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Biomedical subjects

Y Ben-Shlomo

Publications and source records attributed to Y Ben-Shlomo.

At least 19 recordsLinked to original sources
PubMed2006

Stimulation of the caudal zona incerta is superior to stimulation of the subthalamic nucleus in improving contralateral parkinsonism.

Deep brain stimulation (DBS) has an increasing role in the treatment of idiopathic Parkinson's disease. Although, the subthalamic nucleus (STN) is the commonly chosen target, a number of groups have reported that the most effective contact lies dorsal/dorsomedial to the STN (region of the pallidofugal fibres and the rostral zona incerta) or at the junction between the dorsal border of the STN and the latter. We analysed our outcome data from Parkinson's disease patients treated with DBS between April 2002 and June 2004. During this period we moved our target from the STN to the region dorsomedial/medial to it and subsequently targeted the caudal part of the zona incerta nucleus (cZI). We present a comparison of the motor outcomes between these three groups of patients with optimal contacts within the STN (group 1), dorsomedial/medial to the STN (group 2) and in the cZI nucleus (group 3). Thirty-five patients with Parkinson's disease underwent MRI directed implantation of 64 DBS leads into the STN (17), dorsomedial/medial to STN (20) and cZI (27). The primary outcome measure was the contralateral Unified Parkinson's Disease Rating Scale (UPDRS) motor score (off medication/off stimulation versus off medication/on stimulation) measured at follow-up (median time 6 months). The secondary outcome measures were the UPDRS III subscores of tremor, bradykinesia and rigidity. Dyskinesia score, L-dopa medication reduction and stimulation parameters were also recorded. The mean adjusted contralateral UPDRS III score with cZI stimulation was 3.1 (76% reduction) compared to 4.9 (61% reduction) in group 2 and 5.7 (55% reduction) in the STN (P-value for trend <0.001). There was a 93% improvement in tremor with cZI stimulation versus 86% in group 2 versus 61% in group 1 (P-value = 0.01). Adjusted 'off-on' rigidity scores were 1.0 for the cZI group (76% reduction), 2.0 for group 2 (52% reduction) and 2.1 for group 1 (50% reduction) (P-value for trend = 0.002). Bradykinesia was more markedly improved in the cZI group (65%) compared to group 2 (56%) or STN group (59%) (P-value for trend = 0.17). There were no statistically significant differences in the dyskinesia scores, L-dopa medication reduction and stimulation parameters between the three groups. Stimulation related complications were seen in some group 2 patients. High frequency stimulation of the cZI results in greater improvement in contralateral motor scores in Parkinson's disease patients than stimulation of the STN. We discuss the implications of this finding and the potential role played by the ZI in Parkinson's disease.

Aged↗
PubMed2006

The impact of childhood body mass index on timing of puberty, adult stature and obesity: a follow-up study based on adolescent anthropometry recorded at Christ's Hospital (1936-1964).

OBJECTIVE: To examine the impact of childhood body mass index (BMI) on timing of puberty, adult stature and obesity. DESIGN: A retrospective school-based cohort follow-up study. SUBJECTS: A total of 1520 men born between 1927 and 1956 with serial height and weight measurements from the age of 9 to 18, followed up in adulthood at a mean age of 63 years. MEASUREMENTS: Prepubertal (child) BMI; age at peak height velocity (APHV); adult leg length, waist and hip circumference (self-reported), and height and weight (measured). RESULTS: Boys with a higher childhood BMI tended to have an earlier puberty (per s.d. increase in child BMI: -0.31 years, 95% confidence interval (CI): -0.23 to -0.39, P < 0.001). Childhood BMI correlated strongly and positively with adult adiposity, as measured by BMI (1.24 kg/m(2), 95% CI: 1.04-1.45, P < 0.001), waist (1.94 cm, 95% CI: 1.50-2.37, P < 0.001) and hip (1.91 cm, 95% CI: 1.55-2.28, P < 0.001). It correlated inversely with leg length (-0.40 cm, 95% CI: -0.68 to -0.12, P = 0.005), but not significantly with height or trunk length. Boys with a later puberty tended to be taller (per s.d. increase in APHV: 0.57 cm, 95% CI: 0.17-0.97, P = 0.006) and less adipose as adults (-0.55 kg/m(2), 95% CI: -0.33 to -0.77, P < 0.001). CONCLUSION: The long-term consequences of childhood obesity into adulthood are well known, but the potential impact on early pubertal maturation is less well appreciated. The factors that contribute to the onset and persistence of childhood obesity require more public health focus.

Adolescent↗
PubMed2005

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

Adult↗
PubMed2005

Platelet aggregation in whole blood is a paradoxical predictor of ischaemic stroke: Caerphilly Prospective Study revisited.

The Caerphilly Prospective Study demonstrates a paradoxical association of increased ischaemic stroke risk with decreased whole blood adenosine diphosphate (ADP) induced platelet sensitivity. A reanalysis of this association examines whether other haematological indices and prevalent disease at baseline may explain this finding. There were 1506 men free of clinical cardiovascular disease at baseline, with 85 men manifesting a first ischaemic stroke event over 8.3 years of follow-up in this population-based prospective cohort study. Using two different approaches, the paradoxical findings are confirmed and associations are slightly stronger after accounting for red cell, platelet, and white cell indices. A U-shaped relation of stroke with platelet count is noted. These findings are consistent with the existence of sub-clinical endothelial disease and compensatory mechanisms down-regulating ADP-induced aggregation sensitivity. They support an allostasis model of causality for understanding the paradox. A public health approach to prevention could have measurable impact if intervention strategies can be developed to alter early stages of disease appropriate to such mechanisms of causation.

Adenosine Diphosphate↗
PubMed2005

Population based mortality and quality of death certification in progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome).

OBJECTIVE: To estimate the mortality of progressive supranuclear palsy (PSP) and to assess the quality of death certification in patients with PSP who died in England and Wales. METHODS: An analysis was conducted of ICD-9 (International Classification of Diseases, version 9) coded deaths obtained through the Office of National Statistics over an eight year period. RESULTS: The crude annual mortality rate was 1.77 (95% confidence interval, 1.64 to 1.90) cases per million, using the mid-1996 population estimate for England and Wales. Annual mortality increased over time, possibly as a result of increased incidence or increased awareness of the disorder. Forty nine death certificates from deceased patients previously diagnosed clinically showed that the commonest proximate cause of death was pneumonia, occurring in 45% of cases (22/49). The underlying cause of death was cited as pneumonia in 14% of cases (7/49). PSP was mentioned in only 65% of death certificates (32/49). Eight of the 49 cases (16%) underwent necropsy and results were available for five of these cases. PSP was confirmed pathologically in four; the remaining case was diagnosed as Parkinson's disease. CONCLUSIONS: Further research is needed to establish the reasons for the observed increase in mortality. Determining the population mortality rate for PSP using the ICD-9 coding system is problematic but is likely to improve following the introduction of ICD-10 updated codes and coding rules.

Autopsy↗
PubMed2004

C-reactive protein, fibrin D-dimer, and risk of ischemic heart disease: the Caerphilly and Speedwell studies.

BACKGROUND: There is increasing interest in the predictive value of C-reactive protein (CRP) and fibrin D-dimer in the prediction of ischemic heart disease (IHD). We assessed their joint and independent associations with IHD in a large combined analysis of 2 population cohorts. METHODS AND RESULTS: Men aged 49 to 66 years from the general populations of Caerphilly and Speedwell were studied between 1982 and 1988 and re-examined for new IHD events at fixed intervals of approximately 105 months (Caerphilly) and 75 months (Speedwell). 3213 men had CRP and D-dimer measured at baseline and 351 (11%) had a new IHD event. Mean levels of CRP and D-dimer were significantly higher among men in whom IHD developed. The relative odds of IHD in men in the top 20% of the distribution of CRP was 2.97 (95% CI, 2.04, 4.32) and for D-dimer was 2.40 (95% CI, 1.69, 3.40); CRP and D-dimer had additive effects on risk of IHD. Multivariate analysis reduced the size of the relative odds, which remained significant for D-dimer. CONCLUSIONS: Both inflammatory and thrombogenic markers are important (and potentially additive) predictors of coronary risk.

Aged↗
PubMed2004

Dietary restraint and the mis-reporting of anthropometric measures by middle-aged adults.

OBJECTIVE: To assess whether levels of dietary restraint are associated with mis-reporting measures of adiposity by middle-aged adults. DESIGN: Cross-sectional study of middle-aged men and women, the parents of a group of young adults followed up since birth. METHODS: In all, 631 couples were mailed questionnaires and asked to record their height, weight and waist circumference. A paper tape measure with instructions for use was attached. Couples also completed the dietary restraint section of the Dutch Eating Behaviour Questionnaire, and provided information on employment and lifestyle habits. A subsample of participants was then invited to attend a clinic where detailed anthropometric measures were taken. RESULTS: In all, 435 women (69%) and 332 men (55%) completed the questionnaire; of those invited, 182 (85%) women and 102 (61%) men attended a clinic session. Regression analyses showed that the dietary restraint score was associated with the mis-reporting of BMI by women (P<0.01), but not men (test for interaction with gender, P=0.11). In women, the difference between the measured and reported BMI increased by 0.36 kg/m(2) (0.11-0.61) per unit increase in restraint score. This association was independent of age, smoking, social class, slimming, exercise frequency or television viewing time, but was attenuated in models controlling for measured BMI. The dietary restraint score was not associated with mis-reporting of waist circumference in men or women. CONCLUSIONS: Dietary restraint score may be a useful tool for identifying individuals more likely to mis-report anthropometric measurements, although associations may vary by gender.

Analysis of Variance↗
PubMed2004

Do medical students with A-level mathematics have a better understanding of the principles behind evidence-based medicine?

With the advent of evidence-based medicine, medical students, doctors and other healthcare professionals are required to be more skilled in the interpretation and manipulation of numerical data. The authors observed that undergraduate students without A-level mathematics expressed concern as to their ability to cope with an epidemiology and biostatistics course. It was hypothesized that these anxieties reflected differences in attitudes to numerical manipulation rather than any real lack of competence. Mean exam performance scores were compared for 498 first-year medical students between 2000 and 2002 depending on whether the students did or did not have A-level mathematics. The data revealed no difference in performance. Students without mathematics A-level scored marginally worse (-1.1%, 95% CI -3.1% to 0.8%, p=0.20) but were no more likely to fail the exam (odds ratio=0.98, 95% CI 0.40 to 2.6, p=0.9). It is concluded that some students experience 'numerophobia'-- a perceived and, it is thought, disproportionate fear of numbers and simple mathematical manipulation. This may act as a psychological barrier for future evidence-based practitioners.

Adult↗
PubMed2004

The incidence and mortality for meningococcal disease associated with area deprivation: an ecological study of hospital episode statistics.

AIMS: To determine whether incidence, mortality, and case fatality for meningococcal disease (MD) differs by area deprivation, and if this has changed over time. METHODS: The population of children aged less than 5 years with MD was analysed as quintiles of area deprivation scores over two time periods, 1995-99 and 1991-94. Annual age standardised rates were calculated and the association between incidence, mortality, and area deprivation quintiles assessed using Poisson regression and the risk ratios determined. Case fatality was calculated from the odds ratio of mortality by area deprivation score for the two time periods. RESULTS: There were 10,524 cases of MD and 441 deaths (4.2%). Incidence rates were higher for 1995-99 (45.4 per 100,000) compared to 1991-94 (27.4 per 100,000). Mortality rates remained stable over time, indicating a decline in risk of death of around 40%. The incidence rates for the most deprived quintile were around twice those for the most affluent quintile, but this gradient declined over time. A threefold gradient was seen for mortality rates across the top and bottom quintiles, which was constant over time. The odds of mortality did not show a linear pattern, with mortality being lowest in the first and highest in the second and fifth area deprivation quintiles. CONCLUSIONS: These data show that MD incidence and mortality are socially patterned. The determinants of case fatality are more complex and require further investigation.

Child, Preschool↗
PubMed2003

Clinical features and natural history of progressive supranuclear palsy: a clinical cohort study.

OBJECTIVE: To describe clinical features and identify prognostic predictors in progressive supranuclear palsy (PSP). METHODS: Record-based diagnosis according to National Institute of Neurological Disorders and Stroke-Society for Progressive Supranuclear Palsy criteria was performed in 187 cases of PSP. Clinical information was abstracted from patient records. Sixty-two patients (33%) were examined by the investigators. Forty-nine of 62 patients (79%) underwent standardized clinical assessment. Predictors of survival were examined after a mean of 6.4 years. RESULTS: The most common symptoms at disease onset related to mobility (69%). Of patients undergoing standardized clinical assessment, diplopia occurred in 61%, photophobia in 43%, and eyelid apraxia in 43%. Seventy-five cases (40%) died during follow-up. Older age at onset and classification as probable PSP were associated with poorer survival. Onset of falls (hazard ratio 3.28, 95% CI 1.17 to 9.13), speech problems (hazard ratio 4.74, 95% CI 1.10 to 20.4), or diplopia (hazard ratio 4.23, 95% CI 1.23 to 14.6) within 1 year and swallowing problems within 2 years (hazard ratio 3.91, 95% CI 1.39 to 11.0) were associated with a worse prognosis. CONCLUSIONS: Mobility problems are the commonest early feature in PSP and visual symptoms are often functionally disabling. Early falls, speech and swallowing problems, diplopia, and early insertion of a percutaneous gastrostomy predict reduced survival.

Age of Onset↗
PubMed2003

An investigation of fetal, postnatal and childhood growth with insulin-like growth factor I and binding protein 3 in adulthood.

OBJECTIVE: Weight at birth and adult height are positively associated with cancer risk. These patterns may be mediated by the insulin-like growth factor (IGF) axis. We have examined whether pre- and postnatal growth patterns have a long-term influence on adult IGF-I and IGFBP-3 levels. DESIGN: A follow-up study of a randomized controlled trial of milk supplementation in pregnancy and childhood. SUBJECTS: A total of 951 individuals took part in a study of diet and growth in South Wales between 1972 and 1974 followed up from birth until their mid-20s. MEASUREMENTS: Anthopometric measures at birth, postnatally up to 5 years of age and in adulthood, and serum measures of IGF-I and IGF-I to IGFBP-3 ratio at mean age of 25 years. RESULTS: A total of 63 subjects (70%) provided blood for analysis. We found no association between birth dimensions and adult IGF-I. Subjects who exhibited 'catch-down growth' had lower IGF-I levels (P-value for trend 0.02). Adult height was positively related to IGF-I, for every one standard deviation increase in adult height, IGF-I increased by 3.75 ng/dl (95% CI 0.46-7.08, P = 0.03). Adiposity was inversely associated with the IGF-I and IGF-I to IGFBP-3 ratio and positively associated with IGFBP-3. The strength of the associations increased with age. Downward centile crossing at any time in childhood was associated with lower IGF-I whilst the highest levels were observed in subjects who were tall throughout their early life course. Adult height remained a significant predictor of IGF-I even after adjustment for earlier growth. CONCLUSIONS: Our results indicate that IGF-I levels in early adulthood are associated with patterns of childhood growth as well as adult stature and adiposity. These associations suggest the IGFs may contribute to anthropometric associations with cancer risk.

Adult↗
PubMed2002

Novel three-stage ascertainment method: prevalence of PD and parkinsonism in South Tyrol, Italy.

BACKGROUND: A number of community-based studies on the prevalence of PD have been conducted worldwide, but they are often extremely costly and time consuming. OBJECTIVE: To assess the prevalence of PD and parkinsonism for the population aged between 60 and 85 years in South Tyrol, Northern Italy, using a novel population-based three-stage ascertainment method. METHODS: Seven hundred fifty persons aged 60 to 85 years from South Tyrol received a validated screening mail questionnaire for parkinsonism. In the second stage of the ascertainment method, trained primary care physicians (PCP) identified all persons with possible parkinsonism among those screened positive. In the third stage, movement disorders specialists excluded or confirmed the diagnosis in all identified people. RESULTS: The response rate was 87.6%. The prevalence rate per 100 population over 65 years of age was 1.5 (95% CI 0.6 to 2.3) for PD and 2.2 (95% CI 1.2 to 3.3) for parkinsonism after having been adjusted to the 1991 European standard population. Overall, 78% (95% CI 59 to 96%) of patients with parkinsonism were newly detected through the survey. CONCLUSIONS: The prevalence of PD and parkinsonism in people aged over 65 in South Tyrol was similar to that observed in door-to-door surveys in other European countries. The novel three-stage case ascertainment method employed proved a useful tool to substitute for expensive door-to-door surveys for prevalence studies of parkinsonism, detecting a high number of undiagnosed cases, particularly in geographically remote areas.

Aged↗