First Report of Inclisiran Utilization for Hypercholesterolemia Treatment in Real-world Clinical Settings in a Middle East Population.

PURPOSE: Inclisiran is the first small interfering RNA-based treatment approved for reducing pro-atherogenic lipoproteins in patients with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of low-density lipoprotein cholesterol (LDL-C). We report the first evaluation of the effects of inclisiran in a Middle East population. METHODS: We conducted a retrospective review of patients initiating inclisiran treatment at an outpatient diabetology, endocrinology, and cardiology center between May 2021 and December 2022. All patients followed up for 90 days or more, or with at least 1 lipid determination post initiation were included. Participants were categorized into primary prevention (n = 57) and secondary prevention (n = 89) groups according to previous atherosclerotic cardiovascular disease. FINDINGS: Inclisiran was initiated in 146 patients; mean (SD) age was 54.8 (12.12) years, 82 patients (56.2%) were male, 28 patients (19.2%) had received a diagnosis of familial hypercholesterolemia, 89 patients (61%) had received a diagnosis of diabetes mellitus, and 35 patients (23.9%) had a statin intolerance. Median (interquartile range) follow-up was 137 (90 to 193) days. At 90 days, median (interquartile range) reductions in serum LDL-C and triglycerides were -37.9% (-9.5% to -51.2%) and -12.0% (-9.8% to -40.5%), respectively, in primary prevention and -54.1% (-17.1% to -71.4%) and -15.3% (-14% to -38.8%), respectively, in secondary prevention (all, P < 0.001). LDL-C goals were attained in 110 patients (75.3%). Nonattainment of LDL-C goal was attributed to system effect in 26 patients (72.2%), biological effect in 5 patients (13.9%), and discontinuation of treatment in 5 patients (13.9%). Therapy was well tolerated. IMPLICATIONS: This study is the first from the Middle East and North Africa region that reported the real-world efficacy and safety profile of inclisiran in a mixed-risk population of patients with heterozygous familial hypercholesterolemia and other non-familial hypercholesterolemia indications. Clinically meaningful and sustained reductions in pro-atherogenic lipids with good tolerability were observed after inclisiran initiation. Fewer AEs were reported in this predominantly Arabic population, consistent with previous safety reports for inclisiran. It is important to note that no patient stopped inclisiran treatment due to AEs. Strengths of our study included an optimal cohort, patient heterogeneity, and high retention. In addition, we were able to report mean robust effects of inclisiran and good medication tolerability, quite like randomized studies and open-label extension periods. Despite this, our study had some limitations, including selection bias due to the retrospective design and the absence of a comparative group.

Fructosamine as a predictor of incident diabetic microvascular disease in a population with high prevalence of red cell disorders: A cohort study.

AIMS: Fructosamine can be used to estimate glycaemia in individuals in whom HbA1c may be unreliable. We aimed to establish clinically useful fructosamine treatment targets in a population with a high prevalence of conditions affecting erythrocyte survival, including variant haemoglobin and G6PD deficiency. METHODS: Fructosamine was measured on a clinical basis in individuals in whom HbA1c was suspected to be unreliable by their primary physician. Study endpoints were incident retinopathy and albuminuria in individuals with Prediabetes (n = 60), Type 1 (n = 161) or Type 2 diabetes (n = 1350) during follow up of 4.4 ± 2.3 years. RESULTS: Fructosamine ≥ 250 umol/L was significantly associated with incident retinopathy, and fructosamine ≥ 300 umol/L with incident microalbuminuria, in univariate analysis and adjusted for established risk factors. Fructosamine ≥ 250 umol/L was also significantly associated with incident retinopathy in individuals with HbA1c < 7.0% (53 mmol/mol) at inclusion. CONCLUSIONS: In this patient population, a single measurement of fructosamine significantly and independently predicts incident retinopathy in individuals with HbA1c < 7.0% (53 mmol/mol). Routine measurement of fructosamine on at least one occasion is recommended as part of assessment of prediabetes or diabetes mellitus in populations with a high prevalence of conditions affecting erythrocyte lifespan.

The Effect of Coronavirus Disease-19 Pandemic Lockdown and the Overlapping Ramadan Fasting Period on Glucose Control in Insulin-Treated Patients With Diabetes: A Flash Glucose Monitoring Study.

Background: A strict lockdown was enforced during coronavirus disease (COVID-19) pandemic in many countries including the UAE. Lockdown period overlapped with Ramadan which is accompanied by its own drastic changes in lifestyle that include meal timings. Aims: We report the impact of COVID-19 lockdown (between 22/3/2020 and 24/6/2020) on glucose control pre- and postlockdown and during Ramadan, in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) on insulin therapy. Methods: A number of twenty-four patients (19 men, 6 women) who were monitoring their glucose levels using flash glucose monitoring (FGM) and remotely connected to the diabetes clinic in Imperial College London Diabetes Centre (ICLDC), Abu Dhabi, UAE were included. Using the international consensus on the use of continuous glucose monitoring guidelines, analyses of data were performed on glucose management indicator (GMI), time in range (TIR), time in hyperglycemia, time in hypoglycemia, low blood glucose index (LBGI) and high blood glucose index (HBGI). Variables were calculated for each period: 30 days before lockdown 14/2/2020-14/3/2020, 30 days into lockdown and pre-Ramadan 20/3/2020-18/4/2020, and 30 days into lockdown and Ramadan 24/4/2020-23/5/2020, using cgmanalysis package in R-studio software. Results: Mean average glucose (MAG) remained steady before and during lockdown, and no significant differences were observed in TIR, time in hypoglycemia, and LBGI between prelockdown and lockdown periods. However, there was a statistically significant difference in GMI and percentage of time in hyperglycemia (>10.0 mmol/L) between Ramadan and pre-Ramadan during the lockdown period in p = 0.007, 0.006, and 0.004, respectively. Percentage of TIR (3.9-10.0 mmol/L) was significantly lower in Ramadan as compared to pre-Ramadan (50.3% vs. 56.1%; p = 0.026). Mean absolute glucose (MAG) (182.0 mmol/L vs. 166.6 mmol/L, p = 0.007) and HBGI (10.2 (6.8, 14.8) vs. 11.9 (7.9, 17.8), p = 0.037) were significantly higher in Ramadan compared to pre-Ramadan period. There was no statistically significant difference in percentage of time in hypoglycemia (<3.9 mmol/L) and LBGI between Ramadan and pre-Ramadan periods. Conclusion: The lockdown period had no significant effects in the markers of glycemic control in the population studied. However, Ramadan fasting period embedded within this time was associated with several changes that include increase in GMI, HBGI, and glycemic variability similar to what has been reported in other Ramadan studies.

In vitro efficacy of ceftazidime-avibactam, aztreonam-avibactam and other rescue antibiotics against carbapenem-resistant Enterobacterales from the Arabian Peninsula.

OBJECTIVES: Our aim was to assess the susceptibility of carbapenem-resistant Enterobacterales (CRE) from the Arabian Peninsula to a broad spectrum of antibiotics, including fosfomycin, ceftazidime-avibactam, and aztreonam-avibactam. METHODS: 1192 non-repeat CRE isolated in 2009-2017 from 33 hospitals in five countries of the Arabian Peninsula were tested. The minimum inhibitory concentration of 14 antibiotics was determined. Carbapenemase and 16S methylase genes were detected by PCR. Clonality was assessed by PFGE. RESULTS: The highest rate of susceptibility was detected to aztreonam-avibactam (95.5%) followed by colistin (79.8%), fosfomycin (71.8%) and tigecycline (59.9%). Isolates co-producing two carbapenemases (12.4%) were the least susceptible. Aminoglycoside susceptibility was affected by the frequent production of a 16S methylase. Susceptibility to ceftazidime-avibactam was impacted by the high rate of metallo-beta-lactamase producers (46.3%), while aztreonam-avibactam resistance occurred mostly in clonally unrelated, carbapenemase non-producing Escherichia coli. CONCLUSION: Of the currently available drugs: colistin, tigecycline, and ceftazidime-avibactam co-administered with aztreonam appear to be the most effective to treat CRE infections. However, the presence of non-clonal CRE isolates, in which avibactam does not lower the aztreonam MIC below the clinical breakpoint, is of notable concern. Based on the relatively high rate of fosfomycin susceptibility, it would be desirable to license parenteral fosfomycin in the region.

Mortality in paediatric acute myeloid leukaemia.

OBJECTIVE: To analyse the common causes of death in paediatric acute myeloid leukaemia cases at a tertiary care facility. METHODOLOGY: The retrospective study was conducted at the Paediatric Oncology Department of the Combined Military Hospital, Rawalpindi, Pakistan, and comprised newly-registered cases of acute myeloid leukaemia aged <18 years from January 1, 2012, onwards and who completed their treatment before January 31, 2019. Data was retrieved from medical records and was analysed using SPSS 23. RESULTS: Of the 206 cases, 130(63.1%) were males and 76(36.9%) were females. Overall mean age at diagnosis was 5.96±3.57 years (range: 9 months to 15 years). Of the total, 6(2.9%) patients died before the start of treatment. Of the remaining, 43(21.5%) patients died during 1st induction chemotherapy, and 16(8%) during the post-induction period, with overall treatment-related mortality being 65(31.5%). The main cause of death during the first two weeks of induction was infection, while infection followed by multi-organ failure was the main cause of mortality in the second phase. A total of 130(63%) patients completed the treatment. Overall survival was 81(62.3%) while disease-free survival was 77 (59.2%). CONCLUSIONS: Overall treatment-related mortality rate in paediatric acute myeloid leukaemia cases was found to be high. Pregnancies achieved by IVF/ICSI, being complicated with severe OHSS could be related to gestational hypertension.

Diabetes and Ramadan: Utility of flash-glucose monitoring derived markers of glycaemic control and comparison with glycosylated haemoglobin.

AIMS: Flash glucose monitoring (FGM)-derived markers of glucose control and variability and laboratory measured HbA1c among patients with diabetes on insulin in context of Ramadan fasting (RF) were examined and compared. METHODS: FGM data on insulin-treated patients (n = 20, age 42.3 ±â€¯11.4 years; 18 male, 2 female; 13 with type 1 and 7 with type 2 diabetes) who fasted during Ramadan were used to calculate Q-score as an indicator of glycaemia before, during and after RF. Post-hoc analysis in a group of patients (n = 12) who had HbA1c available and appropriate for these periods was performed. Other relevant data were extracted from patient records. RESULTS: Mean glucose (9.6 ±â€¯1.32 v 10.78 ±â€¯1.64 mmol/l; P < 0.0001) and Q-score increased significantly with Ramadan fasting and reduced after Ramadan. Post-hoc subgroup analysis showed a significant rise in eA1c (7.2 ±â€¯0.4%; 55.0 ±â€¯4.4 mmol/mol v 7.7 ±â€¯0.5%; 61.0 ±â€¯5.5 mmol/mol) but not in laboratory HbA1c with Ramadan fasting; eA1c reduced after Ramadan (P = 0.018). CONCLUSIONS: Ramadan fasting was associated with a deterioration in overall glucose control and time in hyperglycaemia in insulin-treated patients. FGM-derived markers are useful and a preferable alternative to HbA1c in Ramadan studies.

Interface structure and composition of MoO3/GaAs(0 0 1).

We studied growth, structure, stress, oxidation state as well as surface and interface structure and composition of thermally-evaporated thin MoO3 films on the technologically important III/V-semiconductor substrate GaAs(0 0 1). The MoO3 films grow with Mo in the 6+ oxidation state. The electrical resistance is tunable by the oxygen partial pressure during deposition from transparent insulating to semi-transparant halfmetallic. In the investigated growth temperature range (room temperature to 200 °C) no diffraction spots are detected by x-ray diffraction. However, high resolution transmission electron microscopy reveals the formation of MoO3 nanocrystal grains with diameters of 5-8 nm. At the interface a ≈3 nm-thick intermediate layer has formed, where the single-crystal lattice of GaAs gradually transforms to the nanocrystalline MoO3 structure. This interpretation is corroborated by our in situ and real-time stress measurements evidencing a two-stage growth process as well as by elemental interface analysis revealing coexistance of Ga, As, Mo, and oxygen in a intermediate layer of 3-4 nm.

Plasmid-Mediated Colistin Resistance Gene mcr-1 in an Escherichia coli ST10 Bloodstream Isolate in the Sultanate of Oman.

AIMS: To identify plasmid-mediated colistin resistance in clinical Enterobacteriaceae isolates in Oman, where this resistance mechanism has not been encountered yet. MATERIALS/METHODS: Twenty-two colistin-resistant Enterobacteriaceae clinical isolates collected between July 2014 and June 2016 in a tertiary care hospital in Muscat were screened by PCR for the mcr-1 and mcr-2 genes. The strain identified as mcr-1 positive was genotyped and its antibiotic susceptibility was established. The mcr-1 containing plasmid was mobilized into Escherichia coli K-12 and its sequence was determined. RESULTS: A single E. coli isolate (OM97) carrying mcr-1 gene was identified, while no strains carrying the mcr-2 gene was found. E. coli OM97 was isolated in June 2016 from blood culture of a male patient with multiple comorbidities. It belonged to ST10. Beyond colistin, it was resistant to amoxicillin-clavulanic acid, piperacillin-tazobactam, amikacin, ciprofloxacin, tetracycline, and cotrimoxazole. The mcr-1 gene was located on a conjugative IncI2-type plasmid of 63722 bp size, which did not harbor any further resistance genes. The genetic surrounding of the mcr-1 gene lacked the ISApl1 element. CONCLUSIONS: Although colistin resistance caused by the mcr-1 gene is not common in our collection of clinical isolates, the occurrence of the plasmid-mediated colistin resistance in an E. coli ST10 strain is of concern as this clonal group was already shown to spread ESBL genes and quinolone resistance worldwide. It is especially worrisome that as the mcr-1 gene occurred in a non-ESBL, carbapenem-susceptible E. coli strain, current susceptibility testing algorithms may not detect its presence.

Effect of HCV infection on hepatic fibrosis in patients of thalassaemia major.

OBJECTIVE: To investigate the effect of HCV infection on hepatic fibrosis in patients of thalassaemia major with iron overload in order to modify Pesaro criteria for classification into prognostic groups for allogenic haemopoietic stem cell transplant in these patients. DESIGN: Cross-sectional comparative study. PLACE AND DURATION OF STUDY: Armed Forces Institute of Pathology, Armed Forces Bone Marrow Transplant Center and Departments of Pediatrics of Military Hospital and Combined Military Hospital, Rawalpindi, from July 2003 to June 2004. SUBJECTS AND METHODS: Twenty-eight HCV- and 18 HCV+ patients of thalassaemia major, who were prospective recipients of allogeneic bone marrow transplant, were included in the study. Serum ferritin was estimated by chemiluminescent immunoassay. Degree of fibrosis in liver biopsy was scored using Knodell s scoring system. Correlation between the two was evaluated statistically through Pearson s correlation coefficient. RESULTS: Mean serum ferritin was lower and degree of hepatic fibrosis was less in hepatitis C negative patients of TM. The correlation between serum ferritin and the degree of hepatic fibrosis was much stronger in hepatitis C negative patients with r value of 0.507 and p value of 0.006, which was statistically significant. CONCLUSION: A strong correlation between serum ferritin and degree of hepatic fibrosis was observed in patients of thalassaemia major not infected with hepatitis C infection. Serum ferritin levels alone are, therefore, not sufficient to assess degree of fibrosis in HCV positive patients of TM.

Childhood visceral leishmaniasis in Muzaffarabad, Azad Jammu and Kashmir: frequency and response to treatment in 61 cases.

OBJECTIVE: To study the epidemiology and status of resistance to antimonial compounds of paediatric hospital population with visceral leishmaniasis in Muzaffarabad, Azad Jammu and Kashmir, Pakistan. METHODS: Children admitted between January to December 1999 in Azad Kashmir Combined Military Hospital Muzaffarabad and diagnosed as Visceral Leishmaniasis by demonstration of Leishmania parasites in bone marrow aspirate were included in the study. Patients received meglumine antimoniate for 21 days. The demographic information and time taken for resolution of fever after initiation of treatment were recorded. RESULTS: During study period out of 3520 paediatric admissions, 61 patients had visceral leishmaniasis. The frequency of disease was 1.73%. Median age of the patients was 18 months. Eighty two percent cases reported during non-winter seasons. Fifty nine (96.7%) patients responded to treatment with antimonial compounds. Median time taken for resolution of fever was 5.7 days. Two of the patients died during the study period. CONCLUSION: Childhood visceral leishmaniasis is common in Muzaffarabad and there is no resistance to antimonial compounds.

Clinicopathological features of childhood visceral leishmaniasis in Azad Jammu & Kashmir Pakistan.

BACKGROUND: In Pakistan visceral leishmaniasis (VL) is endemic in Azad Jammu & Kashmir. Northern Areas and Northwest Frontier Province; the areas which lack adequate diagnostic facilities. This study describes the clinical and laboratory features in 61 cases of childhood VL. METHODS: All the children below 12 years of age who were managed as indoor cases from 1st Jan 1999 to 31st Dec 1999 were included in this study. The diagnosis of VL was established by demonstration of leishmania parasites in bone marrow aspiration. The demographic information, physical signs at presentations and results of complete blood picture and formol gel test were recorded. RESULTS: Median age of the patients was 18 months. Eighty four percent children were malnourished. Mean duration of fever before diagnosis was 45 days. Hepatosplenomegaly was present in all cases with mean enlargement of spleen and liver 6.8 and 3.2 cm respectively. Mean haemoglobin level. WBC and platelet counts were 6.7 g/dl, 4.8 x 109 /l and 70 x 109 /l respectively. Absolute neutrophil count was <1.5 x 109 /l in 61% cases. Mean reticulocyte count was 6.2%. There was significant negative correlation (p= 0.014) between haemoglobin level and spleen size. Formol gel test was positive in all cases. Mean hospital stay to established diagnosis was 8.6 days. CONCLUSION: The clinical and laboratory features of childhood VL in Azad Jammu and Kashmir are similar to Mediterranean type of disease caused by leishmania infantum. Cytopenia with high or normal reticulocyte count provides a useful clue to diagnosis in a febrile patient with hepatosplenomegally in an endemic area.