intervention households reduced consumption of fats and salt compared to differences were total fat, 48% (p<0.0001); ghee, 37% (p=0.005); vegetable oil, 33% (p=0.0001); and salt, 41% (p=0.011). Household visits by trained social workers were effective in achieving reductions in consumption of cooking fat and salt in a lower class urban community.

Cardiovascular Diseases↗

Lateral unicompartmental knee replacement survivorship and clinical experience over 21 years.

We describe 88 knees (79 patients) with lateral unicompartmental osteoarthritis which had been treated by the St Georg Sled prosthesis. At a mean follow-up of nine years (2 to 21) 15 knees had revision surgery, nine for progression of arthritis, six for loosening, four for breakage of a component and four for more than one reason. Six patients complained of moderate or severe pain at the final follow-up. Only five knees were lost to follow-up in the 21-year period. We performed survivorship analysis on the group using revision for any cause as the endpoint. At ten years the cumulative survival rate was 83%, and at 15 years, when ten knees were still at risk, it was 74%. Based on our clinical results and survival rate the St Georg Sled may be considered to be a suitable unicompartmental replacement for isolated lateral compartment osteoarthritis.

Adult↗

Effectiveness of suction drainage after primary or revision total hip and total knee arthroplasty.

Postoperative suction drainage of a surgical wound is aimed at evacuation of wound hematoma. This study evaluated the effectiveness of suction drainage in joint replacement surgery. Surgical wounds in 206 patients with primary or revision hip and knee arthroplasty were assessed according to a set criteria. Forty-eight hours postoperatively, wound hematoma and exudate formation were not related to the use of suction drains. A greater tendency of wound oozing was seen in revision hip arthroplasty performed with postoperative suction drainage. Therefore, postoperative suction drainage did not affect hematoma formation or wound oozing and is thus considered an unnecessary practice.

Aged↗

Predicting risk reduction of coronary disease in patients who are glucose intolerant: a comparison of treatment with fenofibrate and other lipid-modifying agents.

A clinical outcomes model was developed to estimate the ability of fibrates and statins to reduce the relative and absolute risk of developing coronary heart disease (CHD) in patients with diabetes. A database was constructed, drawing on results from 83 applicable published studies. Risk factor outcomes reported by the model were chosen according to those found to be statistically significant in the data set parameters from the Framingham Heart Study. In the analysis, fenofibrate was compared with gemfibrozil (an earlier fibrate) and six 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase-inhibitor or "statin" agents. Among the agents studied, only fenofibrate was found to significantly affect all six cardiovascular disease risk factors used in this analysis. For men with diabetes, the estimated absolute risk of developing CHD after five years of treatment was lowered equally and most effectively by fenofibrate, simvastatin, and atorvastatin, from 10% to 6%. For women with diabetes, fenofibrate and simvastatin reduced absolute risk from 9% to 6% over five years of treatment, while atorvastatin reduced risk from 9% to 6%. An accompanying cost comparison analysis found that reducing absolute risk of CHD in these patients would result in significant reductions in the medical expense of treating cardiac events, and that significant differences in the amount saved were driven by treatment choice. Fenofibrate, simvastatin, and atorvastatin produced the greatest long-term savings.

Coronary Disease↗

Pharmacoeconomics of lipid-lowering agents for primary and secondary prevention of coronary artery disease.

Cardiovascular disease is the leading cause of death and the leading source of healthcare expenditure in the US and most other industrialised countries. Cholesterol lowering by pharmacological means prevents atherosclerotic plaque progression and has been shown to reduce both fatal and nonfatal coronary events in patients with or without coronary artery disease (CAD). Because of their excellent efficacy and safety profiles, the introduction of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (also known an 'statins') in 1987 raised hopes for demonstrating the survival benefit of cholesterol reduction. In the past decade, several large-scale placebo-controlled trials with statin therapy have revisited the relationship between cholesterol reduction, cardiovascular disease and mortality. The West of Scotland Coronary Prevention Study (WOSCOPS) [pravastatin] and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) [lovastatin] have shown significant cardiovascular disease reduction in primary prevention trials of patients with elevated and normal cholesterol levels, respectively. The Scandinavian Simvastatin Survival Study (4S), the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study and the Cholesterol and Recurrent Events (CARE) trial [pravastatin] have shown significant cardiovascular disease reduction in patients with a previous history of CAD with high, moderate and normal cholesterol levels, respectively. Three of these studies (4S, WOSCOPS and LIPID) have shown significant reduction in all-cause mortality, while all the statin secondary prevention trials (4S, CARE and LIPID) have demonstrated significant reduction in cerebrovascular disease/ Earlier cholesterol reduction cost-effectiveness studies with nonstatin treatments (bile acid resins, fibrates, niacin and diet) suggested that only patients at extremely high risk could be treated with lipid therapy in a cost-effective manner. More recently, rigorous outcomes evidence demonstrates that statins, particularly for simvastatin for secondary prevention and lovastatin for primary prevention, have a broadly favourable cost-effectiveness profile. Based on US medical price levels and the available clinical trial data on statins, it would be cost effective [e.g. cost less than $US50,000/year of life saved] to intervene with statin therapy in any patient with an annual CAD risk exceeding 1%. This includes all patients with pre-existing CAD or diabetes mellitus, and many more primary prevention patients than are currently contemplated by the US National Cholesterol Education Panel treatment guidelines. Achieving such a goal will require enormous changes in patient education, clinical perspective, healthcare practice and healthcare finances. But any proven opportunity for saving the lives of 25% of those dying from cardiovascular disease each year deserves to be considered with the utmost seriousness and urgency.

Coronary Disease↗

Economic impact of providing workplace influenza vaccination. A model and case study application at a Brazilian pharma-chemical company.

OBJECTIVE: To develop and apply a model to assess the economic value of a workplace influenza programme from the perspective of the employer. DESIGN: The model calculated the avoided costs of influenza, including treatment costs, lost productivity, lost worker added value and the cost of replacing workers. Subtracted from this benefit were the costs associated with a vaccination programme, including administrative costs, the time to give the vaccine, and lost productivity due to adverse reactions. The framework of the model can be applied to any company to estimate the cost-benefit of an influenza immunisation programme. SETTING: The model developed was applied to 4030 workers in the core divisions of a Brazilian pharma-chemical company. RESULTS: The model determined a net benefit of $US121,441 [129,335 Brazilian reals ($Brz)], or $US35.45 ($Brz37.75) per vaccinated employee (1997 values). The cost-benefit ratio was 1:2.47. The calculations were subjected to a battery of 1-way and 2-way sensitivity analyses that determined that net benefit would be retained as long as the vaccine cost remained below $US45.40 ($Brz48.40) or the vaccine was at least 32.5% effective. Other alterations would retain a net benefit as well, including several combinations of incidence rate and vaccine effectiveness. CONCLUSIONS: The analysis suggests that providing an influenza vaccination programme can incur a substantial net benefit for an employer, although the size of the benefit will depend upon who normally absorbs the costs of treating influenza and compensating workers for lost work time due to illness, as well as the type of company in which the immunisation programme is applied.

Adolescent↗

Managed care research participation and interests.

Recent concerns about the future of American health care research have focused in part on the growth of MCOs, which many believe are uninterested in research participation. Managed care may hinder research by limiting patient access to academic medical centers, and also by heightening competitiveness, which may force these centers to reduce research funding. There may be, however, some incentives for MCOs to participate in research, including the ability to pursue unique research interests as well as attract potential members.

Data Collection↗

Cost-effectiveness of pravastatin in secondary prevention of coronary artery disease.

This study analyzed the cost-effectiveness of pravastatin in secondary prevention of coronary artery disease (CAD). The projected risk model in 445 male patients with established CAD and moderately elevated serum low-density lipoprotein cholesterol used results data from 2 placebo-controlled plaque regression trials: Pravastatin Limitation of Atherosclerosis in the Coronary Arteries and Pravastatin, Lipids, and Atherosclerosis in the Carotids. Framingham Heart Study data were used to project the risk of mortality 10 years after myocardial infarction (MI) for incremental male patients in the placebo group who had MI. A Markov process was used to estimate life-years saved, and decision analysis was used to estimate cost. Depending on the patient-risk profile, the midrange estimated cost per life-year saved with pravastatin in secondary prevention of CAD varied from $7,124 to $12,665, which is favorable compared with other widely accepted medical interventions.

Anticholesteremic Agents↗

Cost-effectiveness of levonorgestrel subdermal implants. Comparison with other contraceptive methods available in the United States.

The objective of this analysis was to evaluate and compare the cost-effectiveness of eight contraceptive methods: condoms, diaphragms, oral contraceptives, intrauterine devices, medroxyprogesterone acetate suspension, levonorgestrel subdermal implants, tubal ligation and vasectomy. Based on a comprehensive review of the literature and various additional data sources, this analysis identified, measured and compared direct costs of the methods, physician visits, treatment of adverse effects and cost of failure (i.e., mean cost for all types of deliveries or first-trimester abortion). Medical benefits (if any) resulting from each contraceptive method were calculated and considered in the analysis as cost savings. The cost of method failure proved to be the greatest influence on cost-effectiveness. Sterilization was identified as the most cost-effective method overall. Of the reversible methods, the intrauterine device was found to be the most cost-effective, followed by levonorgestrel implants.

Adult↗