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Biomedical subjects

Patrick Parfrey

Publications and source records attributed to Patrick Parfrey.

At least 19 recordsLinked to original sources

Therapy insight: management of cardiovascular disease in the renal transplant recipient.

Cardiovascular disease causes the deaths of up to 50% of renal transplant recipients who have a functioning graft. As in other states of chronic kidney disease, both overload cardiomyopathy (chronic heart failure and left ventricular hypertrophy) and ischemic heart disease are evident; age and gender are important risk factors for both of these disorders. Potentially treatable risk factors include smoking, hyperlipidemia, diabetes and hypertension for ischemic heart disease, and anemia, hypertension and diabetes for cardiomyopathy. Although definitive evidence on the effectiveness of interventions is lacking, it seems reasonable to treat renal transplant recipients as patients at the highest risk of cardiovascular disease. Aggressive targeting of lifestyle factors, blood pressure, cholesterol and sugar regulation is likely to have a major impact on patient and graft survival and should be initiated well before transplantation. Maintenance of hemoglobin with erythropoietic agents is controversial but might improve quality of life. Although immunosuppressive agents have distinct effects on cardiovascular risk factors, the impact on outcomes is impossible to predict on the basis of current data, and no firm recommendations can be made.

Cardiovascular Diseases↗

Progressive loss of renal function is an age-dependent heritable trait in type 1 autosomal dominant polycystic kidney disease.

Significant intrafamilial phenotypic variability is well documented in autosomal dominant polycystic kidney disease (ADPKD) and suggests a modifier effect. In this study, variance components analysis was performed to estimate the contribution of genetic factors for within-family renal disease variability in 406 patients from 66 type 1 ADPKD families. Overall, 39% of the study patients had ESRD at their last follow-up, and their renal survival did not differ by gender (P = 0.35, log-rank test). Because their frequency plot of creatinine clearance (Ccr) assumed a bimodal distribution with a marked kurtosis that was not improved by transformations, the study cohort was decomposed into two separate groups (non-ESRD [n = 247] and ESRD [n = 159]) in which the Ccr plots were normally distributed. The heritability (h(2)) of Ccr and age at ESRD (age(ESRD)) and the genetic correlations between these measures and their covariates were estimated. In patients without ESRD, a significant heritability was found for Ccr (h(2) = 0.42; P = 0.0015) after adjusting for age (P = 0.0001), systolic BP (P = 0.0006), and treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (P = 0.00001). Birth year, gender, BMI, diastolic and mean BP, and pack-years of cigarette smoking did not significantly influence the heritability of this trait. In patients with ESRD, age(ESRD) provides a better measure than Ccr, which was very narrowly distributed. A significant heritability was found for age(ESRD) (h(2) = 0.78; P = 0.00009) in these latter patients. None of the above covariates influenced the heritability of this trait. It is concluded that a significant modifier gene effect influences the progression of renal disease in type 1 ADPKD.

Adult↗

Antibiotic utilisation in community practices: guideline concurrence and prescription necessity.

PURPOSE: To evaluate the indications, concurrence with prescribing guidelines and potential necessity for antibiotic (AB) prescriptions written in community practice. METHODS: We reviewed the charts of all patients with infection-related illnesses seen by family physicians during two random days of regular practice between 1 Oct 1997 and 30 Jan 1998. Guideline concurrence of AB prescribing was assessed using regional AB prescribing guidelines. Likelihood of AB indication for respiratory tract infections was assessed using published clinical practice guidelines for determination of likely viral versus bacterial etiology. RESULTS: Of 4218 visits captured, 949 (22%) were for newly acquired infections. Sixty four percent (n=604) of consultations for newly acquired infections resulted in an AB prescription. Based on the doctors' diagnoses, 61% of AB prescriptions were concurrent with prescribing guidelines, 10% were for the wrong drug, 20% were not indicated and in 10% of cases a lower line AB was available. For respiratory tract infections, 12% of these infections were likely bacterial, whereas the physicians determined that 56% were bacterial. CONCLUSIONS: A large proportion of ABs administered in community practices were not in concurrence with community AB prescribing guidelines. Improvements can be made in AB choice and in decisions about likely viral etiology for respiratory tract infections.

Adolescent↗

The clinical epidemiology of contrast-induced nephropathy.

Recent improvements in contrast agents and radiologic imaging tools have resulted in an increasing number of patients undergoing contrast media (CM)-enhanced examinations. Although the majority of patients undergoing these diagnostic and therapeutic procedures experience only mild adverse events, some patient subpopulations are at risk for developing contrast-induced nephropathy (CIN), an adverse event that is associated with high morbidity and mortality. Contrast-induced nephropathy is usually defined as an increase of > or =25% in the serum creatinine level relative to baseline. Pathophysiologic mechanisms underlying this disorder are not fully understood, but it is currently believed that disturbances in renal hemodynamics and a direct effect of CM on renal tubules are involved. In the general population, the incidence of CIN is estimated to be 1% to 6%. However, the risk may be as high as 50% in some patient subgroups. Patients with diabetes and pre-existing renal impairment are at high risk, and CIN incidence increases in patients with multiple comorbidities. The volume and osmolality of CM used also play a role in the development of CIN. Patients who develop CIN are more likely to die in-hospital and, for those who are discharged, 1-year mortality rates are high. Whether this is due to CM, comorbidity, or concurrent comorbid events is unclear. Randomized controlled trials that measure non-renal clinical outcomes are necessary to determine whether interventions that prevent CIN can also prevent non-renal adverse events. A review of the incidence, pathogenesis, and clinical consequences of CIN is provided.

Contrast Media↗

Health care quality from the perspective of health care providers and patients during and shortly after acute care restructuring in Newfoundland and Labrador.

OBJECTIVES: To monitor changes in providers' perceptions of health care quality and the importance of health reform, and in patients' satisfaction with services during and two years after restructuring, comparing the region of the province that was restructured (St John's) with those regions in which hospitals were not aggregated. METHODS: The Employee Attitude Survey questionnaire was sent to acute care providers (n = 5353) to assess personal characteristics and perceptions of the impact of reform on workplace conditions, work-related attitudes and turnover intentions. The response rate for 2000 and 2002 was 42% (n = 1222 and 1034, respectively). Only respondents in both surveys (n = 589) were used in the analysis because study results were the same for both the repeat sample and total samples. A Patient Satisfaction Survey questionnaire was administered to patients discharged from acute care facilities in 2000 (n = 1741) and 2002 (n = 704). Response rates were 82.5% and 90.2%, respectively. RESULTS: Most providers felt, at both time periods, that restructuring of the health care system was a positive step, but felt that health care quality was low. In the St John's region, perceptions of quality and standards of care improved over time. Patients were extremely satisfied with the admission process and hospital stay at both time periods in St John's. However, satisfaction declined in 2002 in regions outside St John's. CONCLUSIONS: Aggregation of acute care hospitals is possible without adverse effects on providers' perceptions of health care quality or on patient satisfaction.

Adult↗

Quality of medical care during and shortly after acute care restructuring in Newfoundland and Labrador.

OBJECTIVES: To critically evaluate the quality of hospital medical care at the beginning, during and shortly after regionalization of health boards in Newfoundland and Labrador, and aggregation of hospitals in the St John's region. METHODS: Retrospective chart audits for the years 1995/96, 1998/99 and 2000/01 (at the beginning, during and after restructuring) focused on outcomes in cardiology, respiratory medicine, neurology, nephrology, psychiatry, surgery and women's health programmes. Where possible, quality of care was judged on measurable outcomes in relation to published statements of likely optimal care. Comparisons were made over time within the St John's region, and separately for hospitals in the rest of the province. RESULTS: There was improvement in the use of thrombolytics and secondary measures post-myocardial infarction in both regions. Mortality and appropriateness of initial antibiotic choice for community-acquired pneumonia remained stable in both regions, with an improvement in admission appropriateness based on the severity in St John's. Aspects of stroke management (referral and time to see allied health professionals, imaging and discharge home) improved in both regions, while mortality remained stable. There was improvement in fistula rate, quality of dialysis and anaemia management in haemodialysis patients, and improvement in the peritoneal dialysis patient peritonitis rate. Readmission rate for schizophrenia remained unchanged. Stable mortality rates were observed for frequently performed surgical procedures. The post-coronary artery bypass grafting (CABG) morbid event rate improved, although access to CABG was not optimal. CONCLUSIONS: Aggregation of acute care hospitals was feasible without attendant deterioration in patient care, and in some areas care improved. However, access to services continued to be a major problem in all regions.

Aged↗

Attitudes and perceptions of registered nurses during and shortly after acute care restructuring in Newfoundland and Labrador.

OBJECTIVES: To monitor changes in registered nurses' perceptions of the impact of seven years of health care restructuring in Newfoundland and Labrador (NL) and to measure the attitudinal and behavioural reactions over four years comparing the St John's region, where hospital aggregation occurred, to other regions of the province. METHODS: Data were collected on acute care nurses' personal characteristics and perceptions of the importance of reform and its impact on workplace conditions and health care quality in 1995, 1999, 2000 and 2002. Nurses' attitudes and intentions were monitored across three time periods (i.e. 1999, 2000 and 2002). RESULTS: Perceived workplace conditions and health care quality, as well as attitudes and behaviours were generally negative. However, there was some improvement over time. The temporal sequence of scores suggests that restructuring had an adverse impact on nurses' attitudes. Few significant regional differences were observed. CONCLUSIONS: Although health services restructuring had an adverse impact on nurses' attitudes, aggregation of hospitals in St John's region was achieved without further deterioration. Provincial wide initiatives are needed to promote more positive work environments and increase the organizational effectiveness.

Attitude of Health Personnel↗

Health care provider outcomes during and shortly after acute care restructuring in Newfoundland and Labrador.

OBJECTIVES: To monitor changes in human resource indicators during six years of restructuring in Newfoundland and Labrador, and to measure providers' perceptions of reform impact and attitudinal and behavioural reactions comparing changes in the St John's region, where hospital aggregation occurred, to other regions. METHODS: Data on human resource indicators from 1995/96 to 2001/02 were obtained and analysed. The Employee Attitude Survey was sent to acute care staff (n = 5353) to assess perceptions of reform impact on workplace conditions, work-related attitudes, turnover intentions and personal characteristics. The response rate for 2000 and 2002 was approximately 42% (n = 1222 and 1034, respectively). Only respondents to both surveys (n = 589) were used in the analysis. RESULTS: Increases in average employee and full-time equivalent numbers occurred in the St John's region, despite hospital closure and aggregation. Increases in staff dislocation and turnover were observed, but paid sick hours decreased. Sick leave and overtime costs increased. Although perceived workplace conditions, and attitudes and behaviours were generally negative, there was evidence of improvement over time, especially in St John's. Few significant regional or provider group differences were observed on most study variables. CONCLUSIONS: Aggregation of hospitals in St John's did not lead to a decrease in employee counts, or deterioration in human resource indicators or attitudes. However, province-wide initiatives are needed to promote more positive work environments and increase organizational effectiveness.

Adult↗

Hospital utilization, efficiency and access to care during and shortly after restructuring acute care in Newfoundland and Labrador.

OBJECTIVES: Since the 1990s restructuring, including regionalization and downsizing, has largely been driven by a desire for cost containment. Regionalization, hospital closure and changes in management processes occurred in Newfoundland and Labrador (NL), Canada between 1995 and 2000. The objectives of the current study were: to describe trends in the utilization of acute care hospital services by residents of NL during and shortly after restructuring; to examine trends in the efficiency of utilization of acute care beds in the province during the same time frame; and to compare the trends in St John's with the rest of the province, taking account of confounding events, in an attempt to understand the impact of aggregation of hospitals in this region. METHODS: Hospital discharge and day surgical data were analysed for all facilities in NL from 1995/96 to 2000/01. Analyses were by facility of service and also by region of residence directly standardized to the provincial population for 1996. Efficiency of bed utilization was examined on three occasions by concurrent utilization review using a modified version of the Appropriateness Evaluation Protocol. Trends in the St John's region (where most tertiary services are located and greater aggregation of hospitals occurred) were compared with the rest of the province. RESULTS: Admissions declined by 14% in St John's facilities and by 17% elsewhere. Inpatient days fell by 9% in St John's and by 12% elsewhere. Average length of stay and Resource Intensity Weight changed little, apart from a rise in the final study year, with the largest change in St John's. Standardized hospital admission rates declined by 10% and inpatient days by 5.6% for residents of St John's region, and by 16% and 14% respectively for residents of other regions. There was no change over time in the use of day surgery. Efficiency of acute care bed use improved in 2002 in St John's, but was unchanged in other regions. Use of acute care beds by elderly patients for extended stay, or when an alternate level of care would have been appropriate, was greater in St John's with the disparity persisting over time. Waiting time for continuing care in the St John's region was unchanged comparing 1995/96 and 1999/00. CONCLUSIONS: The degree to which acute care restructuring or financial pressures and constraints imposed at the provincial level contributed to observed utilization trends is unclear. Aggregation of hospitals in the St John's region may have contributed to more efficient use of acute care beds. Restructuring as carried out did not integrate health care sectors, and problems at the acute care/continuing care boundary were not resolved in St John's, where access to continuing care remained difficult.

Adult↗

Acute care restructuring in Newfoundland and Labrador: the history and impact on expenditure.

OBJECTIVES: To document the history of regionalization and its effects on the Newfoundland and Labrador acute care health system, and to describe changes in acute care expenditure in the St John's region where hospital redesign, closure and aggregation occurred in relation to other regions not exposed to aggregation. METHODS: Interviews were conducted with senior health officials. Transcripts and other reports were reviewed. Financial data were abstracted from audited general ledger statements received from the Ministry of Health. RESULTS: Regionalization achieved its objectives of hospital aggregation in St John's. The average number of full-time equivalent employees increased slightly by 2% (5304-5416). In some regions, integration of services was delayed because of conflict and resistance to change. There was some disparity between the Provincial Government's objectives for cost control and the CEOs' perceptions of economies of scale. Between 1995/96 and 2002/03, total expenditures for the St John's region and the other five regional hospitals increased by 46% and 54%, respectively; total personal income of the population and government revenues increased by only 18% and 16%, respectively. CONCLUSIONS: Regionalization in Newfoundland and Labrador facilitated aggregation of hospitals, but did not control the number of front-line workers and, consequently, total acute care expenditure. Expenditure increased significantly between 1995 and 2002, at a rate which exceeded the increase in government revenues. The government's ability to pay for acute care will not be achieved unless employee costs are controlled or provincial income increases.

Health Care Reform↗

High incidence of childhood type 1 diabetes in the Avalon Peninsula, Newfoundland, Canada.

OBJECTIVE: The aim of this study was to determine the incidence of type 1 diabetes among children aged 0-14 years in the Avalon Peninsula in the Canadian Province of Newfoundland. RESEARCH DESIGN AND METHODS: This was a prospective cohort study of the incidence of childhood type 1 diabetes in children aged 0-14 years who were diagnosed with type 1 diabetes from 1987 to 2002 on the Avalon Peninsula. Identified case subjects during this time period were ascertained from several sources and verified using the capture-recapture technique. Data were obtained from the only pediatric diabetes treatment center for children living on the Avalon Peninsula. RESULTS: Over the study period, 294 children aged 0-14 years from the Avalon Peninsula were diagnosed with type 1 diabetes. The incidence of type 1 diabetes in this population over the period 1987-2002 inclusive was 35.93 with a 95% CI of 31.82-40.03. The incidence over this period increased linearly at the rate of 1.25 per 100,000 individuals per year. CONCLUSIONS: The Avalon Peninsula of Newfoundland has one of the highest incidences of type 1 diabetes reported worldwide. The incidence increased over the 16-year study period.

Adolescent↗

Electrocardiographic left ventricular hypertrophy in renal transplant recipients: prognostic value and impact of blood pressure and anemia.

Left ventricular hypertrophy (LVH) is an independent risk factor for death and cardiovascular disease in the general population and dialysis patients. However, the causes and consequences of LVH have not been well described in renal transplant recipients (RTR). A retrolective cohort study was conducted in 473 RTR who were alive and free of cardiac disease at 1 yr. LVH was defined using the Cornell electrocardiographic (EKG) criteria. A total of 416 patients had an interpretable first-year EKG (88%), and 284 had an interpretable fifth-year EKG (78% of 5-yr survivors). Baseline characteristics were similar in patients with and without EKG. Of 416 patients, 57 had LVH in the first year, whereas 38 of 284 patients had LVH in the fifth year, of which 18 cases were de novo. Baseline LVH was a risk factor for death (RR 1.9 [1.22, 3.22]) and congestive heart failure (CHF) (RR 2.27 [1.08, 4.81]) and was independent of other major prognostic variables. Persistent or de novo LVH in the fifth year predicted subsequent death (RR 2.15 [1.14,4.01]) and CHF (2.71 [1.17, 6.30]). Anemia and diastolic BP were independent risk factors for increasing Cornell voltage (a marker of LV mass) between first and fifth years. Systolic BP was the only predictor of de novo LVH at 5 yr. It seems that EKG LVH is a significant risk factor for death and CHF in RTR and that anemia and hypertension are risk factors for LV growth. Whether aggressive treatment of hypertension and anemia can improve outcomes merits further study.

Adult↗

Genotype-renal function correlation in type 2 autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a common Mendelian disorder that affects approximately 1 in 1000 live births. Mutations of two genes, PKD1 and PKD2, account for the disease in approximately 80 to 85% and 10 to 15% of the cases, respectively. Significant interfamilial and intrafamilial renal disease variability in ADPKD has been well documented. Locus heterogeneity is a major determinant for interfamilial disease variability (i.e., patients from PKD1-linked families have a significantly earlier onset of ESRD compared with patients from PKD2-linked families). More recently, two studies have suggested that allelic heterogeneity might influence renal disease severity. The current study examined the genotype-renal function correlation in 461 affected individuals from 71 ADPKD families with known PKD2 mutations. Fifty different mutations were identified in these families, spanning between exon 1 and 14 of PKD2. Most (94%) of these mutations were predicted to be inactivating. The renal outcomes of these patients, including the age of onset of end-stage renal disease (ESRD) and chronic renal failure (CRF; defined as creatinine clearance < or = 50 ml/min, calculated using the Cockroft and Gault formula), were analyzed. Of all the affected individuals clinically assessed, 117 (25.4%) had ESRD, 47 (10.2%) died without ESRD, 65 (14.0%) had CRF, and 232 (50.3%) had neither CRF nor ESRD at the last follow-up. Female patients, compared with male patients, had a later mean age of onset of ESRD (76.0 [95% CI, 73.8 to 78.1] versus 68.1 [95% CI, 66.0 to 70.2] yr) and CRF (72.5 [95% CI, 70.1 to 74.9] versus 63.7 [95% CI, 61.4 to 66.0] yr). Linear regression and renal survival analyses revealed that the location of PKD2 mutations did not influence the age of onset of ESRD. However, patients with splice site mutations appeared to have milder renal disease compared with patients with other mutation types (P < 0.04 by log rank test; adjusted for the gender effect). Considerable renal disease variability was also found among affected individuals with the same PKD2 mutations. This variability can confound the determination of allelic effects and supports the notion that additional genetic and/or environmental factors may modulate the renal disease severity in ADPKD.

Adult↗

Combined carrier status of prothrombin 20210A and factor XIII-A Leu34 alleles as a strong risk factor for myocardial infarction: evidence of a gene-gene interaction.

Studies associating the prothrombin 20210G>A (FII 20210A), factor V Leiden (FVL), and factor XIII Leu34 (FXIII-A Leu34) alleles with myocardial infarction (MI) have yielded conflicting results. Complicated gene-gene interactions, small sample sizes, and heterogeneous genetic and environmental backgrounds may contribute to opposing findings. Simultaneous analysis of multiple gene variants in a large sample size from a genetically isolated population may overcome these weaknesses. Genotyping was performed in 500 MI patients and 500 control subjects from the genetically isolated Newfoundland population to determine the prevalence of the FII 20210A, FVL, and FXIII-A Leu34 variants and their association with MI. Gene-gene interactions were also analyzed. The prevalence of the FII 20210A allele was higher in MI patients (3.2%) than in control subjects (1.0%; P =.015). The FII 20210A allele was also 5.6-fold higher in MI patients younger than 51 years than in age-matched control subjects (P =.04). FVL showed 3.9-fold higher prevalence in young patients than in patients older than 50 years (P =.004) and 2.7-fold higher than in age-matched control subjects (P =.007). Furthermore, the prevalence of combined carriers of the FXIII-A L34 and FII 20210A alleles was 12-fold higher in MI patients than in control subjects (P =.002) and with 92% penetrance. There was disequilibrium of the FXIII-A Leu34 allele to MI patients carrying the FII 20210A allele as a genetic background. Based on our data, we determined that (1) the FII 20210A allele is a risk factor for MI, possibly important for early onset; (2) FVL may predispose for early-onset MI; (3) the FXIII-A Leu34 allele predisposes for MI in males only; however, (4) interaction between the FII 20210A and FXIII-A Leu34 alleles forms a synergistic coeffect that strongly predisposes for MI, placing combined carriers at high risk for MI.

5' Untranslated Regions↗