Generic orphan drug substitution: a critical analysis of global practices and Saudi Arabia's perspective.

In an era of cost pressure, substituting generic drugs represents one of the main cost-containment strategies of healthcare systems. Despite the obvious financial benefits, in a minority of cases, substitution may require caution or even be contraindicated. In most jurisdictions, to obtain approval, the bioequivalence of generic products with the brand-name equivalent needs to be shown via bioavailability studies in healthy subjects. Rare diseases, defined as medical conditions with a low prevalence, are a group of heterogenous diseases that are typically severe, disabling, progressive, degenerative, and life-threatening or chronically debilitating, and disproportionally affect the very young and elderly. Despite these unique features of rare diseases, generic bioequivalence studies are typically carried out with single doses and exclude children or the elderly. Furthermore, the excipients and manufacturing processes for generic/biosimilar products can differ from the brand products which may affect the shelf-life of the product, its appearance, smell, taste, bioavailability, safety and potency. This may result in approval of generics/biosimilars which are not bioequivalent/comparable in their target population or that meet bioequivalence but not therapeutic equivalence criteria. Another concern relates to the interchangeability of generics and biosimilars which cannot be guaranteed due to the phenomenon of biocreep. This review summarizes potential concerns with generic substitution of orphan drugs and discusses potentially problematic cases including narrow therapeutic index drugs or critical conditions where therapeutic failure could lead to serious complications or even death. Finally, we put forward the need for refining regulatory frameworks, with emphasis on Saudi Arabia, for generic substitution and recent efforts toward this direction.

The impact of child-specific characteristics on warfarin dosing requirements.

Background: The influence of child characteristics on warfarin dosing has been reported; however, there is no consensus on the nature and extent of this effect. Objectives: To investigate the impacts of the demographic and clinical characteristics of children on the warfarin dose required to achieve a therapeutic international normalization ratio (INR). Methods: This retrospective cohort study included children aged 3 months to 14 years old who were prescribed warfarin for 3 months or longer with a "stable INR." The primary outcome was the total daily dose (TDD) and total weekly dose of warfarin required to achieve a therapeutic INR target. Results: We included 127 patients with a mean age of 7.7 ± 3.7 years and a median weight of 22 (IQR, 16-33) kg. Of the sample, 55 patients (43.3%) required a TDD of ≤0.1 mg/kg. The TDD for children younger than 5 years, 5 to 10 years, and older than 10 years were 0.14 ± 0.06 mg/kg, 0.12 ± 0.05 mg/kg, and 0.096 ± 0.04 mg/kg, respectively (P = .002). Overweight and obese children required a smaller TDD than normal-weight children: 0.09 ± 0.05 vs 0.13 ± 0.05 mg/kg (P = .004), which was similar for underweight children. A lower body surface area (<0.5 m2) required a higher dose. All the other variables did not affect warfarin doses. The incidence of a subtherapeutic or supratherapeutic INR was independent of demographic or clinical variables. Conclusion: The study confirmed that the patient demographics affect the daily warfarin dose required to achieve the INR target. However, they do not have any predictive value for the incidence of out-of-range-INR.

Therapeutic benefits of quercetin in traumatic brain injury model exposed to cigarette smoke.

Scientific evidences reported the deleterious effect of cigarette smoking or passive smoking on brain health particularly cognitive functions, blood-brain barrier (BBB) permeability, up-regulation of inflammatory cascades, and depletion of the antioxidant system. These combined effects become more progressive in the events of stroke, traumatic brain injury (TBI), and many other neurodegenerative diseases. In the current study, we investigated the long-term administered therapeutic potential of quercetin in ameliorating the deleterious neurobiological consequences of chronic tobacco smoke exposure in TBI mice. After exposure to 21 days of cigarette smoke and treatment with 50 mg/kg of quercetin, C57BL/6 mice were challenged for the induction of TBI by the weight drop method. Subsequently, a battery of behavioral tests and immunohistochemical analyses revealed the beneficial effect of quercetin on the locomotive and cognitive function of TBI + smoked group mice (p < 0.05 vs control sham). Immunohistochemistry analysis (Nrf2, HO-1, NFkB, caspase 3) demonstrated a marked protection after 21 days of quercetin treatment in the chronic tobacco smoking group possibly by up-regulation of antioxidant pathways, and decreased apoptosis. In conclusion, our findings support the therapeutic effectiveness of quercetin in partly protecting the central neurological functions that become aberrantly impaired in combined habitual cigarette-smoking individuals impacted with TBI.

Evaluation of Salivary Pepsin Levels and Dental Erosion in Patients With Gastroesophageal Reflux Disease.

Background Gastroesophageal reflux disease (GERD) is a common gastrointestinal condition affecting many individuals worldwide. GERD is characterized by esophageal symptoms and may contribute to various extraesophageal symptoms, including dental erosion (DE). This study aimed to estimate the levels of pepsin in the saliva of GERD patients to evaluate and compare the activity of pepsin between the GERD and healthy groups and investigate the prevalence of DE in the GERD group. Methodology In this case-control study, 40 patients with GERD, diagnosed with an endoscope, and 35 healthy subjects were included. Patients and healthy individuals were subjected to the GERD questionnaire (GerdQ). A dental assessment was performed using the Basic Erosive Wear Examination (BEWE). A total score of the BEWE risk level was obtained by summing the scores obtained in each sextant (no risk = ≤2, low risk = 3-8, medium risk = 9-13, and high risk = >13). Five milliliters of unstimulated saliva were collected in a sterile tube. The salivary pepsin levels examined using the enzyme-linked immunosorbent assay were recorded for both groups. Results DE was significantly more frequent in GERD patients compared to healthy subjects. Overall, 32 (80%) GERD patients and 11 (31.4%) healthy individuals had DE risk. The mean salivary pepsin was 43.60 ± 10.61 ng/mL in the GERD group and 20.60 ± 9.27 ng/mL in the healthy group. A statistically significant difference was found in pepsin levels between the two groups (p < 0.001). Conclusions The study concluded that GERD patients had a higher prevalence of DE than healthy individuals. Our findings suggest that elevated salivary pepsin levels and their role as a factor responsible for DE need further evaluation to understand the mechanisms of pepsin-mediated damage leading to DE.

Access and efficacy of university mental health services during the COVID-19 pandemic.

Objective: This study sought to understand the mental health issues, mental health support and efficacy of that support among university students. Participants: All students enrolled in a College of Arts and Sciences at one mid-size university received an email that contained a link to an anonymous, online questionnaire developed and disseminated through PsychData. 162 students completed the questionnaire. Methods: Mixed methods: Data was summarized using descriptive analysis, testing for significance, testing for differences, and content analysis. Results: Participants reported high levels of anxiety (76%) and depression (65%). Results indicated that participant demographics were associated with types of mental access, and support. Unexpected results included lack of knowledge or information on cost, and how to access mental health services hindered access for participants, and although telehealth was the most widely used support, in contrast to other studies, participants indicated a preference for face-to-face mental health services. Conclusion: Results highlight the need for improving communication about and access to mental health services in higher education Recommendations and implications for policy and support services are provided.

Vancomycin dosing required to achieve a therapeutic level in children post-surgical correction of congenital heart disease.

The vancomycin dosing range for safe and effective treatment remains uncertain for children who had corrective surgery for a congenital heart disease (CHD). We aimed to determine the vancomycin dosing requirements for this subgroup of patients. This prospective cohort study included children younger than 14 years old with CHD who received intravenous vancomycin for at least 3 days at the Pediatric Cardiology section of King Abdulaziz Medical City, Riyadh. In total, 140 pediatric patients with CHD were included with a median age of 0.57 years (interquartile range 0.21-2.2). The mean vancomycin total daily dose (TDD), 37.71 ±â€…6.8 mg/kg/day, was required to achieve a therapeutic trough concentration of 7-20 mg/L. The patient's age group and the care setting were significant predictors of the vancomycin dosing needs. Neonates required significantly lower doses of 34 ±â€…6.03 mg/kg/day (P = .002), and young children higher doses of 43.97 ±â€…9.4 mg/kg/day (P = .003). The dosage requirements were independent of the type of cardiac lesion, cardiopulmonary surgery exposure, sex, and BMI percentile. However, the patients in the pediatric cardiac ward required higher doses of vancomycin 41.08 ±â€…7.06 mg/kg/day (P = .039). After the treatment, 11 (8.5%) patients had an elevated Scr, and 3 (2.3%) patients developed AKI; however, none of the patients' sociodemographic factors or clinical variables, or vancomycin therapy characteristics was significantly associated with the renal dysfunction. Overall, the vancomycin TDD requirements are lower in pediatric post-cardiac surgery compared to non-cardiac patients and are modulated by several factors.

Vasopressin associated hyponatremia in critically ill children: A cross-sectional study.

Background: The association of hyponatremia with vasopressin therapy in children is controversial. We aimed to evaluate the incidence and severity of hyponatremia associated with the administration of vasopressin in critically ill pediatric patients. Methods: This retrospective cross-sectional study included children younger than 14 years who were admitted to the pediatric or pediatric cardiac intensive care units and received vasopressin for at least 24 h. Results: In total, 176 critically ill pediatric patients were enrolled, with a median age of 22 days (7.3-146). The mean sodium level was notably decreased from 143.5 mEq/L ± 7.15 at the baseline to 134.3 mEq/L ± 7.7 at the 72-hour measurement after the initiation of vasopressin and varied significantly at all intervals from the baseline measurement (P < 0.001). Twenty-four hours after the discontinuation of vasopressin, more than half of the patients had hyponatremia. The highest proportion had mild hyponatremia (32.8%), followed by moderate hyponatremia (13.1%), and profound hyponatremia (7.5%). The incidence of hyponatremia was independent of gender (P = 0.94) or age group (P = 0.087). However, more than two-thirds of the moderate-profound cases and more than one-third of mild cases were observed in the neonate group (P = 0.043). The vasopressin dose did not affect the incidence (P = 0.25) or the severity of the hyponatremia (P = 0.56). Notably, all laboratory and hemodynamic parameters varied significantly at the end of therapy, compared to the baseline. Conclusions: Continuous monitoring for hyponatremia when children are placed on vasopressin is essential to protect against more severe complications.

An assessment of asthma exacerbations in pediatric patients using a long-acting B2-agonist plus inhaled corticosteroid versus an inhaled corticosteroid alone.

Background: An asthma exacerbation is an anticipated sudden worsening of the disease severity, which usually does not respond to conservative therapy. The management of asthma depends on the severity of the disease symptoms, which includes an inhaled corticosteroid (ICS) and a bronchodilator. This study aimed to assess the efficacy of combining a long-acting B2-agonist (LABA) with ICS, compared to ICS alone, to reduce the incidence of asthma exacerbations in pediatric patients, diagnosed with severe persistent asthma. Methods: A retrospective analysis of the medical records was conducted for 586 children, admitted to the Emergency Department (ED) at King Abdullah Specialized Children Hospital in Riyadh, Saudi Arabia, for the management of severe persistent asthma symptoms, from January 2016 to September 2019. Results: The majority (n = 480, 81.9%) of the patients received fluticasone (Flovent)® as the standard of care ICS treatment for controlling asthma, and a small proportion (n = 106, 18.1%) were treated with a combination of LABA and ICS. A significant increase in the frequency of recurrent asthma exacerbation episodes occurred in the group receiving ICS alone (98.5%), compared to 67.0% in the combination group (p < 0.0001). Moderate to severe exacerbations were significantly higher in the ICS group compared to the combination group (95.6% versus 84.5%, respectively, p = 0.0005). Conclusions: The current results confirm the substantial efficacy of the LABA/ICS combination therapy in reducing the incidence and severity of asthma exacerbations in pediatric patients, compared to ICS alone.

Clinico-pathological predictors of clinical complete response in rectal cancer.

PURPOSE: Prediction of clinical complete response in rectal cancer before neoadjuvant chemo-radiotherapy treatment enables treatment selection. Patients predicted to have complete response could have chemo-radiotherapy, and others could have additional doublet chemotherapy at this stage of their treatment to improve their overall outcome. This work investigates the role of clinical variables in predicting clinical complete response. METHOD: Using the UK-based OnCoRe database (2008 to 2019), we performed a propensity-score matched study of 322 patients who received neoadjuvant chemoradiotherapy. We collected pre-treatment clinic-pathological, inflammatory and radiotherapy-related characteristics. We determined the odds for the occurrence of cCR using conditional logistic regression models. We derived the post-model Area under the Curve (AUC) as an indicator of discrimination performance and stated a priori that an AUC of 0.75 or greater was required for potential clinical utility. RESULTS: Pre-treatment tumour diameter, mrT-stage, haemoglobin, alkaline phosphate and total radiotherapy depths were associated with cCR on univariable and multivariable analysis. Additionally, neutrophil to lymphocyte ratio (NLR), neutrophil-monocyte to lymphocyte ratio (NMLR), lymphocyte count and albumin were all significantly associated with cCR on multivariable analysis. A nomogram using the above parameters was developed with a resulting ROC AUC of 0.75. CONCLUSION: We identified routine clinic-pathological, inflammatory and radiotherapy-related variables which are independently associated with cCR. A nomogram was developed to predict cCR. The performance characteristics from this model were on the prior clinical utility threshold. Additional research is required to develop more associated variables to better select patients with rectal cancer undergoing chemoradiotherapy who may benefit from pursuing a W&W strategy.

The effects of the antecedent use of inhaled steroid on the clinical course of COVID-19: A retrospective study of asthmatic patients.

BACKGROUND: There is conflicting evidence regarding the effect of asthma and its different therapeutic options on COVID-19 severity and the clinical outcomes. AIM: This study aimed to investigate the relationship between using inhaled corticosteroids (ICS) by asthmatic patients and the severity of COVID-19. MATERIALS AND METHODS: This retrospective observational study was conducted from March 15 to October 23, 2020 and included data of all COVID-19 asthmatic patients (n = 287) at King Abdulaziz Medical City. Twelve patients were excluded due to poor medication history documentation or using ICS for non-asthma indication. Ordinal logistic regression was used to determine the clinical variables that affect COVID-19 severity. The clinical outcomes of ICS and non-ICS users were compared. RESULTS: Of the sample (n = 275), 198 (72%) were using ICS therapy. No significant difference was found between ICS and non-ICS users in disease severity (P = 0.12), mortality (P = 0.45), ICU admission (P = 0.78), and the occurrence of complications. However, the number of days on ventilation were significantly increased in ICS users (P = 0.006). Being prescribed the ICS/LABA combination (adj OR: 0.72 [0.15,1.2]; P = 0.021), being hypertensive (adj OR: 0.98 [0.28,1.6]; P = 0.006), having cancer (adj OR: 1.49 [0.12, 2.8]; P = 0.033), or having diabetes (adj OR: 0.75 [0.09, 1.4]; P = 0.024) could not increase the risk for more severe disease. CONCLUSION: Overall, ICS therapy did not alter the COVID-19 severity or mortality in asthmatic patients. The continued use of ICS during the pandemic should be encouraged to prevent asthma exacerbations.

Parenteral versus enteral nutrition in children with post-surgical congenital heart disease.

OBJECTIVE: The association of malnutrition with congenital heart disease (CHD) is well documented. Studies comparing the effects of parenteral nutrition (PN) and enteral feeding (EF) on the post-surgical correction of CHD are not available. We compared the effects of PN with EF on the nutritional status of children post-cardiac surgery. METHODS: A retrospective cohort study was conducted with 72 children aged ≤6 years who had at least one heart surgery between 2010 and 2016. Malnutrition was defined as a weight for height Z-score (WHZ) below -2. The primary endpoint was the change in the mean WHZ Z-score from the baseline. All statistical analyses were performed using SPSS 21.0 [Release 21.0.0.0, IBM, USA]. RESULTS: The sample size realized as 72 (n = 72). The overall prevalence of malnutrition was 48%. The change in height of the PN group was significantly higher than the EF group (14.2 ± 7.6 cm vs. 7.4 ± 6.3, P = 0.010), but the weight change was not significantly different (P = 0.28). The post-surgery Z-scores were significantly lower in the PN group and the Z-score change was marginally smaller (P = 0.086), indicating lower growth levels post-surgery. The PN group had a significantly higher incidence of post-surgical malnutrition (P = 0.046). Patients who received PN had significantly less improvement (more negative change) in the Z-score levels compared to the EF group (PE = -1.42, 95% confidence interval [CI] = [-2.48, -0.35]; P = 0.011). CONCLUSION: Malnutrition occurs frequently with CHD. PN does not add any nutritional benefits compared with EF. EF should always be the preferred method of nutrition unless contraindicated.

Synthesis of porous 2D layered nickel oxide-reduced graphene oxide (NiO-rGO) hybrid composite for the efficient electrochemical detection of epinephrine in biological fluid.

In the present research work, 2D-Porous NiO decorated graphene nanocomposite was synthesized by hydrothermal method to monitored the concentration of epinephrine (EPI). The morphology (SEM and TEM) results confirmed 2D-Porous NiO nanoparticles firmly attached over graphene nanosheets. FTIR and XPS analysis confirmed the formation of nickel oxide formation and complete reduction of GO to rGO. The electrochemical activity of the proposed NiO-rGO/GCE modified electrode on epinephrine was analyzed by simple cyclic voltammetry technique. The proposed low cost NiO-rGO/GCE modified electrode showed excellent catalytic activity over GCE and rGO/GCE electrodes. Due to its high conductivity and charge transfer ability of the NiO-rGO/GCE modified electrode exhibited high sensitivity of EPI at optimized conditions. The anodic peak current of the EPI linearly increases with increasing the concertation of EPI. A wide linear range (50 µM-1000 µM) was achieved with high correlation coefficient (R2 = 0.9986) and the limit of detection (LOD) of NiO-rGO/GCE modified electrode was calculated to be 10 µM. NiO-rGO/GCE electrode showed good stability and repeatability towards the EPI oxidation. Mainly, the proposed NiO-rGO/GCE modified electrode showed good sensitivity of EPI in the human biological fluid with high recovery percentage. The low cost, NiO-rGO/GCE electrode could be the promising sensor electrode for the detection of Epinephrine in the real samples.

Overview of dengue and Zika virus similarity, what can we learn from the Saudi experience with dengue fever?

There is high public health alert in the Kingdom of Saudi Arabia concerning Zika virus infection. So far, there is no reported outbreak. So are we at risk of this disease? Reviewing the literature of recent outbreaks of other infectious diseases in Saudi Arabia may clarify the situation. It is evident that there is some similarity between Zika and dengue regarding vector (Aedes aegypti) which is available in the Kingdom of Saudi Arabia. Furthermore, they have similar transmission process and the required environment for infection. It seems that the Kingdom has learned from previous outbreaks, so they are well prepared to face such challenges. The Saudi Ministry of Health built the command and control center to deal with the pandemic flues. Furthermore, they are trying to create a center for disease control, and they are recruiting local and international experts in monitoring the emerging infections.

Discrimination potential of root canal treated tooth in forensic dentistry.

Forensic Odontology is a vital component of forensic science and one branch involves the application of dental science to the identification of unknown human remains. The aim of this study is to investigate the discriminatory potential for identification of the radiographic morphology of obturated single root canals. Thirty periapical radiographs of patients having endodontic treatment of single rooted canals were selected randomly from the data bank of the digital X- ray system present in the restorative department, University of Science and Technology, Sudan. The post-operative radiographs were considered as an ant-mortem data "Set 1". Ten radiographs from the thirty were reprinted, labelled from (A-J) and considered as a post-mortem data "Set 2". This post-mortem group of 10 radiographs "Set 2" would be compared with the ante-mortem group of 30 radiographs comprising "Set 1". These two sets of radiographs would be examined by 40 dentally trained personnel. The thirty radiographs comprising "Set 1" and the 10 radiographs comprising "Set 2" were provided to each of the examiners who were asked to match the individual post-mortem radiographs ("Set 2") with the ante-mortem radiographs ("Set1"). The result demonstrated that 34 examiners achieved a success rate of 100%, 4 examiners achieved a success rate of 97.5% (1 mismatch) and 2 examiners achieved a success rate of 95% (2 mismatches). The radiographic images of obturated single-rooted teeth in this study were shown to have highly- specific morphological features. It is proposed that, in cases where the ante and post-mortem radiographs of a single-rooted obturated canal show similar morphology, this commonality of morphology can be used as a tool in the identification process.

Duodenal ulcer promoting gene 1 (dupA1) is associated with A2147G clarithromycin-resistance mutation but not interleukin-8 secretion from gastric mucosa in Iraqi patients.

Helicobacter pylori causes peptic ulceration and gastric adenocarcinoma. The aims were to study the influence of dupA1 positivity upon interleukin-8 (IL-8) secretion from gastric mucosa and determine the prevalence of mutations responsible for clarithromycin and fluoroquinolone resistance. DNA was extracted from 74 biopsies and the virulence factors were studied. Levels of IL-8 in gastric mucosa were measured using ELISA and the mutations responsible for clarithromycin and fluoroquinolone resistance were determined using a GenoType-HelicoDR assay. The prevalence of cagA in strains isolated from gastric ulcer (GU) and duodenal ulcer (DU) was significantly higher than those isolated from non-ulcer disease (NUD) (90% and 57.9% versus 33.3%; p 0.01). The vacA s1m1 genotype was more prevalent in patients with DU (73.7%) and GU (70%) than in those with NUD (13.3%) (p 0.01). The prevalence of dupA1 was higher in DU patients (36.8%) than those with GU (10%) and NUD (8.9%) (p 0.01). Multivariate analysis showed that a cagA+/vacA s1i1m2 virulence gene combination was independently associated with the developing peptic ulcer disease (PUD) with increased odds of developing PUD (p 0.03; OR = 2.1). We found no significant difference in the levels of IL-8 secretion in gastric mucosa infected with H. pylori dupA-negative and H. pylori dupA1-positive strains (dupA-negative: mean ± median: 28 ± 26 versus 30 ± 27.1 for dupA1; p 0.6). While 12 strains were clarithromycin resistant, only three isolates were levofloxacin resistant. A significant association was found between dupA1 genotype and A2147G clarithromycin resistance mutation (p <0.01). Further study is needed to explore the relationship between virulence factors and disease process and treatment failure.

Spontaneous clearance of hepatitis C genotype 4 after liver retransplantation.

BACKGROUND: Hepatitis C virus (HCV)-related cirrhosis remains the most common indication for liver transplantation worldwide. Graft reinfection with HCV is nearly universal, causing significant morbidity and mortality. Spontaneous clearance of HCV after liver transplantation and retransplantation is extremely rare. We report a case of spontaneous clearance of HCV genotype 4 that occurred shortly after 2nd liver transplantation. CASE REPORT: A 32-year-old female patient received a cadaveric liver transplant for HCV-related cirrhosis in 2007. She was not treated for HCV before transplantation. The patient developed biopsy-proven HCV recurrence with elevated transaminases and 65,553 IU/mL HCV RNA, genotype 4. She could not tolerate interferon-based treatment. The patient's condition progressively worsened and required a 2nd cadaveric liver transplantation in March 2013. Immunosuppression initially included steroids and Prograf, which was then switched to cyclosporine after the patient developed seizure. She developed acute cellular rejection which was readily treated with immunosuppression adjustment. HCV RNA became negative in April, which was confirmed in May 2013. CONCLUSIONS: Spontaneous clearance of hepatitis C rarely occurs after liver transplantation and is extremely rare after retransplantation. This finding may be explained by alterations in the host immune responses to HCV after transplantation. To our knowledge, this is the first case of spontaneous clearance of HCV genotype 4 after liver retransplantation.

New guaianolide-type sesquiterpene lactones from Inula verbascifolia.

The aerial parts of Inula verbascifolia afforded two new guaianolide-type sesquiterpene lactones. Their structures were determined by spectroscopic methods (IR, MS, 1H NMR, 13C NMR, DEPT, 1H-1H COSY, HMQC, and HMBC).

Congenital myasthenic syndrome associated with epidermolysis bullosa caused by homozygous mutations in PLEC1 and CHRNE.

Mutations in the plectin gene (PLEC1) cause epidermolysis bullosa simplex (EBS), which may associate with muscular dystrophy (EBS-MD) or pyloric atresia (EBS-PA). The association of EBS with congenital myasthenic syndrome (CMS) is also suspected to result from PLEC1 mutations. We report here a consanguineous patient with EBS and CMS for whom mutational analysis of PLEC1 revealed a homozygous 36 nucleotide insertion (1506_1507ins36) that results in a reduced expression of PLEC1 mRNA and plectin in the patient muscle. In addition, mutational analysis of CHRNE revealed a homozygous 1293insG, which is a well-known low-expressor receptor mutation. A skin biopsy revealed signs of EBS, and an anconeus muscle biopsy showed signs of a mild myopathy. Endplate studies showed fragmentation of endplates, postsynaptic simplification, and large collections of thread-like mitochondria. Amplitudes of miniature endplate potentials were diminished, but the endplate quantal content was actually increased. The complex phenotype presented here results from mutations in two separate genes. While the skin manifestations are because of the PLEC1 mutation, footprints of mutations in PLEC1 and CHRNE are present at the neuromuscular junction of the patient indicating that abnormalities in both genes contribute to the CMS phenotype.

The risk of bacteriuria and ureteric stent colonization in immune-compromised patients with double J stent insertion.

PURPOSE: To evaluate the influence of diabetes mellitus (DM), chronic renal failure (CRF), and malignancies on the rate of bacteriuria and double J ureteric stent bacterial colonization. PATIENTS AND METHODS: One hundred and twenty patients were included in this prospective study. Midstream urine samples for culture were obtained before ureteric stent insertion. Patients with negative culture were given ciprofloxacin 500 mg orally q 12 h for 5 days as a prophylaxis. All the stents were removed or changed as indicated after having voided midstream urine sample for culture on the day of stent removal. Stents were sent for culture. Culture was obtained from the outer surface of the stent by gentle scraping with a sterile scalpel. Significant bacteriuria was defined as a count of colony-forming units per milliliter of urine of >10(5). RESULTS: The patients were between 20 and 74 years of age (mean 42.5 + or - 13) and the duration of stent insertion ranged between 14 and 120 days (52.5 + or - 7.2). In 29 patients (24.2%), double J stent bacterial colonization was positive (12 males and 17 females). Of these patients, 27 (22.5%) had positive urine cultures (11 males and 16 females). The most commonly isolated pathogen was Escherichia coli. DM, CRF, or malignancies showed a higher risk for bacteriuria and stent bacterial colonization. CONCLUSION: Immune-compromising diseases such as DM, CRF, and malignancies are proved to be risk factors for urinary tract infection and stent colonization in patients with ureteric stent insertion. Stent cultures are not needed as the same microorganisms grow in urine cultures.