Current status of home blood pressure monitoring in Asia: Statement from the HOPE Asia Network

Hypertension represents a major burden in Asia, with a high prevalence rate but poor level of awareness and control reported in many countries in the region. Home blood pressure monitoring has been validated as an accurate and reliable measure of blood pressure that can help guide hypertension treatment as well as identify masked and white‐coat hypertension. Despite its benefits, there has been limited research into home blood pressure monitoring in Asia. The authors reviewed the current evidence on home blood pressure monitoring in Asia, including but not limited to published literature, data presented at congresses, and national hypertension management guidelines to determine the current utilization of home blood pressure monitoring in clinical practice in the region. Public policies to enable greater access to home blood pressure monitoring and its use in clinical care would add considerably to improving hypertension outcomes in Asia.     

Lack of Cumulative Toxicity Associated With Cabazitaxel Use in Prostate Cancer

Cabazitaxel provided a survival advantage compared with mitoxantrone in patients with castration-resistant prostate cancer refractory to docetaxel. Grade 3 to 4 (G3–4) neutropenia and febrile neutropenia were relatively frequent in the registrative XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer (TROPIC) trial, but their incidence was lower in the Expanded Access Program (EAP). Although cumulative doses of docetaxel are associated with neuropathy, the effect of cumulative doses of cabazitaxel is unknown. In this retrospective review of prospectively collected data, the authors assessed “per cycle” incidence and predictors of toxicity in the Italian cohort of the EAP, with a focus on the effect of cumulative doses of cabazitaxel.The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP. The influence of selected variables on the most relevant adverse events identified was assessed using a Generalized Estimating Equations model at univariate and multivariate analysis.“Per cycle” incidence of G 3 to 4 neutropenia was 8.7%, whereas febrile neutropenia was reported in 0.9% of cycles. All events of febrile neutropenia occurred during the first 3 cycles. Multivariate logistic regression analysis showed that higher prior dose of cabazitaxel was associated with decreased odds of having G3 to 4 neutropenia (OR = 0.90; 95% CI: 0.86–0.93; P < 0.01), febrile neutropenia (OR = 0.52; 95% CI: 0.34–0.81; P < 0.01) and G3 to 4 anemia (OR = 0.93; 95% CI: 0.86–1; P = 0.07). Patients with a body surface area >2 m² presented increased odds of having G 3 to 4 neutropenia (OR = 0.93; 95% CI: 0.86–1; P = 0.07), but decreased odds of having G3 to 4 anemia.Among the toxicities assessed, the authors did not identify any that appeared to be associated with a higher number of cabazitaxel cycles delivered. Prior cumulative dose was associated with reduced G3 to 4 neutropenia and anemia. The apparent protective effect associated with higher doses of cabazitaxel is likely to be affected by early dose reduction and early toxicity-related treatment discontinuation. Because this analysis is limited by its retrospective design, prospective trials are required to assess the optimal duration of cabazitaxel treatment.     

Pooled Analysis of Phase II Trials Evaluating Weekly or Conventional Cisplatin as First-Line Therapy for Advanced Urothelial Carcinoma

BackgroundWeekly gemcitabine with GC every 3-4 weeks is considered conventional first-line chemotherapy for advanced urothelial carcinoma (UC). Weekly split-dose cisplatin with wGC might be less toxic and have similar activity, but has not been compared with GC. We pooled published phase II trials of GC and wGC to compare efficacy and safety.Patients and MethodsTwo trials of wGC and 3 trials of GC were identified. Because the data were not derived from randomized trials, GC and wGC were not formally compared, and exact 95% quasi-binomial confidence intervals (CI), for response rates and grade ≥ 3 toxicities were calculated.ResultsThe 95% CI overlapped, suggesting agreement between wGC and GC. No clear difference in response rates and grade ≥ 3 toxicities between GC and wGC were observed.ConclusionGemcitabine combined with day 1 cisplatin and wGC yielded similar responses and grade ≥ 3 toxicities in advanced UC in a hypothesis-generating pooled analysis of phase II trials. Considering the probable lower nephrotoxicity of fractionated cisplatin, prospective evaluation of wGC might be warranted across cisplatin-eligible and -ineligible patients to develop a single chemotherapy template for the development of combinations with biological agents in a broad population of patients.     

The Impact of Gender on Outcomes in Patients With Metastatic Urothelial Carcinoma

BackgroundAlthough urothelial cancer is more common in men, women with urothelial cancer have inferior survival outcomes. The potential existence of gender-related disparities in patients with metastatic urothelial cancer has not been extensively explored.Patients and MethodsIndividual patient data were pooled from 8 phase II and phase III trials evaluating first-line cisplatin-based combination chemotherapy in patients with metastatic urothelial carcinoma. Adverse events, treatment delivery, response proportions, and survival outcomes were compared between male and female patients.ResultsOf the 543 patients included in the analysis, 100 patients (18%) were women. There was no significant difference in the number of cycles of chemotherapy administered or in the proportions of patients experiencing severe toxicities when comparing male and female patients. There was no difference in the survival distributions between male and female patients (P = .08); the median survival of male patients was 11.7 months (95% confidence interval [CI], 10.5-13.2) compared with 16.2 months for female patients (95% CI, 12.8-20.4). There was no significant difference in survival between men and women when controlling for baseline performance status and/or the presence of visceral metastases.ConclusionFemale patients with metastatic urothelial cancer tolerate cisplatin-based chemotherapy similarly to male patients and achieve comparable clinical outcomes. Although gender-associated survival disparities in patients with metastatic urothelial cancer cannot be completely ruled out, if such disparities exist, they are unlikely related to tolerability or efficacy of chemotherapy.     

Synthesis of primaquine glyco‐conjugates as potential tissue schizontocidal antimalarial agents

Primaquine ( PQ ) is the only drug used to prevent relapse of malaria due to P. vivax and P. ovale, by eradicating the dormant liver form of the parasite (hypnozoites). The side‐effects associated with PQ limits is uses in treatment of malaria. To overcome the premature oxidative deamination and to increase the life span of drug in the biological system, the novel glyco‐conjugates of PQ were synthesized by coupling of primaquine with hexoses in phosphate buffer. The saccharide part of the hybrid molecules thought to direct the drug to the liver, where hypnozoites resides. All the synthesized compounds were fully characterized and evaluated for their radical curative activities. The three compounds viz glucoside ( 15a ), galactoside ( 15b ) and mannoside ( 15c ) with high activity were tested for their activity in rhesus monkeys where the most active compound 15b showed twofold activity (100% radical curative activity at 1.92 mmol/kg) than the standard drug PQ diphosphate (3.861 mmol/kg). It is proposed that results from these studies may be advantageous to develop a new potent tissue schizonticide antimalarial compound.     

Suppression of the hepatic microsomal cytochrome P-450 dependent mixed function oxidase activities in golden hamster during Leishmania donovani infection

Experimental infection of golden hamsters with Leishmania donovani caused significant alterations in the hepatic microsomal mixed function oxidase system. Gross examination of liver indicated hepatomegaly. Microsomal protein contents were only marginally elevated. Cytochrome P-450 as well as haem contents were significantly decreased and it directly correlated with the degree of infection. Cytochrome b5 exhibited elevation at lower degrees of infection which came down to control levels at the peak infection. Concomitant suppression was also noticed in cytochrome P-450 dependent monooxygenase activities, viz. aniline hydroxylase, benzo[a]pyrene hydroxylase and aminopyrine N-demethylase. No significant change was observed in NADH-cytochrome b5 reductase and NADPH-cytochrome c reductase. The results indicate suppression of hepatic microsomal MFO activities during visceral leishmaniasis.     

The molecular structure of 4-(dimethylmaleimido)phenyl methacrylate

The molecular structure of 4-(dimethylmaleimido)phenyl methacrylate was determined by means of X-ray diffraction. Crystals are orthorhombic, space group F2dd, a = 3,993(1) Å, b = 36,650(6) Å, c = 39,460(8) Å and Z = 16; d_calc = 1,360 g · cm^?3, V = 5774,7 ų, M = 285,3, λ = 0,7107 Å, μ (MoK_α) = 1,06 cm^?1, F(000) = 2400. The structure was solved by direct methods and refined to R = 0,062 for 304 observed reflections. The molecule has a synperiplanar conformation as to the C?C and C?O double bonds about C(7)? C(8) and also as to the C?O and C? O bonds about C(7)? O(1).     

Longitudinal Evaluation of Circulating Tumor DNA Using Sensitive Amplicon-Based Next-Generation Sequencing to Identify Resistance Mechanisms to Immune Checkpoint Inhibitors for Advanced Urothelial Carcinoma

Serial evaluation of circulating tumor DNA may allow noninvasive assessment of drivers of resistance to immune checkpoint inhibitors (ICIs) in advanced urothelial cancer (aUC). We used a novel, amplicon-based next-generation sequencing assay to identify genomic alterations (GAs) pre- and post-therapy in 39 patients with aUC receiving ICI and 6 receiving platinum-based chemotherapy (PBC). One or more GA was seen in 95% and 100% of pre- and post-ICI samples, respectively, commonly in TP53 (54% and 54%), TERT (49% and 59%), and BRCA1/BRCA2 (33% and 33%). Clearance of ≥1 GA was seen in 7 of 9 patients responding to ICI, commonly in TP53 (n = 4), PIK3CA (n = 2), and BRCA1/BRCA2 (n = 2). A new GA was seen in 17 of 20 patients progressing on ICI, frequently in BRCA1/BRCA2 (n = 6), PIK3CA (n = 3), and TP53 (n = 3), which seldom emerged in patients receiving PBC. These findings highlight the potential for longitudinal circulating tumor DNA evaluation in tracking response and resistance to therapy.