The relationship of 25-hydroxyvitamin D values and risk of fracture: a population-based retrospective cohort study.

Our study investigates 25-hydroxyvitamin D levels and fracture risk using population-level data. 25-Hydroxyvitamin D values < 12, 12-19, and > 50 ng/mL were not associated with increased risk of fractures overall compared with values 20-50 ng/mL. Severely low levels may be associated with increased risk of osteoporotic fracture, particularly of the wrist. INTRODUCTION: Studies of the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and fracture risk have been inconsistent. We hypothesized that high 25(OH)D concentrations (> 50 ng/mL) would be associated with increased risk of fracture. METHODS: We identified all adult patients living in Olmsted County, Minnesota, between January 1, 2005 and December 31, 2011, who had at least one 25(OH)D measurement. Fracture outcomes were retrieved starting 30 days after 25(OH)D measurement and until patients' final clinical visit as an Olmsted County resident, December 31, 2014, or death. Data were analyzed using Cox proportional hazard regression. RESULTS: Of 11,002 individuals with a 25(OH)D measurement, 5.8% had a 25(OH)D value ˂ 12 ng/mL, and 5.1% had a value > 50 ng/mL. Compared with subjects with 25(OH)D values 20-50 ng/mL (reference group), values < 12, 12-19, and > 50 ng/mL displayed no association with overall fracture risk. After adjusting for a prior diagnosis of osteoporosis/osteopenia, only individuals with values ˂ 12 ng/mL had increased risk of any osteoporotic fracture (aHR = 1.41; 95% CI 1.05-1.89) and wrist fracture (aHR = 2.11; 95% CI 1.27-3.48) compared with the reference group. Compared with the reference group, values ˂ 12 ng/mL were associated with increased risk of any fracture (aHR = 1.35; 95% CI 1.01-1.80), osteoporotic fracture (aHR = 2.18; 95% CI 1.44-3.31), and wrist fracture (aHR = 2.39; 95% CI 1.19-4.81) in subjects without a prior diagnosis of osteoporosis/osteopenia, but not in those with a prior diagnosis of osteoporosis/osteopenia. CONCLUSION: Severely low 25(OH)D levels may be associated with increased risk of osteoporotic fracture, particularly of the wrist, but 25(OH)D values > 50 ng/mL were not associated with increased fracture risk.

The relationship between maternal and child bone density in Nigerian children with and without nutritional rickets.

We found a positive relationship between bone density in Nigerian children with and without rickets and that of their mothers. After treatment, children with rickets had greater bone density than children without rickets, indicating that children genetically programmed to have greater bone density may have a higher risk of rickets. INTRODUCTION: To determine the relationship between bone density in children with and without rickets and that of their mothers METHODS: Using an unmatched case-control design, forearm areal bone mineral density (aBMD) was measured in 52 and 135 Nigerian children with and without rickets and their mothers, respectively. We performed multivariate linear regression analyses to assess the relationship between maternal and child aBMD Z-scores. RESULTS: Forearm aBMD Z-scores in children were associated with maternal aBMD Z-scores at metaphyseal (effect estimate 0.23; 95% CI 0.08 to 0.37) and diaphyseal (effect estimate 0.16; 0.01 to 0.30) sites, after adjustment for rickets in the child, child's age and sex, height-for-age Z-score, and weight-for-age Z-score. In the adjusted model, rickets was inversely associated with child's aBMD Z-score at the diaphyseal site only (- 0.45, - 0.65 to - 0.24). The positive relationship between maternal and child aBMD Z-scores was marginally greater in children with rickets (slope 0.56, r = 0.47) than without rickets (slope 0.19, r = 0.20) at the diaphyseal site only (P = 0.06 for interaction) but not at the metaphyseal site (slopes 0.35 and 0.30, respectively, P = 0.48). After treatment with calcium for 6 months, metaphyseal aBMD Z-scores were greater in children with treated rickets (effect estimate 0.26; 95% CI 0.02 to 0.49) than in those without rickets. CONCLUSION: In Nigerian children with and without rickets, forearm aBMD Z-scores were positively associated with maternal aBMD Z-scores. Active rickets in the child marginally modified the relationship at the diaphyseal site only. After treatment, children with rickets had greater metaphyseal aBMD Z-scores than children without rickets.

US Preventative Services Task Force FRAX threshold has a low sensitivity to detect osteoporosis in women ages 50-64 years.

UNLABELLED: The US Preventative Services Task Force (USPSTF) recommends consideration for screening for osteoporosis in women under age 65 who have an estimated 10-year major osteoporotic fracture risk of 9.3 % or higher. We found that this threshold for osteoporosis screening in women ages 50-64 years old has a low sensitivity to detect osteoporosis. INTRODUCTION: The US Preventative Services Task Force (USPSTF) recommends consideration of dual-energy X-ray absorptiometry (DXA) in women under ages 50-64 with a major osteoporotic fracture (MOF) risk of 9.3 % or higher, as estimated by the fracture risk assessment tool (FRAX) tool. We assessed the performance of the 9.3 % MOF risk threshold for detecting osteoporosis and evaluated whether DXA indication appeared appropriate, based on USPSTF criteria and other risk factors, at our institution. METHODS: We performed a retrospective record review of women ages 50-64.5 years old to determine clinical factors and FRAX scores of women undergoing a DXA at our institution over a 6-month period after the USPSTF recommendations were released and evaluated the sensitivity and specificity of the 9.3 % MOF threshold to detect densitometric osteoporosis. Additionally, using the USPSTF criteria and several additional risk factors, we evaluated the extent of potentially inappropriate DXA use in women ages 50 to 64 years in a large primary care practice in an academic medical center. RESULTS: The analysis included 465 DXA tests. The overall sensitivity and specificity of a FRAX-calculated MOF risk ≥9.3 % was 37 and 74 %, respectively, for the detection of osteoporosis. The receiver operator characteristic curve (ROC) demonstrated an area under the curve of 0.58. Lowering the FRAX risk threshold to 5.5 % would increase the sensitivity of detecting osteoporosis in our population from 37 to 80 % while reducing the specificity from 74 to 27 %. Out of 465 DXAs, 371 (79.8 %) were classified as appropriately ordered per our pre-specified criteria. Of the 120 women with osteoporosis at the hip and/or spine based on T-score values of -2.5 or less, 14 DXAs (11.7 %) were classified as potentially inappropriate based on a FRAX-predicted MOF risk less than 9.3 % and lack of additional pre-specified risk factors. CONCLUSION: We found that the USPSTF-recommended MOF risk threshold of 9.3 % for osteoporosis screening in women ages 50-64 years old has a low sensitivity to detect osteoporosis.

Pharmacokinetics of daily versus monthly vitamin D3 supplementation in non-lactating women.

This study compared serum cholecalciferol and 25-hydroxyvitamin D (25(OH)D) concentrations over four weeks in healthy, non-pregnant, non-lactating females aged 18-40 years, who were randomized to oral cholecalciferol 5000 international units (IU) daily for 28 days or a single dose of 150 000 IU. The study was conducted in Rochester, MN in March and April of 2010. We found no difference in mean 25(OH)D between treatment groups on study day 0 or day 28 (P=0.14 and 0.28, respectively). The daily group had 11 more days of detectable serum cholecalciferol than the single-dose group (P<0.001). There was no difference observed in cholecalciferol area under the curve (AUC28) between groups (P=0.49). However, the single-dose group had a significantly greater mean 25(OH)D AUC28 compared with the daily group (P<0.001).

Obstetrics Risk of HIV Infection among Antenatal Women in a rural Nigerian hospital.

BACKGROUND: Obstetrics risk and practices can lead to the spread of HIV/AIDS. Identification of such obstetrics risk of HIV infection is a useful step in the prevention of transmission of the virus. OBJECTIVE: We sought to determine obstetrics risk of HIV infection in pregnant women attending antenatal clinic in a rural Northern Nigerian hospital. METHODS: We conducted a cross-sectional descriptive study of pregnant women attending antenatal clinic of a rural mission hospital in northern Nigeria between June and October 2005. Data were collected using structured questionnaire. HIV screening and confirmation was carried out on pregnant women after voluntary counseling. RESULTS: 350 pregnant women were enrolled with a mean age (±SD) of 26.8± 6.4years. The highest number of HIV infected women was observed in those who had their first coitus between 16 and 20 years. The age at first coitus was not significantly related to the HIV infection (P=0.41). Neither parity (P=0.13) nor past history of abortion (P=0.42) was associated with HIV infection. None of the 41 women who had their last delivery at home had HIV infection compared with 9.8% of the 194 women who delivered in the hospital or clinic (P=0.008). Forty percent of those who had their last delivery in primary health centre had HIV infection while 22.2% of those who delivered under the care of traditional birth had HIV infection. CONCLUSION: Obstetrics practices may encourage transmission of HIV infection. This calls for re-examination of the obstetrics practices especially in our primary health centers in order to prevent transmission of HIV infection.

HIV risk factors among pregnant women in a rural Nigerian hospital.

OBJECTIVE: Specific risk behaviours and practices promote the spread of HIV/AIDS. Identification of those at risk of the Human Immunodeficiency Virus (HIV) infection is an important step toward prevention of both vertical and horizontal transmission of HIV. This study sought to identify risk factors for HIV infection in pregnant women attending a rural antenatal clinic in Northern Nigerian. METHODS: A cross-sectional descriptive study of pregnant women attending antenatal clinic at a rural mission hospital in Northern Nigeria between June and October 2005 was conducted. Data were collected with a structured questionnaire. HIV screening and confirmation were done for the pregnant women after voluntary counselling. RESULTS: The study enrolled 350 pregnant women with a mean (+/- SD) age of 26.8 +/- 6.4 years. HIV infection was not associated with smoking habits in women, alcohol intake in the women or their partners, prior blood transfusion, history of sexually transmitted infection or history of scarification. In multiple logistic regression, HIV infection was independently associated with suspecting their partner of extramarital sex (adjusted odds ratio 3.8, 95% CI 1.6, 9.0), post-primary education (AOR 2.4, 95% CI 1.1, 5.3), multiple sexual partners (AOR 2.4, 95% CI 0.97, 6.2) and cigarette smoking by a partner (AOR 3.0, 95% CI 0.95, 9.4). CONCLUSION: Multiple partners and extramarital sex remain a hindrance to the fight against HIV infection. Promoting the ABC approach (abstinence, be faithful, condom) may reduce risky behaviour as it has in other parts of Africa.

Arterial biomechanics after destruction of cytoskeleton by Cytochalasin D.

Vascular smooth muscle is a major structural element of the arterial wall. We examined the effects of cytoskeleton destruction, after administration of Cytochalasin D, on the biomechanical properties of porcine common carotids. Compared to untreated, maximally dilated controls, Cytochalasin D-treated arteries have shown a marked increase in compliance in the elastin-dominated pressure range. After weakening the VSM stress-bearing cytoskeleton by Cytochalasin D the artery would expand, reaching a new equilibrium state. This study brings further evidence that VSM is under tension, even when it is under zero load and at maximal vasodilation. This residual tension was released upon partial destruction of the cytoskeleton with Cytochalasin D. From a biomechanical standpoint, this means that the zero stress states of the in-series and parallel elastic components are substantially different.

Sex differences in the clinical presentation of urban Nigerian patients with pulmonary tuberculosis.

BACKGROUND: Differences in clinical presentation of tuberculosis (TB) have been reported in different age groups, gender and in different parts of the world. Study of gender differences in clinical presentation of patients will assist in targeting those at higher risk and ensure successful TB control planning. OBJECTIVE: To describe the differences in clinical presentation and risk factors for TB in male and female Nigerian patients with pulmonary tuberculosis (PTB). METHODS: Patients with cough of more than three weeks duration attending hospitals in Abuja, Nigeria were interviewed with a structured questionnaire. After clinical examination, sputum samples were examined by smear microscopy and one sample was cultured. Haematological examination, serum chemistries, HIV serology, and chest X-ray evaluation were also evaluated. RESULTS: Of 1186 patients who had sputum culture, 731 (62%) were positive for TB: 437 (60%) males and 394 (40%) females. The mean (SD) age of males was significantly greater than that of females, 34 (11) vs. 31 (12) years, rp = 0.001. Male patients were more likely to be employed and better educated than women. More men than women smoked cigarettes. Women were more likely to be co-infected with HIV and less likely to be smear-positive than men. Male patients had more severe radiological disease. CONCLUSION: More men than women appear to present with TB at hospitals in Abuja. Male patients were older and are more likely to have smear-positive TB, whereas, female patients were more likely to be co-infected with HIV.

Oscillatory shear stress and reduced compliance impair vascular functions.

Shear stress has been shown to influence endothelial cell gene expression and morphology. In particular, low and bi-directional shear stress, mimicking conditions at plaque-prone areas, down-regulates the expression of several atheroprotective genes, and up-regulates that of other genes considered as pro-inflammatory. Another mechanical situation thought to have a negative influence on vascular functions is arterial stiffness. Loss of arterial compliance occurs during ageing, in diabetic as well as in hypertensive patients. In this work we investigated the effects of these two particular hemodynamic environments (bi-directional shear stress and reduced compliance), using a recently developed perfusion system allowing to expose native arteries in vitro to complex hemodynamic environments. We were able to show that both plaque-prone shear stress and reduced compliance trigger endothelial dysfunction, but via different mechanisms. Only reduced compliance affected vascular contractility, inducing a dedifferentiation of smooth muscle cells and a consequent loss of norepinephrine sensitivity.

Short-term bleach digestion of sputum in the diagnosis of pulmonary tuberculosis in patients co-infected with HIV.

The bleach digestion of sputum may improve the yield of smear microscopy but has not been validated in patients with HIV. Therefore we assessed the performance of bleach-digested smear microscopy among patients with HIV. One thousand three hundred and twenty one patients with chronic cough submitted three sputum samples for direct smear microscopy and were offered HIV tests. One sample was selected for a bleach-digested smear and another one was cultured. Patients were classified as having 'definite' (>or=2 positive smears), 'very likely' (smear-negative, culture- positive), 'less likely' (one smear-positive, culture-negative) and 'unlikely' (smear and culture negative) tuberculosis (TB). In all, 566/1045 (54%) patients were HIV positive and 731/1186 (62%) were culture positive. The digested smears were positive in 123/125 (98%) 'definite', 4/118 (3%) 'very likely' and 1/174 'unlikely' TB patients with HIV and in 125/127 (98%) 'definite', 2/74 (3%) 'very likely', 4/4 'less likely' and 2/127 'unlikely' TB without HIV. Three direct smears identified 252 (57%) and one digested smear 254 (57%) of the 444 patients with 'definite' or 'very likely' TB. One bleach-digested smear performed similarly to three direct smears. Both methods were less sensitive in HIV-positive patients. Further studies are needed to compare the performance of the two methods under operational conditions.

Sexual problems among married Nigerian women.

We interviewed and examined 293 married women, 15-49 years of age, seeking primary care at a teaching hospital in central Nigeria. One or more sexual problems were identified in 71% of women. The proportion of specific sexual problems was 39% for a desire problem, 40% for an arousal problem, 31% for a sex pain problem and 55% for an orgasmic problem. Poor marital communication, lack of foreplay, Islamic religion and advancing age were independently associated with a desire problem. Absence of foreplay was independently associated with an arousal problem. Lack of foreplay, lower abdominal pain, gynaecological conditions, working outside the home and younger age were independently associated with a sex pain problem. The absence of foreplay, poor marital communication and being a housewife were independently associated with an orgasmic problem. Sexual problems are common among married Nigerian women seeking outpatient care.

Risk factors for dementia in central Nigeria.

Little is known about the prevalence of dementia and its associated risk factors in developing countries. Some studies suggest that the prevalence of dementia is lower in developing countries than it is in high-income nations. We sought to determine risk factors for dementia in elderly persons in central Nigeria. Using the standardized Community Screening Instrument for Dementia, we screened a stratified, random community sample of 280 persons aged 65 years and older for dementia. We examined the independent association of known risk factors with dementia using logistic regression. The overall prevalence of dementia was 6.4% (95% CI 3.8-9.9%). Independent risk factors for dementia included female sex (OR 8.4; 95% CI 1.9-39), body mass index of 18.5 kg/m2 or less (OR 3.5; 95% CI 1.2-9.9), and age (OR 1.05 per year; 95% CI 1.00-1.11). Non-steroidal anti-inflammatory drug (NSAID) use was associated with a reduced risk of dementia (OR 0.20; 95% CI 0.04-0.93). Education, blood pressure, history of stroke, family history of dementia, and rural residence were not significantly associated with dementia in the multivariate model. The prevalence of dementia in central Nigeria may be greater than that found in other developing countries. Female sex, low body mass index, lack of NSAID use, and advancing age were the major risk factors in this population.

HIV and hepatitis B seroprevalence in trauma patients in North Central Nigeria.

BACKGROUND: With the high prevalence rate of HIV and Hepatitis B virus infections in sub-Saharan Africa, infected surgical patients, especially those with fresh open wounds, pose significant danger of occupationally-acquired infections to health workers. METHOD: A two-year double blind study aimed at determining the seroprevalence rates of HIV and Hepatitis B virus infections among trauma patients with fresh open wounds in North Central Nigeria. RESULTS: There were 134 patients with fresh open wounds in this study; their ages ranged between 17-80 years with a mean of 30.9 +/-9.6 years and the male:female ratio was 5:1. All the patients were tested for both HIV and Hepatitis B virus infections. Six(4.5%) patients were positive for HIV-1 while 95(70.9%) patients were positive for Hepatitis B. In all, 3(2.2%) male and 3(2.2%) female patients tested positive for HIV-1 while 77(57.4%) males and 18(13.4%) females tested positive for Hepatitis B; 5(3.7%) patients tested positive for both HIV and Hepatitis B. Though every social class was represented, HIV infection rate was higher in Social Class V than in Social Class 1 but the class incidence rate for Hepatitis B was about the same ranging between 1.2 and 1.6 for both the upper and lower classes. The significance of this study was that the incidence of Hepatitis B virus infection in trauma patients was remarkably higher than the incidence of HIV infection. The implication is that emphasis on control of exposure of health care workers to blood borne infections in the workplace should be as strong for Hepatitis B virus infection as it is for HIV. CONCLUSION: The main finding of this study was the determination of the seroprevalence of HIV and Hepatitis B virus infections in trauma patients with open wounds which underpinned the dangers they pose to health care workers.

Microbiological validation of smear microscopy after sputum digestion with bleach; a step closer to a one-stop diagnosis of pulmonary tuberculosis.

BACKGROUND: Smear microscopy is relatively insensitive for the diagnosis of TB. The digestion of sputum with household bleach prior to smear preparation has been reported to improve its sensitivity. This method has not been validated. METHODS: Seven hundred and fifty six patients with symptoms suggestive of pulmonary TB (PTB) were asked to submit 3 sputum specimens for direct microscopy. One specimen was selected at random for culture and another specimen was digested to prepare a further smear. The WHO case definition (>or=2 positive smears or one positive smear and positive culture) was used to compare the sensitivity and specificity of the smears. FINDINGS: Four hundred and fifty five (60%) patients were culture-positive. Of these, 235 (31%) had "definite" PTB and 223 (29%) "very likely" PTB (smear-negative, culture-positive). The WHO case definition identified 51% (235/458) of the patients with "definite" or "very likely" PTB. One digested smear detected 219 (93%) of the 235 patients with "definite" PTB and 10 patients with "very likely" PTB (sensitivity (95%CI) 50% (45-55%); specificity 99% (97-100%)). The positive and negative predictive values for one digested smear were 98% (95-99%) and 56% (52-60%) respectively, which were not different (p>0.5) to the WHO case definition (100% and 57%, respectively). INTERPRETATION: One bleach-digested smear is as sensitive and specific as the WHO case definition for the diagnosis of PTB.

Causes of lead toxicity in a Nigerian city.

BACKGROUND: Up to 70% of young Nigerian children have been reported to have blood lead concentrations > or =10 microg/dl. AIMS: To better elucidate risk factors for lead toxicity among Nigerian families with children at risk for lead toxicity. METHODS: Two geographic wards in Jos, Nigeria were selected for study, one previously reported to have a high mean blood lead level (37 (SD 13) microg/dl) and one with a lower mean blood lead level (17 (SD 10) microg/dl) in young children. Data pertaining to potential risk factors for lead exposure were collected from children and adults in 34 households. RESULTS: The mean (SD) blood lead concentration of 275 subjects, aged 3 weeks to 90 years, was 8.7 (5.7) microg/dl (range 1-34 microg/dl); 92 (34%) had concentrations > or =10 microg/dl. In multivariate analysis, an age of 5 years and under, flaking house paint, residence near a gasoline seller, male gender, increasing maternal and paternal education, and use of a lead ore eye cosmetic were independently associated with greater blood lead concentration. Vehicle ownership was associated with reduced lead concentration. Compared with the low-lead ward, residence in the high-lead ward remained significantly associated with greater lead values, indicating that additional factors likely contribute to lead exposure. CONCLUSION: Although the cause of increased lead levels in Jos appears to be multi-factorial, several remediable sources contribute to lead exposure in Nigeria.

Comparison of human herpesvirus 8 and Epstein-Barr virus seropositivity among children in areas endemic and non-endemic for Kaposi's sarcoma.

Human herpesvirus 8 (HHV-8) is the etiologic agent of Kaposi's sarcoma (KS). Several studies indicate horizontal HHV-8 transmission among children in areas where KS is endemic, but few studies have assessed acquisition of HHV-8 by children in low seroprevalence areas. Antibody screening was carried out for HHV-8 and Epstein-Barr virus (EBV) on 787 serum specimens from children living in two areas where HHV-8 is not endemic, the United States (US) and Germany, and on 184 specimens from children living in a KS-endemic area (Nigeria). For children in the US and Germany, the results showed low HHV-8 seroprevalence rates (3-4%). However, US children aged 6 months to 5 years had higher HHV-8 antibody titers than did 6-17-year-old children (P < 0.01), a finding consistent with more recent infections being detected in the younger children. Compared with seroprevalence rates and antibody titers in US and German children, those in Nigerian children were significantly higher, and seroprevalence increased with age. There was no evidence of cross-reactivity between assays for HHV-8 and EBV, despite the genetic similarity of these two herpesviruses. The data indicate that HHV-8 transmission among children where HHV-8 is not endemic occurs, but is uncommon. The findings also suggest that HHV-8 antibodies, as measured by current tests, may not persist for long periods in populations at low risk for KS and that vertical transmission is rare, although longitudinal studies are necessary to address directly these issues.

Bioelectrical impedance analysis of the body composition of Nigerian children with calcium-deficiency rickets.

Children with calcium-deficiency rickets experience increased urinary excretion of both essential and non-essential amino acids compared to non-rachitic children of the same age. Chronic wastage of amino acids into the urine could lead to a deficit in fat-free mass (FFM) in rachitic children. We therefore determined the FFM of children with calcium-deficiency rickets in northern Nigeria using bioelectrical impedance analysis. Because of the leg deformities present in the rachitic subjects, we calculated a 'corrected' height for each rachitic subject using the relationship between arm length and height in non-rachitic subjects over the same age range (r = 0.94). A total of 28 children (4 male and 24 female), 2-9 years of age with calcium-deficiency rickets and an equal number of age- and gender-matched controls were recruited into the study. Resistance and reactance measurements were obtained for all subjects and the total body water was calculated using age-specific equations. FFM was then calculated using age- and gender-specific hydration constants. No significant differences were found in the weights or FFM between the rachitic subjects and the controls (8.41 kg +/- 2.19 vs. 8.85 kg +/- 1.90, respectively). We conclude that chronic urinary wastage of amino acids by rachitic children does not result in a deficit in FFM.

Vitamin D receptor polymorphisms and nutritional rickets in Nigerian children.

Nutritional rickets is common in Nigeria where vitamin D deficiency is rare and dietary insufficiency of calcium is common. It occurs more commonly in siblings of affected children than of unaffected children. Postulating that vitamin D receptor (VDR) polymorphisms might relate to the susceptibility of some Nigerian children to develop rickets in the setting of low calcium intake, we compared the VDR genotypes, as determined by the presence or absence of Bsm I, Apa I, Taq I, and Fok I restriction enzyme cleavage sites, between 105 children with active nutritional rickets and 94 subjects representative of the community from which the rachitic children came. In the rickets group, the ff genotype was less common than in the community group, and the FF genotype was relatively increased (f allele frequency, 17% in rachitic children and 26% in the community group, p = 0.03). Neither individual allele frequencies for the other polymorphisms nor combinations of genotypes at different sites were different between the rachitic and community groups. Although it is not clear why a presumed better-functioning VDR variant (F allele) is associated with an increased risk of developing rickets, this study raises the possibility that VDR alleles might be important in determining an individual's susceptibility to developing rickets when faced with dietary calcium deficiency.