Therapeutic applications of germline testing for cancer predisposition genes in Asia in the real world.

BACKGROUND: Germline genetic testing is traditionally carried out in patients suspected with hereditary cancer syndrome for enhanced cancer surveillance and/or preventive strategies, but is increasingly carried out for therapeutic indications. MATERIALS AND METHODS: We conducted a retrospective review of patients who underwent germline genetic testing at our centre to determine the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility. RESULTS: From 2000 to 2022, 1154 cancer patients underwent germline testing, with the majority (945/1154) tested with multi-gene panels. Four hundred and eleven (35.6%) patients harboured a PGV and 334 (81%) were clinically actionable. BRCA1/2 accounted for 62.3% of actionable mutations, followed by mismatch repair (18%), and other homologous recombination repair (HRR) genes (19.7%). One hundred and fifty-two germline-positive patients have advanced cancers, and 79 received germline-directed therapies (poly ADP ribose polymerase inhibitors = 75; immunotherapy = 4). Median duration of immunotherapy and poly ADP ribose polymerase were 20.5 months (range 5-40 months) and 8 months (range 1-76 months), respectively. Among BRCA/HRR mutation carriers who received platinum-based chemotherapy, pathological complete response rate in the neoadjuvant setting was 53% (n = 17 breast cancers) and objective response rate was >80% in the advanced setting (n = 71). CONCLUSIONS: One-third of cancer patients tested carried a PGV and ∼80% were clinically actionable. Three-quarters of germline-positive advanced cancer patients received germline-directed therapies in the real world, underscoring the practical utility of germline testing to guide cancer therapeutics.

What influences use of dental services by the Korean disabled people? The role of perceived barriers in dental care system.

OBJECTIVE: To identify the perceived barriers to dental care for disabled people in South Korea using the revised Andersen's model of access to health care. BASIC RESEARCH DESIGN: Cross-sectional analytic interview study. PARTICIPANTS: Korean people with a disability residing in residential facilities, or those at home who attend vocational rehabilitation facilities, special schools, or welfare facilities, were sampled from Seoul and non-Seoul areas in 2016 and were interviewed face-to-face. In total, 456 disabled Koreans, or their primary caregivers participated. RESULTS: Household income, disability duration and perceived barriers in the dental care system were perceived to impact on dental care utilisation, while the need for dental care services did not significantly explain the use of dental care by disabled people in South Korea. Those with low household incomes were less likely to use dental care services, compared to people with moderate and high household incomes. As disability duration increased, disabled people were more likely to use dental services. Those who perceived the barriers to dental care as higher were less likely to use dental services. CONCLUSION: These data suggest that policies are needed to support disabled people with low household incomes. Lowering barriers in the dental care system may encourage people with disabilities to access timely and adequate dental services.

Effect of leg-length discrepancy following total hip arthroplasty on collapse of the contralateral hip in bilateral non-traumatic osteonecrosis of the femoral head.

AIMS: The purpose of this study was to examine whether leg-length discrepancy (LLD) following unilateral total hip arthroplasty (THA) affects the incidence of contralateral head collapse and subsequent THA in patients with bilateral osteonecrosis, and to determine factors associated with subsequent collapse. PATIENTS AND METHODS: We identified 121 patients with bilateral non-traumatic osteonecrosis who underwent THA between 2003 and 2011 to treat a symptomatic hip, and who also exhibited medium-to-large lesions (necrotic area ≥ 30%) in an otherwise asymptomatic non-operated hip. Of the 121 patients, 71 were male (59%) and 50 were female (41%), with a mean age of 51 years (19 to 71) at the time of initial THA. All patients were followed for at least five years and were assessed according to the presence of a LLD (non-LLD vs LLD group), as well as the LLD type (longer non-operated side vs shorter non-operated side group). RESULTS: Overall, 68 hips (56%) became painful and progressed to collapse at a mean of 2.6 years (0.2 to 13.8), resulting in 59 THAs (49%). The five-year collapse-free survival rate for the non-LLD group was 59% (95% confidence interval (CI) 46.8 to 71.8) compared with 45% (95% CI 32.9 to 57.5) for the LLD group (p = 0.036), and 66% (95% CI 55.2 to 77.2) for the longer non-operated side group compared with 32% (95% CI 19.1 to 44.9) for the shorter non-operated side group (p < 0.001). Multivariate regression analyses found that large lesions had a higher risk of collapse than medium-size lesions (odds ratio (OR) 4.19, 95% confidence interval (CI) 1.69 to 10.38; p = 0.002). Meanwhile, patients with a LLD < 3 mm (OR 0.20, 95% CI 0.08 to 0.52; p = 0.001) or a longer non-operated leg (OR 0.11, 95% CI 0.04 to 0.28; p < 0.001) after THA were less likely to experience a subsequent collapse. CONCLUSION: We found that LLD may be a modifiable risk factor for femoral head collapse. Minimizing LLD and particularly avoiding a shorter non-operated limb after THA may lead to a lower risk of collapse of the asymptomatic hip in patients with bilateral non-traumatic osteonecrosis. Cite this article: Bone Joint J 2019;101-B:303-310.

Tumor molecular profiling of responders and non-responders following pembrolizumab monotherapy in chemotherapy resistant advanced cervical cancer.

Optimal treatment for advanced cervical cancer after first line chemotherapy remains undefined. Immune checkpoint inhibition with pembrolizumab, a programmed cell death protein 1(PD-1) inhibitor, is under investigation. We analyzed the micro-environmental and molecular genetic profile of tumors from 4 patients with metastatic cervical cancer treated with off-label second-line pembrolizumab in an effort to identify predictive biomarkers. All patients received 2 mg/kg of pembrolizumab, 3-weekly until disease progression. Immunohistochemistry(IHC) for PD-1, PD-L1, CD3 and CD8, as well as next generation sequencing (NGS) for 50 cancer-related genes were performed on tumor samples. All patients tolerated treatment well with no discontinuation of treatment due to toxicity. One patient experienced dramatic and prolonged partial response, and remains stable on pembrolizumab with a progression free survival (PFS) of 21 months at the time of reporting of this series. Three patients experienced disease progression as best response. In the exceptional responder, there was no tumoral expression of PD-L1, however, combined positive score (CPS) for PD-L1 was 1 and we identified somatic mutations in ERBB4(R612W), PIK3CA(E542K) and RB1(E365K). In 2 patients, despite progressive disease defined by RECIST v1.1, symptom stabilization on pembrolizumab was observed. The tumors of both patients had PD-1 expression in ≥1% of stromal lymphocytes. All patients with response or clinical benefit had CPS for PD-L1 ≥ 1. NGS revealed PIK3CA mutations in 3 tumors. Pembrolizumab is a promising therapeutic option in advanced cervical cancer. Further evaluation of biomarkers may guide optimal patient selection.

The biological response to laser-aided direct metal-coated Titanium alloy (Ti6Al4V).

OBJECTIVES: Laser-engineered net shaping (LENS) of coated surfaces can overcome the limitations of conventional coating technologies. We compared the in vitro biological response with a titanium plasma spray (TPS)-coated titanium alloy (Ti6Al4V) surface with that of a Ti6Al4V surface coated with titanium using direct metal fabrication (DMF) with 3D printing technologies. METHODS: The in vitro ability of human osteoblasts to adhere to TPS-coated Ti6Al4V was compared with DMF-coating. Scanning electron microscopy (SEM) was used to assess the structure and morphology of the surfaces. Biological and morphological responses to human osteoblast cell lines were then examined by measuring cell proliferation, alkaline phosphatase activity, actin filaments, and RUNX2 gene expression. RESULTS: Morphological assessment of the cells after six hours of incubation using SEM showed that the TPS- and DMF-coated surfaces were largely covered with lamellipodia from the osteoblasts. Cell adhesion appeared similar in both groups. The differences in the rates of cell proliferation and alkaline phosphatase activities were not statistically significant. CONCLUSIONS: The DMF coating applied using metal 3D printing is similar to the TPS coating, which is the most common coating process used for bone ingrowth. The DMF method provided an acceptable surface structure and a viable biological surface. Moreover, this method is automatable and less complex than plasma spraying.Cite this article: T. Shin, D. Lim, Y. S. Kim, S. C. Kim, W. L. Jo, Y. W. Lim. The biological response to laser-aided direct metal-coated Titanium alloy (Ti6Al4V). Bone Joint Res 2018;7:357-361. DOI: 10.1302/2046-3758.75.BJR-2017-0222.R1.

A systematic review of methods to measure family co-participation in physical activity.

The family environment is key in influencing children's health behaviours. Encouraging family co-participation in physical activity may therefore be an effective approach to increasing children's physical activity levels. Yet, little is known about how to best assess family co-participation in physical activity. This review summarizes methods to measure family co-participation in physical activity, which was defined as joint physical activities including at least one healthy child (0-18 years) and one other family member. Methods were identified through a systematic literature search, cross-referencing pre-selected reviews and contacting research groups. Thirty-seven measurement methods were included. Questionnaires were the most common method used, with the majority assessing frequency of co-participation and few also assessing duration and type. Reliability and internal consistency of scales were often reported, but rarely specified for the item(s) relevant to co-participation. Other methods of measuring co-participation included diaries, event history calendars, direct observations and accelerometry combined with diary, ecological momentary assessment or global positioning systems (GPS). Whilst a large number of measurement methods of family co-participation in physical activity exist, few are comprehensive and/or report acceptable psychometric properties. Future work should focus on reaching consensus in defining family co-participation in physical activity, and subsequently developing reliable and valid measures.

Predisposing factors associated with atypical femur fracture among postmenopausal Korean women receiving bisphosphonate therapy: 8 years' experience in a single center.

The risk factors for atypical femur fracture in patients exposed to bisphosphonates for at least 1 year were examined. Prolonged and continuous use of bisphosphonates, long-term use of glucocorticoids, and a higher body mass index were associated with increased risk of atypical femur fracture. INTRODUCTION: The purpose of the present study is to determine whether rheumatoid arthritis (RA) and other clinical factors are associated with an increased risk of bisphosphonate (BP)-related atypical femur fracture (AFF). METHODS: A retrospective nested case-control study of patients who had taken BPs for at least 1 year was conducted. Patients with AFF were identified by reviewing surgical and radiographic records. Three controls with no history of AFFs were randomly selected and age- and sex-matched to each patient with AFFs. Cox proportional hazard models were used to analyze the independent contribution of risk factors to BP-related AFF. RESULTS: Among the 35,104 patients prescribed BPs for at least 1 year, 43 females (mean age, 68 years) suffered AFFs (0.12%). Patients with AFFs were exposed to BPs for a mean of 7.3 years. Patients with AFFs were exposed to BPs for longer than those without AFFs and continued treatment without a drug holiday. More patients with AFF than controls had taken glucocorticoids and disease-modifying anti-rheumatic drugs. Multivariate Cox regression analyses estimated that long-term use of glucocorticoids, prolonged exposure to BP without cessation, and every 1 kg/m2 increase in the body mass index (BMI) increased the hazard ratio for AFFs by 3.0, 5.2, and 1.2, respectively. CONCLUSIONS: Prolonged and continuous use of BPs, long-term use of glucocorticoids, and a higher BMI increase the risk of AFFs. Switching long-term BP and glucocorticoid users to other bone-protective agents should be considered.

Preventing childhood obesity in Asia: an overview of intervention programmes.

The rapid economic growth in Asia in the past few decades has contributed to the global increase in childhood obesity prevalence. Yet, little is known about obesity prevention efforts in this region. This systematic review provides an overview of child obesity prevention programmes in Asia. Searches were performed in six electronic databases. Out of 4,234 studies, 17 were included, among them 11 controlled trials (of which five were randomized). Only one study was published before 2007. Identified studies were predominantly conducted in China and Thailand and targeted primary school children in a school setting. Most studies implemented different programmes, frequently targeting behavioural modification through nutrition/health education lectures and/or physical activity sessions. Programme effects related to obesity outcome measures were mixed. Most substantial effects were found for outcomes such as improved health knowledge and/or favourable lifestyle practices. The relatively small number of relevant publications in Asia highlights the need for scientific evaluations of existing and future programmes. This will help ensure the implementation and dissemination of evidence-based approaches that have been proven to be effective in the Asian context. Targeting preschool settings and applying a comprehensive multisectoral approach may increase the effectiveness and sustainability of childhood obesity prevention programmes.

Lytic to temperate switching of viral communities.

Microbial viruses can control host abundances via density-dependent lytic predator-prey dynamics. Less clear is how temperate viruses, which coexist and replicate with their host, influence microbial communities. Here we show that virus-like particles are relatively less abundant at high host densities. This suggests suppressed lysis where established models predict lytic dynamics are favoured. Meta-analysis of published viral and microbial densities showed that this trend was widespread in diverse ecosystems ranging from soil to freshwater to human lungs. Experimental manipulations showed viral densities more consistent with temperate than lytic life cycles at increasing microbial abundance. An analysis of 24 coral reef viromes showed a relative increase in the abundance of hallmark genes encoded by temperate viruses with increased microbial abundance. Based on these four lines of evidence, we propose the Piggyback-the-Winner model wherein temperate dynamics become increasingly important in ecosystems with high microbial densities; thus 'more microbes, fewer viruses'.

Low-flow hypothermic crystalloid perfusion is superior to cold storage during prolonged heart preservation.

BACKGROUND: Preservation of donor hearts for transplantation has traditionally been performed with the use of static cold storage. We have developed and tested a novel gravity-powered system of cold crystalloid perfusion for prolonged donor heart preservation. METHODS: Greyhounds were anesthetized; their hearts were arrested with cold cardioplegic solution and excised. Hearts were allocated to 12 hours of perfusion preservation (n = 6) or cold storage in ice (n = 5). Non-preserved hearts (n = 5) served as a normal reference group. Perfusion hearts were perfused (20 mL/min, 8-12°C) with a novel oxygenated nutrient-containing preservation solution. After preservation, the recovery of the hearts was assessed in a blood-perfused working heart rig over 2 hours in terms of function, blood lactate level, myocardial adenosine triphosphate, and histology. RESULTS: After 2 hours of reperfusion, in comparison with cold storage hearts, perfused heart function curves showed superior recovery of cardiac output (P = .001), power (P = .001), and efficiency (0.046 ± 0.01 vs 0.004 ± 0.003 joules/mL O2, P = .034). Myocardial adenosine triphosphate content (mmol/mg protein) was reduced significantly from the normal level of 26.5 (15.9, 55.8) to 5.08 (0.50, 10.4) (P = .049) in cold storage hearts but not in perfused hearts. Over a period of 2 hours, lactate levels in the blood perfusate were significantly lower in the perfusion group than in the cold storage group (P < .05). CONCLUSIONS: Continuous hypothermic crystalloid perfusion provides myocardial preservation superior to cold storage for long-term heart preservation, with potential applicability to marginal and donation after circulatory death hearts.

Quantifying the natural history of breast cancer.

BACKGROUND: Natural history models of breast cancer progression provide an opportunity to evaluate and identify optimal screening scenarios. This paper describes a detailed Markov model characterising breast cancer tumour progression. METHODS: Breast cancer is modelled by a 13-state continuous-time Markov model. The model differentiates between indolent and aggressive ductal carcinomas in situ tumours, and aggressive tumours of different sizes. We compared such aggressive cancers, that is, which are non-indolent, to those which are non-growing and regressing. Model input parameters and structure were informed by the 1978-1984 Ostergotland county breast screening randomised controlled trial. Overlaid on the natural history model is the effect of screening on diagnosis. Parameters were estimated using Bayesian methods. Markov chain Monte Carlo integration was used to sample the resulting posterior distribution. RESULTS: The breast cancer incidence rate in the Ostergotland population was 21 (95% CI: 17-25) per 10 000 woman-years. Accounting for length-biased sampling, an estimated 91% (95% CI: 85-97%) of breast cancers were aggressive. Larger tumours, 21-50 mm, had an average sojourn of 6 years (95% CI: 3-16 years), whereas aggressive ductal carcinomas in situ took around half a month (95% CI: 0-1 month) to progress to the invasive ≤10 mm state. CONCLUSION: These tumour progression rate estimates may facilitate future work analysing cost-effectiveness and quality-adjusted life years for various screening strategies.

Analysis of the association between air pollution and allergic diseases exposure from nearby sources of ambient air pollution within elementary school zones in four Korean cities.

The objectives of this study were to survey elementary school students regarding the environmental conditions of their elementary schools and to assess the relationship between air pollution and allergic disease using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Therefore, this study was designed as a cross-sectional study. In this study, seven elementary schools were selected and they were classified into three categories. The selection included one school with no traffic-related or other pollutants, three with traffic-related pollutants, and three with traffic-related and other pollutants from industrial and filling station sources. The ISAAC questionnaire survey was given to all of the students except to those in the 1st grade who were presumed to be less likely to be exposed to the school environment than the remainder of the students attending those seven schools. The assessment of allergic disease was conducted on a total of 4,545 students. Three school zones with critical exposure were selected within each school and they were evaluated based on the levels of black carbon (BC), PM10, SO2, NO2, and O3. There was a significant increase in the risks based on the odds ratios of treatment experiences (within 1 year) for allergy-related diseases such as asthma and allergic rhinitis (a) in the school group with traffic-related pollutants and the school group with complex pollutants were 2.12 (1.41-3.19) and 1.59 (1.06-2.37), respectively, in comparison to the school groups with no exposure to pollutants. This was determined based on the odds ratio of symptoms and treatment experiences for allergy-related diseases by group based on the home town zone as a reference. Also, in the case of atopic dermatitis, the odds ratio of treatment experiences (within 1 year) was 1.42 (1.02-1.97), which indicated elevated risks compared to the students in the S1 school. A regression analysis was used to assess the relationship between the substances and the symptomatic experiences within the last year. There were significant increases in the odds ratio of the symptoms associated with allergic rhinitis and the BC and SO2 in the complex pollution areas. The results of the assessment of the relationship between atopic dermatitis-associated symptoms and O3 showed that the odds ratio increased with statistical significance.

Diversity and decay ability of basidiomycetes isolated from lodgepole pines killed by the mountain pine beetle.

When lodgepole pines (Pinus contorta Douglas ex Louden var. latifolia Engelm. ex S. Watson) that are killed by the mountain pine beetle (Dendroctonus ponderosae) and its fungal associates are not harvested, fungal decay can affect wood and fibre properties. Ophiostomatoids stain sapwood but do not affect the structural properties of wood. In contrast, white or brown decay basidiomycetes degrade wood. We isolated both staining and decay fungi from 300 lodgepole pine trees killed by mountain pine beetle at green, red, and grey stages at 10 sites across British Columbia. We retained 224 basidiomycete isolates that we classified into 34 species using morphological and physiological characteristics and rDNA large subunit sequences. The number of basidiomycete species varied from 4 to 14 species per site. We assessed the ability of these fungi to degrade both pine sapwood and heartwood using the soil jar decay test. The highest wood mass losses for both sapwood and heartwood were measured for the brown rot species Fomitopsis pinicola and the white rot Metulodontia and Ganoderma species. The sap rot species Trichaptum abietinum was more damaging for sapwood than for heartwood. A number of species caused more than 50% wood mass losses after 12 weeks at room temperature, suggesting that beetle-killed trees can rapidly lose market value due to degradation of wood structural components.

Degrading ability of oligocyclic aromates by Phanerochaete sordida selected via screening of white rot fungi.

Seventy-nine white rot strains were screened to determine if they had the potential for use in the degradation of oligocyclic aromates (PAHs) by measuring their dye-decoloration rate. Fourteen strains that were selected based on their dye-decoloration rate were then evaluated for the ability to tolerate various levels of PAHs spiked in agar medium. The ability of white rot fungi to degrade 3- or 4-ring PAHs (anthracene, phenanthrene, fluoranthene, pyrene) was determined. Two strains of Phanerochaete sordida (KUC8369, KUC8370) were possible PAHs degraders, degrading a significantly greater amount of phenanthrene and fluoranthene than the culture collection strain P. chrysosporium (a known PAHs degrader). The production of manganese peroxidase, the only extracellular ligninolytic enzyme detected during the cultivation, was evaluated.

Pharmacokinetics and pharmacodynamics of docetaxel with or without ketoconazole modulation in chemonaive breast cancer patients.

BACKGROUND: We previously found 70 mg flat-dose docetaxel coadministered with ketoconazole to modulate CYP3A4 to be the maximum tolerated dose that resulted in comparable docetaxel area under the plasma concentration-time curve (AUC) as 75-100 mg/m² docetaxel. PATIENTS AND METHODS: We compared cycle 1 docetaxel pharmacokinetics and pharmacodynamics between ketoconazole-modulated (70 mg flat-dose docetaxel, n = 31) and conventional-dosed docetaxel (75 mg/m², n = 51) in chemonaive breast cancer patients in two sequential phase II studies. RESULTS: Ketoconazole-modulated docetaxel resulted in reduced docetaxel clearance (22.05 ± 8.29 versus 36.52 ± 13.39 l/h, P < 0.001), similar docetaxel AUC (3.93 ± 2.77 versus 3.77 ± 2.70 mg/l·h, P = 0.794) and tumor efficacy (cycle 1 responder 52% versus 55%) and less day 8 neutrophil suppression (1.24 ± 1.02 × 109/l versus 0.47 ± 0.56 × 109/l, P < 0.001), grade 4 neutropenia (32.3% versus 72.0%, P < 0.001) and febrile neutropenia (3.2 versus 23.5%, P = 0.015), compared with conventional-dosed docetaxel. Chinese had the lowest docetaxel clearance, highest AUC and most myelosuppression, followed by Malays and Indians, in response to ketoconazole-modulated docetaxel, while no significant interethnic differences were observed with conventional-dosed docetaxel. CONCLUSIONS: Ketoconazole-modulated docetaxel achieved similar docetaxel AUC and tumor efficacy but reduced neutrophil suppression and febrile neutropenia at ∼40% reduced dose, representing a feasible alternative to conventional-dosed docetaxel. Interethnic differences in CYP3A4 inhibition by ketoconazole exist and are important when evaluating the impact of concomitant medications.

Economic cost of osteoporotic hip fractures in Singapore.

INTRODUCTION: The incidence of osteoporotic hip fractures in Singapore as well as in Asia will gradually increase with an ever ageing population. The objectives of this study were to understand the costs of hip fractures in our community and to analyse the various factors that lead to higher inpatient costs for hip fractures. METHODS: We prospectively reviewed 80 elderly patients with osteoporotic hip fractures. The relevant patients' clinical data was correlated with the inpatient hospitalisation costs. We reviewed the cost and management practices of hip fractures published in the literature and compared them with our findings. RESULTS: We found that our patients treated surgically incurred lower costs and had a shorter inpatient stay compared to those treated conservatively. The mean hospitalisation cost for patients treated surgically was S$10,515 and the mean length of stay was 16 days. We found that the length of stay, a longer delay to surgery, male gender, having ASA 3 score, and development of postoperative complications led to higher inpatient hospital costs. CONCLUSION: With the identification of various clinical factors that are associated with high inpatient costs, we can further shorten our hip fracture patients' stay as well as reduce the hospitalisation costs.

PXR, CAR and HNF4alpha genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients.

Previously studied candidate genes have failed to account for inter-individual variability of docetaxel and doxorubicin disposition and effects. We genotyped the transcriptional regulators of CYP3A and ABCB1 in 101 breast cancer patients from 3 Asian ethnic groups, that is, Chinese, Malays and Indians, in correlation with the pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin. While there was no ethnic difference in docetaxel and doxorubicin pharmacokinetics, ethnic difference in docetaxel- (ANOVA, P=0.001) and doxorubicin-induced (ANOVA, P=0.003) leukocyte suppression was observed, with Chinese and Indians experiencing greater degree of docetaxel-induced myelosuppression than Malays (Bonferroni, P=0.002, P=0.042), and Chinese experiencing greater degree of doxorubicin-induced myelosuppression than Malays and Indians (post hoc Bonferroni, P=0.024 and 0.025). Genotyping revealed both PXR and CAR to be well conserved; only a PXR 5'-untranslated region polymorphism (-24381A>C) and a silent CAR variant (Pro180Pro) were found at allele frequencies of 26 and 53%, respectively. Two non-synonymous variants were identified in HNF4alpha (Met49Val and Thr130Ile) at allele frequencies of 55 and 1%, respectively, with the Met49Val variant associated with slower neutrophil recovery in docetaxel-treated patients (ANOVA, P=0.046). Interactions were observed between HNF4alpha Met49Val and CAR Pro180Pro, with patients who were wild type for both variants experiencing least docetaxel-induced neutropenia (ANOVA, P=0.030). No other significant genotypic associations with pharmacokinetics or pharmacodynamics of either drug were found. The PXR-24381A>C variants were significantly more common in Indians compared to Chinese or Malays (32/18/21%, P=0.035) Inter-individual and inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of the transcriptional regulators PAR, CAR and HNF4alpha cannot account for this variability.

Inadequate dietary calcium intake in elderly patients with hip fractures.

INTRODUCTION: Calcium supplementation and pharmacotherapy are recommended in the preventive management of osteoporosis. Many previous studies report of underdiagnosis and undertreatment of osteoporosis among elderly patients with hip fractures. We undertook this study to determine the dietary calcium levels in our local elderly population who were admitted with hip fractures. METHODS: 77 patients, between the ages of 60 and 98 years of age, and admitted to our department between January 2001 and September 2001 for hip fractures, were studied. The dietary calcium intakes of these patients were determined by a food frequency questionnaire and a detailed diet history. Bone mineral density (BMD) studies were performed on 55 of these patients to confirm the diagnosis of osteoporosis. RESULTS: The mean daily calcium intake was found to be 650 mg. Only six of our hip fracture patients (7.8 percent) had a daily calcium intake above the recommended levels of 1,000 mg per day. For the 55 patients who had BMD performed, only one patient had a BMD within the normal range. 34 patients (64.2 percent) had hip T-scores in the osteoporotic range and 18 patients (33.9 percent) had hip T-scores in the osteopenic range. We found that the patients with BMD in the osteoporotic and osteopenic ranges had no significant difference in the dietary calcium intake. CONCLUSION: The dietary calcium intake of our elderly patients with hip fractures is insufficient. They would benefit from dietary education and calcium supplements to prevent deterioration in bone density and subsequent osteoporotic fractures.