Poor birth weight recovery among low birth weight/preterm infants following hospital discharge in Kampala, Uganda

<p>Abstract</p> <p>Background</p> <p>Healthy infants typically regain their birth weight by 21 days of age; however, failure to do so may be due to medical, nutritional or environmental factors. Globally, the incidence of low birth weight deliveries is high, but few studies have assessed the postnatal weight changes in this category of infants, especially in Africa. The aim was to determine what proportion of LBW infants had not regained their birth weight by 21 days of age after discharge from the Special Care Unit of Mulago hospital, Kampala.</p> <p>Methods</p> <p>A cross sectional study was conducted assessing weight recovery of 235 LBW infants attending the Kangaroo Clinic in the Special Care Unit of Mulago Hospital between January and April 2010. Infants aged 21 days with a documented birth weight and whose mothers gave consent to participate were included in the study. Baseline information was collected on demographic characteristics, history on pregnancy, delivery and postnatal outcome through interviews. Pertinent infant information like gestation age, diagnosis and management was obtained from the medical records and summarized in the case report forms.</p> <p>Results</p> <p>Of the 235 LBW infants, 113 (48.1%) had not regained their birth weight by 21 days. Duration of hospitalization for more than 7 days (AOR: 4.2; 95% CI: 2.3 - 7.6; p value < 0.001) and initiation of the first feed after 48 hours (AOR: 1.9; 95% CI 1.1 - 3.4 p value 0.034) were independently associated with failure to regain birth weight. Maternal factors and the infant's physical examination findings were not significantly associated with failure to regain birth weight by 21 days of age.</p> <p>Conclusion</p> <p>Failure to regain birth weight among LBW infants by 21 days of age is a common problem in Mulago Hospital occurring in almost half of the neonates attending the Kangaroo clinic. Currently, the burden of morbidity in this group of high-risk infants is undetected and unaddressed in many developing countries. Measures for consideration to improve care of these infants would include; discharge after regaining birth weight and use of total parenteral nutrition. However, due to the pressure of space, keeping the baby and mother is not feasible at the moment hence the need for a strong community system to boost care of the infant. Close networking with support groups within the child's environment could help alleviate this problem.</p

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Diazo-transfer reaction with diphenyl phosphorazidate

Diphenyl phosphorazidate (DPPA) was used as the azide source in a one-pot synthesis of 2,2-disubstituted 3-amino-2H-azirines 1 (Scheme 1). The reaction with lithium enolates of amides of type 2, bearing two substituents at C(2), proceeded smoothly in THF at 0°; keteniminium azides C and azidoenamines D are likely intermediates. Under analogous reaction conditions, DPPA and amides of type 3 with only one substituent at C(2) gave 2-diazoamides 5 in fair-to-good yield (Scheme 2). The corresponding 2-diazo derivatives 6-8 were formed in low yield by treatment of the lithium enolates of N,N-dimethyl-2-phenylacetamide, methyl 2-phenylacetate, and benzyl phenyl ketone, respectively, with DPPA. Thermolysis of 2-diazo-N-methyl-N-phenylcarboxamides 5a and 5b yielded 3-substituted 1,3-dihydro-N-methyl-2H-indol-2-ones 9a and 9b, respectively (Scheme 3). The diazo compounds 5 - 8 reacted with 1,3-thiazole-5(4H)-thiones 10 and thiobenzophenone (13) to give 6-oxa-1,9-dithia-3-azaspiro[4.4]nona-2,7-dienes 11 (Scheme 4) and thiirane-2-carboxylic acid derivatives 14 (Scheme 5), respectively. In analogy to previously described reactions, a mechanism via 1,3-dipolar cycloaddition, leading to 2,5-dihydro-1,3,4-thiadiazoles, and elimination of N2 to give the ‘thiocarbonyl ylides’ of type H or K is proposed. These dipolar intermediates with a conjugated C=O group then undergo either a 1,5-dipolar electrocyclization to give spiroheterocycles 11 or a 1,3-dipolar electrocyclization to thiiranes 14