Cost and burden of informal caregiving of dependent older people in a rural Indian community.

BACKGROUND: Lack of state supported care services begets the informal caregiving by family members as the mainstay of care provided to the dependent older people in many Low and Middle Income Countries (LMICs), including India. Little is known about the time spent on caregiving, its cost and the burden experienced by these informal caregivers. We aimed to estimate the costs of informal caregiving and to evaluate the nature as well as correlates of caregivers' burden in a rural Indian community. METHODS: We assessed 1000 people aged above 65 years, among whom 85 were dependent. We assessed their socioeconomic profiles, disability, health status and health expenditures. Their caregivers' socio-demographic profiles, mental health, and the time spent on caregiving were assessed using standard instruments. Caregiver's burden was evaluated using Zarit Burden Scale. We valued the annual informal caregiving costs using proxy good method. We employed appropriate non-parametric multivariate statistics to evaluate the correlates of caregivers' burden. RESULTS: Average time spent on informal caregiving was 38.6 (95% CI 35.3-41.9) hours/week. Estimated annual cost of informal caregiving using proxy good method was 119,210 US$ in this rural community. Mean total score of Zarit burden scale, measuring caregivers' burden, was 17.9 (95% CI 15.6-20.2). Prevalence of depression among the caregivers was 10.6% (95% CI 4.1-17.1%). Cerebrovascular disease, Parkinson's disease, higher disability, insomnia and incontinence of the dependent older people as well as the time spent on helping Activities of Daily Living and on supervision increased caregiver's burden significantly. CONCLUSIONS: Cost and burden of informal caregiving are high in this rural Indian community. Many correlates of burden, experienced by caregivers, are modifiable. We discuss potential strategies to reduce this burden in LMICs. Need for support to informal caregivers and for management of dependent older people with chronic disabling diseases by multidisciplinary community teams are highlighted.

Induced abortion and breast cancer among parous women: a Danish cohort study.

OBJECTIVE: We investigated whether induced abortion is associated with breast cancer when lifestyle confounders, including smoking and alcohol consumption, are adjusted for. Design. Prospective cohort study. SETTING: Danish women from the Diet, Cancer and Health study. POPULATION: A total of 25,576 women. METHODS: We obtained exposure data from baseline questionnaires filled in by the women between 1993 and 1997. Information on breast cancer and emigration was retrieved from Danish national registries. The study power was approximately 85% when applying a minimum detection hazard ratio of 1.2. MAIN OUTCOME MEASURES: Long-term effects of induced abortion on the risk of breast cancer among women above 50 years of age. RESULTS: During a follow up of approximately 12 years, 1215 women were diagnosed with breast cancer. When comparing parous women who had an abortion with parous women who never had an abortion, there was no association between breast cancer risk and induced abortion (ever vs. never), with a hazard ratio 0.95 (95% confidence interval 0.83-1.09), regardless of whether the abortion occurred before the first birth (hazard ratio 0.86; 95% confidence interval 0.65-1.14), or after the first birth (hazard ratio 0.97; 95% confidence interval 0.84-1.13). CONCLUSIONS: Our study did not show evidence of an association between induced abortion and breast cancer risk.

Epidemiology of non-hereditary angioedema.

The prevalence of non-hereditary angioedema was investigated in a general population sample (n = 7,931) and in a sample of Danish patients (n = 7,433) tested for deficiency of functional complement C(1) esterase inhibitor protein (functional C(1) INH). The general population sample (44% response rate) reported a lifetime prevalence of 7.4% for angioedema. In both groups symptoms were most frequent in the lips, head, neck, eyes and tongue. In the C(1) INH test normal group angioedema was still active at the time of the study in 53% of the patients, and 36% reported symptoms in the throat, 23% in the abdominal area, 17% had diarrhoea, 11% had vomiting and 6% fainted during attacks. Non-hereditary angioedema has high lifetime prevalence and becomes chronic in approximately 50% of affected patients. Symptoms in the larynx and throat, as well as non-specific symptoms, such as dizziness and abdominal pain, were more frequent than previously reported.

Injury risk in Danish youth and senior elite handball using a new SMS text messages approach.

OBJECTIVE: To assess the injury incidence in elite handball, and if gender and previous injuries are risk factors for new injuries. METHODS: Cohort study of 517 male and female elite handball players (age groups under (u)16, u-18 and senior). Participants completed a web survey establishing injury history, demographic information and sports experience, and provided weekly reports of time-loss injuries and handball exposure for 31 weeks by short message service text messaging (SMS). Injuries were further classified by telephone interview. RESULTS: The weekly response rate ranged from 85% to 90% illustrating the promise of the SMS system as a tool in injury surveillance. Of 448 reported injuries, 165 injuries (37%) were overuse injuries and 283 (63%) traumatic injuries. Knee (19%) and ankle (29%) were the most common traumatic injuries. The injury incidence during match play was 23.5 (95% CI 17.8 to 30.4), 15.1 (95% CI 9.7 to 22.2), 11.1 (95% CI 7.0 to 16.6) injuries per 1000 match hours among senior, u-18 and u-16 players, respectively. U-18 male players had an overall 1.76 (95% CI 1.10 to 2.80) times higher risk of injury compared to females. Having had two or more previous injuries causing absence from handball for more than 4 weeks increased the risk of new injury in the u-16 group (IRR: 1.79 (95% CI 1.03 to 3.11)-2.23 (95% CI 1.22 to 4.10)). CONCLUSION: The incidence of time-loss injuries in elite handball was higher during match play than previously reported in recreational handball. Previous injuries were a risk factor for new injuries among u-16 players. Male players had a significant higher injury rate in the u-18 group.

Traits of ADHD and autism in girls with a twin brother: a Mendelian randomization study.

It has been hypothesized that prenatal exposure to testosterone may be associated with traits of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD). We conducted a population-based study of dizygotic female twins to elucidate this hypothesis, assuming that the sex of the co-twin influences the level of prenatal exposure to testosterone. We invited parents of 24,552 3- to 15-year-old twins to answer questionnaires on traits of ADHD and ASD. We analysed the data using a proportional odds model with sex of the co-twin as an instrumental variable for prenatal exposure to testosterone of female twins. We received responses for 6,339 girls from dizygotic twin pairs. Odds ratios for male versus female co-twin were 0.71 (95 % confidence interval 0.61-0.81) for ADHD traits and 0.74 (0.66-0.83) for ASD traits, indicating that a twin brother reduces traits of ADHD and ASD in females. In conclusion, we found that female twins with a twin brother scored significantly lower in parent-reported traits of ADHD and ASD than those with a twin sister. The reason for this may be parental reporting bias, or confounding by unmeasured variables, or a causal effect of an intrauterine environment modified by the sex of the co-twin in the opposite direction of what we expected.

Polymorphisms in the tumor necrosis factor alpha and interleukin 1-beta promoters with possible gene regulatory functions increase the risk of preterm birth.

OBJECTIVE: To investigate the relation between 19 selected single nucleotide polymorphisms in three cytokine genes, tumor necrosis factor alpha (TNFA), interleukin 1-beta (IL1B) and interleukin 6 (IL6) and preterm birth (<37 weeks' gestation). DESIGN: Case-control association study. SAMPLE: A total of 117 singleton pregnant Danish Caucasian women, including 62 preterm birth cases and 55 controls (birth>or=37 weeks). METHODS: Genotyping was performed using TaqMan probes and traditional sequencing. Descriptive statistics were carried out with Fisher's exact test and Wilcoxon rank-sum test. All genetic data were tested for Hardy-Weinberg equilibrium and analyzed using logistic regression, 2x2 proportions or chi(2). Haplotypes were estimated for each gene and permutation used for association testing. RESULTS: Women carrying the TNFA -857 C>T rare allele (T) and those homozygous for the IL1B -31 T>C and IL1B -511 C>T rare alleles (C and T) have an increased risk of preterm birth with OR 3.1 (95% CI: 1.0-10.3) and OR 6.4 (95% CI: 1.3-60.5), respectively. Two estimated TNFA haplotypes were associated with preterm birth with OR 3.1 (p=0.037) and OR 2.7 (p=0.045). CONCLUSION: Polymorphisms in the cytokine genes TNFA and IL1B may increase the risk of preterm birth, possibly by a dysregulation of the immune system in pregnancy.

Health service use, out-of-pocket payments and catastrophic health expenditure among older people in India: the WHO Study on global AGEing and adult health (SAGE).

BACKGROUND: Healthcare financing through out-of-pocket payments and inequities in healthcare utilisation are common in low and middle income countries (LMICs). Given the dearth of pertinent studies on these issues among older people in LMICs, we investigated the determinants of health service use, out-of-pocket and catastrophic health expenditures among older people in one LMIC, India. METHODS: We accessed data from a nationally representative, multistage sample of 2414 people aged 65 years and older from the WHO's Study on global AGEing and adult health in India. Sociodemographic characteristics, health profiles, health service utilisation and out-of-pocket health expenditure were assessed using standard instruments. Multivariate zero-inflated negative binomial regression models were used to evaluate the determinants of health service visits. Multivariate Heckman sample selection regression models were used to assess the determinants of out-of-pocket and catastrophic health expenditures. RESULTS: Out-of-pocket health expenditures were higher among participants with disability and lower income. Diabetes, hypertension, chronic pulmonary disease, heart disease and tuberculosis increased the number of health visits and out-of-pocket health expenditures. The prevalence of catastrophic health expenditure among older people in India was 7% (95% CI 6% to 8%). Older men and individuals with chronic diseases were at higher risk of catastrophic health expenditure, while access to health insurance lowered the risk. CONCLUSIONS: Reducing out-of-pocket health expenditure among older people is an important public health issue, in which social as well as medical determinants should be prioritised. Enhanced public health sector performance and provision of publicly funded insurance may protect against catastrophic health expenses and healthcare inequities in India.

Patient-specific errors in agreement between International Normalized Ratios measured by a whole blood coagulometer and by a routine plasma-based method.

We applied a new statistical method to improve comparisons between systems measuring prothrombin time (PT) by splitting disagreement into systematic errors, which can be eliminated, and random errors, which can not. We found that the disagreement between International Normalized Ratio (INR) measurements based on plasma and whole blood was significantly patient-dependent.

Precision of INR measured with a patient operated whole blood coagulometer.

INTRODUCTION: The objective of the present study was to evaluate the precision of a portable whole blood coagulometer (CoaguChek S) in the hands of self-managing patients on oral anticoagulant therapy (OAT). MATERIALS AND METHODS: Fifteen patients on self-managed OAT performed measurements of INR by two types of portable whole blood coagulometers (CoaguChek and CoaguChek S) at home for 10 weeks. RESULTS: The coefficient of variation (CV) of INRs determined at home by CoaguChek S by patients on self-managed OAT was 5.5% (95% confidence limits: 4.9%, 6.1%). The biological CV of INR within and between patients was 15.0% and 14.7%, respectively. CONCLUSION: The precision of CoaguChek S is satisfactory.

Mechanical heart valve patients can manage oral anticoagulant therapy themselves.

OBJECTIVES: Thromboembolism and anticoagulant related bleeding are still the most common complications in mechanical heart valve patients. Management of the oral anticoagulant therapy is therefore a key determinant for these clinical complications. We hypothesize that patients selected to self-managed oral anticoagulant therapy have a better treatment quality than patients in conventional oral anticoagulant therapy. The aim of this study was to assess the time within the therapeutic International Normalized Ratio (INR) target range and the incidence of clinical complications in our group of patients, and compare these data with published data on conventional management. METHODS: Mechanical heart valve patients (N=94) with a mean age of 47.6 years (range 4.2-76.6 years) were trained in home blood analysis of INR using a CoaguChek home coagulometer and coumarin dosage adjustment. After training, the patients were followed by weekly INR measurements. The therapeutic range was a target INR +/-0.5. The indications for initiating oral anticoagulant therapy were: aortic valve (N=62), mitral valve (N=29), tricuspid valve (N=1) and multiple valves (N=2). RESULTS: The mean observation time was 2.1 years (range 0.04-6.2 years), and the total number of patient-years was 197. The patients were within the therapeutic INR target range for a median of 76.0% (range 32.1-100.0%) of the time. There were two major thromboembolic events and five major bleedings events, comprised of two deep vein thromboses (both in the same patient), four episodes of epistaxis and one case of gastrointestinal bleeding. All the events required short hospitalization, and after treatment all the patients were discharged from the hospital without any sequelae or other complications. Using published work as references the expected number of major thromboembolic and bleeding complications in conventional management was four and 12, respectively. CONCLUSIONS: Self-management of oral anticoagulant therapy provides a good treatment quality for mechanical heart valve patients. We therefore consider self-management of oral anticoagulant therapy as an equally as good or potentially better treatment option for selected patients compared to conventional management.

Longitudinal and cross-sectional studies of HIV-1 RNA and DNA loads in blood and the female genital tract.

OBJECTIVE: To examine if correlates of HIV-1 genital shedding in cross-sectional studies can be used to determine the risk of shedding in individual HIV-1-positive women. STUDY DESIGN: Longitudinal samples from blood and cervix were obtained from 18 HIV-1 infected women, and HIV-1 RNA and cell-associated DNA virus, and beta-chemokine levels, were measured. Associations between variables were analyzed at both individual and group level. RESULTS: The variation over time was 2.9-, 2.1-, and 2.3-fold in plasma RNA, PBMC DNA and cervical RNA load, respectively, and reached 6.2-fold in cervical DNA load. Differences were observed between associations in individual- and group-level comparisons, suggesting that a separate reservoir of HIV replication may exist in the genital tract of some women, which is influenced by local environmental factors. CONCLUSIONS: Our study underscores the importance of caution during contact with genital fluids at all stages of infection and disease regardless of treatment and HIV-1 blood loads.

[Self-management of oral anticoagulant therapy in children with congenital heart defects]. / Selvstyring af peroral antikoagulationsbehandling hos børn med medfødte hjertesygdomme.

INTRODUCTION: Self-management of oral anticoagulation has been shown to produce a better quality of treatment than conventional management when assessed in selected adults. We have extended the concept of self-management to include children with congenital cardiac disease on the hypothesis that it is also possible in this subset of patients. Our aim was to assess the quality of self-management in children with congenital cardiac disease. MATERIAL AND METHODS: We trained 14 children aged from 2.2 to 15.6 years, with a mean age of 9.7 years, and their parents, in domiciliary analysis of the international normalised ratio (INR) and the necessary dose adjustment of the oral anticoagulant therapy. The curriculum for training covered 27 weeks, and the patients and their parents were followed up for a period of up to 31 months by weekly measurement of the INR values obtained. RESULTS: The patients were observed over a mean of 547 days (range: 214-953 days). They were within the therapeutic targeted range of the INR for a median of 65.5% of the time (range: 17.6-90.4%. None of the patients experienced thromboembolic or bleeding complications requiring doctoral intervention. All the patients and their parents expressed full satisfaction with the treatment. DISCUSSION: Self-management of oral anticoagulation provides a good quality of treatment and is safe and feasible in selected children with congenital cardiac disease.

Patients with rheumatoid arthritis treated with methotrexate (MTX): concentrations of steady-state erythrocyte MTX correlate to plasma concentrations and clinical efficacy.

OBJECTIVE: To investigate the accumulation of methotrexate (MTX) in circulating erythrocytes and the association with pharmacokinetic variables, weekly dose, and clinical efficacy in 2 cohorts of patients with chronic active rheumatoid arthritis (RA) undergoing MTX monotherapy. METHODS: Seventy-six patients with RA were included in this open prospective study: 40 were included before initiation of MTX therapy. Laboratory analyses, intracellular MTX concentrations in erythrocytes (Ery-MTX), and clinical examinations including toxicity data were performed prospectively for 52 weeks. Plasma concentrations of MTX were measured and area under the plasma concentration versus time curve (AUC) was estimated along with other pharmacokinetic variables in a population based software model. RESULTS: Ery-MTX rose after initiation of therapy and reached a steady state after 6-8 weeks. The correlation between steady-state Ery-MTX and dose was poor (r(2) = 0.16), whereas steady-state Ery-MTX levels correlated strongly with the estimated AUC (r(2) = 0.51, log-transformed variables). Both steady-state Ery-MTX levels and estimated AUC were significantly higher in patients responding to MTX therapy than in patients classified as nonresponders according to American College of Rheumatology core criteria and were similar to patients on longterm MTX therapy. CONCLUSION: Our results indicate that clinical efficacy and Ery-MTX may have a causal relation and that measurement of Ery-MTX or estimation of AUC in a software model provides useful guidelines to the clinician when starting MTX therapy in patients with RA. The latter can be performed immediately after initiation of therapy.

Macrophage serum markers in pneumococcal bacteremia: Prediction of survival by soluble CD163.

OBJECTIVE: Soluble CD163 (sCD163) is a new macrophage-specific serum marker. This study investigated sCD163 and other markers of macrophage activation (neopterin, ferritin, transcobalamin, and soluble urokinase plasminogen activator receptor [suPAR]) as prognostic factors in patients with pneumococcal bacteremia. DESIGN: Observational cohort study. SETTING: Five university hospitals in Denmark. PATIENTS: A total of 133 patients with Streptococcus pneumoniae bacteremia (positive blood culture) and 133 age- and gender-matched controls. INTERVENTIONS: Samples were collected for biochemical analyses at the time of first positive blood culture. MEASUREMENTS AND MAIN RESULTS: sCD163 was highly correlated with other macrophage markers and was significantly elevated (median [25-75 percentiles], 4.6 mg/L [2.8-8.9]) compared with healthy controls (2.7 mg/L [2.1-3.3], p < .0001). Increased levels were observed in patients who needed intensive care (hemodialysis, p = .0011; hypotension, p = .0014; mechanical ventilation, p = .0019). Significantly lower levels of sCD163, ferritin, transcobalamin, and suPAR (but not C-reactive protein) were measured in patients > or =75 yrs. In patients <75 yrs, all macrophage markers were increased in patients who died from their infection compared with survivors, whereas no change was observed in any of the markers in the very old age. At cutoff levels of 9.5 mg/L (sCD163) and 1650 nmol/L (C-reactive protein), the relative risk for fatal outcome in patients <75 yrs was 10.1 (95% confidence interval 3.4-31.0) and 7.0 (95% confidence interval 2.4-21.6) for sCD163 and C-reactive protein, respectively. In a multivariate logistic regression model for patients <75 yrs, ferritin, transcobalamin, neopterin, and suPAR contained no significant information on the probability of survival when sCD163 and CRP were known (p = .25). CONCLUSIONS: Macrophage marker response in pneumococcal bacteremia was compromised in old age. In patients <75 yrs old, sCD163 was superior to other markers, including C-reactive protein, in predicting fatal disease outcome.

Limited protective effect of the CCR5Delta32/CCR5Delta32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus.

The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2% of the Scandinavian population) and a rapid disease course. His HIV V3 region contained genotypic features attributable to X4 virus and resembled functionally verified X4 virus and virus from patients treated with a CD4 cell-stimulating drug, tucaresol. Age-related differences in disease progression rate and survival time were seen for CCR5/CCR5 patients. Surprisingly, no protective effect of the CCR5/CCR5Delta32 genotype on disease progression or survival was seen for children but was evident for adults. Age group-related immunologic differences might explain this variation, and transmission route and/or viral phenotype variation within donor virus may be related to the limited protection of the CCR5Delta32/CCR5Delta32 genotype. Sequence comparisons indicate that X4 virus can be selected in vivo due to either absence of CCR5 receptors or relative increase of CXCR4 receptors.