Risk factors and assessment for cardiovascular disease among HIV-positive patients attending a Nigerian tertiary hospital

Introduction: cardiovascular risk factors are prevalent in HIV-positive patients which places them at increased risk for cardiovascular disease (CVD). We aimed to determine the risk factors and risk assessment for CVD in HIV-positive patients with and without antiretroviral therapy. Methods: this was a cross-sectional study of HIV-positive patients attending the Lagos University Teaching Hospital, Nigeria. Anthropometric and blood pressure measurements were performed; fasting lipid profile, plasma glucose, homocysteine and hsCRP were determined, as well as prevalences and risk assessments. Statistical tests were used to compare the groups and p-value <0.05 was considered to be significant. Results: 283 subjects were recruited for this study (100 HIV-positive treatment-naive, 100 HIV-positive treated and 83 HIV negative controls). Compared to the controls, mean (sd) values were significantly higher among HIV-treated subjects: waist circumference=88.7 (10.4), p=0.035; systolic bp= 124.9 (20.7), p=0.014; glucose= 5.54 (1.7), p=0.015; triglyceride= 2.0 (1.2), p<0.001; homocysteine= 10.9 (8.9-16.2), p=0.0003; while hsCRP= 2.9 (1.4-11.6), p=0.002 and HDL-C=0.9 (0.4), p=<0.0001 were higher among the HIV-naïve subjects. Likewise, higher prevalences of the risk factors were noted among the HIV-treated subjects except low HDL-C (p<0.001) and hsCRP (p=0.03) which were higher in the HIVnaïve group. Risk assessment using ratios showed high risk for CVD especially in the HIV-naïve group. The median range for Framingham risk assessment was 1.0 - 7.5%. Conclusion: Risk factors and risk assessment for CVD are increased in HIV-positive patients with and without antiretroviral therapy.Routine evaluation and risk assessment for CVD irrespective of therapy status is necessary to prevent future cardiovascular events.Pan African Medical Journal 2016; 2

Phase 3 CLEAR study in patients with advanced renal cell carcinoma: outcomes in subgroups for the lenvatinib-plus-pembrolizumab and sunitinib arms

IntroductionThe phase 3 CLEAR study demonstrated that lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma (RCC). Prognostic features including presence and/or site of baseline metastases, prior nephrectomy, and sarcomatoid features have been associated with disease and treatment success. This subsequent analysis explores outcomes in patients with or without specific prognostic features.MethodsIn CLEAR, patients with clear cell RCC were randomly assigned (1:1:1) to receive either lenvatinib (20 mg/day) plus pembrolizumab (200 mg every 3 weeks), lenvatinib (18 mg/day) plus everolimus (5 mg/day), or sunitinib alone (50 mg/day, 4 weeks on, 2 weeks off). In this report, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were all assessed in the lenvatinib-plus-pembrolizumab and the sunitinib arms, based on baseline features: lung metastases, bone metastases, liver metastases, prior nephrectomy, and sarcomatoid histology.ResultsIn all the assessed subgroups, median PFS was longer with lenvatinib-plus-pembrolizumab than with sunitinib treatment, notably among patients with baseline bone metastases (HR 0.33, 95% CI 0.21–0.52) and patients with sarcomatoid features (HR 0.39, 95% CI 0.18–0.84). Median OS favored lenvatinib plus pembrolizumab over sunitinib irrespective of metastatic lesions at baseline, prior nephrectomy, and sarcomatoid features. Of interest, among patients with baseline bone metastases the HR for survival was 0.50 (95% CI 0.30–0.83) and among patients with sarcomatoid features the HR for survival was 0.91 (95% CI 0.32–2.58); though for many groups, median OS was not reached. ORR also favored lenvatinib plus pembrolizumab over sunitinib across all subgroups; similarly, complete responses also followed this pattern.ConclusionEfficacy outcomes improved following treatment with lenvatinib-plus-pembrolizumab versus sunitinib in patients with RCC—irrespective of the presence or absence of baseline lung metastases, baseline bone metastases, baseline liver metastases, prior nephrectomy, or sarcomatoid features. These findings corroborate those of the primary CLEAR study analysis in the overall population and support lenvatinib plus pembrolizumab as a standard of care in 1L treatment for patients with advanced RCC.Clinical trial registrationClinicalTrials.gov, identifier NCT0281186

The Design Synthesis and Antimalarial Activity of Novel Diamidines, Diguanidines, Substituted Fluorenes and Their Prodrugs

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The cost of treating skin cancers in a teaching hospital in Makurdi, Nigeria

Background: Patients with skin cancer are fairly common in our practice. We lack data on the cost of treating these patients. This data is important for policy formulation and resource allocation. We studied the socioeconomic burden of skin cancer on patients presenting to our institution.Methods: A 3-year retrospective study of patients with histologically-confirmed skin cancers presenting to the Benue State University Teaching Hospital, Makurdi from April 1, 2012 to March 31, 2015 was done. Relevant data was extracted from the patients' records.Results: Records were available for 43 patients with a mean age of 46±18 years. The total direct cost of treatment was ? 8.741m with a median of ? 0.173m and interquartile range of ? 0.229m. The care of squamous cell carcinoma (SCC) patients, who made up the largest proportion of patients, took up 46.7% of the total cost and melanoma 39.1%. Melanoma had the highest average cost per patient of ? 0.312m. The relative youth and active employment of the patients contributed to the indirect costs by creating a significant loss of productivity.Conclusion: Skin cancer care places a significant burden on the patients, their families and the entire society.Key words: Skin cancer, economic burden, care, Makurdi, Nigeri

Cumulative Rehearsal and Auditory Verbal Memory of Persons with Down Syndrome

One of the characteristics of persons with Down syndrome is poor memory, especially the Auditory-Verbal Memory (AVM). Lack of verbal memory among persons with Down syndrome is one major factor that inhibits learning. This is why the effort towards enhancing AVM of persons with Down syndrome is evolving. This study, therefore, investigated the efficacy of cumulative rehearsal on auditory verbal memory of persons with Down syndrome with speech production and gender as moderator variables. A 2 x 2 x 2 factorial matrix of pretest-posttest control group experimental design was used in the study. A sample of thirty participants was drawn from a population of 44 persons with Down syndrome and randomly assigned to control and experimental groups in two special schools; National Orthopaedic Special School, Igbobi, and Modupe Cole Memorial Childcare and Treatment Home/School, Akoka. Data was collected using a validated self-developed instrument, Auditory Verbal Memory Assessment Scale (AVMAS) (r-0.86). Two hypotheses were tested using ANCOVA. Findings from the study revealed that: cumulative rehearsal therapy significantly impacted the auditory-verbal memory of persons with Down syndrome, with significant improvement observed. There was no significant interaction effect of speech level and gender with the therapy. It was thus concluded that cumulative rehearsal therapy is effective in enhancing auditory-verbal memory and so recommended for the improvement of AVM of persons with Down syndrome

Lenvatinib dose, efficacy, and safety in the treatment of multiple malignancies.

INTRODUCTION: Lenvatinib is an oral multitargeted tyrosine kinase inhibitor that has shown efficacy and manageable safety across multiple cancer types. The recommended starting doses for lenvatinib differ across cancer types and indications based on whether it is used as monotherapy or as combination therapy. AREAS COVERED: This review covers clinical trials that established the dosing paradigm and efficacy of lenvatinib and defined its adverse-event profile as a monotherapy; or in combination with the mTOR inhibitor, everolimus; or the anti-PD-1 antibody, pembrolizumab; and/or chemotherapy. EXPERT OPINION: Lenvatinib has been established as standard-of-care either as a monotherapy or in combination with other anticancer agents for the treatment of radioiodine-refractory differentiated thyroid carcinoma, hepatocellular carcinoma, renal cell carcinoma, and endometrial carcinoma, and is being investigated further across several other tumor types. The dosing and adverse-event management strategies for lenvatinib have been developed through extensive clinical trial experience. Collectively, the data provide the rationale to start lenvatinib at the recommended doses and then interrupt or dose reduce as necessary to achieve required dose intensity for maximized patient benefit. The adverse-event profile of lenvatinib is consistent with that of other tyrosine kinase inhibitors, and clinicians are encouraged to review and adopt relevant symptom-management strategies

Biomarker analyses in patients with advanced renal cell carcinoma (aRCC) from the phase 3 CLEAR trial

4504 Background: In the primary analysis of CLEAR, lenvatinib + pembrolizumab (L+P) significantly improved efficacy vs sunitinib (S) in treatment-naïve patients with aRCC (Motzer 2021). Results were confirmed at the final prespecified OS analysis (Motzer 2024). We report biomarker analyses from CLEAR. Methods: PD-L1 IHC 22C3 pharmDx and NGS assays (ImmunoID NeXT platform: WES and RNA-Seq) were performed on archival tumor specimens. To identify somatic alterations including mutations and copy-number variations, paired PBMC samples were used as reference. For RNA-Seq/IHC-derived analyses, a continuous value analysis was performed adjusting by KPS score for: each gene-signature score (T-cell inflamed gene-expression profile [GEP], and non-GEP signatures including proliferation, angiogenesis, hypoxia, MYC, WNT, and other signatures [Cristescu 2022]) vs best overall response (BOR); non-GEP signatures vs BOR adjusted by GEP; and PD-L1 CPS vs BOR. Cutoff analyses were performed for biomarkers that showed significant association in the continuous value analysis. Cutoff values (1st tertile of GEP, or median of non-GEP, signatures) were determined based on combined L+P and S arms. WES analyses were descriptively summarized if TMB/INDEL burden and mutation status of key RCC driver genes were associated with BOR. Results: There were no notable differences in baseline characteristics and tumor responses in biomarker analysis sets vs the ITT population. In the L+P arm, the continuous GEP signature score was not associated with BOR. The MYC signature score was negatively associated with BOR (2-sided test, significance criteria 0.1; FDR-adjusted p=0.013/0.012 with/without adjustment by GEP signature score, respectively). The ORRs (95% CI) for the MYC-high and -low groups were 66.3% (56.1-75.6) and 84.0% (75.0-90.8), respectively. In the S arm, the continuous GEP signature score was positively associated with BOR (2-sided test, significance criteria 0.05; p=0.010). The ORRs (95% CI) for the GEP-high and -low groups were 46.9% (38.1-55.9) and 28.8% (18.3-41.3), respectively. The angiogenesis signature was positively associated with BOR (2-sided test, significance criteria 0.1; FDR-adjusted p=0.046/0.088 with/without adjustment by GEP signature score, respectively). The ORRs (95% CI) for the angiogenesis-high and -low groups were 52.1% (41.6-62.5) and 30.4% (21.7-40.3), respectively. PD-L1 CPS and TMB/INDEL burden were not associated with BOR in L+P or S arms. ORR was higher with L+P vs S, regardless of the deleterious mutation status of BAP1, VHL, PBRM1, SETD2, and KDM5C—frequently mutated genes in RCC. Conclusions: The superiority of L+P vs S in ORR does not appear to be impacted by gene-expression signatures for tumor-induced proliferation, angiogenesis, hypoxia, MYC, or WNT, or by PD-L1 status, TMB/INDEL burden or mutation status of RCC driver genes. Clinical trial information: NCT02811861

Final prespecified overall survival (OS) analysis of CLEAR: 4-year follow-up of lenvatinib plus pembrolizumab (L+P) vs sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC)

4502 Background: In the phase 3 CLEAR trial, L+P showed clinically meaningful and statistically significant benefits in PFS (primary endpoint) and OS, and improved ORR compared with S in 1L aRCC (Motzer NEJM 2021). Here, we report 4-yr follow-up results from the final prespecified OS analysis of CLEAR (data cutoff: 31 Jul 2022). Methods: Treatment-naïve pts (n=1069) who had aRCC with a clear-cell component were randomized (1:1:1) to receive: L 20 mg PO QD + P 200 mg IV Q3W; or L 18 mg + everolimus 5 mg PO QD; or S 50 mg PO QD (4 wks on/2 wks off). Stratification factors were geographic region and MSKCC prognostic risk group. This final prespecified OS analysis was triggered by ~304 death events in 2 arms. OS, PFS, ORR, duration of response (DOR), and PFS on next-line therapy (PFS2) were assessed for L+P and S. PFS, ORR and DOR were assessed per independent review using RECIST v1.1. Nominal P-values are shown. Results: At a median follow-up (IQR) of 49.8 mos (41.4–53.1) for L+P and 49.4 mos (41.6–52.8) for S, 149 and 159 deaths had occurred, respectively. OS benefit with L+P vs S was maintained (HR, 95% CI; 0.79, 0.63–0.99). OS favored L+P vs S across MSKCC risk groups (HR, 95% CI; favorable [fav]: 0.89, 0.53–1.50; intermediate [int]: 0.81, 0.62–1.06; poor: 0.59, 0.31–1.12). PFS benefit of L+P vs S was maintained (HR, 95% CI; 0.47, 0.38–0.57). PFS favored L+P vs S across MSKCC risk groups (HR, 95% CI; fav: 0.46, 0.32–0.67; int: 0.51, 0.40–0.65; poor: 0.18, 0.08–0.42). ORR was greater with L+P (71.3%; complete response [CR], 18.3%) vs S (36.7%; CR, 4.8%) (relative risk, 95% CI; 1.94, 1.67–2.26). Less pts in the L+P arm (181/355, 51.0%) received subsequent anticancer therapies compared with the S arm (246/357, 68.9%); 56 (15.8%) and 195 (54.6%) received PD-1/PD-L1 checkpoint inhibitors, respectively. Analysis of OS adjusted for subsequent therapies will be presented. PFS2 was longer with L+P vs S (43.3 vs 25.9 mos; HR, 95% CI; 0.63, 0.51–0.77). Grade ≥3 treatment-related adverse events occurred in 74.1% and 60.3% pts in the L+P and S arms, respectively. Conclusions: L+P continues to demonstrate clinically meaningful benefit vs S in OS, PFS, ORR, and CR in the 1L treatment of pts with aRCC at 4-yr follow-up, thus supporting the robustness of the primary analysis data from CLEAR. Clinical trial information: NCT02811861 .[Table: see text