Fracture risk assessment in older adults using a combination of selected quantitative computed tomography bone measures: a subanalysis of the Age, Gene/Environment Susceptibility-Reykjavik Study.

Bone mineral density (BMD) and geometric bone measures are individually associated with prevalent osteoporotic fractures. Whether an aggregate of these measures would better associate with fractures has not been examined. We examined relationships between self-reported fractures and selected bone measures acquired by quantitative computerized tomography (QCT), a composite bone score, and QCT-acquired dual-energy X-ray absorptiometry-like total femur BMD in 2110 men and 2682 women in the Age, Gene/Environment Susceptibility-Reykjavik Study. The combined bone score was generated by summing gender-specific Z-scores for 4 QCT measures: vertebral trabecular BMD, femur neck cortical thickness, femur neck trabecular BMD, and femur neck minimal cross-sectional area. Except for the latter measure, lower scores for QCT measures, singly and combined, showed positive (p < 0.05) associations with fractures. Results remained the same in stratified models for participants not taking bone-promoting medication. In women on bone-promoting medication, greater femur neck cortical thickness and trabecular BMD were significantly associated with fracture status. However, the association between fracture and combined bone score was not stronger than the associations between fracture and individual measures or total femur BMD. Thus, the selected measures did not all similarly associate with fracture status and did not appear to have an additive effect on fracture status.

Hazard of recurrence among women after primary breast cancer treatment--a 10-year follow-up using data from SEER-Medicare.

BACKGROUND: Few studies have used SEER-Medicare data to describe recurrence of breast cancer after primary treatment for U.S. women. METHODS: We used SEER-Medicare data to estimate the annual hazard rate (HR) of recurrence for women with breast cancer between 1991 and 1997 with 10 years of follow-up. The Kaplan-Meier method was used to derive the HR. Multivariate Cox proportional hazards model was used to estimate the relative hazard of the recurrence-associated prognostic factors. RESULTS: Of 20,027 women, 36.8% had recurrence within 10 years, with most of these recurrences (81.9%) occurring within 5 years after diagnosis. Women with stage III cancer showed the highest HR peak and largest magnitude than women with stage I or II disease (both P < 0.01) within the first 5 years. Women with negative tumor hormone receptor status had a higher peak hazard of developing recurrence within the first 5 years (P < 0.01), but the hazards were remarkably lower beyond 5 years of follow-up than in women with positive or unknown hormone receptor status (P > 0.05). Women with poorly differentiated histologic grade tumors showed higher HR in the first 5 years than women with other grades after primary treatment (both P < 0.01). The increased risk of recurrence of breast cancer was associated with advanced stage, moderate and poorly differently grades, and negative hormone receptor status (all P < 0.01). CONCLUSION: The HRs of the recurrence are dynamic over 10 years and are markedly determined by prognostic factors at diagnosis. IMPACT: Our study suggests that the optimal follow-up may differ among women.

Trends in colorectal cancer incidence by anatomic site and disease stage in the United States from 1976 to 2005.

OBJECTIVE: The objectives of the current study were to examine the trends in incidence rates of subsite-specific colorectal cancer at all stages in a large US population and to explore the impact of age and sex on colorectal cancer incidence. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) 9 registries. Colorectal cancer incidence was divided into 3 anatomic subsite groupings: proximal colon, distal colon, and rectum. Incidence rates and relative risk were calculated using the SEER*Stat software provided by the National Cancer Institute. RESULTS: From 1976 to 2005, age-adjusted incidence of proximal colon, distal colon, and rectal cancers per 100,000 population have steadily decreased from 22.5, 18.8, and 19.2 to 21.1, 11.7, and 13.6, respectively, contributing to the overall decline in the incidence of colorectal cancer from 60.5 to 46.4. Distal colon cancer had the greatest incidence decline (-37.79%), whereas the most minimal change in the incidence rates occurred for proximal colon cancer (-6.37%) because of increased incidence rates of ascending colon (24.8%) and hepatic flexure (21.3%) over 30 years. The steadily increased proportion of proximal colorectal cancer subsites was observed in both men and women starting at age 50 although women experienced a greater increase than did men. CONCLUSIONS: Overall incidence rate of colorectal cancer decreased over the past 3 decades. The percent of ascending colon and hepatic flexure cancers diagnosed at early stages (localized and regional) increased. The finding on sex difference over years suggests that great attention should be paid in the future studies to male and female disparities.

Histopathologic correlation of endoscopic ultrasound findings of chronic pancreatitis in human autopsies.

OBJECTIVES: To provide histologic correlation of endoscopic ultrasound (EUS) findings believed to represent chronic pancreatitis (CP). METHODS: Eighteen postmortem pancreatic specimens in patients dying of all causes were examined in vitro by EUS for features of CP: (1) echogenic foci, (2) hypoechoic foci, (3) echogenic main pancreatic duct (MPD), (4) accentuated lobular pattern, (5) cysts, (6) irregular MPD, (7) dilated MPD, (8) side branch dilation, and (9) calculi. The pancreata were then examined by 2 pathologists (blinded to the EUS/clinical findings) for histopathologic features of CP. RESULTS: Six specimens were autolyzed, and in 1 specimen, MPD could not be seen by EUS. In the other 11 patients, 10 had evidence of CP by EUS (> or =3 features) and by histopathologic examination (> or =2 features). One patient did not have CP by both EUS and histologic examination. CONCLUSIONS: Endoscopic ultrasound accurately detected CP, when compared with histopathologic examination. The presence of 3 or more features of CP correlates with the histologic diagnosis of CP, however, up to 3 features are frequently present in elderly patients dying of all causes. Future studies should address the clinical relevance and the specificity of EUS findings of CP in the older population.

Effect of spaceflight on ability of monocytes to respond to endotoxins of gram-negative bacteria.

Astronauts live and work in relatively crowded, confined environments on the Space Shuttle and the International Space Station. They experience a unique set of stressors that contribute to a diminishment of many immune responses. This study investigated the ability of the shuttle crew members' monocytes to respond to gram-negative endotoxin that they could encounter during infections. Blood specimens were collected from 20 crew members and 15 control subjects 10 days before launch, 3 to 4 h after landing, and 15 days after landing and from crew members during their annual medical examination at 6 to 12 months after landing. When challenged with gram-negative endotoxin, the crew member's monocytes collected at all three time points produced lower levels of interleukin-6 (IL-6) and IL-1beta and higher levels of IL-1ra and IL-8 compared to those of control subjects. Cytokines were assessed by measuring the number of cells positive for intracellular cytokines. These values returned to normal 6 to 12 months after landing, except for IL-1ra, which was still higher (five- to sixfold) than in controls. This phenomenon was accompanied by an increased expression of Toll-like receptor 4 and decreased expression of CD14 on the crew members' monocytes at all time points. There were also increased levels of the lipopolysaccharide binding protein in the plasma of the crew members 3 to 4 h and 15 days after landing. This study shows that spaceflight-associated factors (in-flight and preflight) modulate the response of monocytes to gram-negative endotoxins.

Optimal frequency of imiquimod (aldara) 5% cream for the treatment of external genital warts in immunocompetent adults: a meta-analysis.

BACKGROUND: Postmarketing research has explored the optimal application schedule of imiquimod 5% cream for treatment of external anogenital warts. OBJECTIVES: We systemically reviewed the published literature on the efficacy and safety of the medication when applied either by a three times per week or once-daily regimen for 16 weeks. METHODS: MEDLINE (1966 to Feb 10, 2007), Scopus (1996 to Feb 10, 2007), and Cochrane Library (Issue 1, 2007) databases were searched for randomized trials on the medication. Primary efficacy outcome was the proportion of patients completely cleared of warts by end of treatment. Two primary safety outcomes were as follows: (a) proportion of patients who withdrew and (b) proportion of patients who required at least one rest period from treatment because of drug-related adverse events. RESULTS: Six studies were selected for subgroup analysis of circumcised men, uncircumcised men, and women. The once-daily compared to three times per week regimen did not improve treatment efficacy in any of the 3 subgroups (P <0.05), but resulted in greater incidence and severity of local skin reactions. There was no difference in medication-related withdrawals between the 2 regimens, although significantly more women and uncircumcised men required at least one rest period with the once-daily than the three times per week treatment schedule (P <0.05). CONCLUSIONS: The optimal application schedule of imiquimod 5% cream for external anogenital warts is three times per week.

Can U.S. GI fellowship programs meet American Society for Gastrointestinal Endoscopy recommendations for training in EUS? A survey of U.S. GI fellowship program directors.

BACKGROUND: American Society for Gastrointestinal Endoscopy (ASGE) EUS training and credentialing guidelines exist, but the capability of U.S. GI fellowships to meet these guidelines has not been assessed. OBJECTIVE: To ascertain the capability of U.S. GI fellowship programs to meet ASGE guidelines for EUS training in the context of 3-year and advanced GI fellowships. METHODS: U.S. GI fellowship programs were surveyed for the presence or the absence, type, and extent of EUS training. Demographics regarding the programs and the program directors were obtained. MAIN OUTCOME MEASUREMENTS: Data on the annual total EUS volume and data on EUS performed by 3-year and/or advanced-year fellows were collected and analyzed. RESULTS: Ninety-one of 142 contactable GI programs responded (64%); 72% of programs performed >200 EUS/y and thus could train >or=1 EUS trainee/y. For 3-year GI fellows, 55% received less than 3 months of training, with 43% not receiving actual "hands-on" EUS experience, and 61% not learning EUS-guided FNA. The median EUS performed by 3-year fellows was 50 (0-350). Programs that offer advanced endoscopy fellowship had a median advanced-trainee EUS volume of 200 procedures (range, 50-1100 procedures). Of advanced fellows, 20% failed to receive "hands-on" training and 52% performed <200 procedures. We observed a significant difference in the median EUS volume performed by 3-year versus advanced-year fellows (P<.001). Program director variables did not correlate with training EUS volumes. CONCLUSIONS: The majority of U.S. GI fellowship programs have established the EUS volume to train at least 1 EUS fellow, per ASGE guidelines; however, most 3-year and many advanced fellows are currently receiving insufficient EUS training.

EUS training and practice patterns among gastroenterologists completing training since 1993.

BACKGROUND: EUS training and practice patterns vary widely. The aim of this study was to assess EUS training methods, volumes, and practice patterns, and to obtain subjective assessment of endoscopic competence from endosonographers. METHODS: A survey was sent to over 1400 U.S. and international gastroenterologists who completed training since 1993. We assessed demographics, whether EUS is performed, how EUS training was obtained, and volume and type of EUS procedures performed in training and at present. Subjective assessment of adequacy of training was also obtained. RESULTS: A total of 157 physicians responded, including 76 EUS performers, of whom 67% completed advanced endoscopy fellowship, 14% were EUS trained during GI fellowship, and 19% learned via other means. EUS performers were subgrouped into those who had and had not completed advanced endoscopy fellowship, and those within and outside of an academic practice. There were significant associations between the number of upper EUS, pancreaticobiliary, and EUS-guided FNAs performed during training (p < 0.001 for all 3 groups) and completion of advanced endoscopy fellowship. Physicians in academic practice performed more EUS and FNAs per month than physicians in other types of practice (p values <0.001 and 0.001, respectively); 93.3% of respondents felt they received adequate instruction in diagnostic EUS, regardless of type of training; 88.9% of EUS performers felt they received adequate instruction in performing FNA. CONCLUSIONS: Most EUS performers are in academic practice. Those with advanced training obtained higher training volumes and perform higher volumes of EUS. The majority of respondents felt well trained regardless of training type and the number of procedures performed during training. This is the first analysis to assess these aspects of EUS training and practice.

Substitution of liothyronine at a 1:5 ratio for a portion of levothyroxine: effect on fatigue, symptoms of depression, and working memory versus treatment with levothyroxine alone.

OBJECTIVE: To attempt to confirm a previous report of superior effectiveness of using two thyroid hormones rather than one hormone to treat hypothyroidism. METHODS: This trial attempted to replicate prior findings, which suggested that substituting 12.5 microg of liothyronine (LT(3)) for 50 microg of levothyroxine (LT(4)) might improve mood, cognition, and physical symptoms in patients with primary hypothyroidism. Additionally, this trial aimed to extend the previous findings to fatigue and to assess for differential effects in subjects with low fatigue and high fatigue at baseline. A randomized, double-blind, two-period, crossover design was used. At an endocrinology and diabetes clinic, 30 adult subjects with primary hypothyroidism stabilized on LT(4) were recruited. Patients randomly assigned to treatment sequence 1 received their standard LT(4) dose in one capsule and placebo in another. Patients assigned to sequence 2 received their usual LT(4) dose minus 50 microg in one capsule and 10 microg of LT(3) in the other. At the end of the first 6 weeks, subjects were crossed over to receive the other treatment. Carryover and treatment effects were assessed by t tests. RESULTS: Of the 30 enrolled study subjects, 27 completed the trial. The mean LT(4) dose was 121 +/- 26 microg/day at baseline. No significant differences in fatigue and symptoms of depression were found between treatments. Measures of working memory were unchanged. During substitution treatment, the free thyroxine index was reduced by 0.7 (P<0.001), total serum thyroxine was reduced by 3.0 microg/dL (P<0.001), and total serum triiodothyronine was increased by 20.5 ng/dL (P = 0.004). CONCLUSION: With regard to the outcomes measured, substitution of LT(3) at a 1:5 ratio for a portion of baseline LT(4) yielded no better results than did treatment with the original dose of LT(4) alone.

Evidence-based reproductive health care in Cameroon: population-based study of awareness, use and barriers.

OBJECTIVE: To estimate the prevalence of awareness and use of evidence-based reproductive health interventions and to describe the barriers associated with the use of evidence-based interventions among health providers in north-west Cameroon. METHODS: In February 2004, a population-based descriptive study of the awareness and use of 13 evidence-based interventions targeted health workers providing reproductive health care. Their awareness and use of a composite of four vital interventions was also evaluated. These were peripartum use of antiretrovirals to prevent transmission of HIV, antenatal corticosteroid administration, magnesium sulfate prophylaxis and active management of placental delivery with uterotonics. In-depth interviews with key informants were conducted as part of a qualitative substudy to discover the barriers to the use of evidence-based interventions. FINDINGS: Overall, 91.4% (328/359) of reproductive health workers were surveyed. Their awareness of evidence-based interventions varied from 29% for the use of antenatal corticosteroids to 97% for the use of iron and folic acid supplementation during pregnancy. Their use of these interventions ranged from 10.2% for antenatal corticosteroids to 94.8% for iron and folic acid supplementation. Only 50/322 (15.5%; 95% confidence interval (CI)=11.8-20.0) of health workers were aware of all four vital interventions, and only 12/312 (3.8%; 95% CI=2.0- 6.6) reported using all of them regularly. A total of 26 key informants participated in the qualitative substudy. A deficiency in the education and training of health workers, especially a lack of continuing education, was commonly identified as the most important barrier to their awareness of evidence-based practices. A lack of awareness and a lack of supplies and materials were the main barriers to practice. CONCLUSION: The awareness and practice of important evidence-based reproductive health interventions were less than optimal. To improve maternal and perinatal outcomes both remedial programmes to enhance awareness, including continuing education for health workers, and the provision of necessary supplies are needed.