Optimization and evaluation of venlafaxine hydrochloride fast dissolving oral films

Three factors, three levels (3³) full factorial design was used to develop venlafaxine HCl fast dissolving oral films (FDOFs) to optimize the concentrations of the film forming polymer; hydroxypropyl methylcellulose HPMC (X1), superdisintegrant; sodium starch glycolate SSG, (X2) and glycerol as the film plasticizer (X3). Effects of the three factors on the disintegration time (Y1), swelling index (Y2), and dissolution efficiency at 15 min; DE%15 (Y3) of the prepared FDOFs were evaluated by using statistical models. The optimized film formula was characterized in term of x-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and morphological characteristics.Disintegration time was found to increase with the increase in HPMC (X1) concentration, and the shortest disintegration time (21.67 ± 2.08 s) was observed in case of F2 formula (lowest HPMC level and highest glycerol level in absence of SSG). The highest swelling index (3.64 ± 0.59) was observed in case of film formula F1 (medium concentrations of both HPMC and glycerol and highest SSG concentration. The results also indicated that as the concentration of HPMC increased the DE%15 decreased. SSG (X2), with highest value (72.33 ± 1.71%) was recorded for in case of F12 (using 2% HPMC, 5%SSG and 1.5% glycerol). The optimized FDOF formula derived by the statistical models suggested 2% HPMC, 5% SSG, and 1% glycerol.The data obtained from DSC and XRPD revealed no interaction between drug and FDOT excipients. In addition, XRPD studies proved that the venlafaxine HCl was homogeneously dispersed in the film matrix.     

Predictors of renal replacement therapy and mortality in children with chronic kidney disease

Objectives:

To study the epidemiology of chronic kidney disease (CKD) in children, and to look for risk factors to predict renal replacement therapy (RRT) and mortality.

Methods:

This is a retrospective cohort study conducted at King Abdulaziz University Hospital, Jeddah, Saudi Arabia between 2006 and 2014, where the files of 1,000 children with CKD were reviewed. We determined the effect of consanguinity and hypertension, and being a Saudi indigene on mortality and RRT. We compared children with congenital versus non-congenital causes of CKD.

Results:

The mean±standard deviation age at presentation was 4.9±4.3 years. The median duration of follow up was 1.5 (interquartile range [IQR]: 0.4-4.0) years. Only 9.7% of children received RRT, and 8.3% died. The underlying etiology for CKD was congenital in 537 children. The congenital CKD group presented at a younger age group (3.5±4.0 versus 6.6±3.9 years, p<0.0001), had more advanced stages of CKD (p<0.0001), higher rates of consanguinity (75.4% versus 47.1%, p<0.0001), and RRT (p<0.004) than children with non-congenital CKD. Risk factors for RRT among children with CKD include being a Saudi indigene (relative risk [RR]=1.49, 95% confidence interval (CI): 1.01-2.21), and hypertensive (RR=5.29, 95% CI: 3.54-7.91). The risk factor for mortality was hypertension (RR=2.46, 95% CI: 1.66-3.65).

Conclusion:

Congenital causes of CKD represent the main etiology of CKD in children living in the western province of Saudi Arabia. Significant risk factors for RRT include congenital CKD, Saudi nationality, and hypertension. Hypertension is also a predictor of mortality in children with CKD.Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function, present for more than 3 months with implications for health.1 Children with CKD who are on renal replacement therapy (RRT) have higher mortality rate, which is at least 30-fold higher than their age-matched peers.2 Epidemiological information on the incidence and prevalence of pediatric CKD in children is currently limited,3 particularly in developing countries. Furthermore, most of the available epidemiological data are from end-stage kidney disease (ESKD) registries, and information on the earlier stages of pediatric CKD is still lacking.4 The early stages of CKD in the pediatric population are in most cases asymptomatic, and are therefore under-diagnosed and under-reported.4 Direct comparisons of the incidence and prevalence rate of pediatric CKD are complex since each pediatric CKD registries uses different definition; some depend on the estimated glomerular filtration rate (eGFR), while others use serum creatinine levels. The incidence in Europe was consistent between 11-12 per million of the age-related population (pmarp) for CKD stages 3-5, and 8 pmarp for CKD stages 4-5.4 Data available on the exact prevalence of various kidney diseases in the Arab world is very limited. Most of the data come from small studies and are of limited generalizability.5 In Kuwait, the mean incidence was found to be as high as 38 pmarp, while the prevalence was as also high at 329 pmarp in 2003.6 An incidence of 11 pmarp and a prevalence of 51 pmarp has been reported in Jordanian children.7 The epidemiological data of CKD in children is very scarce in Saudi Arabia. One study from Asir reported that the mean annual incidence of CRF of 15.6 per million children, the mean annual incidence of ESRF is 9.2 per million children, and congenital anomalies of the urinary system constitute the most common cause of chronic renal failure (CRF).8 Another study from Jeddah reported similar results.9 All these studies enrolled a small number of children (less that 100). In the light of a limited data available regarding the epidemiology of CKD in children in Saudi Arabia, we performed a retrospective study to examine the risk factors for RRT and mortality among children with CKD.     

Epidemiology of infant burn in Eastern Saudi Arabia

Objectives:

To identify the epidemiology, pattern, outcome, and impact of infant burns in Eastern Saudi Arabia.

Methods:

We conducted a retrospective review of admitted infants charts over 4 years (2008-2013) at the Burn Unit of King Fahad Hospital, Hofuf, Al-Ahsa, Saudi Arabia. The charts were reviewed for age, gender, etiology, site of injury, total body surface area (TBSA), depth of burn, hospital stay, and discharge status.

Results:

The total number of admissions to the Burn Unit was 510 cases. Out of these cases, 84 were infants, constituting 16.5% of total admissions. Scald burn was the most common etiology affecting 73 infants (86.9%). The highest percentage of total body surface area was between 5-10%, which occurred in 41 infants (48.8%). The average hospital stay was 10 days. No infant mortality was reported during this period.

Conclusion:

The prevalence of burns among infants in our hospital is high, and preventive measures must be implemented to decrease the occurrence of burns in this age group.Al-Ahsa is the largest governorate in Saudi Arabia’s Eastern Province, with a population of 1,079,156 people in 2010.1 Saudi Arabia is a young populated country, as 30.7% is below the age of 14.2 The number of pediatric burns is reportedly high in Saudi Arabia, mostly due to household hazards or due to habits that can be a possible burn source such as drinking tea and coffee from hot pots.3,4 Limited data is available on infant burns, worldwide.5 There is a scarcity of published data on infant burns from Saudi Arabia. The aim of this study is to identify the epidemiology, pattern, outcome, and impact of infant burns in eastern Saudi Arabia. Determine the burden of infant burns on the hospital by determining the number of infant admissions, and length of stay in the hospital. Finally start a preventive measures and public awareness to decrease the incidence of these burns.     

Calcium Antagonists in Patients with Type 2 Diabetes and Hypertension

Hypertension is twice as common in patients with diabetes compared to those without diabetes. It accounts for up to 75% of cardiovascular disease risk leading to the substantial increase in morbidity and mortality. Control of blood pressure in people with diabetes has been shown in randomized controlled trials to decrease cardiovascular risk and improve outcome especially in preventing stroke. A target blood pressure goal of <130/80 mm Hg is currently recommended for patients with diabetes. However, less than 1/3 of these patients achieve such a goal. This is in part due to the inherent difficulty in controlling blood pressure in these patients where hypertension is usually associated with increased salt sensitivity, volume expansion and isolated systolic hypertension. Therefore, patients with diabetes usually require multiple medications for optimal blood pressure control. Calcium channel antagonists have been shown in large clinical trials to be both safe and effective in controlling blood pressure in diabetic patients and will continue to play a major role in the management of hypertension in this population, particularly in the combination therapy that these patients usually require.     

Oncology research in Saudi Arabia over a 10-year period: A synopsis

Objectives:To assess the quality and quantity of Saudi publications in oncology over a 10-year period.Methods:A systematic PubMed search was conducted between January 2008 and December 2017 to retrieve all Saudi oncology publications. Data about the articles was collected. The level of evidence (LOE) was independently assessed by 2 authors. Two 5-year periods (2008-2012 and 2013-2017) were compared using the relevant parameters. Clinicaltrials.gov was also searched for all oncology trials registered in Saudi Arabia.Results:A total of 839 publications met our inclusion criteria. The most common type of research was case series, totaling 32% of all publications. Clinical trials formed less than 2% of the total. The LOE was I, II, III, and IV in 0.3%, 2.1%, 58.4%, and 39.3% of the included publications, respectively. The LOE was the same in the 2 periods. There were more publications in international journals (p=0.004), more international collaborations (p=0.001), and higher journal impact factors (p=0.037) in 2013-2017 than in 2008-2012. Only 76 registered clinical trials were found in the Clinicaltrials.gov registry.Conclusion:Despite an increase in the number of Saudi publications in the field of oncology over time, the LOE did not change. There were, however, some improvements in the international collaboration and journal impact factor, as well as an increase in the number of studies published in international journals. These observations call for a national strategy to improve oncology research in Saudi Arabia.     

Measuring resistant-genotype transmission of malaria parasites: challenges and prospects

Increased gametocytemia in infections with resistant strains of Plasmodium species and their enhanced transmissibility are a matter of concern in planning and evaluating the impact of malaria control strategies. Various studies have determined weekly gametocyte carriage in response to antimalarial drugs in clinical trials. The advent of molecular biology techniques makes it easy to detect and quantify gametocytes, the stages responsible for transmission, and to detect resistant genotypes of the parasite. With the validation of molecular markers of resistance to certain antimalarial drugs, there is a need to devise a simpler formula that could be used with these epidemiological antimalarial resistance tools. Theoretical models for transmission of resistant malaria parasites are difficult to deploy in epidemiological studies. Therefore, devising a simple formula that determines the potential resistant-genotype transmission of malaria parasites should provide further insights into understanding the spread of drug resistance. The present perspective discusses gametocytogenesis in the context of antimalarial treatment and drug resistance. It also highlights the difficulties in applying the available theoretical models of drug resistance transmission and suggests Rashad’s devised formula that could perhaps be used in determining potentially transmissible resistant genotypes as well as in mapping areas with high potential risk for the transmission of drug-resistant malaria. The suggested formula makes use of the data on gametocytes and resistant genotypes of malaria parasites, detected by molecular techniques in a certain geographical area within a particular point in time, to calculate the potential risk of resistant genotype transmission.     

Association study of human leukocyte antigen-DRB1 alleles with rheumatoid arthritis in south Tunisian patients

The aim of this study is to explore relationship between HLA-DRB1 alleles and the susceptibility and clinical features of rheumatoid arthritis (RA) in the south Tunisian population. We studied 142 RA patients and 123 controls matched for age, sex, and ethnicity. HLA-DRB1 genotyping and HLA-DRB1*04 subtypes were performed using polymerase chain reaction/sequence-specific primers. Association was assessed based on the χ (2) test and odds ratio with 95% confidence interval. For multiple comparisons, p value was corrected (p (c)) with Bonferroni test. Two alleles, HLA-DRB1*04 (p=0.045, p(c)=NS) and HLA-DRB1*10 (p=0.021, p(c)=NS), were found to have increased frequencies in RA patients compared to controls. In contrast HLA-DRB1*08 allele was found to have a decreased frequency in patients compared to controls (p=0.044, p(c)=NS). Molecular subtyping of the most prevalent allele (DRB1*04) revealed increased frequencies of HLA-DRB1*04:05 in patients compared to controls (p=0.013, p(c)=NS) whereas HLA-DRB1*04:02 showed a protective effect (p=0.005, p(c)=0.04). Moreover, stratified analyses indicated statistically significant associations between HLA-DRB1*04 allele and anti-cyclic peptides antibodies positivity (ACPA(+)) and rheumatoid factor positivity (RF(+); p(c)=0.03, for both subgroups), HLA-DRBI*10 and ACPA(+) and the presence of another autoimmune disease (p(c)=0.05 and p(c)=0.007, respectively), and HLA-DRB1*04:05 and RF(+) and erosion (p(c)=0.005 and p(c)=0.049; respectively). A significant decrease in the frequency of the DRB1*04:02 allele was observed in patients with ACPA(+) and RF(+) subgroups (p(c)=0.04 and p(c)=0.02, respectively). Our results showed that there was a trend of positive association of HLA-DRB1*04 and HLA-DRB1*10 with RA as such and significant associations with the disease severity in the south Tunisian population.     

Renal impairment in children with posterior urethral valves

Background

Posterior urethral valves (PUV) are a common cause of end-stage renal failure in childhood. Our aim was to describe a cohort of patients with PUV and to investigate the predictors of renal impairment.

Methods

We performed a retrospective chart review of children with PUV who were followed at King Abdulaziz University hospital between 2002 and 2011.

Results

The cohort comprised 68 boys. There was a significant difference in the duration of follow-up (p?=?0.024), nadir serum creatinine (p?<?0.001), and last known serum creatinine level (p?=?0.001) between the patients with and without renal impairment. The duration of follow-up appeared to be a significant predictor for serum creatinine doubling (p?=?0.003; odds ratio, 1.8). There was no difference in the age of presentation, age at the time of the study, and first or last serum creatinine between children who initially had vesicostomy and children who had ablation.

Conclusions

Ablation of PUV or vesicostomy did not influence kidney function in our study cohort. Children with a normal nadir serum creatinine who presented early had a better outcome.