Impact of multimorbidity and polypharmacy on mortality after cancer: a nationwide registry-based cohort study in Denmark 2005-2017.

BACKGROUND: Concurrent chronic diseases and treatment hereof in patients with cancer may increase mortality. In this population-based study we examined the individual and combined impact of multimorbidity and polypharmacy on mortality, across 20 cancers and with 13-years follow-up in Denmark. MATERIALS AND METHODS: This nationwide study included all Danish residents with a first primary cancer diagnosed between 1 January 2005 and 31 December 2015, and followed until the end of 2017. We defined multimorbidity as having one or more of 20 chronic conditions in addition to cancer, registered in the five years preceding diagnosis, and polypharmacy as five or more redeemed medications 2-12 months prior to cancer diagnosis. Cox regression analyses were used to estimate the effects of multimorbidity and polypharmacy, as well as the combined effect on mortality. RESULTS: A total of 261,745 cancer patients were included. We found that patients diagnosed with breast, prostate, colon, rectal, oropharynx, bladder, uterine and cervical cancer, malignant melanoma, Non-Hodgkin lymphoma, and leukemia had higher mortality when the cancer diagnosis was accompanied by multimorbidity and polypharmacy, while in patients with cancer of the lung, esophagus, stomach, liver, pancreas, kidney, ovarian and brain & central nervous system, these factors had less impact on mortality. CONCLUSION: We found that multimorbidity and polypharmacy was associated with higher mortality in patients diagnosed with cancer types that typically have a favorable prognosis compared with patients without multimorbidity and polypharmacy. Multimorbidity and polypharmacy had less impact on mortality in cancers that typically have a poor prognosis.

Temporal changes in the probability of live birth among female survivors of childhood cancer: A population-based Adult Life After Childhood Cancer in Scandinavia (ALiCCS) study in five nordic countries.

BACKGROUND: During the past 4 decades, there has been a growing focus on preserving the fertility of patients with childhood cancer; however, no large studies have been conducted of live births across treatment decades during this period. Therefore, the authors estimated the potential birth deficit in female childhood cancer survivors and the probability of live births. METHODS: In total, 8886 women were identified in the 5 Nordic cancer registries in whom a childhood cancer had been diagnosed during 1954 through 2006. A population comparison cohort of 62,903 women was randomly selected from the central population registries matched by age and country. All women were followed for live births recorded in medical birth registries. The cumulative probability and the risk ratio (RR) with 95% confidence intervals (CIs) of a live birth were calculated by maternal age across treatment decades. RESULTS: The probability of a live birth increased with treatment decade, and, at age 30 years, the rate for survivors most recently diagnosed was close to the rate among the general population (1954-1969: RR, 0.65 [95% CI, 0.54-0.78]; 1970s: RR, 0.67 [95% CI, 0.60-0.74]; 1980s: RR, 0.69 [95% CI, 0.64-0.74]; 1990s: RR, 0.91 [95% CI, 0.87-0.95]; 2000s: RR, 0.94 [95% CI, 0.91-0.97]). CONCLUSIONS: Female childhood cancer survivors had a lower probability of a live birth than women in the general population, although, in survivors diagnosed after 1989, the probability was close to that of the general population. Because the pattern of live births differs by cancer type, continuous efforts must be made to preserve fertility, counsel survivors, and refer them rapidly to fertility treatment if necessary. LAY SUMMARY: The purpose of this study was to compare the probability of giving birth to a liveborn child in female survivors of childhood cancer with that of women in the general population. Survivors of childhood cancer had a lower probability of live births than women in the general population, although survivors diagnosed after 1989 had a probability close to that of the general population. Continuing focus on how to preserve the potential for fertility among female patients with childhood cancer during treatment is important to increase their chances of having a child.

Psychiatric disorders in individuals with neurofibromatosis 1 in Denmark: A nationwide register-based cohort study.

The aim of this study was to assess the risks of psychiatric disorders in a large cohort of 905 individuals with NF1 and 7614 population comparisons matched on sex and year of birth. The cohort was linked to the Danish Psychiatric Central Research Register to ascertain information on hospital contacts for psychiatric disorders based on the International Classification of Diseases version 8 and 10. The hazard ratio (HR) for a first psychiatric hospital contact was higher in girls (4.19, 95% confidence interval [CI] 1.81-9.69) and boys with NF1 (5.02, 95% CI 3.27-7.69) <7 years of age than in the population comparisons. Both sexes had increased HRs for developmental disorders, including attention deficit/hyperactivity disorders, autism spectrum disorders, and intellectual disabilities in childhood. Females with NF1 had also increased HRs for unipolar depression, other emotional and behavioral disorders, and severe stress reaction and adjustment disorders in early adulthood. The HRs for psychoses, schizophrenia, bipolar disorders, and substance abuse were similar in individuals with NF1 and the population comparisons. Finally, the cumulative incidence of a first hospital contact due to any psychiatric disorder by age 30 years was 35% (95% CI 29-41) in females and 28% (95% CI 19-37) in males with NF1. Thus, screening for psychiatric disorders may be important for early diagnosis and facilitation of appropriate and effective treatment in individuals with NF1.

Vitamin D-fortified foods improve wintertime vitamin D status in women of Danish and Pakistani origin living in Denmark: a randomized controlled trial.

PURPOSE: Low vitamin D status is prevalent worldwide. We aim to investigate the effect of vitamin D fortification on serum 25-hydroxyvitamin D (25(OH)D) concentration in women of Danish and Pakistani origin at risk of vitamin D deficiency. METHODS: A 12-week randomized, double-blinded, placebo-controlled intervention trial during winter time, designed to provide 20 µg vitamin D3/day through fortified yoghurt, cheese, eggs and crisp bread, and assess the change in serum 25(OH)D. Participants were 143 women of Danish and Pakistani origin, living in Denmark, randomized into four groups, stratified by ethnicity. RESULTS: Mean (SD) baseline 25(OH)D concentrations among women of Danish and Pakistani origin were 49.6 (18) and 46.9 (22) nmol/L, respectively (P = 0.4). While 9% of Danish women had 25(OH)D < 30 nmol/L, the prevalence among women of Pakistani origin was 24%. Median (IQR) vitamin D intake among Danish and Pakistani women at endpoint was 32.0 (27.0, 34.4) µg/day and 24.2 (19.2, 30.8) µg/day, respectively. Endpoint serum 25(OH)D increased in fortified groups to 77.8 (14) nmol/L among Danish women and 54.7 (18) nmol/L among women of Pakistani origin (P < 0.01). At endpoint, 0% in the Danish-fortified group and 3% in the Pakistani-fortified group had 25(OH)D < 30 nmol/L, compared with 23 % and 34% in their respective control groups. CONCLUSIONS: Vitamin D fortification of four different foods for 12 weeks during winter was effective in increasing serum 25(OH)D and reducing the prevalence of very low vitamin D status among women of Danish and Pakistani origin. CLINICALTRIALS. GOV WITH IDENTIFIER: NCT02631629.

Associations between adherence to the Danish Food-Based Dietary Guidelines and cardiometabolic risk factors in a Danish adult population: the DIPI study.

Diet is recognised as one modifiable lifestyle factor for ischaemic heart disease (IHD). We aimed at investigating the associations between adherence to the Danish Food-Based Dietary Guidelines (FBDG) indicated by a Dietary Quality Index (DQI) and selected cardiometabolic risk factors in a cross-sectional study with 219 Danish adult participants (59 %women; age 31-65years) with a minimum of one self-rated risk marker of IHD. Information regarding diet was obtained using web-based dietary assessment software and adherence to the Danish FBDG was expressed by a DQI calculated from 5 food and nutrient indicators (whole grain, fish, fruit and vegetables, energy from saturated fat and from added sugar). Background information, blood samples and anthropometrics were collected and blood pressure was measured. Linear regression analyses were used to evaluate the association between DQI and cardiometabolic risk factors. DQI was inversely associated with LDL:HDL ratio and TAG (-0·089 per unit; 95 % CI -0·177, -0·002 and -5 % per unit; 95 % CI -9, 0, respectively) and positively associated with HDL-cholesterol (0·047 mmol/l per unit; 95 % CI 0·007, 0·088). For men, DQI was inversely associated with BMI (-3 %per unit; 95 % CI -5, -1), trunk fat (-1 % per unit; 95 % CI -2, -1), high-sensitivity C-reactive protein (-30 % per unit; 95 % CI -41, -16 %), HbA1c (-0·09 % per unit; 95 % CI -0·14, -0·04), insulin (-13 % per unit; 95 % CI -19, -7) and homoeostatic model assessment-insulin resistance (-14 % per unit; 95 % CI -21, -7). In women, DQI was positively associated with systolic blood pressure (2·6 mmHg per unit; 95 % CI 0·6, 4·6). In conclusion, higher adherence to the current Danish FBDG was associated with a more beneficial cardiometabolic risk profile in a Danish adult population with a minimum of one self-rated risk factor for IHD.

Validation of Reported Whole-Grain Intake from a Web-Based Dietary Record against Plasma Alkylresorcinol Concentrations in 8- to 11-Year-Olds Participating in a Randomized Controlled Trial.

BACKGROUND: Whole-grain (WG) intake is important for human health, but accurate intake estimation is challenging. Use of a biomarker for WG intake provides a possible way to validate dietary assessment methods. OBJECTIVE: Our aim was to validate WG intake from 2 diets reported by children, using plasma alkylresorcinol (AR) concentrations, and to investigate the 3-mo reproducibility of AR concentrations and reported WG intake. METHODS: AR concentrations were analyzed in fasting blood plasma samples, and WG intake was estimated in a 7-d web-based diary by 750 participants aged 8-11 y in a 2 school meal × 3 mo crossover trial. Reported WG intake and plasma AR concentrations were compared when children ate their usual bread-based lunch (UBL) and when served a hot lunch meal (HLM). Correlations and cross-classification were used to rank subjects according to intake. The intraclass correlation coefficients (ICCs) between subjects' measurements at baseline and after the UBL were used to assess reproducibility. RESULTS: Correlations between reported WG wheat + rye intake and plasma AR were 0.40 and 0.37 (P < 0.001) for the UBL and the HLM diets, and 78% and 77% were classified in the same or adjacent quartiles for the UBL and HLM diets, respectively. The ICC over 3 mo was 0.47 (95% CI: 0.38, 0.55) for plasma total ARs and 0.64 (95% CI: 0.58, 0.70) for reported WG intake. Correlations were higher when using the AR C17:0 homolog as a biomarker, reflecting rye intake instead of plasma total ARs [UBL: r = 0.47; HLM: r = 0.43, P < 0.001; ICC = 0.51 (95% CI: 0.43, 0.59)]. CONCLUSIONS: Self-reported WG wheat + rye intake among children showed moderate correlations with plasma AR concentrations. Substantial intraindividual variation was found in WG intake and plasma AR concentrations. The AR homolog C17:0 may be used as a biomarker for WG intake when the WG intake primarily comes from rye as in the present study. This trial was registered at clinicaltrials.gov as NCT01457794.

Effects of school meals based on the New Nordic Diet on intake of signature foods: a randomised controlled trial. The OPUS School Meal Study.

A New Nordic Diet (NND) was developed in the context of the Danish OPUS Study (Optimal well-being, development and health for Danish children through a healthy New Nordic Diet). Health, gastronomic potential, sustainability and Nordic identity were crucial principles of the NND. The aim of the present study was to investigate the effects of serving NND school meals compared with the usual packed lunches on the dietary intake of NND signature foods. For two 3-month periods, 834 Danish children aged 8-11 years received NND school meals or their usual packed lunches brought from home (control) in random order. The entire diet was recorded over 7 consecutive days using a validated Web-based Dietary Assessment Software for Children. The NND resulted in higher intakes during the entire week (% increase) of root vegetables (116 (95 % CI 1·93, 2·42)), cabbage (26 (95 % CI 1·08, 1·47)), legumes (22 (95 % CI 1·06, 1·40)), herbs (175 (95 % CI 2·36, 3·20)), fresh berries (48 (95 % CI 1·13, 1·94)), nuts and seeds (18 (95 % CI 1·02, 1·38)), lean fish and fish products (47 (95 % CI 1·31, 1·66)), fat fish and fish products (18 (95 % CI 1·02, 1·37)) and potatoes (129 (95 % CI 2·05, 2·56)). Furthermore, there was a decrease in the number of children with zero intakes when their habitual packed lunches were replaced by NND school meals. In conclusion, this study showed that the children increased their intake of NND signature foods, and, furthermore, there was a decrease in the number of children with zero intakes of NND signature foods when their habitual packed lunches were replaced by school meals following the NND principles.

Vitamin D status and its determinants in children and adults among families in late summer in Denmark.

The impact of the familial relationship on vitamin D status has not been investigated previously. The objective of the present cross-sectional study was to assess serum 25-hydroxyvitamin D (25(OH)D) concentration and its determinants in children and adults among families in late summer in Denmark (56°N). Data obtained from 755 apparently healthy children (4-17 years) and adults (18-60 years) recruited as families (n 200) in the VitmaD study were analysed. Blood samples were collected in September-October, and serum 25(OH)D concentration was measured by liquid chromatography-tandem MS. Information on potential determinants was obtained using questionnaires. The geometric mean serum 25(OH)D concentration was 72·1 (interquartile range 61·5-86·7) nmol/l (range 9-162 nmol/l), with 9 % of the subjects having 25(OH)D concentrations < 50 nmol/l. The intra-family correlation was 0·27 in all subjects, 0·24 in the adults and 0·42 in the children. Serum 25(OH)D concentration was negatively associated with BMI (P< 0·001) and positively associated with dietary vitamin D intake (P= 0·008), multivitamin use (P= 0·019), solarium use (P= 0·006), outdoor stay (P= 0·001), sun preference (P= 0·002) and sun vacation (P< 0·001), but was not associated with lifestyle-related factors in the adults when these were assessed together with the other determinants. In conclusion, the majority of children and adults among the families had serum 25(OH)D concentrations >50 nmol/l in late summer in Denmark. Both dietary and sun-related factors were determinants of vitamin D status and the familial component was stronger for the children than for the adults.

Dietary effects of introducing school meals based on the New Nordic Diet - a randomised controlled trial in Danish children. The OPUS School Meal Study.

The OPUS (Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (NND)) School Meal Study investigated the effects on the intake of foods and nutrients of introducing school meals based on the principles of the NND covering lunch and all snacks during the school day in a cluster-randomised cross-over design. For two 3-month periods, 834 Danish children aged 8-11 years from forty-six school classes at nine schools received NND school meals or their usual packed lunches brought from home (control) in random order. The whole diet of the children was recorded over seven consecutive days using a validated Web-based Dietary Assessment Software for Children. The NND resulted in higher intakes of potatoes (130 %, 95 % CI 2·07, 2·58), fish (48 %, 95 % CI 1·33, 1·65), cheese (25 %, 95 % CI 1·15, 1·36), vegetables (16 %, 95 % CI 1·10, 1·21), eggs (10 %, 95 % CI 1·01, 1·19) and beverages (6 %, 95 % CI 1·02, 1·09), and lower intakes of bread (13 %, 95 % CI 0·84, 0·89) and fats (6 %, 95 % CI 0·90, 0·98) were found among the children during the NND period than in the control period (all, P< 0·05). No difference was found in mean energy intake (P= 0·4), but on average children reported 0·9 % less energy intake from fat and 0·9 % higher energy intake from protein during the NND period than in the control period. For micronutrient intakes, the largest differences were found for vitamin D (42 %, 95 % CI 1·32, 1·53) and iodine (11 %, 95 % CI 1·08, 1·15) due to the higher fish intake. In conclusion, the present study showed that the overall dietary intake at the food and nutrient levels was improved among children aged 8-11 years when their habitual packed lunches were replaced by school meals following the principles of the NND.

Mpox Awareness, Risk Reduction, and Vaccine Acceptance among People with HIV in Washington, DC.

People with HIV (PWH) are disproportionally affected by mpox and at risk of severe complications. We assessed mpox knowledge, adoption of preventive behaviors, and vaccination attitudes among PWH enrolled in a longitudinal HIV cohort in Washington, DC, the DC Cohort. We conducted uni- and multivariable analyses comparing participants by vaccination status and HIV risk group, and multinomial regression to identify factors associated with vaccine acceptance. Among 430 PWH, 378 (87.9%) were aware of mpox. Among 373 participants with vaccination status data, 101 (27.1%) were vaccinated, 129 (34.6%) planned to vaccinate, and 143 (38.3%) did not plan to vaccinate. The three vaccination groups differed significantly by age, race, education, HIV risk group, recent STI status, and level of mpox worry (all p < 0.05). A higher proportion of men who have sex with men (MSM) reported limiting their number of sexual partners compared to non-MSM (p < 0.0001). Multinomial regression models comparing vaccinated to unvaccinated PWH found age, education, mode of HIV transmission/gender, and survey period were significantly associated with vaccination status (all p < 0.05). High levels of mpox awareness were observed among this cohort of PWH with more MSM employing risk reduction behaviors and being vaccinated. Ensuring that PWH, regardless of gender, sexual orientation, or age, understand the risks of mpox may improve vaccination uptake.

Characterizing Indicators of Engagement in HIV-Associated Healthcare and Clinical Outcomes among People with HIV and Mpox in Washington, DC: A Nested Case-Control Study of the DC Cohort.

The high proportion of people with HIV (PWH) in the 2022-2023 mpox outbreak has raised questions surrounding the association between HIV and mpox. The objectives of this study were to evaluate the association between engagement in HIV-associated healthcare and mpox diagnosis, as well as to characterize cases of mpox among PWH. The DC Cohort is a longitudinal cohort of PWH in Washington, DC. We conducted a 5:1 (controls:cases) nested case-cohort study on male participants, matching age and care site. Cases were participants with an identified mpox diagnosis. Conditional logistic regression was used to assess the impact of indicators of engagement in HIV-associated healthcare on mpox diagnosis. We identified 70 cases of mpox in DC Cohort participants randomly matched to 323 controls, for a total of 393 participants included in the analysis. Study participants were primarily non-Hispanic Black (72.3%) with a median age of 41 (IQR: 36, 50). There was no association between engagement in care and mpox diagnosis; however, low CD4 was associated with increased odds of mpox diagnosis (aOR: 4.60 (95% CI: 1.23, 17.11)). Among a cohort of PWH, engagement in care was not associated with mpox diagnosis, suggesting that the overrepresentation of PWH among mpox cases is not due to surveillance bias.

Breast cancer in women using digoxin: tumor characteristics and relapse risk.

INTRODUCTION: Digoxin use is associated with increased incidence of breast and uterus cancers. We postulated that digoxin use might affect tumor characteristics and increase relapse risk in women with breast cancer. METHODS: Incident breast cancer cases in Danish women (n = 49,312; 1995 to 2008) were identified. Analyses were conducted in women 20 to 74 years old. Relapse hazard ratios (HR) were compared in women using and not using digoxin, adjusting for age, calendar period, protocol, tumor size, nodal involvement, histology grade, estrogen-receptor (ER) status, and anti-estrogen therapy in Cox regression models. RESULTS: At diagnosis, tumors in digoxin users were more likely ER+ (85.4% vs. 78.6%: P = 0.002) and have grade 1 ductal histology (37.2% vs. 25.7%; P = 0.004), compared to non-users. 45 relapses occurred in women already using digoxin at breast cancer diagnosis (1,487 person-years); 24 relapses occurred in women later starting digoxin (384 person-years). Overall relapse risk HR in digoxin users was 1.13 (95% confidence interval: 0.88, 1.46) compared to non-users. Relapse risk in digoxin users was significantly increased in the first year (2.19; 1.26, 3.78) but not thereafter (0.99; 0.74, 1.32) (P = 0.02 for difference in HRs). First-year relapse hazard was high in digoxin-using women with ER+ tumors (2.51; 1.39, 4.55) but not ER- tumors (0.72; 0.10, 5.27). Recurrence hazard was not significantly changed among digoxin-using women also using tamoxifen. CONCLUSIONS: Breast cancers arising in digoxin-using women had better prognostic features. After adjustment for markers, overall breast cancer relapse risk in digoxin users was not increased significantly, although recurrence hazards for ER+ tumors were higher in the first year following diagnosis.

Impacts of Austerity on Urogenital Infection Rates in Active Duty Servicewomen.

INTRODUCTION: Female warfighters are at increased risk of urogenital infections (UGIs) when serving in austere environments with varying levels of access to water, sanitation, and hygiene resources. Urogenital infections among servicewomen were among the top five reported medical encounters and one of the top seven reasons for medical evacuation from deployed locations between 2008 and 2013. In this study, we examine the use of water and sanitation resources across three environments (home duty station, field training, and deployment) and analyze associations between water, sanitation, and hygiene resource access and UGIs during training or deployment. The analyses are based on answers from 751 diverse active duty servicewomen (ADSW) at a large military installation in the southeastern USA. MATERIALS AND METHODS: Data for this population-based, prospective, cross-sectional survey design were collected during the administration of the Military Women's Readiness Urogenital Health Questionnaire. This research study was guided by two specific research questions derived from self-reported data in sections 2 and 3 of the questionnaire. RESULTS: The sample consisted of an extremely diverse pool of U.S. Army ADSW attached to highly operational units with robust field training and deployment tempos. Over one-half of the participants reported being diagnosed with one or more UGIs before military service. Of that participant group, more than 76.0% experienced one or more infections since joining the military. We found that the majority of UGIs occurred while U.S. Army ADSW were at their home duty stations rather than during field training or deployment. Of the three types of UGIs, bacterial vaginosis is more often associated with water and sanitation constraints. None of the water factors were significantly associated with UGIs during deployment. Intentional dehydration was not associated with UGIs in either field training or deployment, but intentionally delaying urination was associated with a significant increase in the odds of developing urinary tract infection during deployment. We identified trends in hygiene practices that may put ADSW at a higher risk for UGIs. CONCLUSIONS: Austere conditions, which may exist in any service environment, pose risks to the urogenital health and wellness of a female warfighter. Access to clean water and sanitation resources in military settings is essential for optimal health and operational readiness. It is necessary to identify and investigate critical research and policy gaps in need of investment and support for successful, evidence-based integration of female warfighters into military combat roles and to optimize their performance.

Patterns in Urogenital Health in Active Duty Servicewomen: A Prospective Cross-Sectional Survey Evaluating Impacts of Water, Sanitation, and Hygiene Resources Across Three Military Environments.

INTRODUCTION: Female warfighters are at risk for sex-specific and frequently unrecognized urogenital health challenges that may impede their ability to serve. The constraints on water, sanitation, and hygiene (WASH) resources by austere environments, whether at home or abroad, require women to practice unhealthy hygiene behaviors that jeopardize their urogenital health. In this manuscript, we examine the use of WASH resources by U.S. Army active duty servicewomen (ADSW) across three settings-home duty, field training, and deployment-to determine how the changing availability of WASH resources alters hygiene and sanitation practices in austere environments. Additionally, we report findings from a previously developed theoretical framework for determining the impacts of austere environments on ADSW's hygiene knowledge, behaviors, and outcomes. MATERIALS AND METHODS: This study used a prospective, cross-sectional survey design with population sampling and generalized ordered logit regression models. We recruited ADSW assigned to a large military installation in the southeastern United States after conducting a structured field hygiene training for female readiness. RESULTS: We surveyed a highly diverse sample of 751 ADSW and found that the use of WASH resources significantly differs between field training and deployment. Clean running water significantly differed among all settings, with nearly 70% reporting clean running water to be rarely or never available during field training. Bathing facility types significantly differed in each setting, with Cadillac bathrooms more often used during deployment than during field training and wipe baths more often used during field training than during deployment. We found that women were significantly less likely to wash their private areas more than 2 days a week during field training, compared to deployment. Women reported changing their underwear ≤2 times per week in field training environments as compared to during deployment. Soap and water were reported as the most common ways of washing in both home duty stations and during deployment, followed by wipes at home duty stations and in deployed settings. Participants reported wipes as their primary bathing method during field training, followed by soap and water. Participants used intentional dehydration or delayed urination more frequently in field training than during deployment. Women reported significant differences in holding their urine between field training and deployment, with principal reasons reported as "dirty facilities" and "distance to the nearest restroom." Significantly, they reported safety concerns when bathing, using the bathroom, or toileting facilities across the three settings. CONCLUSIONS: This is the first study to characterize sex-specific challenges by a large sample of operational ADSW and to explore the use of WASH resources in home duty, field training, and deployment settings. The results show that field training is more austere than deployed settings, indicating that austerity, not deployment, increases the urogenital infection risk for ADSW. With women more integrated into the military strategy than at any time in U.S. history, military leaders can use our results to develop interventions that ameliorate the unique challenges that influence the military readiness and overall health of female warfighters.

Pneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences methotrexate/6-mercaptopurine dosing but not event-free survival for childhood acute lymphoblastic leukemia.

Trimethoprim-sulfamethoxazole (TMP/SMX) is used in children with acute lymphoblastic leukemia (ALL) to prevent Pneumocystis pneumonia (PCP). We explored to which extent TMP/SMX influenced methotrexate (MTX)/6-mercaptopurine (6MP) dosage, myelosuppression, and event-free survival (EFS) during maintenance therapy. Of 447 study patients treated by the NOPHO ALL92 protocol, 120 patients received TMP/SMX continuously for 2-7 d/wk (TMP/SMX(2-7) ) and 287 patients never received TMP/SMX (TMP/SMX(never) ). Ten patients (all TMP/SMX(never) ) developed PCP, eight of which occurred within 7 months from the start of maintenance therapy. The TMP/SMX(2-7) group received lower oral 6MP doses than TMP/SMX(never) patients (50.6 vs. 63.9 mg/m(2) /d; P<0.001) but had lower absolute neutrophil counts (ANC) (median 1.7 vs. 2.0 × 10(9) /L; P<0.001). In Cox multivariate analysis, higher ANC levels (P=0.04) and male gender (P=0.06) were related to reduced EFS. ANC had no effect on EFS among TMP/SMX(2-7) patients (P=0.40) but did for TMP/SMX(never) patients (P=0.02). The difference in the effect on EFS between TMP/SMX(2-7) and TMP/SMX(never) patients was not significant (P=0.46). EFS did not differ between TMP/SMX(2-7) and TMP/SMX(never) patients (0.83 vs. 0.83; P=0.82). These results suggest that TMP/SMX is effective in preventing PCP and may have an antileukemic effect. TMP/SMX should be given the entire duration of maintenance therapy.

Individualized toxicity-titrated 6-mercaptopurine increments during high-dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukaemia. A Nordic Society of Paediatric Haematology and Oncology (NOPHO) pilot study.

This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m(2), ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m(2) per day if they did not develop myelotoxicity within 2 weeks after HDM. 6MP could be increased in 31 patients (81%). Toxicity was acceptable and did not differ significantly between groups. Patients receiving 75 mg/m(2) per day had significantly shorter duration of treatment interruptions of 6MP than the remaining patients (P = 0·03). This study shows individualized toxicity-titrated 6MP dosing during consolidation is feasible without increased risk of toxicity.

Risk of Depression After Radical Prostatectomy-A Nationwide Registry-based Study.

BACKGROUND: Development of depression in prostate cancer patients depends on multiple disease- and patient-related factors. OBJECTIVE: To investigate the risk of depression following radical prostatectomy focussing on the impact of surgery and subsequent treatment with salvage radiation or androgen deprivation therapy. DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort study of 5570 men who underwent radical prostatectomy in Denmark from 1998 to 2011 was identified in the Danish Prostate Cancer Registry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data on covariates and primary outcome defined as a hospital contact for depression or a redeemed antidepressant prescription were obtained from nationwide Danish registries. The risk of depression was evaluated using cumulative incidence functions and Cox models with time since surgery as an underlying time scale. Exposure to salvage procedures was included as time-varying covariates, and analyses were adjusted for confounders. RESULTS AND LIMITATIONS: The cumulative incidence of depression was increased in men who had undergone surgery compared with cancer-free men throughout follow-up of up to 18yr, particularly among men on androgen deprivation therapy. Compared with no subsequent treatment, the risk of depression was increased with subsequent androgen deprivation therapy (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.4-2.3), salvage radiation (HR 1.3, 95% CI 1.0-1.6), and the treatments combined (HR 2.2, 95% CI 1.8-2.8) after adjustments for age, year of surgery, income, and cohabitation status. Further adjustment for comorbidity hardly changed the estimates. CONCLUSIONS: Radical prostatectomy and subsequent salvage procedures increase the risk of depression, and men with subsequent androgen deprivation therapy are mainly at risk. Clinicians should thus be aware of depressive symptoms in patients receiving treatment for postsurgical relapse. PATIENT SUMMARY: In a population-based study, we found that radical prostatectomy and subsequent treatments with either radiation or endocrine manipulation significantly increased the risk of developing clinical depression.

The epidemiology of Leishmania donovani infection in high transmission foci in India.

OBJECTIVE: Visceral Leishmaniasis (VL) is highly prevalent in Bihar, India. India and its neighbours aim at eliminating VL, but several knowledge gaps in the epidemiology of VL may hamper that effort. The prevalence of asymptomatic infections with Leishmania donovani and their role in transmission dynamics are not well understood. We report data from a sero-survey in Bihar. METHODS: Demographic and immunological surveys were carried out in July and November 2006, respectively in 16 highly VL endemic foci in Muzaffarpur district in Bihar. Household and individual information was gathered and capillary blood samples were collected on filter papers. Direct agglutination test (DAT) was used to determine infected individuals (cut-off titre 1:1600). DAT results were tabulated against individual and household variables. A multivariate generalized estimating equation (GEE) model was used to study the prevalence of serologically positive individuals taking into account the clustering at household and cluster levels. RESULTS: Of study subjects 18% were DAT positive, and this proportion increased with age. Women had a significantly lower prevalence than men >14 years old. Owning domestic animals (cows, buffaloes or goats) was associated with a higher risk of being DAT positive [OR 1.16 (95% CI 1.01-1.32)], but socio-economic status was not. CONCLUSIONS: Prevalence of leishmanial antibodies was high in these communities, but variable. Demographic factors (i.e. marriage) may explain the lower DAT positivity in women >14 years of age. Within these homogeneously poor communities, socio-economic status was not linked to L. donovani infection risk at the individual level, but ownership of domestic animals was.

Epidemiology of Leishmania donovani infection in high-transmission foci in Nepal.

OBJECTIVE: Nepal reports a visceral leishmaniasis (VL) incidence of 5 per 10 000 per year on the basis of notification by health facilities, but little community-based epidemiological information exists. We report data on prevalence rates of Leishmania donovani infection in ten communities in East Nepal. METHODS: Ten clusters with highest VL incidence rates were purposefully selected in Nepal. All households were mapped and socio-demographic data and data on past VL incidence were collected. An exhaustive serological survey was performed of individuals aged >2 years, by collecting finger prick blood on filter paper in November-December 2006. The samples were tested by direct agglutination, and a titre >or=1:1600 was taken as marker of infection. A generalized estimating equation (GEE) model was used to assess risk factors for Direct Agglutination Test (DAT) positivity taking into account the clustering at household and village level. RESULTS: The sero-survey (n = 5397) showed an infection prevalence rate of 9%, (range 5-15% per cluster) with higher prevalence in men (9.9%) than in women (8.3%) (P = 0.049). Male gender, increasing age and poverty were significant risk factors in the final GEE model. CONCLUSION: Leishmania infection rate in high-transmission areas in Nepal is associated with gender, age and socio-economic status.

Escitalopram in obsessive-compulsive disorder: response of symptom dimensions to pharmacotherapy.

INTRODUCTION: There is a substantial body of evidence that obsessive-compulsive disorder (OCD) symptoms can be grouped into a series of discrete dimensions, and some evidence that not all OCD symptom dimensions respond equally well to pharmacologic or psychotherapeutic intervention. The response of OCD symptom dimensions to 12 weeks of treatment with escitalopram or placebo was investigated. METHODS: Data from a randomized, double-blind, placebo-controlled study of escitalopram in 466 adults with OCD were analyzed. Exploratory factor analysis of individual items of the Yale-Brown Obsessive-Compulsive Scale checklist was performed and subscale scores based on the extracted factors were determined. Analyses of covariance were undertaken to determine whether inclusion of each subscale score in these models impacted on the efficacy of escitalopram versus placebo. RESULTS: Exploratory factor analysis of individual Yale-Brown Obsessive-Compulsive Scale items yielded 5 factors (contamination/cleaning, harm/checking, hoarding/symmetry, religious/sexual, and somatic/hypochondriacal). Analyses of covariance including all the subscales demonstrated that escitalopram was more effective than placebo. There was a significant interaction for the hoarding/symmetry factor, which was associated with a poor treatment response. CONCLUSION: Escitalopram shows good efficacy across the range of OCD symptom dimensions. Nevertheless, hoarding/symmetry was associated with a poorer treatment response. Hoarding/symmetry may be particularly characteristic of an early-onset group of OCD patients, with the involvement of neurotransmitters other than serotonin. Further work is needed to delineate fully the subtypes of OCD, and their correlates with underlying psychobiology and treatment responsivity.