Journal of Advances in Medical and Pharmaceutical Sciences

Early Haematological Response and Short-Term Safety of Frontline Imatinib in Adults with Chronic Myeloid Leukaemia: A Retrospective Study in a Resource-Limited Setting

2026-07-16T11:20:38+00:00

Background: Imatinib mesylate is a tyrosine kinase inhibitor that has transformed the treatment of chronic myeloid leukaemia. However, information on its real-world use among sub-Saharan African populations remains limited.

Aims: This study evaluated early haematological response and recorded adverse drug reactions among Sudanese adults receiving first-line imatinib for Philadelphia chromosome-positive chronic myeloid leukaemia.

Methods: A single-centre retrospective cohort study was conducted using the medical records of 89 adults with Philadelphia chromosome-positive chronic myeloid leukaemia who were registered and treated at Khartoum Oncology Hospital in 2019. The hospital was the only authorised dispensing site for the Glivec® International Patient Assistance Program in Sudan during the study period. Patients in the chronic phase received imatinib at an initial dose of 400 mg/day, whereas those in the accelerated phase received 600 mg/day. Haematological parameters and recorded adverse drug reactions were assessed at baseline and after one and three months of treatment. Data were analysed using SPSS.

Results: Of the 89 patients, 52.0% were male, and 37.1% were aged 31–40 years. At diagnosis, 95.5% had chronic-phase disease and 95.5% had splenomegaly. Complete haematological response was achieved by 79.8% of patients at one month and 94.4% at three months. Haematological adverse reactions were the most frequently recorded toxicities, including neutropenia in 20.2% and thrombocytopenia in 10.1%. Seven patients, representing 7.9% of the total cohort and 18.4% of those with recorded adverse drug reactions, permanently discontinued imatinib and transitioned to a second-generation tyrosine kinase inhibitor. Accelerated-phase disease was associated with a lower complete haematological response rate and a greater likelihood of an elevated white blood cell count at three months, although this finding was based on only four accelerated-phase patients. Age and sex were not significantly associated with response.

Conclusion: A high proportion of patients achieved an early complete haematological response following cytoreductive bridging and initiation of imatinib. Interpretation is limited by preceding hydroxyurea exposure, retrospective ascertainment of adverse reactions, short follow-up, and the absence of routine molecular and cytogenetic monitoring. Improved access to standardised molecular testing would strengthen treatment-response assessment and long-term CML care in resource-limited settings.

Effectiveness of Diuretics Compared with Other Antihypertensive Agents in the Control of Hypertension in Black Adults: A Systematic Review

2026-07-16T10:41:27+00:00

Background: Hypertension is highly prevalent among Black adults and contributes substantially to stroke, heart failure, kidney disease, and premature cardiovascular morbidity. Thiazide and thiazide-like diuretics are widely recommended as foundational antihypertensive agents, but their comparative effectiveness against calcium-channel blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and alpha-blockers remains clinically important.

Objective: To systematically review evidence published from 1 January 2000 to 30 March 2026 on the effectiveness of diuretic-based antihypertensive therapy compared with other antihypertensive agents for blood-pressure control and clinical outcomes in Black adults with hypertension.

Methods: A PRISMA 2020-, PRISMA-S-, and SWiM-aligned systematic review without meta-analysis was conducted as a completed open-source verification search. The search used PubMed/MEDLINE, PubMed Central, Europe PMC, publisher pages, ClinicalTrials.gov-linked records, guideline pages, DOI checks, and citation chasing. Subscription-database export counts were unavailable. Eligible reports were randomized trials, trial subgroup analyses, secondary trial analyses, indirect comparative analyses, and comparative observational studies involving Black adults with hypertension and a diuretic comparator.

Results: The open-source verification search logged 37 records. Seven methodologic or guideline records were separated from clinical screening, leaving 30 clinical candidate records. After screening and eligibility assessment, 10 reports from four evidence families were included: ALLHAT, PEAR/PEAR-2, CREOLE, and a large HCA Healthcare retrospective cohort. ALLHAT provided the strongest evidence that chlorthalidone was at least comparable to amlodipine and more favorable than lisinopril or doxazosin for several cardiovascular outcomes in Black participants. CREOLE showed that amlodipine-containing dual regimens, including amlodipine plus hydrochlorothiazide, lowered blood pressure more effectively than perindopril plus hydrochlorothiazide in Black African adults. PEAR/PEAR-2 suggested favorable hydrochlorothiazide response compared with atenolol for night blood pressure and greater blood-pressure lowering with chlorthalidone than hydrochlorothiazide, although the latter comparison was indirect. Observational evidence suggested lower cardiovascular event likelihood with calcium-channel blockers than with diuretics but was at serious risk of confounding.

Conclusions: Diuretics, particularly chlorthalidone and hydrochlorothiazide-containing regimens, are effective antihypertensive options in Black adults. Evidence most strongly supports thiazide/thiazide-like diuretics over ACE inhibitors, beta-blockers, and alpha-blockers as default initial therapy for uncomplicated hypertension, while calcium-channel blockers are also highly effective and may be particularly useful in combination therapy. Certainty is moderate for major randomized-trial evidence and lower for indirect, post hoc, and observational findings. No pooled estimate was calculated because of clinical, methodological, comparator, and outcome heterogeneity.

Limb-girdle Muscular Dystrophy Type 2I/R9: Future Gene Therapy Options of an Extremely Rare Fukutin Protein-related Dystroglycanopathy

2026-07-16T11:15:03+00:00

Limb-girdle muscular dystrophy type 2I, now designated R9 (LGMD2I/R9), is an autosomal recessive dystroglycanopathy caused by biallelic pathogenic variants in the fukutin-related protein (FKRP) gene. Loss of FKRP glycosyltransferase activity disrupts the ribitol-phosphate-mediated glycosylation of alpha-dystroglycan, reducing matriglycan formation and weakening the link between the sarcolemma and the extracellular matrix. The resulting phenotype ranges from mild, adult-onset limb-girdle weakness to a severe congenital muscular dystrophy, and frequently includes dilated cardiomyopathy and restrictive respiratory failure. No disease-modifying treatment is currently licensed, and management remains supportive. Over the past decade, three broad experimental strategies have moved toward clinical evaluation: adeno-associated virus (AAV)-mediated gene replacement, small-molecule substrate supplementation with ribitol, and combinatorial approaches that pair gene replacement with muscle-anabolic transgenes such as follistatin. Registered early-phase AAV-FKRP programmes and the placebo-controlled FORTIFY trial of oral ribitol provide important translational context, but peer-reviewed clinical efficacy and long-term safety data remain limited; interim registry, conference and sponsor-reported findings should therefore be interpreted cautiously. This narrative review synthesises the molecular pathophysiology of FKRP-related dystroglycanopathy, appraises the natural history and outcome measures relevant to trial design, and critically evaluates the preclinical and early clinical evidence for gene-based and substrate-based therapies. It concludes with a discussion of unresolved translational barriers and a forward-looking assessment of the therapeutic pipeline for this ultra-rare neuromuscular disorder.