Browsing by Author "Weeks, Andrew D."

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    The Bacterial and Viral Complexity of Postinfectious Hydrocephalus in Uganda
    (Science translational medicine, 2020) Paulson, Joseph N.; Williams, Brent L.; Hehnly, Christine; Mishra, Nischay; Sinnar, Shamim A.; Zhang, Lijun; Ssentongo, Paddy; Kabachelor, Edith Mbabazi; Wijetunge, Dona S. S.; Bredow, Benjamin von; Mulondo, Ronnie; Kiwanuka, Julius; Bajunirwe, Francis; Bazira, Joel; Bebell, Lisa M.; Burgoine, Kathy; Couto-Rodriguez, Mara; Ericson, Jessica E.; Erickson, Tim; Ferrari, Matthew; Gladstone, Melissa; Guo, Cheng; Haran, Murali; Hornig, Mady; Isaacs, Albert M.; Kaaya, Brian Nsubuga; Kangere, Sheila M.; Kulkarni, Abhaya V.; Kumbakumba, Elias; Li, Xiaoxiao; Limbrick, David D.; Magombe, Joshua; Morton, Sarah U.; Mugamba, John; Ng, James; Olupot, Peter Olupot; Onen, Justin; Peterson, Mallory R.; Roy, Farrah; Sheldon, Kathryn; Townsend, Reid; Weeks, Andrew D.; Whalen, Andrew J.; Quackenbush, John; Ssenyonga, Peter; Galperin, Michael Y.; Almeida, Mathieu; Atkins, Hannah; Warf, Benjamin C.; Lipkin, W. Ian; Broach, James R.; Schiff, Steven J.
    Postinfectious hydrocephalus (PIH), often following neonatal sepsis, is the most common cause of pediatric hydrocephalus world-wide, yet the microbial pathogens remain uncharacterized. Characterization of the microbial agents causing PIH would lead to an emphasis shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention. We examined blood and CSF from 100 consecutive cases of PIH and control cases of non-postinfectious hydrocephalus (NPIH) in infants in Uganda. Genomic testing was undertaken for bacterial, fungal, and parasitic DNA, DNA and RNA sequencing for viral identification, and extensive bacterial culture recovery. We uncovered a major contribution to PIH from Paenibacillus, upon a background of frequent cytomegalovirus (CMV) infection. CMV was only found in CSF in PIH cases. A facultatively anaerobic isolate was recovered. Assembly of the genome revealed a strain of P. thiaminolyticus. In mice, this isolate designated strain Mbale, was lethal in contrast with the benign reference strain. These findings point to the value of an unbiased pan-microbial approach to characterize PIH in settings where the organisms remain unknown, and enables a pathway towards more optimal treatment and prevention of the proximate neonatal infections.
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    Effect of pre-operative bicarbonate infusion on maternal and perinatal outcomes among women with obstructed labour in Mbale hospital: A double blind randomized controlled trial
    (PLoS ONE, 2021) Musaba, Milton W.; Wandabwa, Julius N.; Ndeezi, Grace; Weeks, Andrew D.; Mukunya, David; Waako, Paul; Nankabirwa, Victoria; Tulyamuhika Mugabe, Kenneth; Semakula, Daniel; Tumwine, James K.; Barageine, Justus K.
    Oral bicarbonate solution is known to improve both maternal and perinatal outcomes among women with abnormal labor (dystocia). Its effectiveness and safety among women with obstructed labor is not known. Objective To determine the effect and safety of a single-dose preoperative infusion of sodium bicarbonate on maternal and fetal blood lactate and clinical outcomes among women with obstructed labor (OL) in Mbale hospital. Methods We conducted a double blind, randomized controlled trial from July 2018 to September 2019. The participants were women with OL at term (�37 weeks gestation), carrying a singleton pregnancy with no other obstetric emergency, medical comorbidity or laboratory derangements.
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    Incidence and determinants of perinatal mortality among women with obstructed labor in eastern Uganda: a prospective cohort study
    (Maternal health, neonatology and perinatology, 2021) Musaba, Milton W.; Ndeezi, Grace; Barageine, Justus K.; Weeks, Andrew D.; Wandabwa, Julius N.; Mukunya, David; Waako, Paul; Odongkara, Beatrice; Arach, Agnes; Tulya-muhika Mugabe, Kenneth; Kasede Napyo, Agnes; Nankabirwa, Victoria; Tumwine, James K.
    In Uganda, the incidence and determinants of perinatal death in obstructed labour are not well documented. We determined the incidence and determinants of perinatal mortality among women with obstructed labour in Eastern Uganda. Methods: Between July 2018 and September 2019, 584 with obstructed labour were recruited and followed up to the 7th day postnatal. Information on maternal characteristics, obstetric factors and laboratory parameters was collected. Each patient received the standard perioperative care. We used a generalized linear model for the Poisson family, with a log link and robust variance estimation to determine the association between the exposure variables and perinatal death.
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    The MamaMiso study of self-administered misoprostol to prevent bleeding after childbirth in rural Uganda: a community-based, placebo-controlled randomised trial
    (BMC Pregnancy and Childbirth, 2015) Weeks, Andrew D.; Ditai, James; Ononge, Sam; Faragher, Brian; Frye, Laura J.; Durocher, Jill; Mirembe, Florence M.; Byamugisha, Josaphat; Winikoff, Beverly; Alfirevic, Zarko
    600 mcg of oral misoprostol reduces the incidence of postpartum haemorrhage (PPH), but in previous research this medication has been administered by health workers. It is unclear whether it is also safe and effective when self-administered by women. Methods: This placebo-controlled, double-blind randomised trial enrolled consenting women of at least 34 weeks gestation, recruited over a 2-month period in Mbale District, Eastern Uganda. Participants had their haemoglobin measured antenatally and were given either 600mcg misoprostol or placebo to take home and use immediately after birth in the event of delivery at home. The primary clinical outcome was the incidence of fall in haemoglobin of over 20 % in home births followed-up within 5 days. Results: 748 women were randomised to either misoprostol (374) or placebo (374). Of those enrolled, 57 % delivered at a health facility and 43 % delivered at home. 82 % of all medicine packs were retrieved at postnatal follow-up and 97 % of women delivering at home reported self-administration of the medicine. Two women in the misoprostol group took the study medication antenatally without adverse effects. There was no significant difference between the study groups in the drop of maternal haemoglobin by >20 % (misoprostol 9.4 % vs placebo 7.5 %, risk ratio 1.11, 95 % confidence interval 0.717 to 1.719). There was significantly more fever and shivering in the misoprostol group, but women found the medication highly acceptable. Conclusions: This study has shown that antenatally distributed, self-administered misoprostol can be appropriately taken by study participants. The rarity of the primary outcome means that a very large sample size would be required to demonstrate clinical effectiveness.
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    Umbilical vein oxytocin for the treatment of retained placenta (Release Study): a double-blind, randomised controlled trial
    (The Lancet, 2010) Weeks, Andrew D.; Alia, Godfrey; Vernon, Gillian; Namayanja, Annette; Gosakan, Radhika; Majeed, Tayyaba; Hart, Anna; Jafri, Hussain; Nardin, Juan; Carroli, Guillermo; Fairlie, Fiona; Raashid, Yasmin; Mirembe, Florence; Alfirevic, Zarko
    Retained placenta is associated with post-partum hemorrhage. Meta-analysis has suggested that umbilical injection of oxytocin could increase placental expulsion without the need for a surgeon or anesthetic. We assessed the effect of high-dose umbilical vein oxytocin as a treatment for retained placenta. In this double-blind, placebo-controlled trial, hemodynamically stable women with a retained placenta for more than 30 min were recruited from 13 sites in the UK, Uganda, and Pakistan. 577 women were randomly assigned by a computer-generated randomization list stratified by center to 30 mL saline containing either 50 IU oxytocin (n=292) or 5 mL water (n=285), which was injected into the placenta through an umbilical vein catheter. All trial participants, study workers, and data handlers were masked to individual allocations. The primary outcome was the need for manual removal of the placenta. Analysis was by intention to treat. This study is registered, number ISRCTN 13204258.