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Thromboembolic and other events following valve replacement in a pediatric population treated with antiplatelet agents.

To determine if anticoagulation therapy is necessary after valve replacement with the St. Jude Medical prosthesis in young subjects, 30 consecutive patients were studied. They ranged in age from 4 to 20 years, and each had undergone valve replacement some time between February, 1982, and June, 1984. There was 1 hospital death (3.3%; 70% confidence limits [CL] = 0.4% to 10.9%). The 29 hospital survivors were treated with aspirin and dipyridamole. All patients were followed up. There were 5 late deaths (17.2%; 70% CL = 9% to 27%), at a mean of 8 months postoperatively. Follow-up revealed that 7 thromboembolic events occurred in 7 of the hospital survivors (24.1%; 70% CL = 15% to 35%). Hemiparesis occurred in 1 patient, and documented valve thrombosis and death occurred in another. Transient sensorimotor deficits were found in the 5 other patients. Prosthetic valve endocarditis developed in 1 hospital survivor (3.5%; 70% CL = 0.4% to 11%) and resulted in late death. There were no reoperations in the hospital survivors. We conclude that the St. Jude Medical prosthesis is useful for valve replacement in the young because of its low profile, durability, and hemodynamic characteristics. However, we recommend that these patients receive full anticoagulation therapy.

Adolescent↗

Population requirement for primary knee replacement surgery: a cross-sectional study.

OBJECTIVES: To determine the population requirement for total knee replacement (TKR) in England. METHODS: Population-based study using an age/sex-stratified random sample of 28 080 individuals aged 35 yr and over. Incident disease was estimated from prevalence by statistical modelling. The New Zealand priority criteria for major joint replacement were used for case selection. RESULTS: Patients with knee disease were less likely than those with equally severe hip disease to have been referred to a specialist, to have consulted an orthopaedic surgeon or to be on a waiting list for joint replacement. The estimated annual requirement of TKRs in England, based on New Zealand Scores alone, was 55,800 (95% CI 40 700-70,900), contrasting sharply with an annual provision of 29,300 actually observed. However, in contrast to previously reported hip replacement data, when patient willingness to undergo surgery was considered, this estimate decreased considerably. CONCLUSIONS: There appears to be an underprovision of TKR in England. This may be due in part to differences in perception of disease severity and likely response to surgery between patients and general practitioners on one hand, and rheumatologists and orthopaedic surgeons on the other.

Adult↗

The impact of clinical trials on the use of hormone replacement therapy. A population-based study.

BACKGROUND: The last 5 years of trial data demonstrate the ineffectiveness of hormone replacement therapy (HRT). The impact of these trials on age-specific HRT use, HRT discontinuation, and regional HRT variation has not been evaluated extensively. OBJECTIVE: To characterize the relation between HRT trial dissemination and age-specific HRT use, HRT discontinuation, and regional HRT variation before and after the trials' publication. DESIGN: Using the Medco Health database, we analyzed HRT prescription filling, discontinuation, and regional variation among women > or =55 years from May 1998 to May 2003. MEASUREMENTS AND MAIN RESULTS: Approximately 340,000 women were eligible for Medco benefits each month. Within 3 months of the Women's Health Initiative (WHI), HRT prescriptions declined from 12.5% to 9.4%, P< or =.0001. When stratified by age, a statistically significant decline in HRT post-WHI occurred in all age groups, with the biggest decline among women > or =55 to 64 (18% to 11%, P< or =.0001). Among HRT users, we found statistically significant increases in discontinuation in 2002 (67%) compared with 2001 (53%, P<.0001). Prior to the WHI there was substantial regional variation in HRT use, with the West South Central and mid-Atlantic having the highest and lowest proportions, respectively (19% vs 6%, P< or =.0001). Despite a relative decline in HRT use of 25% to 42% across all regions, substantial geographic variation remained. CONCLUSIONS: Hormone replacement therapy use decreased significantly immediately post-WHI, suggesting that trial results can have a rapid effect on practice. Marked regional variation in HRT use persisted after the WHI, suggesting that local practice patterns exert a strong effect on clinical behavior even after new evidence is available.

Age Distribution↗

Cancer among patients on renal replacement therapy: a population-based survey in Lombardy, Italy.

Longer and better survival of End-Stage Renal Disease (ESRD) patients undergoing renal replacement therapy (RRT) is now associated with a higher prevalence of new elderly patients receiving renal replacement therapy (dialysis). In order to help clarify the association of cancer risk with RRT, the incidence of cancer in a population-based cohort of uraemic patients in the Region of Lombardy, northern Italy, was undertaken using data from the Lombardy Regional Dialysis and Renal Transplant Registry. A total of 479 cases of cancer of all sites was recorded in this population. There were statistically significantly elevated risks of primary liver cancer, kidney cancer, thyroid cancer, lymphoma and multiple myeloma. When the data were examined according to primary renal diseases, there did not appear to be any particular association between excess cancer risk and the underlying pathology. While some caution must be expressed in interpreting these data, due to the relatively small numbers of cases expected in many of the disease entities, the results indicate an excess of renal-cell and liver carcinomas and lymphomas in patients receiving RRT and highlight the necessity of careful follow-up and awareness of these associations, together with the need for early detection of such tumours.

Aged↗

[Patterns of use of hormone replacement therapy in 2 Italian populations].

We analysed the pattern of hormone replacement therapy (HRT) use, over the period 1990-92, in a random sample of 76,537 women (45-74 years old) resident in the province of Rome, and in 1994 among all women (45-74 years old) resident in the Umbria region; data were collected through the regional drug prescription monitoring systems. During the three-year period an estimated 3.8% of women were prescribed HRT, among these 42% received estrogen with concomitant progestin therapy. The prevalence of use increased from 1.5% in 1990 to 2.2% in 1992 mainly because of an increased use of skin patches. In the Umbria region, out of the 166,112 women, 2.1% received at least one estrogen prescription. The prevalence of use increased in younger age classes but is almost unchanged over the sixties.

Aged↗

The impact of coronary heart disease in determining use of hormone replacement therapy in a general practice population.

The use of hormone replacement therapy (HRT) for cardiovascular risk reduction remains uncertain. Although previous epidemiological surveys have suggested a clear benefit and nearly 50% mortality risk reduction with HRT in postmenopausal women, recent randomised trials have largely failed to support this. The epidemiological surveys may have been biased in a number of ways including the possibility that HRT users in these studies may have been healthier and taken a greater interest in modifying cardiovascular risks. The aim of the present study was to determine to what extent the revelations from all these trials have influenced HRT prescribing in general practice, in relation to cardiovascular disease. We reviewed 140 women on HRT and 140 age-matched controls from one city centre general practice in the west of Birmingham who were randomly selected by computer. The main indication for HRT use was presence of symptoms associated with oestrogen deficiency. The prevention of osteoporosis accounted for 7.1% of HRT indications, while the primary prevention of CHD was not an issue discussed by either the patient or the GP. Among non-users, 86.4% did not have a known contraindication and many did not have serum lipid measurements or estimations of cardiovascular risk. There was no difference between HRT users and non-users for smoking habits and presence of cardiovascular risk factors including diabetes, hypertension and coronary heart disease. HRT users were also less likely to undergo investigations, such as cervical smear tests and mammograms. In conclusion, this survey reflects the current uncertainty surrounding the use of HRT for cardiovascular risk prevention. Importantly, women on HRT may not be any healthier than non-users, nor do they seek more preventive care than non-users. This is contrary to previous presumptions that selection and prevention bias were the explanation for the apparent cardioprotective effects of HRT.

Adult↗

Koinophilia replaces random mating in populations subject to mutations with randomly varying fitnesses.

Koinophilia, the avoidance of sexual mates bearing strange phenotypic features, or displaying odd behaviour, would, if it evolved, profoundly influence the evolutionary process. A stochastic computer model was therefore devised to investigate the evolution of an initially rare koinophilic trait in panmictic populations, subject to mutations with randomly varying fitnesses. Individual genomes consisted of 50 genes. Mutations occurred at a rate of 0.005, 0.01 or 0.02 per gene per generation. The mean and maximum fitness of mutations could be varied, as could the proportion of beneficial mutations. The carriers of the koinophilic trait avoided, with adjustable degrees of intensity, mates displaying unusual phenotypic features (traits with population frequencies < 0.5); panmictic individuals mated randomly. The results show that koinophilia tends to replace panmixis whenever the preference for common phenotypic traits is strongly expressed, when few mutations are beneficial (1% instead of 10%), or when the maximum fitness of mutations is low (1.2 instead of 2.0). The mutation rate and mean fitness of mutations had only minor effects on the relative advantage of koinophilia.

Animals↗

The influence of socioeconomic status on utilization and outcomes of elective total hip replacement: a multicity population-based longitudinal study.

OBJECTIVE: In countries with universal health coverage, socioeconomic status is not expected to influence access to effective treatment and its prognosis. We tested whether socioeconomic status affects the rates of elective total hip replacement and whether it plays a role in early and late outcomes. DESIGN: Multicity population-based longitudinal study. SETTING AND PARTICIPANTS: From Hospital Registries of four Italian cities (Rome, Milan, Turin, and Bologna), we identified 6140 residents aged 65+ years undergoing elective total hip replacement in 1997-2000. MAIN OUTCOME MEASURES: An area-based (census block) income index was used for each individual. Poisson regression yielded rate ratios (RR) of population occurrence by income level. Logistic regression estimated odds ratios (OR) of selected outcomes within 90 days. Cox proportional hazard models evaluated effects of income on rates of revision of total hip replacement and mortality up to 31 December 2004. Analyses were adjusted for age, gender, city of residence, and coexisting medical conditions. RESULTS: Low-income people were less likely than high-income counterparts to undergo total hip replacement [RR = 0.87, 95% confidence interval (CI) 0.81-0.95]; the effect was stronger among those aged 75+ years (RR = 0.76, 95% CI = 0.66-0.86). Low income was associated with higher risk of acute adverse medical events (P trend = 0.05) and of general infections and decubitus ulcer (P trend = 0.02) within 90 days. The effects were even higher among those aged 75+ years. No effects were found either for orthopaedic complications within 90 days or for revision and mortality. CONCLUSIONS: Total hip replacement is underutilized among elderly deprived individuals. Disadvantaged patients seem more vulnerable to acute adverse medical events after surgery. The evidence of unmet need and poor prognosis of low social class people has important implications for health care policy.

Aged↗

Population need for renal replacement therapy in Thames regions: ethnic dimension.

OBJECTIVES: To determine the use of renal replacement therapy by ethnic origin and to ascertain the variation in provision of such therapy and to relate this to the distribution of ethnic minority populations. DESIGN: Analysis of retrospective and cross sectional data from 19 renal units. SETTING: All four Thames regional health authorities. SUBJECTS: Patients resident in the Thames regions who were accepted as new patients for renal replacement therapy during 1991 and 1992 and the patients who were already undergoing such treatment between December 1992 and April 1993. MAIN OUTCOME MEASURES: Rates of acceptance for and prevalence of renal replacement therapy among white, black, and Asian people. RESULTS: The average annual acceptance rates per million in 1991-2 were 61 for white people, 175 for black people, and 178 for Asians, and the prevalences per million were 351, 918, and 957 respectively. The relative risks increased with age. A threefold increase in the acceptance rate occurred in people aged under 55 in both the black and Asian populations, suggesting that the higher rates are probably not due to factors related to access alone. Treatment rates varied considerably among districts, reflecting both the distribution of ethnic minority populations and access to services. CONCLUSION: Black and Asian people receive and have a greater need for renal replacement therapy, and the need will increase as these populations age. These findings have important implications for the provision of renal services in districts with a high proportion of ethnic minorities and for the management of diabetes mellitus and hypertension, two important causes of end stage renal failure in these populations.

Adolescent↗

Important factors for use of hormone replacement therapy: a population-based study of Swedish women. The Women's Health in Lund Area (WHILA) Study.

OBJECTIVE: The aim of this study was to delineate the use of hormone replacement therapy (HRT) among women who were born between December 2, 1935, and December 1, 1945, and living in the Lund area of southern Sweden and to analyze factors that contribute to the acceptance and continuation of HRT. METHODS: All women received a generic questionnaire pertaining to demographic background, lifestyle, health behavior, and climacteric symptoms and underwent a personal interview. An interim analysis was carried out on 3,900 women. We mailed a hormone questionnaire to the women who were using HRT (n = 1,875). This hormone questionnaire covered, for example, menopausal status, complaints, and alterations in and efficacy of HRT use, as well as the reasons for discontinuing HRT use. RESULTS: A total of 1,415 (76%) women answered the hormone questionnaire. Forty-eight percent were HRT ever users, and 32% were current users. Mean duration of HRT use was 47 months. The most common incentives for HRT use were alleviation of menopausal symptoms (72%) and prevention of bone loss (50%) and/or cardiovascular disease (31%). Forty-seven percent of HRT users reported that they had changed regimens at least once. HRT users had higher education, full-time work, and a higher consumption of alcohol but less consumption of cigarettes. They reported higher frequencies of climacteric symptoms, past histories of premenstrual syndrome, use of oral contraceptives, and hysterectomy. They also had a higher consumption of healthcare resources. A total of 177 women withdrew from therapy. The most common reasons for discontinuation of HRT were weight gain, anxiety of cancer, bleeding, breast tenderness, and emotional problems. Compared with current users, past users had less positive as well as fewer negative effects of HRT. Several variables contributed to compliance, including education, full-time work, regular exercise, low frequency of persistent climacteric symptoms, and alteration of regimens. CONCLUSION: Education, working conditions, lifestyle, interest in prevention, and severity of the climacteric symptoms are determinants for both acceptance of and compliance with HRT.

Cardiovascular Diseases↗

Molecular evidence of Wolbachia infection in natural populations of tropical odonates.

Wolbachia are endosymbiotic bacteria that cause reproductive alterations in numerous arthropod species. Using a PCR-based method, we found that, out of 33 odonate species, four species were infected with Wolbachia. This finding represents the first record of Wolbachia infection in tropical odonates. Identical wsp gene sequences were found in the Wolbachia-infected common odonate species, Agriocnemis f. femina, collected from different locations in Thailand. The infection frequencies in several natural populations suggest that replacement of uninfected populations by Wolbachia-infected ones has recently occurred in this damselfly species.

Animals↗

Biogeography and evolution of the genus Homo.

The debate about the origins of modern humans has traditionally focussed on two contrasting views. Multi-regional evolution proposes that present-day populations worldwide are the descendants of in situ evolution after an initial dispersal of Homo erectus from Africa during the Lower Pleistocene. The alternative, Out-of-Africa 2, proposes that all present-day populations are descended from a recent common ancestor that lived in East Africa approximately 150 000 years ago, the population of which replaced all regional populations. The weight of the evidence is now in favour of Out-of-Africa 2, and discussion is now dominated by the causes of the dispersal of modern humans out of Africa and the outcome of contact with other populations. Fresh approaches, from disciplines hitherto peripheral to the debate, such as evolutionary ecology, and new discoveries are challenging established views, particularly the prevalent idea that biologically superior modern humans were the cause of the demise of all other populations of Homo worldwide. Climate-driven ecological change has been, as with many other taxa, the driving force in the geographical range dynamics of the genus Homo.

Journal Article↗

Changes in the epidemiology of thalassemia in North America: a new minority disease.

OBJECTIVE: Changing patterns of immigration to North America, along with improved treatment, have altered the clinical spectrum of thalassemia, one of the world's most common genetic diseases. The new demography of the disease, with its widely variable phenotypes, has implications for its diagnosis, counseling, and management. Characterization of the new spectrum of this ancient disease, now predominated by minority groups, is essential for optimizing survival. METHODS: The National Institutes of Health-sponsored North American Thalassemia Clinical Research Network (TCRN) conducted a cross-sectional study of 721 patients with thalassemia syndromes. A detailed chart review was undertaken to define the relationships between ethnic origins, genotype, and phenotype. These results were compared with 3 previous surveys of similar regions. To determine if the TCRN patient epidemiology is representative of North American patients, 87 additional programs were reviewed, and hemoglobinopathy programs from the 2 largest thalassemia regions, Ontario and California, were analyzed. RESULTS: A total of 721 patients completed analysis in the TCRN study, including 389 (54%) patients with beta-thalassemia major, 105 (15%) patients with beta-thalassemia intermedia, 95 (13%) patients with hemoglobin E-beta-thalassemia, and 132 (18%) patients with alpha-thalassemia. beta-Thalassemia predominated in Eastern North America. Hemoglobin E-beta-thalassemia and alpha-thalassemia were common on the Western continent. Genotype broadly correlated with the clinical phenotype. However, there was marked heterogeneity in clinical phenotype among patients with similar globin mutations. In beta-thalassemia disorders, coinheritance of the alpha-thalassemia trait, triplication of alpha-thalassemia genes, and heterozygosity for the dominant beta-thalassemia allele affected the clinical phenotype. In alpha-thalassemia disorders, structural mutations such as hemoglobin H-Constant Spring resulted in a severe hemoglobin H phenotype. Sixty percent of patients received regular transfusions, and 86% received regular iron-chelation therapy. Increased survival and decreasing birth rates of Mediterranean patients resulted in an aging Greek/Italian population being replaced by a young Asian/Middle Eastern population. Now, Asian patients account for >50% of the thalassemia population. Evidence of increasing survival is reflected in an advancing mean age of white patients with thalassemia major (25 years, up from 11 years in 1974). The results of the non-TCRN thalassemia survey confirm these observations and describe a young multiethnic thalassemia population distributed throughout North America. Newborn-screening results suggest that thalassemia births in North America are increasing and reflect the change in genotype and phenotype observed in the TCRN populations. CONCLUSIONS: The epidemiology of thalassemia in North America reflects a heterogeneous group of diseases with new ethnicities, genotypes, and phenotypes. In these communities, physicians will need to provide education, prenatal diagnosis, counseling, and management of this newly diverse group of patients.

Adolescent↗

Performance of bioprostheses and mechanical prostheses in age group 61-70 years.

BACKGROUND AND AIM OF THE STUDY: The performance of bioprostheses (BP) and mechanical prostheses (MP) from valve-related composites of complications and combined major thromboembolism and hemorrhage were considered in order to facilitate decision-making for the patient age group of 61-70 years. METHODS: The aortic valve replacement (AVR) population (BP, n = 619; MP, n = 303) was differentiated by age, concomitant coronary artery bypass, diabetes mellitus, chronic obstructive pulmonary disease (COPD) and preoperative renal failure. The mitral valve replacement (MVR) population (BP, n = 353; MP, n = 312) was differentiated by valve type, age, concomitant coronary artery bypass, ejection fraction, NYHA and preoperative renal failure. RESULTS: Actual freedom from reoperation for AVR was 92.1 +/- 1.5% for BP and 98.7 +/- 6.6% for MP, and for MVR was 74.5 +/- 2.6% for BP and 93.8 +/- 2.2% (12 years) for MP. Actual freedom from major thromboembolism and hemorrhage for AVR was 85.1 +/- 1.7% for BP and 76.9 +/- 3.6% for MP, and for MVR was 82.7 +/- 2.4% for BP and 76.7 +/- 3.8% (12 years) for MP. Linearized rates were undifferentiated for major thromboembolism. The hemorrhage rate for AVR-BP was 0.55%/pt-yr and for AVR-MP was 2.3%/pt-yr (p < 0.0001); for MVR-BP, the rate was 0.69%/pt-yr and for MVR-MP was 1.85%/pt-yr (p = 0.0011). The only predictor of AVR reoperation was age, and predictors for MVR reoperation were prosthesis type and follow up NYHA class. Predictors of AVR major thromboembolism and hemorrhage were prosthesis type, age, diabetes mellitus and COPD. There were no predictors of MVR major thromboembolism and hemorrhage. CONCLUSION: For the age group of 61-70 years, MP are recommended for MVR to protect from BP reoperation, whilst for AVR BP are recommended to protect from anticoagulant hemorrhage. Freedom from reoperation for AVR was undifferentiated for BP and MP at 12-15 years.

Age Factors↗

Genetic approaches to malaria control: how long the road?

Malaria control schemes based on the yet untested concept of replacing vector populations with mosquitoes of the same species unable to transmit the parasite offer one more means of attacking this important public health problem. Research is underway in several laboratories aimed at defining factors that can act to interrupt the development of the malaria parasite in the mosquito host, the genetic basis for such refractory mechanisms, methods for introducing genes coding for refractory mechanisms into the mosquito genome, and methods for replacing vector populations in the field. The complexities of such an undertaking are many and varied, but the potential impact of a successful replacement strategy on the epidemiology of malaria in the target area could be significant.

Animals↗

[T4 and T8 lymphocytic populations after total hip replacement].

Immunosuppression is involved in the occurrence of sepsis after surgical trauma. A postoperative lymphocytopenia is a recognised fact. In the opposite, studies on T-lymphocytes helpers (CD 4) and suppressors (CD 8) resulted in conflicting results. The aim of this study was to assess the variations in these two T-lymphocyte sub-populations using strongly standardized conditions in order to minimize the risk of non specific variations: same surgeon, same surgical technique, blood samples collected just before induction, immediately and 24 hours after surgery, automatized measures (Technicon H1). The results confirmed the lymphocytopenia, 24 hours after surgery, but no differences on CD 4 and CD 8 percentages were noted. It is concluded that during the first 24 postoperative hours surgery does not change the relative proportions of T-helpers and T-suppressors. Their measurement is not more useful than total lymphocyte count for assessment of postoperative immunosuppression.

Aged↗

Biological problems with the replacement of a vector population by Plasmodium-refractory mosquitoes.

Attempts are being made to backcross into Anopheles gambiae s.s. the gene(s) which cause zoophily in Anopheles quadriannulatus. Such a backcrossed strain might be preferable to a Plasmodium-refractory strain as a basis for genetic control because a refractory strain could select for evasion of refractoriness in the wild Plasmodium population. The species composition of the malaria vector population in several Tanzanian villages was overwhelmingly An. gambiae s.s. in a normal rainy season, but consisted of four species, all proved by ELISA and/or PCR to carry P. falciparum sporozoites, at the time of the heavy rains associated with El Niño. Thus any scheme, for malaria transmission control by replacement of vectors by genetically-manipulated non-vectors, would have to be able to replace more than one species.

Animals↗

Variability in anticoagulation control predicts thromboembolism after mechanical cardiac valve replacement: a 23-year population-based study.

OBJECTIVE: To assess optimal control of blood anticoagulation to maximize antithrombotic protection after mechanical cardiac valve replacement. DESIGN: A population-based study of 96 patients with a mean follow-up of 7.7 years (range, 1 month to 23 years) was performed in Olmsted County, Minnesota, and 10,301 prothrombin time (PT) ratios were determined after mechanical heart valve replacement. MATERIAL AND METHODS: PT ratios were analyzed in a new time-dependent Cox proportional-hazards model by defining an algorithm for comparing variability in PT ratios at each month of follow-up and relating these to thromboembolic events. The new method was compared with several conventional time-independent definitions. RESULTS: During 740 person-years of follow-up, 19 of 96 patients (20%) had 27 thromboembolic events. Of these 19 patients, 8 (42%) had events within 3 months after valve replacement. Freedom from any thromboembolic event was 72% at 15 years. The event rate was high (7.5% per year) during high variability and low (0.9% per year) during low variability in the PT ratio. This relationship was lost when time dependence was removed. More PT ratios were less than 1.5 during high (27%) than during low (19%) variability. Several conventional definitions of adequacy of anticoagulation that averaged PT ratios before a thromboembolic event or throughout follow-up or that compared the proportion of PT ratios above or below a fixed ratio did not define or only partially defined different thromboembolic risks. CONCLUSION: Periods of high and low variability of PT ratios define high and low risk of thromboembolism, respectively.

Adult↗