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Abstract: Objectives: Lactation may influence future progression to type 2 diabetes after gestational diabetes mellitus (GDM). However, biomarkers associated with progression to glucose intolerance have not been examined in relation to lactation intensity among postpartum women with previous GDM. This study investigates whether higher lactation intensity is related to more favorable blood lipids, lipoproteins and adipokines after GDM pregnancy independent of obesity, socio-demographics and insulin resistance. Methods: The Study of Women, Infant Feeding, and Type 2 Diabetes (SWIFT) is a prospective cohort study that recruited 1035 women diagnosed with GDM by the 3-h 100g oral glucose tolerance tests (OGTTs) after delivery of a live birth in 2008–2011. Research staff conducted 2-h 75 g OGTTs, and assessed lactation intensity, anthropometry, lifestyle behaviors and socio-demographics at 6–9 weeks postpartum (baseline). We assayed fasting plasma lipids, lipoproteins, non-esterified free fatty acids, leptin and adiponectin from stored samples obtained at 6–9 weeks postpartum in 1007 of the SWIFT participants who were free of diabetes at baseline. Mean biomarker concentrations were compared among lactation intensity groups using multivariable linear regression models. Results: Increasing lactation intensity showed graded monotonic associations with fully adjusted mean biomarkers: 5%–8% higher high-density lipoprotein cholesterol (HDL-cholesterol), 20%–28% lower fasting triglycerides, 15%–21% lower leptin (all trend P-values<0.01), and with 6% lower adiponectin, but only after adjustment for insulin resistance (trend P-value=0.04). Conclusion: Higher lactation intensity was associated with more favorable biomarkers for type 2 diabetes, except for lower plasma adiponectin, after GDM delivery. Long-term follow-up studies are needed to assess whether these effects of lactation persist to predict progression to glucose intolerance. [Copyright &y& Elsevier]

Abstract: Purpose: Women with breast cancer are at increased risk for femur fracture. Contributing factors include estrogen deficiency, cancer-related therapies, or direct bone involvement. This study examines fracture subtypes in women with prior breast cancer experiencing a femur fracture. Methods: Women age ≥50 years old with a history of invasive breast cancer who experienced a femur fracture were identified during 2005–2012. Fracture site was classified by hospital diagnosis (for hip) and/or radiologic findings (for femoral diaphysis), with subtype classification as pathologic, atypical or fragility fracture. Clinical characteristics were ascertained using health plan databases and disease registries. Results: There were 802 women with prior breast cancer who experienced a femur fracture. The mean age at fracture was 80.5±9.6 years, with most fractures (93.8%) occurring in the hip and only 6.2% in the femoral diaphysis. However, diaphyseal fractures accounted for 23.6% of fractures in younger women (age ≤65 years). Pathologic fractures comprised 9.6% of total fractures (56.0% of diaphyseal fractures) and accounted for half the fractures in younger women. An atypical fracture pattern was seen in 1% of all femur fractures and 16.0% of diaphyseal fractures, with prior bisphosphonate exposure in all atypical fracture cases. Conclusion: Most femur fractures in women with prior breast cancer occurred in the hip. Among younger women and those experiencing diaphyseal fractures, a larger proportion were pathologic and some were found to be atypical. Further studies should examine risk factors for femur fracture in women with breast cancer with specific attention to fracture subtype and pharmacologic exposures. [Copyright &y& Elsevier]

Abstract: Objective: Strong earthquakes not only cause death and property damage, but also have continuous repercussions on the survivors' health. This study investigates the impact of the 1999 Chi-chi earthquake to understand how an earthquake disaster affects healthcare utilization differently between individuals who lost co-resident family members (victims) and those who did not (non-victims). Methods: We utilize the household registration records from the Ministry of the Interior as well as claim data from the Bureau of National Health Insurance in Taiwan from 1998 to 2000. Such datasets enable us to identify the relationship of the survivors with the dead and contain the residents' detailed healthcare utilization records. The difference-in-differences method is used to explore the changes in healthcare utilization. Results: Our results indicate that the victims had a higher probability of using inpatient care than the non-victims; and the victims who lost their parents tended to use more inpatient services than the other victims. As for the changes in outpatient utilization, the difference between victims and non-victims, and among victims who lost different family members appears to be statistically insignificant. Conclusion: Compared to non-victims, victims were more likely to use inpatient care after the Earthquake, particularly the victims who lost parents. However, the impacts of the Earthquake on outpatient care are statistically indifferent between victims and non-victims. One possible explanation is that the abundance of primary care and social support services provided by emergency medical assistance teams and/or non-governmental organizations after the Earthquake had substituted for regular outpatient utilization. [Copyright &y& Elsevier]

Background: Poor physical performance and frailty are associated with elevated risks of death and disability. Chronic kidney disease (CKD) is also strongly associated with these outcomes. The risks of poor physical performance and frailty among CKD patients, however, are not well established. Methods: We measured the Short Physical Performance Battery (SPPB; a summary test of gait speed, chair raises and balance; range 0-12) and the five elements of frailty among 1,111 Chronic Renal Insufficiency Cohort participants. Adjusting for demographics and multiple comorbidities, we fit a linear regression model for the outcome of SPPB score and an ordinal logistic regression model for frailty status. Results: Median (interquartile range, IQR) age was 65 (57-71) years, median estimated glomerular filtration rate (eGFR) for non-dialysis patients was 49 (36-62) ml/min/1.73 m2, and median SPPB score was 9 (7-10). Seven percent of participants were frail and 43% were pre-frail. Compared with the SPPB score for eGFR >60 ml/min/1.73 m2, the SPPB was 0.51 points lower for eGFR 30-59; 0.61 points lower for eGFR 15-29, and 1.75 points lower for eGFR <15 (p < 0.01 for all comparisons). eGFR 30-59 (odds ratio, OR 1.45; p = 0.024), eGFR 15-29 (OR 2.02; p = 0.002) and eGFR <15 (OR 4.83; p < 0.001) were associated with worse frailty status compared with eGFR >60 ml/min/1.73 m2. Conclusions: CKD severity was associated with poor physical performance and frailty in a graded fashion. Future trials should determine if outcomes for CKD patients with frailty and poor physical performance are improved by targeted interventions. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Using Taiwan's Labor Insurance dataset and the difference-in-differences model, this study investigates the possible incentives of utilizing the average insured monthly earnings for the period beginning 3 years prior to retirement as the basis for old-age benefit calculations. In the study, those who had retired in 2007 were categorized into the experimental group, while those whowere qualified to retire but had not retired for the ensuing 3 years were categorized into the control group. The results indicate that after controlling for all influential factors such as gender and years of service, the incentive displayed a positive impact. On average, it had increased the insured earnings by 10.7%. Changing the benefit calculation formula to using the average monthly amounts of the highest 60 months of insured earning would not generate much impact. Using a much longer period as the basis for benefit calculation can help to alleviate or even eliminate the incentive impact, thus removing the extra financial burden caused by the incentive mechanism embedded in the benefit calculation formula of the labor insurance system. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the spectrum and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) occurring with oral bisphosphonate therapy. Materials and Methods: We assembled a retrospective cohort of patients who had developed oral BRONJ according to the 2009 American Association of Oral and Maxillofacial Surgeons criteria and received care within Kaiser Permanente, Northern California, during 2004 to 2011. Patients with intravenous bisphosphonate exposure were excluded. The demographic factors, comorbidities, pharmacologic exposure, maxillofacial findings, and outcomes were ascertained from the clinical and radiologic records. Results: We identified 30 cases of oral BRONJ (median age 77 years, 87% women). All had received oral bisphosphonate for osteoporosis/osteopenia (median duration 4.4 years, interquartile range 1.9 to 6.6). More than one half (57%) had comorbidities or relevant drug exposure, including rheumatoid arthritis, diabetes, glucocorticoid therapy, and disease-modifying antirheumatic medications. Extractions preceded BRONJ in 17 patients and trauma in 3; 10 developed BRONJ spontaneously. Overall, 83% had healed within 3 to 52 months, although the relative rate of healing varied by antecedent factor and/or the presence of comorbid conditions/exposures. Nearly all patients with trauma-related and spontaneous BRONJ healed within 1 year (median 7.0 and 7.5 months, respectively) compared with those developing BRONJ after extraction, in whom the median time to healing was 18 months (P < .0001). Patients with relevant comorbidities had a lower probability of healing (P = .0002) and a longer median time to healing (20 months) than patients without comorbidities (7.5 months). Conclusions: We found that postextraction patients and those with comorbid conditions/exposures showed refractory BRONJ with prolonged healing times. Practitioners should be aware that the BRONJ clinical course and outcome varies depending on the antecedent factor and comorbidity status. [Copyright &y& Elsevier]

Abstract: Area under the receiver operating characteristics (AUROC) curve is often used to evaluate risk models. However, reclassification tests provide an alternative assessment of model performance. We performed both evaluations on results from FRAX (World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK), a fracture risk tool, using Kaiser Permanente Northern California women older than 50yr with bone mineral density (BMD) measured during 1997–2003. We compared FRAX performance with and without BMD in the model. Among 94,489 women with mean follow-up of 6.6yr, 1579 (1.7%) sustained a hip fracture. Overall, AUROCs were 0.83 and 0.84 for FRAX without and with BMD, suggesting that BMD did not contribute to model performance. AUROC decreased with increasing age, and BMD contributed significantly to higher AUROC among those aged 70yr and older. Using an 81% sensitivity threshold (optimum level from receiver operating characteristic curve, corresponding to 1.2% cutoff), 35% of those categorized above were reassigned below when BMD was added. In contrast, only 10% of those categorized below were reassigned to the higher risk category when BMD was added. The net reclassification improvement was 5.5% (p <0.01). Two versions of this risk tool have similar AUROCs, but alternative assessments indicate that addition of BMD improves performance. Multiple methods should be used to evaluate risk tool performance with less reliance on AUROC alone. [Copyright &y& Elsevier]

We observed an independent association between vitamin D insufficiency and higher carotid intima-media thickness in a cross-sectional analysis of 139 HIV-infected persons. If confirmed, these findings support a clinical trial of vitamin D supplementation to reduce cardiovascular events in HIV-infected persons. [ABSTRACT FROM AUTHOR]

Purpose: Radiographic features in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) are well described, but less is known in bisphosphonate-exposed individuals with stage 0 disease (clinical symptoms without exposed necrotic bone) considered at risk for BRONJ. We sought to characterize radiographic findings in a subgroup of patients with concerning clinical symptoms and bisphosphonate exposure to identify imaging features that may presage development of BRONJ. Materials and Methods: A dental symptom survey was returned by 8,572 Kaiser Permanente Health Plan members receiving chronic oral bisphosphonate therapy, and 1,005 patients reporting pertinent dental symptoms or complications after dental procedures were examined. Those without BRONJ but with concerning symptoms were referred for clinical evaluation, including imaging. Among the subset who received maxillofacial imaging, we identified those with stage 0 disease and abnormal radiographic features. Results: There were a total of 30 patients without exposed bone but with concerning symptoms who received maxillofacial imaging (panoramic radiography or computed tomography) in the context of clinical care. Among these 30 patients, 10 had stage 0 disease with similar radiographic features of regional or diffuse osteosclerosis in clinically symptomatic areas, most with extension beyond the involved site. Other findings in these 10 patients included density confluence of cortical and cancellous bone, prominence of the inferior alveolar nerve canal, markedly thickened and sclerotic lamina dura, uniform periradicular radiolucencies, cortical disruption, lack of bone fill after extraction, and a persisting alveolar socket. None had exposed bone develop during 1-year follow-up. The remaining 20 patients had normal or localized radiographic findings consistent with odontogenic pathology. Conclusion: In 10 of 30 symptomatic patients referred for clinical evaluation and imaging, a consistent finding was conspicuous osteosclerosis in clinically symptomatic areas characteristic of stage 0 disease. These data support the need to better understand radiographic features associated with bisphosphonate exposure and to determine whether osteosclerosis is a specific finding indicative of the risk for progression to BRONJ. [Copyright &y& Elsevier]

Reports on a study of the enlargement of the dorsocervical fat pad (buffalo hump) in men with HIV-1 infection. The speculation that the finding is associated with protease-inhibitor treatment; Methods; Findings; Interpretation.

The article offers information on several trends in long-term oral bisphosphonate use. Topics discussed include information on the concerns for rare adverse side effects and revised national practice guidelines reducing treatment of low-risk women; examines the importance of late non-adherence in long-term bisphosphonates continuation; and the temporal reductions in long-term bisphosphonates continuation.

Background: Bisphosphonate (BP) therapy has been associated with atypical femur fracture (AFF). However, the threshold of treatment duration leading to increased AFF risk is unclear. In a retrospective cohort of older women initiating BP, we compared the AFF risk associated with treatment for at least three years to the risk associated with treatment less than three years.Methods: We used observational data from a large population of female members of an integrated healthcare system who initiated oral BP during 2002-2014. Women were retrospectively followed for incident AFF confirmed by radiologic adjudication. Demographic data, pharmacologic exposures, comorbidity, bone density, and fracture history were ascertained from electronic health records. Inverse probability weighting was used to estimate risk differences comparing the cumulative incidence (risk) of AFF if women discontinued BP within three years to the cumulative incidence of AFF if women continued BP for three or more years, adjusting for potential time-dependent confounding by the aforementioned factors.Results: Among 87,820 women age 45-84 years who initiated BP (mean age 68.6, median T-score - 2.6, 14% with prior major osteoporotic fracture), 16,180 continued BP for three or more years. Forty-six confirmed AFFs occurred during follow-up in the two groups. AFF-free survival was greater for BP treatment < 3 years compared to treatment ≥3 years (p = 0.004 comparing areas under survival curves). At five years, the risk of AFF was 27 per 100,000 (95% confidence interval, CI: 8-46) if women received BP treatment < 3 years and 120 per 100,000 (95% CI: 56-183) if women received BP treatment ≥3 years (risk difference 93 per 100,000, 95% CI: 30-160). By ten years, the risks were 27 (95% CI: 8-46) and 363 (95% CI: 132-593) per 100,000 for BP treatment < 3 and ≥ 3 years, respectively (risk difference 336 per 100,000, 95% CI: 110-570).Conclusions: Bisphosphonate treatment for 3 or more years was associated with greater risk of AFF than treatment for less than 3 years. Although AFFs are uncommon among BP-treated women, this increased risk should be considered when counseling women about long-term BP use. Future studies should further characterize the dose-response relationship between BP duration and incident AFF and identify patients at highest risk. [ABSTRACT FROM AUTHOR]

Context The association between bone mineral density (BMD) and breast arterial calcification (BAC) remains poorly understood and controversial. Objective The objective of this article is to examine the association between BMD and BAC in a large cohort of postmenopausal women undergoing routine mammography. Design A cross-sectional analysis of baseline data from a multiethnic cohort was performed. Setting The setting for this analysis is an integrated health care delivery system in Northern California in the United States. Patients A total of 1273 women age 60 to 79 years (mean age, 67 years) were recruited within 12 months of screening mammography. Main outcome measure A BAC score (mg) was obtained from digital mammograms using a novel densitometry method. BAC presence was defined as a BAC score greater than 0 mg, and severe BAC as a BAC score greater than 20 mg. Results Overall, 53% of women had osteopenia and 21% had osteoporosis. The prevalence of BAC greater than 0 mg was 29%, 30%, and 29% among women with normal BMD, osteopenia, and osteoporosis, respectively (P  = 0.98). The prevalence of BAC greater than 20 mg was 5%, 3%, and 5% among women with normal BMD, osteopenia and osteoporosis, respectively (P  = .65). The odds ratios (ORs) of BAC greater than 0 mg vs BAC = 0 mg after multivariable adjustment were 1.09 (95% CI, 0.81-1.48; P  = .54) for osteopenia and 0.99 (95% CI, 0.69-1.48; P  = .98) for osteoporosis. The adjusted ORs for BAC greater than 20 mg vs BAC 20 mg or less were 1.03 (95% CI, 0.52-2.01; P  = .93) for osteopenia and 1.89 (95 CI, 0.81-4.47; P  = .14) for osteoporosis. Conclusion Our findings do not support an association of either osteopenia or osteoporosis with BAC presence or severity among postmenopausal women. [ABSTRACT FROM AUTHOR]

Background: Few large cohort studies have examined the prevalence of diabetes mellitus (DM), hypertension (HTN), coronary artery disease (CAD), obesity, and smoking among middle-aged and older adults in the major Asian-American ethnic groups and Native Hawaiian/Pacific Islanders (PIs). The aim of this study was to evaluate how prevalence of these conditions and risk factors differs across Asian-American and PI ethnic groups and compares with an aggregated All Asian-American racial group.Methods: This study used a cohort of 1.4 million adults aged 45 to 84 who were Kaiser Permanente Northern California health plan members during 2016. The cohort included approximately 274,910 Asian-Americans (Chinese, Filipino, Japanese, Korean, Southeast Asian, South Asian, other), 8450 PIs, 795,080 non-Hispanic whites, 107,200 blacks, and 210,050 Latinos. We used electronic health record data to produce age-standardized prevalence estimates of DM, HTN, CAD, obesity (using standard and Asian thresholds), and smoking for men and women in all racial/ethnic subgroups and compared these subgroups to an aggregated All Asian-American racial group and to whites, blacks, and Latinos.Results: We found large differences in health burden across Asian-American ethnic subgroups. For both sexes, there were 16 and > 22 percentage point differences between the lowest and highest prevalence of DM and HTN, respectively. Obesity prevalence among Asian subgroups (based on an Asian BMI ≥ 27.5 kg/m2 threshold) ranged from 14 to 39% among women and 21 to 45% among men. Prevalence of smoking ranged from 1 to 4% among women and 5 to 14% among men. Across all conditions and risk factors, prevalence estimates for Asian-American and PI ethnic groups significantly differed from those for the All Asian-American group. In general, Filipinos and PIs had greater health burden than All Asians, with prevalence estimates approaching those of blacks.Conclusions: In a population of middle-aged and older adult Northern California health plan members, we found substantive differences in prevalence of chronic cardiovascular conditions, obesity, and smoking across Asian-American ethnic groups and between Asian-American ethnic groups and an aggregated All Asian racial group. Our study confirms that reporting statistics for an aggregated Asian-American racial group masks meaningful differences in Asian-American ethnic group health. [ABSTRACT FROM AUTHOR]

Summary: Background: Limited research on alanine aminotransferase (ALT) screening for metabolic dysfunction‐associated steatotic liver disease (MASLD) among US Asian/Pacific Islander (PI) children necessitates investigation in this heterogeneous population. Objective: Examine ALT elevation among Asian/PI children with overweight or obesity. Methods: Elevated ALT prevalence (clinical threshold) and association with body mass index ≥85th percentile were compared among 18 402 Asian/PI and 25 376 non‐Hispanic White (NHW) children aged 9–17 years using logistic regression. Results: ALT elevation was more prevalent among Asian/PI (vs. NHW) males with overweight (4.0% vs. 2.7%), moderate (7.8% vs. 5.3%) and severe obesity (16.6% vs. 11.5%), and females with moderate (5.1% vs. 3.0%) and severe obesity (10.2% vs. 5.2%). Adjusted odds of elevated ALT were 1.6‐fold and ~2‐fold higher for Asian/PI (vs. NHW) males and females (with obesity), respectively. Filipino, Chinese and Southeast Asian males had 1.7–2.1‐fold higher odds, but Native Hawaiian/PI (NHPI) and South Asian males did not significantly differ (vs. NHW). Filipina and Chinese females with obesity had >2‐fold higher odds, Southeast and South Asian females did not differ and NHPI findings were mixed (vs. NHW). Conclusion: High elevated ALT prevalence among Asian/PI children with overweight and obesity emphasizes the need for MASLD risk assessment and examination of ethnic subgroups. [ABSTRACT FROM AUTHOR]

Background: Contemporary data comparing weight status and diabetes (DM) prevalence among U.S. East Asians and Filipinos are limited. Methods: Among 23,050 Chinese and 28,201 Filipinos aged 45-64 years (mean age 55±6) with a 2016 outpatient visit in a U.S. integrated healthcare delivery system, body mass index (BMI) and DM prevalence (based on clinical diagnosis and pharmacotherapy) were ascertained. BMI was classified using Asian-specific thresholds: healthy or underweight (BMI <23), overweight (23-27.4) and obese (≥27.5 kg/m2). Differences were examined by subgroups and log-binomial regression was used to examine the independent association of ethnicity and DM risk. Results: Among Chinese women (14,871) and men (8,179) and Filipino women (18,406) and men (9,795), overweight/obesity was higher in men vs. women and Filipino vs. Chinese (Figure, BMI distribution). Obesity was highest in Filipino men (50%). DM prevalence was highest in those with obesity; however, Filipinos of both sexes had higher DM prevalence across all weight categories (Figure) compared to Chinese, with a relative risk of 1.7 (CI 1.6-1.8), adjusting for age, BMI and sex. Conclusion: Filipino adults have substantially higher BMI and independently higher risk of DM compared to Chinese adults. While limited to adults receiving healthcare, the data highlight the need for heightened DM surveillance and targeted care in high risk ethnic populations. Disclosure: K. Gu: None. N.P. Gordon: None. M. Chandra: None. G. Lau: None. J.R. Gonzalez: None. J.C. Lo: Research Support; Self; Amgen Inc. Research Support; Spouse/Partner; GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Sanofi-Aventis. Research Support; Self; Sanofi-Aventis. Funding: Kaiser Permanente Northern California [ABSTRACT FROM AUTHOR]