The risk of PD-L1 expression misclassification in triple-negative breast cancer

Breast Cancer Research and Treatment - Stratification of patients with triple-negative breast cancer (TNBC) for anti-PD-L1 therapy is based on PD-L1 expression in tumor biopsies. This study sought...     

Improving Crotalidae polyvalent immune Fab reconstitution times

Background

Crotalidae polyvalent immune Fab (CroFab) is used to treat rattlesnake envenomations in the United States. Time to infusion may be a critical factor in the treatment of these bites. Per manufacturer's instructions, 10 mL of sterile water for injection (SWI) and hand swirling are recommended for reconstitution. We wondered whether completely filling vials with 25 mL of SWI would result in shorter reconstitution times than using 10-mL volumes and how hand mixing compared to mechanical agitation of vials or leaving vials undisturbed.

Methods

Six sets of 5 vials were filled with either 10 mL or 25 mL. Three mixing techniques were used as follows: undisturbed; agitation with a mechanical agitator; and continuous hand rolling and inverting of vials. Dissolution was determined by observation and time to complete dissolution for each vial. Nonparametric 2-tailed P values were calculated.

Results

Filling vials completely with 25 mL resulted in quicker dissolution than using 10-mL volumes, regardless of mixing method (2-tailed P = .024). Mixing by hand was shorter than other methods (P < .001). Reconstitution with 25 mL and hand mixing resulted in the shortest dissolution times (median, 1.1 minutes; range, 0.9-1.3 minutes). This appeared clinically important because dissolution times using 10 mL and mechanical rocking of vials (median, 26.4 minutes) or leaving vials undisturbed (median, 33.6 minutes) was several-fold longer.

Conclusion

Hand mixing after filling vials completely with 25 mL results in shorter dissolution times than using 10 mL or other methods of mixing and is recommended, especially when preparing initial doses of CroFab.     

Structural and in Vitro Functional Characterization of a Menthyl TRPM8 Antagonist Indicates Species-Dependent Regulation

TRPM8 antagonists derived from its cognate ligand, (−)-menthol, are underrepresented. We determine the absolute stereochemistry of a well-known TRPM8 antagonist, (−)-menthyl 1, using VCD and 2D NMR. We explore 1 for its antagonist effects of the human TRPM8 (hTRPM8) orthologue to uncover species-dependent inhibition versus rat channels. (−)-Menthyl 1 inhibits menthol- and icilin-evoked Ca²⁺ responses at hTRPM8 with IC₅₀ values of 805 ± 200 nM and 1.8 ± 0.6 μM, respectively, while more potently inhibiting agonist responses at the rat orthologue (rTRPM8 IC₅₀ (menthol) = 117 ± 18 nM, IC₅₀ (icilin) = 521 ± 20 nM). Whole-cell patch-clamp recordings of hTRPM8 confirm the 1 inhibition of menthol-stimulated currents, with an IC₅₀ of 700 ± 200 nM. We demonstrate that 1 possesses ≥400-fold selectivity for hTRPM8 versus hTRPA1/hTRPV1. (−)-menthyl 1 can be used as a novel chemical tool to study hTRPM8 pharmacology and differences in species commonly used in drug discovery.     

Preliminary Effectiveness Study of Coping Power Program for Aggressive Children in Pakistan

Aggression is a characteristic feature of many psychiatric disorders. To address the scarceness for evidence-based interventions for behavioral problems in Pakistan, we evaluated the effectiveness of culturally adapted version of Coping Power Program. The purpose of the study was to determine the extent to which Coping Power Program is capable of reducing aggressive behavior and improving competent behavior, when delivered in a different culture, i.e., Pakistan. With randomized control trial (RCT) of pre- and post-testing, 112 fourth grade boys were allocated to Coping Power intervention condition and waitlist control condition. The intervention group showed significant reduction in aggression at post assessment, in comparison to control group. Boys who received Coping Power intervention also showed improvements in behavior, social skills, and social cognitive processes, with better anger control and problem solving strategies, in comparison to the control group. The results of the study provide preliminary evidence, supporting the effectiveness of Coping Power Program for Pakistani children. Despite its limitations, the results of this study are promising and suggest that Coping Power is an effective intervention to reduce behavioral problems and promote healthy and positive behaviors in children, even when implemented in different contexts with greater potential for violence exposure.     

Prevalence of diabetes mellitus and population attributable fractions for coronary heart disease and stroke mortality in the WHO South-East Asia and Western Pacific regions

The aims of this study were to obtain the most recent representative data for the prevalence of diabetes in adult populations in the World Health Organisation's South-East Asia and Western Pacific regions and to quantify the contribution of diabetes to the burden of mortality from cardiovascular diseases in these regions. Previous reports indicate that there are 83 million individuals with diabetes in the Asia-Pacific region, but since many of the country-specific estimates were not from nationally representative studies, this figure may not accurately reflect the current burden of diabetes. Information on the prevalence of diabetes was obtained by searching Medline and government health websites. Data were available from 12 countries representing 78% of the total population of the Asia-Pacific region. Six of 10 countries with complete data reported a prevalence of diabetes exceeding those estimates currently cited by the World Health Organization; three of which have also already exceeded the World Health Organization projections for 2030. In the 12 countries in the region with nationally representative data, the prevalence of diabetes ranged from 2.6% to 15.1%. Hazard ratios from the Asia Pacific Cohort Studies Collaboration were used to calculate population attributable fractions for diabetes for fatal cardiovascular diseases in the region. Population attributable fractions ranged from 2% to 12% for coronary heart disease, 1% to 6% for haemorrhagic stroke, and 2% to 11% for ischaemic stroke. Accurate estimates of the prevalence of diabetes are of great importance and standard methods are needed for periodic surveillance across the Asia-Pacific region and elsewhere.     

The burden of overweight and obesity in the Asia–Pacific region

The rise in the prevalence of overweight and obesity (body mass index ≥25 kg m⁻²) is, in part, a negative consequence of the increasing economic developments of many lower‐ and middle‐income countries in the Asia–Pacific region. To date, there has been no systematic quantification of the scale of the problem in countries of this region. From the most recent nationally representative estimates for the prevalence of overweight and obesity in 14 countries of the region, it is apparent that overweight and obesity is endemic in much of the region, prevalence ranging from less than 5% in India to 60% in Australia. Moreover, although the prevalence in China is a third of that in Australia, the increase in prevalence in China over the last 20 years was 400% compared with 20% in Australia. In addition, across various countries in the region, the population attributable fractions because of overweight and obesity ranged from 0.8% to 9.2% for coronary heart disease mortality, 0.2% to 2.9% for haemorrhagic stroke mortality, and 0.9% to 10.2% for ischaemic stroke mortality. These results indicate that consequences of overweight and obesity for health and the economy of many of these countries are likely to increase in coming years.     

Hepatitis B vaccine boosters: Is there a clinical need in high endemicity populations?

The Steering Committee for the Prevention and Control of Infectious Diseases in Asia recently conducted a survey of primary-care physicians in Asia, which revealed that many physicians administer boosters in their clinical practice and that there is considerable variation and uncertainty among physicians regarding this practice. This paper serves as a response to physicians' uncertainties by reviewing the literature regarding the administration of hepatitis B vaccine boosters in high endemicity areas and presenting the Steering Committee's guidelines for booster administration. While there are few data to support a need for routine hepatitis B vaccine boosters as a public health measure, they help to provide reassurance of immunity against breakthrough infection in certain risk groups. In clinical practice, primary-care physicians must exercise their judgment regarding the need for booster vaccination on an individual basis. This paper examines the available literature on the administration and value of hepatitis B vaccine boosters, explores the differences between the public health approach and clinical practice, and provides guidelines for those who use boosters in high endemicity Asian populations. Relevant articles were identified through searches of MEDLINE (1975-2003) and the Cochrane Library, using 'hepatitis B' and 'booster' as primary search terms. Guidelines for those who decide to administer hepatitis B vaccine boosters include: boosting approximately 10-15 years after primary vaccination; boosting rather than not when monitoring of antibody levels is not feasible; boosting immunocompromised patients when the antibody to hepatitis B surface antigen titer falls below 10 mIU/mL; and boosting healthcare workers based on the endemicity of the particular country.     

Comparison of guidelines for the management of hypertension: Similarities and differences between international and Asian countries; perspectives from HOPE‐Asia Network

Guidelines on the management of hypertension have been developed by various professional bodies and institutions to primarily address the issues of diagnosis, treatment, and control in order to rationalize and improve the management of hypertension. Hypertension guidelines across the world have recently been updated following the new and controversial lower blood pressure threshold of ≥130/80 mmHg for the diagnosis of hypertension adopted by the Americans. While there are differences between the major as well as between the Asian national guidelines, there were also many similarities. This paper discusses and highlights the differences and similarities between the major international guidelines of the American College of Cardiology/American Heart Association, of the European Society of Cardiology/European Society of Hypertension, and of the International Society of Hypertension and also compares them with the Asian guidelines.     

Regional differences in office and self‐measured home heart rates in Asian hypertensive patients: AsiaBP@Home study

Increased heart rate is a predictor of cardiovascular disease, heart failure, and all‐cause mortality. In those with high heart rates, interventions for heart rate reduction have been associated with reductions in coronary events. Asia is a diverse continent, and the prevalences of hypertension and cardiovascular disease differ among its countries. The present analysis of AsiaBP@Home study data investigated differences among resting heart rates (RHRs) in 1443 hypertensive patients from three Asian regions: East Asia (N = 595), Southeast Asia (N = 680), and South Asia (N = 168). This is the first study to investigate self‐measured RHR values in different Asian countries/regions using the same validated home BP monitoring device (Omron HEM‐7130‐AP/HEM‐7131‐E). Subjects in South Asia had higher RHR values compared with the other two regions, and the regional tendency found in RHR values was different from that found in BP values. Even after adjusting for age, sex, BMI, habitual alcohol consumption, current smoking habit, shift worker, hyperlipidemia, diabetes, chronic kidney disease, history of heart failure, and beta‐blocker use, both office and home RHR values in South Asia were the highest among Asia (mean values ± SE of office: East Asia [E] 75.2 ± 1.5 bpm, Southeast Asia [Se] 76.7 ± 1.5 bpm, South Asia [S] 81.9 ± 1.4 bpm; home morning: [E] 69.0 ± 1.2 bpm, [Se] 72.9 ± 1.2 bpm, [S] 74.9 ± 1.1 bpm; home evening: [E] 74.6 ± 1.2 bpm, [Se] 78.3 ± 1.2 bpm, [S] 83.8 ± 1.1 bpm). Given what is known about the impact of RHR on heart disease, our findings suggest the possible benefit of regionally tailored clinical strategies for cardiovascular disease prevention.