Julie A. Simpson

Annual high-dose oral vitamin D and falls and fractures in older women: A randomized controlled trial

CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor. OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture. DESIGN, SETTING, AND PARTICIPANTS A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008. INTERVENTION 500,000 IU of cholecalciferol or placebo. MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels. RESULTS Women in the cholecalciferol (vitamin D) group had 171 fractures vs 135 in the placebo group; 837 women in the vitamin D group fell 2892 times (rate, 83.4 per 100 person-years) while 769 women in the placebo group fell 2512 times (rate, 72.7 per 100 person-years; incidence rate ratio [RR], 1.15; 95% confidence interval [CI], 1.02-1.30; P = .03). The incidence RR for fracture in the vitamin D group was 1.26 (95% CI, 1.00-1.59; P = .047) vs the placebo group (rates per 100 person-years, 4.9 vitamin D vs 3.9 placebo). A temporal pattern was observed in a post hoc analysis of falls. The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02). In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing. CONCLUSION Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12605000658617; isrctn.org Identifier: ISRCTN83409867.

The impact of chronic urticaria on the quality of life

The impact of chronic urticaria (CU) on the quality of life is undocumented. We assessed quality of life in patients with CU, including patients with associated delayed pressure urticaria (DPU). One hundred and forty–two out–patients completed self–administered questionnaires: a disease–specific, purpose designed questionnaire, and the Nottingham health profile (NHP). Many patients reported problems attributable to their skin condition in facets of everyday life including home management, personal care, recreation and social interaction, mobility, emotional factors, sleep, rest and work. The NHP part I scores showed restriction in the areas of mobility, sleep, energy, and demonstrated pain, social isolation and altered emotional reactions. Part II of the NHP showed that patients experienced difficulties in relation to work, looking after the home, social life, home relationships, sex life, hobbies and holidays. The patients with DPU had significantly more problems with mobility, gardening and choice of clothing than the uncomplicated CU patients. They also suffered more pain, had more problems with work and were more restricted in their hobbies.

A Quantitative Analysis of the Microvascular Sequestration of Malaria Parasites in the Human Brain

Microvascular sequestration was assessed in the brains of 50 Thai and Vietnamese patients who died from severe malaria (Plasmodium falciparum, 49; P. vivax, 1). Malaria parasites were sequestered in 46 cases; in 3 intravascular malaria pigment but no parasites were evident; and in the P. vivax case there was no sequestration. Cerebrovascular endothelial expression of the putative cytoadherence receptors ICAM-1, VCAM-1, E-selectin, and chondroitin sulfate and also HLA class II was increased. The median (range) ratio of cerebral to peripheral blood parasitemia was 40 (1.8 to 1500). Within the same brain different vessels had discrete but different populations of parasites, indicating that the adhesion characteristics of cerebrovascular endothelium change asynchronously during malaria and also that significant recirculation of parasitized erythrocytes following sequestration is unlikely. The median (range) ratio of schizonts to trophozoites (0.15:1; 0.0 to 11.7) was significantly lower than predicted from the parasite life cycle (P < 0.001). Antimalarial treatment arrests development at the trophozoite stages which remain sequestered in the brain. There were significantly more ring form parasites (age < 26 hours) in the cerebral microvasculature (median range: 19%; 0-90%) than expected from free mixing of these cells in the systemic circulation (median range ring parasitemia: 1.8%; 0-36.2%). All developmental stages of P. falciparum are sequestered in the brain in severe malaria.

Effects of Plasmodium vivax malaria in pregnancy

BACKGROUND Plasmodium vivax is more common than P. falciparum as a cause of malaria in many parts of the tropics outside Africa. P. falciparum infection has harmful effects in pregnancy, but the effects of P. vivax have not been characterised. We investigated the effects of P. vivax infection during pregnancy. METHODS Since 1986, pregnant Karen women living in camps for displaced people on the western border of Thailand have been encouraged to attend antenatal clinics. Karen women were screened for malaria and anaemia at each week of pregnancy until delivery, and pregnancy outcome recorded. We compared the effects of P. vivax infection on anaemia and pregnancy outcome with those of P. falciparum and no malaria infection in the first pregnancy recorded at the antenatal clinics. FINDINGS There were 634 first episodes of pure P. vivax malaria in 9956 women. P. vivax malaria was more common in primigravidae than in multigravidae and was associated with mild anaemia and an increased risk of low birthweight (odds ratio 1.64 [95% CI 1.29-2.08], p<0.001). The birthweight was a mean of 107 g (95% CI 61-154) lower in women with P. vivax infection than in uninfected women. By contrast with P. falciparum malaria, the decrease in birthweight was greater in multigravidae. P. vivax malaria was not associated with miscarriage, stillbirth, or with a shortened duration of pregnancy. INTERPRETATION P. vivax malaria during pregnancy is associated with maternal anaemia and low birthweight. The effects of P. vivax infection are less striking than those of P. falciparum infection, but antimalarial prophylaxis against P. vivax in pregnancy may be justified.

Statistical approaches for assessing the relative validity of a food-frequency questionnaire: use of correlation coefficients and the kappa statistic.

OBJECTIVE To compare different statistical methods for assessing the relative validity of a self-administered, 150-item, semi-quantitative food-frequency questionnaire (FFQ) with 4-day weighed diet records (WR). DESIGN Subjects completed the Scottish Collaborative Group FFQ and carried out a 4-day WR. Relative agreement between the FFQ and WR for energy-adjusted nutrient intakes was assessed by Pearson and Spearman rank correlation coefficients, the percentages of subjects classified into the same and opposite thirds of intake, and Cohens weighted kappa. SUBJECTS Forty-one men, mean age 36 (range 21-56) years, and 40 women, mean age 33 (range 19-58) years, recruited from different locations in Aberdeen, Scotland. RESULTS Spearman correlation coefficients tended to be lower than Pearson correlation coefficients, and were above 0.5 for 10 of the 27 nutrients in men and 17 of the 27 nutrients in women. For nutrients with Spearman correlation coefficients above 0.5, the percentage of subjects correctly classified into thirds ranged from 39 to 78%, and weighted kappa values ranged from 0.23 to 0.66. CONCLUSIONS Both Spearman correlation coefficients and weighted kappa values are useful in assessing the relative validity of estimates of nutrient intake by FFQs. Spearman correlation coefficients above 0.5, more than 50% of subjects correctly classified and less than 10% of subjects grossly misclassified into thirds, and weighted kappa values above 0.4 are recommended for nutrients of interest in epidemiological studies.

Secondary prevention clinics for coronary heart disease: four year follow up of a randomised controlled trial in primary care

Abstract Objectives: To evaluate the effects of nurse led clinics in primary care on secondary prevention, total mortality, and coronary event rates after four years. Design: Follow up of a randomised controlled trial by postal questionnaires and review of case notes and national datasets. Setting: Stratified, random sample of 19 general practices in north east Scotland. Participants: 1343 patients (673 intervention and 670 control) under 80 years with a working diagnosis of coronary heart disease but without terminal illness or dementia and not housebound. Intervention: Nurse led secondary prevention clinics promoted medical and lifestyle components of secondary prevention and offered regular follow up for one year. Main outcome measures: Components of secondary prevention (aspirin, blood pressure management, lipid management, healthy diet, exercise, non-smoking), total mortality, and coronary events (non-fatal myocardial infarctions and coronary deaths). Results: Mean follow up was at 4.7 years. Significant improvements were shown in the intervention group in all components of secondary prevention except smoking at one year, and these were sustained after four years except for exercise. The control group, most of whom attended clinics after the initial year, caught up before final follow up, and differences between groups were no longer significant. At 4.7 years, 100 patients in the intervention group and 128 in the control group had died: cumulative death rates were 14.5% and 18.9%, respectively (P=0.038). 100 coronary events occurred in the intervention group and 125 in the control group: cumulative event rates were 14.2% and 18.2%, respectively (P=0.052). Adjusting for age, sex, general practice, and baseline secondary prevention, proportional hazard ratios were 0.75 for all deaths (95% confidence intervals 0.58 to 0.98; P=0.036) and 0.76 for coronary events (0.58 to 1.00; P=0.049) Conclusions: Nurse led secondary prevention improved medical and lifestyle components of secondary prevention and this seemed to lead to significantly fewer total deaths and probably fewer coronary events. Secondary prevention clinics should be started sooner rather than later. What is already known on this topic Several effective interventions exist for the secondary prevention of coronary heart disease, but implementing them in practice has proved difficult Secondary prevention programmes for coronary heart disease have improved short term outcomes such as processes of care and quality of life What this study adds Short term improvements in uptake of secondary prevention produced by nurse led clinics are maintained in the longer term Improved medical and lifestyle components of secondary prevention produced by nurse led clinics seem to lead to fewer total deaths and coronary events

Impact of tobacco control policies and mass media campaigns on monthly adult smoking prevalence.

OBJECTIVES We sought to assess the impact of several tobacco control policies and televised antismoking advertising on adult smoking prevalence. METHODS We used a population survey in which smoking prevalence was measured each month from 1995 through 2006. Time-series analysis assessed the effect on smoking prevalence of televised antismoking advertising (with gross audience rating points [GRPs] per month), cigarette costliness, monthly sales of nicotine replacement therapy (NRT) and bupropion, and smoke-free restaurant laws. RESULTS Increases in cigarette costliness and exposure to tobacco control media campaigns significantly reduced smoking prevalence. We found a 0.3-percentage-point reduction in smoking prevalence by either exposing the population to televised antismoking ads an average of almost 4 times per month (390 GRPs) or by increasing the costliness of a pack of cigarettes by 0.03% of gross average weekly earnings. Monthly sales of NRT and bupropion, exposure to NRT advertising, and smoke-free restaurant laws had no detectable impact on smoking prevalence. CONCLUSIONS Increases in the real price of cigarettes and tobacco control mass media campaigns broadcast at sufficient exposure levels and at regular intervals are critical for reducing population smoking prevalence.

The Relationship between Anti-merozoite Antibodies and Incidence of Plasmodium falciparum Malaria: A Systematic Review and Meta-analysis

A systematic review and meta-analysis examining the association between anti-merozoite antibody responses and incidence of Plasmodium falciparum malaria by Freya Fowkes and colleagues aids identification of antigens that confer protection from malaria.

Parasite Multiplication Potential and the Severity of Falciparum Malaria

The multiplication rates and invasiveness of Plasmodium falciparum parasites isolated from adult Thai patients hospitalized with uncomplicated malaria (n=34) were compared with those from persons with severe malaria (n=42). To simulate severe malaria and control for host effects, the in vitro cultures were adjusted to 1% parasitemia and used the same red blood cell donor. P. falciparum isolates from persons with severe malaria had initial cycle multiplication rates in vitro that were 3-fold higher than those from uncomplicated malaria (median [95% confidence interval], 8.3 [7. 1-10.5] vs. 2.8 [1.7-3.9]; P=.001). Parasites causing severe malaria exhibited unrestricted red blood cell invasion, whereas those from uncomplicated malaria were restricted to a geometric mean of 40 (31%-53%) of red blood cells. P. falciparum parasites causing severe malaria were less selective and multiplied more at high parasitemias than those causing uncomplicated malaria.

Dietary antioxidants and primary prevention of age related macular degeneration: systematic review and meta-analysis.

Objective To evaluate the effectiveness of dietary antioxidants in the primary prevention of age related macular degeneration (AMD). Design Systematic review and meta-analysis. Data sources Search of seven databases without limits on year or language of publication, and retrieval of references in pertinent reviews and articles. Methods Two reviewers independently searched the databases and selected the studies, using standardised criteria. Randomised clinical trials and prospective cohort studies were included. Of the 4192 abstracts initially identified, 12 studies (nine prospective cohort studies and three randomised clinical trials) met the selection criteria and were included. Data extraction and study quality evaluation were independently reviewed, using standardised criteria. Results were pooled quantitatively using meta-analytic methods. Results The nine prospective cohort studies included 149 203 people, with 1878 incident cases of early AMD. The antioxidants investigated differed across studies, and not all studies contributed to the meta-analysis of each antioxidant. Pooled results from prospective cohort studies indicated that vitamin A, vitamin C, vitamin E, zinc, lutein, zeaxanthin, α carotene, β carotene, β cryptoxanthin, and lycopene have little or no effect in the primary prevention of early AMD. The three randomised clinical trials did not show that antioxidant supplements prevented early AMD. Conclusions There is insufficient evidence to support the role of dietary antioxidants, including the use of dietary antioxidant supplements, for the primary prevention of early AMD.