Trends in Initial Management of Prostate Cancer in New Hampshire

Purpose Prostate cancer management strategies are evolving with increased understanding of the disease. Specifically, there is emerging evidence that ‘‘low-risk’’ cancer is best treated with observation, while localized ‘‘high-risk’’ cancer requires aggressive curative therapy. In this study, we evaluated trends in management of prostate cancer in New Hampshire to determine adherence to evidence- based practice. Methods From the New Hampshire State Cancer Registry, cases of clinically localized prostate cancer diagnosed in 2004–2011 were identified and classified according to D’Amico criteria. Initial treatment modality was recorded as surgery, radiation therapy, expectant management, or hormone therapy. Temporal trends were assessed by Chi-square for trend. Results Of 6,203 clinically localized prostate cancers meeting inclusion criteria, 34, 30, and 28 % were low-, intermediate-, and high-risk disease, respectively. For lowrisk disease, use of expectant management (17–42 %, p\0.001) and surgery (29–39 %, p\0.001) increased, while use of radiation therapy decreased (49–19 %, p\0.001). For intermediate-risk disease, use of surgery increased (24–50 %, p\0.001), while radiation decreased (58–34 %, p\0.001). Hormonal therapy alone was rarely used for low- and intermediate-risk disease. For high-risk patients, surgery increased (38–47 %, p = 0.003) and radiation decreased (41–38 %, p = 0.026), while hormonal therapy and expectant management remained stable. Discussion There are encouraging trends in the management of clinically localized prostate cancer in New Hampshire, including less aggressive treatment of low-risk cancer and increasing surgical treatment of high-risk disease

New Malignancies after Squamous Cell Carcinoma and Melanomas: A Population-Based Study from Norway

Skin cancer survivors experience an increased risk for subsequent malignancies but the associated risk factors are poorly understood. This study examined the risk of a new primary cancer following an initial skin cancer and assessed risk factors associated with second primary cancers

Lifestyle and Other Factors Explain One-Half of the Variability in the Serum 25-Hydroxyvitamin D Response to Cholecalciferol Supplementation in Healthy Adults

Background: Many factors have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentrations in observational studies, with variable consistency. However, less information is available on factors affecting the magnitude of changes in serum 25(OH)D resulting from vitamin D supplementation. Objective: This study aimed to identify factors associated with the serum 25(OH)D response to supplementation with 1000 IU cholecalciferol/d during the first year of a large, multicenter, randomized, placebo-controlled colorectal adenoma chemoprevention trial. Methods: Eligible older adults who were not vitamin D–deficient [serum 25(OH)D12 ng/mL] were randomly assigned in a modified 2 3 2 factorial design to 1 of 4 groups: daily 1000 IU cholecalciferol, 1200 mg Ca as carbonate, both, or placebo. Women could elect 2-group (calcium 6 cholecalciferol) random assignment. In secondary analyses, we used multivariable models to assess factors associated with serum 25(OH)D concentrations in all enrollees (n = 2753) and with relative changes in serum 25(OH)D after 1 y cholecalciferol supplementation among those randomly assigned (n = 2187). Results: In multivariable models, 8 factors accounted for 50% of the variability of proportional change in serum 25(OH)D after cholecalciferol supplementation. Larger increases were associated with being female (34.5% compared with 20.5%; P \u3c 0.001) and with lower baseline serum 25(OH)D (P \u3c 0.0001), optimal adherence to study pill intake (P = 0.0002), wearing long pants and sleeves during sun exposure (P = 0.0002), moderate activity level (P = 0.01), use of extra vitamin D–containing supplements during the trial (P = 0.03), and seasons of blood draw (P # 0.002). Several genetic polymorphisms were associated with baseline serum 25(OH)D and/or serum response, but these did not substantially increase the models of R2 values. Other factors, including body mass index, were associated with serum 25(OH)D at baseline but not with its response to supplemental cholecalciferol. Conclusions: The factors that most affected changes in serum 25(OH)D concentrations in response to cholecalciferol supplementation included sex, baseline serum 25(OH)D, supplement intake adherence, skin-covering clothes, physical activity, and season. Genetic factors did not play a major role. This trial was registered at www.clinicaltrials.gov as NCT00153816

The Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas

BACKGROUND Epidemiologic and preclinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia. To further study the chemopreventive potential of these nutrients, we conducted a randomized, double-blind, placebo-controlled trial of supplementation with vitamin D, calcium, or both for the prevention of colorectal adenomas. METHODS We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy. We randomly assigned 2259 participants to receive daily vitamin D3 (1000 IU), calcium as carbonate (1200 mg), both, or neither in a partial 2Å~2 factorial design. Women could elect to receive calcium plus random assignment to vitamin D or placebo. Follow-up colonoscopy was anticipated to be performed 3 or 5 years after the baseline examinations, according to the endoscopist’s recommendation. The primary end point was adenomas diagnosed in the interval from randomization through the anticipated surveillance colonoscopy. RESULTS Participants who were randomly assigned to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter, relative to participants given placebo. Overall, 43% of participants had one or more adenomas diagnosed during follow-up. The adjusted risk ratios for recurrent adenomas were 0.99 (95% confidence interval [CI], 0.89 to 1.09) with vitamin D versus no vitamin D, 0.95 (95% CI, 0.85 to 1.06) with calcium versus no calcium, and 0.93 (95% CI, 0.80 to 1.08) with both agents versus neither agent. The findings for advanced adenomas were similar. There were few serious adverse events. CONCLUSIONS Daily supplementation with vitamin D3 (1000 IU), calcium (1200 mg), or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over a period of 3 to 5 years. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00153816.

Risk of Death from Cardiovascular Disease Associated with Low-level Arsenic Exposure Among Long-term Smokers in a US Population-based Study

High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic’s effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, in relation to natural-log transformed toenail arsenic concentrations. In this US population, although we observed no overall association, arsenic exposure measured from toenail clipping samples was related to an increased risk of ischemic heart disease mortality among long-term smokers (as reported at baseline), with increased hazard ratios among individuals with ≥ 31 total smoking years (HR: 1.52, 95% CI: 1.02, 2.27), ≥ 30 pack-years (HR: 1.66, 95% CI: 1.12, 2.45), and among current smokers (HR: 1.69, 95% CI: 1.04, 2.75). These results are consistent with evidence from more highly exposed populations suggesting a synergistic relationship between arsenic exposure and smoking on health outcomes and support a role for lower-level arsenic exposure in ischemic heart disease mortality

The proposal for a third medical school in New Zealand: A community-engaged graduate entry medical program

New Zealand has a maldistributed workforce that is heavily dependent on recruiting international medical graduates. Shortages are particularly apparent in high needs communities and in general scope specialties in provincial regions. The University of Waikato in partnership with the Waikato District Health Board has proposed a third medical school for New Zealand which will concentrate on addressing the workforce needs of disadvantaged rural and provincial communities. The proposed program is a community engaged, graduate entry medical course

Does Travel Time to a Radiation Facility Impact Patient Decision-making Regarding Treatment for Prostrate Cancer? A Study of the New Hampshire State Cancer Registry

Purpose: We sought to determine whether further distance from a radiation center is associated with lower utilization of external beam radiation therapy (XRT). Methods: We retrospectively identified patients with a new diagnosis of localized prostate cancer (CaP) within the New Hampshire State Cancer Registry from 2004 to 2011. Patients were categorized by age, D’Amico risk category, year of treatment, marital status, season of diagnosis, urban/rural residence, and driving time to the nearest radiation facility. Treatment decisions were stratified into those requiring multiple trips (XRT) or a single trip (surgery or brachytherapy). Multivariable regression analysis was performed. Results: A total of 4,731 patients underwent treatment for newly diagnosed CaP during the study period, including 1,575 multitrip (XRT) and 3,156 singletrip treatments. Of these, 87.6% lived within a 30-minute drive to a radiation facility. In multivariable analysis, time to the nearest radiation facility was not associated with treatment decisions (P = .26). However, higher risk category, older age, married status, and winter diagnosis were associated with XRT (P \u3c .05). More recent year of diagnosis and urban residence were associated with single-trip therapy (primarily surgery) (P \u3c .05). There was a significant interaction between travel time and season of diagnosis (P = .03), as well as a marginally significant interaction with urban/rural status (P = .07). Conclusion: Overall, further travel time to a radiation facility was not associated with lower utilization of XRT. These data are encouraging regarding access to care for CaP in New Hampshire

Changes in Beliefs Identify Unblinding in Randomized Controlled Trials: A Method to Meet CONSORT Guidelines

Double-blinded trials are often considered the gold standard for research, but significant bias may result from unblinding of participants and investigators. Although the CONSORT guidelines discuss the importance of reporting evidence that blinding was successful , it is unclear what constitutes appropriate evidence. Among studies reporting methods to evaluate blinding effectiveness, many have compared groups with respect to the proportions correctly identifying their intervention at the end of the trial. Instead, we reasoned that participants\u27 beliefs, and not their correctness, are more directly associated with potential bias, especially in relation to self-reported health outcomes. During the Water Evaluation Trial performed in northern California in 1999, we investigated blinding effectiveness by sequential interrogation of participants about their blinded intervention assignment (active or placebo). Irrespective of group, participants showed a strong tendency to believe they had been assigned to the active intervention; this translated into a statistically significant intergroup difference in the correctness of participants\u27 beliefs, even at the start of the trial before unblinding had a chance to occur. In addition, many participants (31%) changed their belief during the trial, suggesting that assessment of belief at a single time does not capture unblinding. Sequential measures based on either two or all eight questionnaires identified significant group-related differences in belief patterns that were not identified by the single, cross-sectional measure. In view of the relative insensitivity of cross-sectional measures, the minimal additional information in more than two assessments of beliefs and the risk of modifying participants\u27 beliefs by repeated questioning, we conclude that the optimal means of assessing unblinding is an intergroup comparison of the change in beliefs (and not their correctness) between the start and end of a randomized controlled trial

The epidemiology of incomplete abortion in South Africa

Objective. To describe the epidemiology of incomplete abortion (spontaneous miscarriage and illegally induced) in South Africa.Design. Multicentre, prospective, descriptive study.Setting. Fifty-six public hospitals in nine provinces (a stratified, random sample of all hospitals treating gynaecological emergencies).Patients. All women of gestation under 22 weeks who presented with incomplete abortion during the 2-week study period.Main outcome measures. Incidence of, morbidity associated with and mortality from incomplete abortion.Main results. An estimated 44 686 (95% Cl 35 633 - 53 709) women per year were admitted to South Africa's public hospitals with incomplete abortion. An estimated 425 (95% Cl 78 - 735) women die in public hospitais from complications of abortion. Fifteen per cent (95% Cl 13 18) of patients have severe morbidity while a further 19% (95% Cl 16 - 22) have moderate morbidity, as assessed by categories designed for the study which largely reflect infection. There were marked inter-provincial differences  and inter-age group differences in trimester of presentation and proportion of patients with appreciable morbidity.Conclusions. Incomplete abortions and, in particular, unsafe abortions are an important cause of mortality and morbidity in South Africa. The methods used in this study underestimate the true incidence for reasons that are discussed. A high priority should be given to the prevention of unsafe abortion