Health equality, race and pharmacogenomics.

Pharmacogenomics is increasingly moving into mainstream clinical practice. Careful consideration must be paid to inclusion of diverse populations in research, translation and implementation, in the historical and social context of population stratification, to ensure that this leads to improvements in healthcare for all rather than increased health disparities. This review takes a broad and critical approach to the current role of diversity in pharmacogenomics and addresses potential pitfalls in order to raise awareness for prescribers. It also emphasizes evidence gaps and suggests approaches that may minimize negative consequences and promote health equality.

[Assessment of pathological biopsy and safety margin of specimens from breast cancer patients with breast conversing surgery].

Breast-conserving surgery (BCS) has now become one of the optimal surgical choices for early invasive breast cancer. The pathological diagnosis of margin in breast-conserving specimen is very important. There is no acknowledge on the approaches of pathological biopsy and safety margin diagnosis of breast conserving surgery. This paper will compare the biopsy and diagnosis methods of breast-conserving surgery specimens between Tianjin Medical University Cancer Institute and Hospital in China and MD Anderson Cancer Center in the United States. We summarize our biopsy method and diagnostic criteria to explore how to accurately evaluate the margin of breast-conserving surgery specimen from a pathological point of view, and to escort a successful breast-conserving surgery.

Scoring System to Triage Patients for Spine Surgery in the Setting of Limited Resources: Application to the Coronavirus Disease 2019 (COVID-19) Pandemic and Beyond.

BACKGROUND: As of May 4, 2020, the coronavirus disease 2019 (COVID-19) pandemic has affected >3.5 million people and touched every inhabited continent. Accordingly, it has stressed health systems worldwide, leading to the cancellation of elective surgical cases and discussions regarding health care resource rationing. It is expected that rationing of surgical resources will continue even after the pandemic peak and may recur with future pandemics, creating a need for a means of triaging patients for emergent and elective spine surgery. METHODS: Using a modified Delphi technique, a cohort of 16 fellowship-trained spine surgeons from 10 academic medical centers constructed a scoring system for the triage and prioritization of emergent and elective spine surgeries. Three separate rounds of videoconferencing and written correspondence were used to reach a final scoring system. Sixteen test cases were used to optimize the scoring system so that it could categorize cases as requiring emergent, urgent, high-priority elective, or low-priority elective scheduling. RESULTS: The devised scoring system included 8 independent components: neurologic status, underlying spine stability, presentation of a high-risk postoperative complication, patient medical comorbidities, expected hospital course, expected discharge disposition, facility resource limitations, and local disease burden. The resultant calculator was deployed as a freely available Web-based calculator (https://jhuspine3.shinyapps.io/SpineUrgencyCalculator/). CONCLUSIONS: We present the first quantitative urgency scoring system for the triage and prioritizing of spine surgery cases in resource-limited settings. We believe that our scoring system, although not all encompassing, has potential value as a guide for triaging spine surgical cases during the COVID pandemic and post-COVID period.

Improving the knowledge and behavior of workplace chemical exposures in Vietnamese-American nail salon workers: a randomized controlled trial.

OBJECTIVES: We assessed the efficacy of trainings with Vietnamese nail salon owners and workers on knowledge and behaviors that could reduce exposures to toxic chemicals in nail products. METHODS: We trained Vietnamese salon owners in California (n = 77) who then trained their workers (n = 200) on best practices. In a cluster randomized controlled trial, we assessed the efficacy of the training on change in knowledge and self-reported behaviors. Data were collected from 2013 to 2016 and analyzed from 2016 to 2017. RESULTS: Compared to the control group, the intervention group had significantly greater increases in knowledge about: safer nail polishes [odds ratio (OR) 3.7 (95% confidence interval (CI) 1.9, 7.2)]; proper ventilation methods (OR 4.2; 95% CI 2.2, 8.1); recommended glove types (OR 3.4; 95% CI 1.9, 6.3); and recommended product handling and storage (OR 4.1; 95% CI 1.7, 9.9). The intervention also increased best practices: using safer nail polishes (OR 3.6; 95% CI 1.9, 6.8); reading product labels (OR 2.6; 95% CI 1.3, 5.0); and wearing long sleeves (OR 2.4; 95% CI 1.3, 4.2). CONCLUSIONS: The owner-to-worker intervention with culturally and linguistically appropriate training for salon owners who then trained workers was effective in promoting knowledge and self-reported behaviors that can reduce workplace chemical exposures.

Effects of testosterone supplementation therapy on lipid metabolism in hypogonadal men with T2DM: a meta-analysis of randomized controlled trials.

Testosterone supplementation may be effective for the treatment of hypogonadism in men with type 2 diabetes mellitus (T2DM), but the evidence from randomized controlled trials (RCTs) is inconclusive. We aimed to systematically summarize results from intervention studies and assess the effects of testosterone supplementation therapy (TST) on lipid metabolism in RCTs of hypogonadal men with T2DM by meta-analysis. PubMed, Embase, and Cochrane Library databases were searched for studies reporting the effect of TST on lipid metabolism in hypogonadal men with T2DM until December 31, 2016. Seven RCTs from 252 trials, enrolling a total of 612 patients in the experimental and control groups with a mean age of 58.5 years, were included in this study. The pooled results of the meta-analysis demonstrated that TST significantly decreased TC and TG levels in hypogonadal men with T2DM compared with the control group, with mean differences (MDs) of -6.44 (95% CI: -11.82 to -1.06; I2  = 28%; p = 0.02) and -27.94 (95% CI: -52.33 to -3.54; I2  = 76%; p = 0.02). Subgroup analyses revealed that the heterogeneity (I2  = 76%) of TG originated from different economic regions, in which economic development, genetic and environmental factors, and dietary habits affect lipid metabolism of human, with a decrease (I2  = 45%) in developed countries. Additionally, subgroup analyses showed that TST increased HDL-C level in developing countries compared with the control group (MD = 2.79; 95% CI: 0.73 to 4.86; I2  = 0%; p = 0.008), but there was no improvement in developed countries (MD = 1.02; 95% CI: -4.55 to 6.60; I2  = 91%; p = 0.72). However, LDL-C levels were not improved consistently. Because the relationship between lipid metabolism and atherosclerosis is unequivocal, TST, which ameliorates lipid metabolism, may decrease the morbidity and mortality of cardiovascular disease in hypogonadal men with T2DM by preventing atherogenesis.

Perfusion weighted imaging in the assessment of the pathology and outcomes of lateral medullary infarction.

This series case report aimed to elucidate the underlying pathology and outcomes of lateral medullary infarction (LMI) using perfusion weighted imaging (PWI). Four patients were diagnosed with LMI based on high-field diffusion-weighted magnetic resonance imaging (MRI-DWI) and PWI. The national institutes of health stroke scale (NIHSS) scores were recorded on days 1, 7, and 30, and the Barthel index was assessed on days 7 and 30. Three patients exhibited relative regional hypoperfusion of medullary lesion in the perfusion maps. Two cases exhibited ipsilateral hypoperfusion in the inferior cerebellum, whereas one patient exhibited a relatively regional hyperperfusion in the medulla oblongata. The LMI patients with a high NIHSS score and low Barthel index on days 7 and 30 exhibited regional hypoperfusion. This report of 4 LMI cases provides preliminary evidence that regional hypoperfusion may contribute to worse outcomes in LMI.

Treatment of childhood acute lymphoblastic leukemia in central America: a lower-middle income countries experience.

BACKGROUND: Five Asociación de Hemato-Oncología de Centroamérica (AHOPCA) countries have used an adapted BFM-based protocol for childhood acute lymphoblastic leukemia (ALL). PROCEDURE: In the AHOPCA-ALL 2008 protocol, patients were stratified by age, white blood cell count, immunophenotype, central nervous system involvement, day 8 prednisone response, and morphologic bone marrow response to induction therapy. Patients at Standard Risk (SR) received a three-drug induction regimen, a reinduction phase, and maintenance with protracted intrathecal therapy. Those at Intermediate (IR) and High Risk (HR) received, in addition, daunorubicin during induction therapy, a consolidation phase and two or three reinduction phases respectively. RESULTS: From August 2008 through July 2012, 1,313 patients were enrolled: 353 in SR, 548 in IR, 412 in HR. During induction therapy, 3.0% of patients died, 2.7% abandoned treatment, 1.1% had resistant ALL, and 93.2% achieved morphological complete remission (CR). Deaths and abandonment in first CR occurred in 2.7% and in 7.0% of patients, respectively. The relapse rate at a median observation time of 2.1 years was 15.0%. At 3 years, the event-free survival (EFS) and overall survival (OS), with abandonment considered as an event, were 59.4% (SE 1.7) and 68.2% (SE 1.6). Three-year EFS was 68.5% (SE 3.0), 62.1% (SE 2.6), and 47.8% (SE 3.2) for SR, IR, and HR groups. Adolescents had a significantly higher relapse rate (P = 0.001). CONCLUSIONS: This experience shows that common international studies are feasible in lower-middle income countries. Toxic deaths, abandonment of treatment, and relapses remain major obstacles to the successful treatment. Alternative treatment strategies may be beneficial.

Universal prophylaxis is cost effective in cytomegalovirus serology-positive kidney transplant patients.

BACKGROUND: The economic merit of universal prophylaxis and preemptive therapy in the management of cytomegalovirus (CMV) infection for serology positive (R+) kidney transplant patients remains undefined. We performed cost effectiveness and cost utility modeling comparing these two approaches. METHODS: The incidence of CMV infection under universal prophylaxis and preemptive therapy was determined among 653 R+ patients from our institution and 416 R+ patients from various clinic trials, respectively. Standardized decision tree analysis and Markov transitional models were used to calculate cost and quality-adjusted life years (QALYs) from the prototypical clinical data and published literature. Incremental cost effectiveness and cost utility were calculated as dollars for one case of infection avoided and one QALY gained over 10 years, respectively. One- and two-way sensitivity analyses were performed. RESULTS: The incidence of CMV infection was 4.1% and 55.5% within the first year after transplant for universal prophylaxis and preemptive therapy, respectively. Compared with preemptive therapy, universal prophylaxis incurred $1464 more in direct cost while saving $7309 in indirect cost, and resulted in a net gain of 0.209 in QALYs per patient over a 10-year period. Thus, universal prophylaxis dominates over preemptive therapy with a cost saving of $27,967 for 1 QALY gained. This cost saving was sensitive to the variation in the rate of CMV infection and disease with each approach. CONCLUSION: Universal prophylaxis in CMV R+ kidney transplant patients is clinically effective and cost saving. It should be considered as the preferred approach.

Depressive symptoms in older female carers of adults with intellectual disabilities.

BACKGROUND: This survey study aims to examine the prevalence and factors associated with depressive symptoms among primary older female family carers of adults with intellectual disabilities (ID). METHOD: In total, 350 female family carers aged 55 and older took part and completed the interview in their homes. The survey package contained standardised scales to assess carer self-reported depressive symptoms, social support, caregiving burden and disease and health, as well as adult and carer sociodemographic information. Multiple linear regressions were used to identify the factors associated with high depressive symptoms in carers. RESULTS: Between 64% and 72% of these carers were classified as having high depressive symptoms. The factors associated with carer self-reported depressive symptoms were carer physical health, social support and caregiving burden; overall, the carer self-reported physical health was a stronger factor associated with depressive symptoms than their physical disease status. The level of the adult with ID's behavioural functioning and the carer age, marital status, employment status, education level and the family income level were not significantly associated with carer depressive symptoms. CONCLUSIONS: The factors identified in this study as correlating with self-reported depressive symptoms suggest that researchers and mental health professionals should collaborate to help improve the physical health and social support networks of the most vulnerable older female family carers. This should reduce depressive symptoms directly among this high-risk group.

Clinical and economic outcomes of rabbit antithymocyte globulin induction in adults who received kidney transplants from living unrelated donors and received cyclosporine-based immunosuppression.

STUDY OBJECTIVE: To evaluate the efficacy, safety, and costs of rabbit antithymocyte globulin (TMG) induction in patients who received kidney transplants from living unrelated donors. DESIGN: Retrospective cohort study. SETTING: Large academic medical center. PATIENTS: Eighty-seven patients who received kidney transplants from living unrelated donors: 40 of the recipients underwent transplantation between January 1, 2003, and December 31, 2004, and did not receive TMG induction (no induction group); 47 underwent transplantation between January 1, 2005, and June 30, 2006, and received TMG induction (induction group). All patients received cyclosporine-based immunosuppression. MEASUREMENTS AND MAIN RESULTS: Biopsy-proven acute rejection, posttransplantation complications, and inpatient hospital costs for the first 12 months after transplantation were compared between groups using standard univariate statistical analyses. Induction significantly decreased the occurrence of biopsy-proven acute rejection versus no induction (2% vs 48%, p<0.001). Fifty percent of rejection episodes in the no induction group required hospitalization, and 46% of rejection episodes required TMG treatment. Slightly elevated initial costs associated with TMG induction were offset by lower costs related to rejection treatment. Total inpatient costs for the 12 months after transplantation were comparable between the groups (no induction $66,038 vs induction $74,183, p>0.05). For the no induction versus induction groups, no significant differences in cytomegalovirus disease (5% vs 6%), malignancy (3% vs 2%), graft failures (5% vs 6%), mortality (5% vs 4%), and serum creatinine concentrations (mean +/- SD 1.4 +/- 0.3 vs 1.5 +/- 0.3 mg/dl) were observed at 12 months (p>0.05 for all comparisons). CONCLUSION: Five-day TMG induction effectively reduced the 1-year acute rejection rate without significantly increasing total inpatient costs or posttransplantation complications among recipients of kidney transplants from living unrelated donors.

Six-month prophylaxis is cost effective in transplant patients at high risk for cytomegalovirus infection.

The risk of late-onset cytomegalovirus (CMV) infection remains a concern in seronegative kidney and/or pancreas transplant recipients of seropositive organs despite the use of antiviral prophylaxis. The optimal duration of prophylaxis is unknown. We studied the cost effectiveness of 6- versus 3-mo prophylaxis with valganciclovir. A total of 222 seronegative recipients of seropositive kidney and/or pancreas transplants received valganciclovir prophylaxis for either 3 or 6 mo during two consecutive time periods. We assessed the incidence of CMV infection and disease 12 mo after completion of prophylaxis and performed cost-effectiveness analyses. The overall incidence of CMV infection and disease was 26.7% and 24.4% in the 3-mo group and 20.9% and 12.1% in the 6-mo group, respectively. Six-month prophylaxis was associated with a statistically significant reduction in risk for CMV disease (HR, 0.35; 95% CI, 0.17 to 0.72), but not infection (HR, 0.65; 95% CI, 0.37 to 1.14). Cost-effectiveness analyses showed that 6-mo prophylaxis combined with a one-time viremia determination at the end of the prophylaxis period incurred an incremental cost of $34,362 and $16,215 per case of infection and disease avoided, respectively, and $8,304 per one quality adjusted life-year gained. Sensitivity analyses supported the cost effectiveness of 6-mo prophylaxis over a wide range of valganciclovir and hospital costs, as well as variation in the incidence of CMV disease. In summary, 6-mo prophylaxis with valganciclovir combined with a one-time determination of viremia is cost effective in reducing CMV infection and disease in seronegative recipients of seropositive kidney and/or pancreas transplants.

Assessment of vehicular pollution in China.

As the motor vehicle population in China continues to increase at an annual rate of approximately 15%, air pollution related to vehicular emissions has become the focus of attention, especially in large cities. There is an urgent need to identify the severity of this pollution in China. Based on an investigation into vehicle service characteristics, this study used a series of driving cycle tests of in-use Chinese motor vehicles for their emission factors in laboratories, which indicated that CO and HC emission factors are 5-10 times higher, and NOx 2-5 times higher, than levels in developed countries. The MOBILE5 model was adapted to the Chinese situation and used to calculate the emission of pollutants from motor vehicles. Results show that vehicle emission is concentrated in major cities, such as Beijing, Guangzhou, Shanghai, and Tianjin. Motor vehicle emissions contribute a significant proportion of pollutants in those cities, with contribution rates of CO and NOx greater than 80% and 40%, respectively, in Beijing and Guangzhou. Urban air quality is far worse than the national ambient air quality standard. In conclusion, although China has a relatively small number of motor vehicles, most of them are concentrated within metropolitan areas, and their emissions are closely related to urban air pollution problems in large cities.

Clinicopathological characteristics of atypical cystic duct (ACD) of the breast: assessment of ACD as a precancerous lesion.

To clarify the clinicopathological features of an atypical cystic duct (ACD) as defined by Tsuchiya's criteria as a precancerous lesion of the breast, we used 200 whole mammary gland serial sections of breast cancer. Forty-four (22%) of the 200 breast cancer patients had ACD breast lesions. The frequency of patients with ACD increased in premenopausal women (P = 0.001). There was no correlation between the ACD-present group and the ACD-absent group for immunohistochemical status of the estrogen receptor (ER), progesterone receptor (PgR), p53, or c-erbB2; Ki-67 labeling index of cancer tissues; size of tumor, or lymph node metastases. A number of ACD lesions displayed continuity to cancer lesions. In 500 serial sections of a paraffin-embedded tissue of a ACD case at 3 microm intervals, an apparent transition from ACD into ductal carcinoma in situ was observed. Immunohistochemical analysis using alpha-smooth muscle actin showed that myoepithelial cells of ACD stained strongly, and their nuclei and cytoplasm were thinning. In 16 of the 44 (36%) ACD-present patients, carcinoma cells stained positive for p53. Within those 16 cases, 12 cases (75%) were positive for p53 in ACD lesions. There was a significant correlation between the expression of p53 protein in malignant cells and ACD (P = 0.001). All 44 ACD lesions had no staining of c-erbB2, regardless of staining in malignant lesions. The mean Ki-67 labeling index of ACD lesions was low (0.3%), suggesting that ACD had a low proliferative rate. We suggest that ACD is the precancerous breast lesion because of a histologic continuum between ACD and malignancy, and because of p53 protein expression in ACD.

Human BAC ends quality assessment and sequence analyses.

End sequences from bacterial artificial chromosomes (BACs) provide highly specific sequence markers in large-scale sequencing projects. To date, we have generated >300,000 end sequences from >186,000 human BAC clones with an average read length of >460 bp for a total of 141 Mb covering approximately 4.7% of the genome. Over 60% of the clones have BAC end sequences (BESs) from both ends representing more than fivefold coverage of the human genome by the paired-end clones. Our quality assessments and sequence analyses indicate that BESs from human BAC libraries developed at The California Institute of Technology (CalTech) and Roswell Park Cancer Institute have similar properties. The analyses have highlighted differences in insert size for different segments of the CalTech library. Problems with the fidelity of tracking of sequence data back to physical clones have been observed in some subsets of the overall BES dataset. The annotation results of BESs for the contents of available genomic sequences, sequence tagged sites, expressed sequence tags, protein encoding regions, and repeats indicate that this resource will be valuable in many areas of genome research.

[Ecological risk assessment and its application].

Ecological risk assessment, closely linked to environmental toxicology, is becoming one of the most widely expanding disciplines in environmental science. A number of frameworks for ecological risk assessment have been developed by the USEPA, Environment Canada and European Commission in recent years. This review described the common elements, the process and steps of ecological risk assessment. In addition to drawing upon the recent published literature, we have developed some examples of applications based on our collective experiences in conducting ecological risk assessments.

Assessment of lesion pathology in multiple sclerosis using quantitative MRI morphometry and magnetic resonance spectroscopy.

Quantitative measurement of MRI-defined brain lesions can provide an index of the extent and activity of disease in multiple sclerosis patients. However, the relationships between these indices and clinical features are not well-understood. Heterogeneity of the pathological changes underlying MRI lesions may be an important factor determining the correlation between MRI lesion volumes and clinical measures. Recent studies have suggested that with magnetic resonance spectroscopy (MRS), it may be possible to define chemical changes that better reflect the pathological changes in multiple sclerosis. Here we report results of combined quantitative brain T2-weighted MRI lesion volume and proton MRS examinations that demonstrate heterogeneity of the chemical pathology underlying brain lesions in patients selected on the basis of similar clinical disability but differing with respect to the presence or absence of clinical relapses. We examined 29 patients with disease characterized by either clear relapses with at least partial remissions (RR) or secondary, chronic progression after an earlier history of a more relapsing and remitting course (SP). Total hemispheric lesion volume was greater (P < 0.04) in the RR (32.5 +/- 20.9 cm3) than in the SP (16.2 +/- 9.0 cm3) patients, despite the longer duration of disease in the latter group. Central brain N-acetyl aspartate: creatine (NAA:Cr) ratios were reduced relative to normal controls (4.0 +/- 0.3, n = 19) by similar amounts in the two patients groups (RR, 3.1 +/- 0.5; SP, 3.2 +/- 0.4; P < 0.0001). The ratio lesion volume:(NAA:Cr) was greater for the RR group (11.7 +/- 9.3 cm3) than for the SP group (5.4 +/- 3.3 cm3, P < 0.05), implying a greater average degree of axonal loss per unit lesion volume defined by MRI for subjects in the SP group or, alternatively, a greater proportion of lesions without axonal damage or loss in the RR group. Our results emphasize a limitation of using T2-weighted MRI lesion volume alone and suggest that combined analysis of MR-based chemical and imaging data might allow improved non-invasive assessment of lesion pathology in order to better understand its relationship to clinical features of multiple sclerosis.

State-of-the-art breast reconstruction.

Many breast reconstruction procedures have been performed with success and satisfaction. These methods can be categorized as implant reconstruction, local tissue with implant, autologous tissue, and free flaps. Implant reconstruction, immediate or delayed, has been the easiest and most fulfilling experience for the surgeon and the patient. Local tissue with implant and autologous tissue are usually available to those patients with anterior chest tissue deficiency or those who prefer autologous tissue without the fear of implant material. Free flap reconstruction is often selected when no other procedures are appropriate for the patient. Individual procedures must be familiar to the patient and the surgeon. Other factors such as time involved, cost of hospital stay, recovery time, and associated complications are discussed in this article. Refinement and nipple areolar reconstruction are an intimate part of breast reconstruction, but these are usually the decisions made by the patient that must be respected.