Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Whole-body hypothermia, cerebral magnetic resonance biomarkers, and outcomes in neonates with moderate or severe hypoxic-ischemic encephalopathy born at tertiary care centers vs other facilities: A nested study within a randomized clinical trial(American Medical Association, 2023) Thayyil, S.; Montaldo, P.; Krishnan, V.; Ivain, P.; Pant, S.; Lally, P.J.; Bandiya, P.; Benkappa, N.; Kamalaratnam, C.N.; Chandramohan, R.; Manerkar, S.; Mondkar, J.; Jahan, I.; Moni, S.C.; Shahidullah, M.; Rodrigo, R.; Sumanasena, S.; Sujatha, R.; Burgod, C.; Garegrat, R.; Mazlan, M.; Chettri, I.; Babu, S.P.; Joshi, A.R.; Swamy, R.; Chong, K.; Pressler, R.R.; Bassett, P.; Shankaran, S.IMPORTANCE: The association between place of birth and hypothermic neuroprotection after hypoxic-ischemic encephalopathy (HIE) in low- and middle-income countries (LMICs) is unknown. OBJECTIVE: To ascertain the association between place of birth and the efficacy of whole-body hypothermia for protection against brain injury measured by magnetic resonance (MR) biomarkers among neonates born at a tertiary care center (inborn) or other facilities (outborn). DESIGN, SETTING, AND PARTICIPANTS: This nested cohort study within a randomized clinical trial involved neonates at 7 tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh between August 15, 2015, and February 15, 2019. A total of 408 neonates born at or after 36 weeks' gestation with moderate or severe HIE were randomized to receive whole-body hypothermia (reduction of rectal temperatures to between 33.0 °C and 34.0 °C; hypothermia group) for 72 hours or no whole-body hypothermia (rectal temperatures maintained between 36.0 °C and 37.0 °C; control group) within 6 hours of birth, with follow-up until September 27, 2020. EXPOSURE: 3T MR imaging, MR spectroscopy, and diffusion tensor imaging. MAIN OUTCOMES AND MEASURES: Thalamic N-acetyl aspartate (NAA) mmol/kg wet weight, thalamic lactate to NAA peak area ratios, brain injury scores, and white matter fractional anisotropy at 1 to 2 weeks and death or moderate or severe disability at 18 to 22 months. RESULTS: Among 408 neonates, the mean (SD) gestational age was 38.7 (1.3) weeks; 267 (65.4%) were male. A total of 123 neonates were inborn and 285 were outborn. Inborn neonates were smaller (mean [SD], 2.8 [0.5] kg vs 2.9 [0.4] kg; P = .02), more likely to have instrumental or cesarean deliveries (43.1% vs 24.7%; P = .01), and more likely to be intubated at birth (78.9% vs 29.1%; P = .001) than outborn neonates, although the rate of severe HIE was not different (23.6% vs 17.9%; P = .22). Magnetic resonance data from 267 neonates (80 inborn and 187 outborn) were analyzed. In the hypothermia vs control groups, the mean (SD) thalamic NAA levels were 8.04 (1.98) vs 8.31 (1.13) among inborn neonates (odds ratio [OR], -0.28; 95% CI, -1.62 to 1.07; P = .68) and 8.03 (1.89) vs 7.99 (1.72) among outborn neonates (OR, 0.05; 95% CI, -0.62 to 0.71; P = .89); the median (IQR) thalamic lactate to NAA peak area ratios were 0.13 (0.10-0.20) vs 0.12 (0.09-0.18) among inborn neonates (OR, 1.02; 95% CI, 0.96-1.08; P = .59) and 0.14 (0.11-0.20) vs 0.14 (0.10-0.17) among outborn neonates (OR, 1.03; 95% CI, 0.98-1.09; P = .18). There was no difference in brain injury scores or white matter fractional anisotropy between the hypothermia and control groups among inborn or outborn neonates. Whole-body hypothermia was not associated with reductions in death or disability, either among 123 inborn neonates (hypothermia vs control group: 34 neonates [58.6%] vs 34 [56.7%]; risk ratio, 1.03; 95% CI, 0.76-1.41), or 285 outborn neonates (hypothermia vs control group: 64 neonates [46.7%] vs 60 [43.2%]; risk ratio, 1.08; 95% CI, 0.83-1.41). CONCLUSIONS AND RELEVANCE: In this nested cohort study, whole-body hypothermia was not associated with reductions in brain injury after HIE among neonates in South Asia, irrespective of place of birth. These findings do not support the use of whole-body hypothermia for HIE among neonates in LMICs.Item Arthrogryposis multiplex congenita in a child with congenital fractures: a case report(BioMed Central, London, 2022) Dayasiri, K.; Jayaweera, H.Background: Bruck syndrome is an exceedingly rare form of osteogenesis imperfecta, inherited autosomal recessively and presenting with the concurrence of bone fragility and congenital contractures of large joints. The disease usually progresses relentlessly to result in recurrent fractures, short stature, severe kyphoscoliosis, and susceptibility to recurrent respiratory tract infections.Case presentation: The index child was a male newborn to healthy, nonconsanguineous, Sinhalese parents. The child had multiple contractures involving all large joints with pterigium formation in addition to congenital fractures involving left humerus and ulna at birth. The phenotypic features in this child were highly suggestive of Bruck syndrome. Genetic counseling was offered to the parents, although specific genetic testing could not be undertaken due to lack of resources. Bone and skin biopsy were not performed since only palliative care was possible. Over the course, he developed recurrent severe chest infections due to poor muscle tone, weak cough reflex, and pooling of secretions. Unfortunately, he succumbed at the age of 7 months following severe pneumonia.Conclusion: The association of arthrogryposis with osteogenesis imperfecta is extremely rare and known as Bruck syndrome. Early diagnosis during the antenatal period is helpful in genetic counseling, assessment of severity, and exploration of therapeutic options.Item Gastrointestinal disorders in children admitted to a tertiary care paediatric unit in Sri Lanka(Wiley Blackwell Scientific Publications, 2008) Devanarayana, N.M.; Adikari, A.M.D.B.; Sanjeewa, P.A.B.; Rajindrajith, S.OBJECTIVES : Gastrointestinal diseases, including diarrhoea and abdominal pain, are common presenting complains in children admitted to hospitals. In those with abdominal pain, non-specific abdominal pain is the commonest diagnosis at discharge. This study evaluated the gastrointestinal disorders in children admitted to a tertiary care general paediatric unit in Sri Lanka. METHODS: Records of all neonates, infants and children admitted to University paediatric unit in North Colombo Teaching Hospital, Ragama, Sri Lanka, during 12 month period from 01/10/2006 to 30/09/2007, were evaluated. Demographic information, details regarding the symptoms, exam nation findings, investigations, treatments and diagnosis at discharge were analysed retrospectively. RESULTS: Of the 5202 patients admitted during the study period, 167 (3.2%) had gastrointestinal disorders [90 (54.9%) were males, mean age 6.3 years, SD 2.5 years, range 2–13 years]. Common presenting complains were diarrhoea [79 (47.3%)], abdominal pain [62 (37.1%)], constipation [10 (6%)] and vomiting [8 (4.8%)]. Most common discharge diagnosis was acute gastroenteritis (AGE) [57 (45.5%)]. Of 62 children presented with abdominal pain, only 23 (36.1%) had exact diagnosis at the discharge (AGE 13, gastritis 3, constipation 4, gastro-oesophageal reflux 1, typhoid fever 1, functional abdominal pain 1). CONCLUSIONS: Diarrhoea and abdominal pain accounted for more than 80% of hospital admissions due to gastrointestinal disorders. Nearly two third of patients admitted due to abdominal pain had no diagnosis at discharge. Even though, Rome III criteria are widely available, only one patient was diagnosed as having functional gastrointestinal disorder.Item Transplacental transfer of dengue(Sri Lanka Medical Association, 2014) Ekanayake, C.D.; Padumadasa, S.; Premaratna, R.; Rajindrajith, S.; Samaranayake, W. W.Item Nutrition in early life, immune-programming and allergies: the role of epigenetics(Allergy and Immunology Society of Thailand, 2013) Amarasekera, M.; Prescott, S.L.; Palmer, D.J.Early life nutritional exposures are significant determinants of the development and future health of all organ systems. The dramatic rise in infant immune diseases, most notably allergy, indicates the specific vulnerability of the immune system to early environmental changes. The associated parallel rise in metabolic diseases including obesity, childhood type 2-diabetes and non-alcoholic fatty liver disease highlights the interplay between modern dietary patterns and increasing abnormalities of both immune and metabolic health. The low-grade inflammation that characterize these non-communicable diseases (NCDs) suggests a central role of the immune system in the pathogenesis of these conditions. Understanding how environmental influences disrupt the finely balanced development of immune and metabolic programing is of critical importance. Diet-sensitive pathways are likely to be crucial in these processes. While epigenetic mechanism provides a strong explanation of how nutritional exposures can affect the fetal gene expression and subsequent disease risk, other diet-induced tissue compositional changes may also contribute directly to altered immune and metabolic function. Although modern dietary changes are complex and involve changing patterns of many nutrients, there is also interest in the developmental effects of specific nutrients such as folic acid levels, which have clear epigenetic effects on programming. Here we examine the current knowledge of the nutritional-programming of immune health and how research into nutritional-epigenetics in the context of allergic disease as one of the earliest onset NCDs can expand our knowledge to discover the biological processes sensitive to nutritional exposures in early life to prevent later disease risk.Item Neonatal mortality in Sri Lanka: timing, causes and distribution(Informa Healthcare, 2009) Rajindrajith, S.; Mettananda, S.; Adihetti, D.; Goonawardana, R.; Devanarayana, N.M.OBJECTIVE: To evaluate the timing, causes and distribution of neonatal deaths in Sri Lanka, to provide information for policy makers, to undertake appropriate measures to achieve the Millennium Development Goals. METHODS: All neonatal deaths, reported to the Registrar General's Office, Sri Lanka, from 1997 to 2001, were included in the analysis. RESULTS: During this 5-year period, 17,946 neonatal deaths have occurred, of them 90.5% have occurred during the first week of life. The leading causes were preterm deliveries (33.2%), infections (19.8%) and cardiac anomalies (17.4%). The neonatal mortality rates (NMR) were higher in districts with specialised neonatal care facilities and high concentration of estates. CONCLUSIONS: Approximately 3600 neonates die in Sri Lanka annually, even though it has a lower NMR compared to rest of the South Asia. Neonatal deaths were higher in the major cities and in the estate sector. The majority of neonatal deaths were due to complications of preterm birth, neonatal sepsis and cardiac anomalies.Item Effect of mebendazole therapy in pregnancy on birth outcome(Lancet Publishing Group, 1999) de Silva, N.R.; Sirisena, J.; Gunasekera, D.P.S.; Ismail, M.M.; de Silva, H.J.BACKGROUND: In areas endemic for hookworm, routine antenatal mebendazole therapy could greatly reduce the prevalence of anaemia in pregnancy. At present, however, this is not a widely accepted control strategy because of a lack of data on the safety of the drug. We assessed the effect of mebendazole therapy during pregnancy on birth outcome. METHODS: A cross-sectional study was done in Sri Lanka, where prescription of mebendazole to women in the second trimester of pregnancy is recommended. Two hospitals were chosen for the study, and women who gave birth there between May, 1996, and March, 1997, were recruited. We compared the rates of major congenital defects, stillbirth, perinatal death, and low birthweight (less or equal 1500 g) among babies of mothers who had taken mebendazole during pregnancy with those whose mothers had not taken an anthelmintic (controls). FINDINGS: The rate of major congenital defects was not significantly higher in the mebendazole group than in the control group (97 [1.8 percent] of 5275 vs 26 [1.5 percent] of 1737; odds ratio 1.24 [95 percent CI 0.8-1.91], p equal 0.39). Among 407 women who had taken mebendazole in the first trimester (contrary to medical advice), 10 (2.5 percent) had major congenital defects (odds ratio vs controls 1.66 [0.81-3.56], p equal 0.23). The proportions of stillbirths and perinatal deaths were significantly lower in the mebendazole group (1.9 vs 3.3 percent, 0.55 [95 percent CI 0.4-0.77]), as was the proportion of low-birthweight babies (1.1 vs 2.3 percent 0.47 [95 percent CI 0.32-0.71]). INTERPRETATION: Mebendazole therapy during pregnancy is not associated with a significant increase in major congenital defects, but our results indicate that it should be avoided during the first trimester. This therapy could offer beneficial effects to pregnant women in developing countries, where intestinal helminthiases are endemic.Item Neonatal and post-neonatal mortality in the Galle district(Sri Lanka Medical Association, 1994) Fonseka, P.; Wijewardene, K.; de Silva, D.G.H.; Goonaratna, C.; Wijeyasiri, W.A.DESIGN: Descriptive study. SETTING: Galle district in Sri Lanka. SUBJECTS: 350 infant deaths of singleton births. MEASUREMENTS: Association between variables. RESULTS: Neonatal: post-neonatal death ratio was 3.2:1, and 62.3% (218) were early neonatal deaths. First day deaths comprised 28.6% (100); 67.8% (237) died at the Teaching Hospital. A high incidence (65.7%) of low birthweight (LBW) was noted. Mean birthweights of neonates and post-neonates were 1925 +/- 729 and 2520 +/- 620 gram respectively, and the difference between means was statistically significant (p < 0.001). LBW and related disorders were the major cause of death in 44% (154) of the total sample, and in 55.8% (149) of neonates. Infections were the commonest cause (55.8%) of death in post-neonates. Pediatric clinical assessment to differentiate small-for-dates (SFD) was not recorded in 90.3%. Statistically significant associations were found between the period of death (neonatal and post-neonatal) and the following variables: period of gestation (p < 0.001); birthweight (p < 0.001) and cause of death (p < 0.001). CONCLUSIONS: There was a high incidence of neonatal deaths and a high proportion of early neonatal deaths. About one-third of deaths occurred on the first day of life. Incidence of LBW was high. The major cause of death was LBW and related disorders in the total sample and in neonates. Assessment of SFD was not carried out in the vast majority of infants.Item Birthweight and sociobiological factors in Ilorin, Nigeria(Cambridge University Press, 1991) Ebomoyi, E.; Adetoro, O.O.; Wickremasinghe, A.R.Social and biological factors influencing birthweight of 3053 Ilorin babies were studied. The mean birth weights were 2.998 kg +/- 0.133 (SD) for males and 2.932 kg +/- 0.154 (SD) for females. Multiple regression analysis showed that maternal weight, height, age, education and ethnicity, and child's sex, significantly affected birthweight of infants. Some quadratic and interaction terms also contributed significantly to the prediction of birthweight. The strategies to control the incidence of low birth weight are discussed.