Systemically administered central nervous system drugs induced ocular side effects: a review

Several systemic drugs have reported ocular and visual side effects that affect patient management. It is imperative to be familiar with the associated side effects which can be mild or transient and may seriously threaten vision. This article deals briefly with the mechanisms and reasons that account for the impact that systemically administered central nervous system (CNS) drugs can exert on the visual or ocular system. The eye care practitioner can be instrumental in detecting and reporting ocular side effects, advising patients and collaborating with other members of the patient’s healthcare team. One of the difficulties include becoming familiar with the countless systemic medications prescribed to patients. Another is being able to correlate a particular side effect with a suspected drug. Several of the ocular adverse effects such as glaucoma, cataract, blurred vision, color vision, optic neuritis, maculopathy, dry eye, etc., are vision threatening and often patients fail to recognize or describe the symptoms appropriately. Therefore, physicians and paramedical members like staff nurses, clinical pharmacists and other members must make adequate observations while recommending these drugs to patients

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Urinary reducing substances in neonatal intrahepatic cholestasis caused by citrin deficiency

Neonatal cholestasis due to citrin deficiency is an autosomal recessive metabolic disorder caused by mutations in SLC25A13 gene. Mutations in this gene have a relatively high prevalence in East-Asian races compared to European or Afro-Caribbean races. Mutations in both sets of chromosomes often lead to self-limiting early onset cholestasis and growth retardation referred as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). It is associated with a wide range of metabolic derangements including galactosemia and aminoacidemia, which can be detected on the newborn blood spot screening. Galactose, being a reducing sugar, can also be detected using Clinitest® (Clinitest® Reagent Tablets, Bayer Corporation, Diagnostics Division, Elkhart, IN, USA), a common screening test used in the work up of metabolic and hepatic diseases. In the western population classical galactosemia is often suspected when non glucose reducing substances are detected in the urine of infants with cholestasis. However in East-Asian races the prevalence of classical galactosemia is very low whilst galactosemia due to altered uridine diphosphate-galactose epimerase activity in NICCD is more common. We present a case of NICCD in an East-Asian infant with cholestasis and persistently positive urine reducing substance. Conclusion: NICCD deficiency should be considered as a differential diagnosis in any infant with cholestasis and persistently positive urinary reducing substances

Exclusive enteral nutrition with concomitant early thiopurine use was effective in maintaining steroid-free remission in a Southeast Asian cohort of children with Crohn’s disease

Abstract Background Exclusive enteral nutrition (EEN) is as effective as corticosteroids in inducing remission in children with Crohn’s disease (CD). However, over 50% of these children relapse by 12 months of diagnosis. Thiopurines are commonly prescribed as maintenance therapy for CD, but evidence for its efficacy is controversial. Data on the effectiveness of EEN in Southeast Asian (SEA) children with CD is scarce. This study aims to evaluate the efficacy of EEN induction therapy in a cohort of SEA children with newly diagnosed CD. The secondary aim was to evaluate concomitant early azathioprine (EAZ) use in determining remission rate at 6 and 12 months. Methods Case records of all children with newly diagnosed CD from 2011 to 2014 were reviewed and relevant demographic as well as clinical data were extracted. The primary outcome measure was the number of patients who completed EEN induction therapy and achieved remission (Paediatric Crohn’s Disease Activity Index; PCDAI≤10). Factors influencing duration of remission were evaluated in particular early azathioprine (EAZ) defined as starting azathioprine within one month of diagnosis versus late azathioprine (LAZ) use. Results Forty children with newly diagnosed CD were identified. Thirty-three children: 67% boys, median age 13y (range 3–17) completed 8 weeks of EEN induction therapy and 91% achieved remission. Significant improvements were seen in PCDAI scores (32.7 ± 9.2 to 4.2 ± 5.1; p < 0.001), mean BMI z-score (− 1.38 ± 1.57 to − 0.82 ± 1.27; p = 0.004) and baseline inflammatory markers: Erythrocyte Sedimentation Rate (51.6 ± 30.1 mm/h to 13.3 ± 7.1 mm/h; p < 0.0001) C-Reactive Protein (44.6 ± 51.0 mg/L to 5.2 ± 7.6 mg/L; p = 0.001), Albumin (30.7 ± 7.5 g/L to 38.7 ± 3.9 g/L; p < 0.0001), Platelets (464 ± 161 × 109 to 370 ± 111 × 109; p < 0.0001),. Early azathioprine initiation was associated with a remission rate of 80 and 73% at 6 and 12 months respectively. Remission was also maintained for longer duration in EAZ vs LAZ groups (p = 0.048). Conclusion EEN effectively induces remission in this cohort of SEA children with newly diagnosed CD. Early initiation of thiopurine with EEN induction therapy is effective in maintaining steroid-free remission for at least one year