Defining alcohol-related phenotypes in humans. The Collaborative Study on the Genetics of Alcoholism.

Alcoholism is a disease that runs in families and results at least in part from genetic risk factors. The Collaborative Study on the Genetics of Alcoholism (COGA) is a Federally funded effort to identify and characterize those genetic factors. The study involves more than 1,000 alcoholic subjects and their families, with researchers conducting comprehensive psychological, physiological, electrophysiological, and genetic analyses of the participants. These analyses have identified several traits, or phenotypes, that appear to be genetically determined, such as the presence of alcohol dependence, the level of response to alcohol, the presence of coexisting depression, or the maximum number of drinks a person consumes per occasion. Genetic analyses have identified regions on several chromosomes that are associated with these phenotypes and need to be studied further

Correlation between Pulse Pressure Variation (PPV) and Adequacy of Intra-vascular Volume as reflected by time to urine output in renal transplant recipients: An Observational study

OBJECTIVES: 1. To determine a correlation between PPV at the time of graft revascularization and Time to urine output. 2. To determine the best target PPV to achieve early post transplant diuresis. METHODS: 33 adult patients undergoing elective renal transplantation were studied. Intravascular volume was maintained with intravenous fluids, targeting a CVP of 10-15 mm of Hg. PPV was also monitored but not used to influence fluid management. Both CVP and PPV were monitored continuously and recorded every 15 minutes. The values measured at the time of release of the vascular cross clamps were assumed to indicate the situation at the time of graft reperfusion. The outcome measure used to assess intravascular volume was time to urine output following reperfusion in seconds (TUO). It was considered desirable for time to urine output to be ≤ 120 seconds. RESULTS AND CONCLUSIONS: It was found that PPV did not have a linear correlation with time to urine output. ROC analysis revealed that the most appropriate cut off to use was 10%, 83.33% had a time to urine output of over 120seconds. Therefore it could be used as a parameter to monitor the state of intravascular volume and aid in intra-operative fluid management of patients undergoing renal transplantation

Maternal mortality at the Korle Bu Teaching Hospital, Accra, Ghana: A five-year review

Maternal death is a major global health issue with the highest impact in low-income countries. Despite some modest decline in the maternal mortality rates in Ghana since the 1990’s, this has been below expectation. The aim of this study was to describe the trends and contributory factors to maternal mortality at the Korle Bu Teaching Hospital (KBTH), Accra, Ghana. We performed a retrospective chart review of all maternal deaths at KBTH from 2015 to 2019. Data were analyzed using SPSS version 23. A p-value of <0.05 was considered statistically significant. Over the period, there were 45,676 live births, 276 maternal deaths and a maternal mortality ratio of 604/100,000 live births (95% CI: 590/100,000 - 739/100,000). The leading causes of maternal death were hypertensive disorders (37.3%), hemorrhage (20.6%), Sickle cell disease (8.3%), sepsis (8.3%), and pulmonary embolism (8.0%). Significant factors associated with maternal mortalities at the KBTH were: women with no formal education [AOR 3.23 (CI: 1.73 - 7.61)], women who had less than four antenatal visits [AOR 1.93(CI: 1.23-3.03)], and emergency cesarean section [AOR 3.87(CI: 2.51-5.98)]. Hypertensive disorders remain the commonest cause of the high maternal mortality at KBTH. Formal education and improvement in antenatal visits may help prevent these deaths. La mortalité maternelle est un problème de santé mondial majeur ayant le plus grand impact dans les pays à faible revenu.Malgré une légère baisse du taux de mortalité maternelle au Ghana depuis les années 1990, cela a été au-dessous des attentes. Le but de cette étude était de décrire les tendances et les facteurs qui contribuent à la mortalité maternelle à l’Hôpital Universitaire de Korle Bu (KBTH), Accra Ghana. Nous avons effectué un examen rétrospectif des dossiers concernant les décès maternels à KBTH de 2015 à 2019. Les données ont analysé à l’aide de SPSS version 23. Une valeur p de <0,05 était considérée comme statistiquement significatif. Sur la période, il y a eu 45 676 naissances, 276 décès maternels et un taux de mortalité maternelle de 604/100 000 naissances (IC à 95% : 590/100 000 – 739/100 000). Les causes principales des décès maternels étaient les troubles hypertensifs (37,3%), les hémorragies (20,6%), la drépanocytose (8,3%) la septicémie (8,3%) et l’embolie pulmonaire (8,0%). Les facteurs importants associés aux mortalités maternelles à KBTH étaient : les femmes sans éducation formelle [AOR 3,23 (IC : 1,73-7,61)], les femmes qui ont eu moins de quatre visites prénatales [AOR 1.93 (IC : 1,23-3,03)] et l’urgence césarienne [AOR 3,87(IC : 2,51- 5,98)]. Les troubles hypertensifs restent la cause le plus fréquente de la mortalité maternelle à KBTH. Une éducation formelle et une amélioration des visites prénatales peuvent aider à éviter ces décès

Assessing the Functionality of an Emergency Obstetric Referral System Among Public Healthcare Facilities in A Low Resource Setting: An Application of Process Mapping Approach

Abstract Background: Weak referral systems remain a major concern influencing timely access to the appropriate level of care during obstetric emergencies, particularly for Low-and Middle-Income Countries, including Ghana. It is a serious factor threatening the achievement of the maternal health Sustainable Development Goal. The objective of this study is to establish process details of emergency obstetric referral systems across different levels of public healthcare facilities to deepen understanding of systemic barriers and preliminary solutions in an urban district, using Ablekuma in Accra, Ghana as a case study.Methods: The study is an analytical cross-sectional study. Nine (9) in-depth interviews (IDI) were carried out for a three-weeks period in June and July 2019 after informed consent with two (2) Obstetrics &amp; Gynaecology consultants, two (2) Residents, one family physician, and four (4) Midwives managing emergency obstetric referral across different levels of facilities. Purposeful sampling technique was used to collect data that included a narration of the referral process, and challenges experienced with each step. Qualitative data was transcribed, coded by topics and thematically analysed. Transcribed narratives were used to draft a process map and analyze the defects within the emergency obstetric referral system.Results: Out of the 33 main activities in the referral process within the facilities, the study identified that 24 (73%) had a range of barriers in relation to communication, transport system, resources (space, equipment and physical structures), staffing (numbers and attitude), Healthcare providers (HCP) knowledge and compliance to referral policy and guideline, and financing for referral. These findings have implication on delay in accessing care. HCP suggested that strengthening communication and coordination, reviewing referral policy, training of all stakeholders and provision of essential resources would be beneficial. Conclusion: Our findings clearly establish that the emergency obstetric referral system between a typical teaching hospital in an urban district of Accra-Ghana and periphery referral facilities, is functioning far below optimum levels. This suggests that the formulation and implementation of policies should be focused around structural and process improvement interventions, strengthening collaborations, communication and transport along the referral pathway is likely to ensure that women receive timely and quality care.</jats:p

Assessing the functionality of an emergency obstetric referral system and continuum of care among public healthcare facilities in a low resource setting: an application of process mapping approach

Abstract Background Weak referral systems remain a major concern influencing timely access to the appropriate level of care during obstetric emergencies, particularly for Low-and Middle-Income Countries, including Ghana. It is a serious factor threatening the achievement of the maternal health Sustainable Development Goal. The objective of this study is to establish process details of emergency obstetric referral systems across different levels of public healthcare facilities to deepen understanding of systemic barriers and preliminary solutions in an urban district, using Ablekuma in Accra, Ghana as a case study. Methods The study is an analytical cross-sectional study. Nine [1] targeted interviews were carried out for a three-week period in June and July 2019 after informed written consent with two [2] Obstetrics &amp; Gynaecology consultants, two [2] Residents, one family physician, and four [3] Midwives managing emergency obstetric referral across different levels of facilities. Purposeful sampling technique was used to collect data that included a narration of the referral process, and challenges experienced with each step. Qualitative data was transcribed, coded by topics and thematically analysed. Transcribed narratives were used to draft a process map and analyze the defects within the emergency obstetric referral system. Results Out of the 34 main activities in the referral process within the facilities, the study identified that 24 (70%) had a range of barriers in relation to communication, transport system, resources (space, equipment and physical structures), staffing (numbers and attitude), Healthcare providers (HCP) knowledge and compliance to referral policy and guideline, and financing for referral. These findings have implication on delay in accessing care. HCP suggested that strengthening communication and coordination, reviewing referral policy, training of all stakeholders and provision of essential resources would be beneficial. Conclusion Our findings clearly establish that the emergency obstetric referral system between a typical teaching hospital in an urban district of Accra-Ghana and peripheral referral facilities, is functioning far below optimum levels. This suggests that the formulation and implementation of policies should be focused around structural and process improvement interventions, strengthening collaborations, communication and transport along the referral pathway. These suggestions are likely to ensure that women receive timely and quality care. </jats:sec

Assessing the functionality of an emergency obstetric referral system among public healthcare facilities in a low resource setting: an application of process mapping approach

Abstract Background: Weak referral systems remain a major concern influencing timely access to the appropriate level of care during obstetric emergencies, particularly for Low-and Middle-Income Countries, including Ghana. It is a serious factor threatening the achievement of the maternal health Sustainable Development Goal. The objective of this study is to establish process details of emergency obstetric referral systems across different levels of public healthcare facilities to deepen understanding of systemic barriers and preliminary solutions, using Ablekuma district in Accra, Ghana as a case study.Methods: The study is an analytical cross-sectional study. Nine (9) in-depth interviews (IDI) were carried out for a three-weeks period in June and July 2019 after informed consent with two (2) Obstetrics &amp; Gynaecology consultants, two (2) Residents, one family physician, and four (4) Midwives managing emergency obstetric referral across different levels of facilities. Data collected included a narration of the referral process, and challenges experienced with each step. Qualitative data was transcribed, coded by topics and thematically analysed. Transcribed narratives were used to draft a process map and analyze the defects within the emergency obstetric referral system.Results: Out of the 33 main activities in the referral process within the facilities, 24 (73%) had a range of barriers in relation to communication, transport system, resources (space, equipment and physical structures), staffing (numbers and attitude), HCP knowledge and compliance of referral policy and guideline, and financing for referral. Healthcare providers suggested that strengthening communication and coordination, review of referral policy, training of all stakeholders and provision of essential resources would be beneficial.Conclusion: Our findings clearly establish that the emergency obstetric referral system in Ablekuma district, Accra-Ghana is functioning far below optimum levels. This suggests that the formulation and implementation of policies should be focused around structural and process improvement interventions likely to ensure that women receive timely and quality care.</jats:p

Abstract 552: Targeting brain tumors with PLX3397, an inhibitor of the CSF-1 receptor kinase

Abstract Cancer growth in the brain incites a neuroinflammatory response that becomes a defining feature of the brain tumor microenvironment. Microglia and macrophages provide important functions that support the invasiveness of glioblastoma. Other cancer types that become metastatic to brain also rely on the microenvironment to support angiogenesis. PLX3397 is a potent inhibitor of the transmembrane tyrosine kinase receptor for colony stimulating factor-1 (CSF-1R). The CSF-1R is required for the differentiation and activation of microglia and macrophages. Oral administration of PLX3397 to mice at 20 mg/kg qd significantly reduces the microglia/macrophage marker, Iba1, as determined by western blotting. PLX3397 penetrates the blood-brain barrier, as determined through pharmacokinetic analysis, with brain levels reaching substantial fractions of the concurrent plasma levels. PLX3397 is highly bound to plasma albumin, and therefore the levels attained in the brain likely affect Iba1 levels through a local inhibition of brain microglia and macrophages, although a peripheral effect may also contribute. Culture of glioblastoma cell lines including U87, and treatment with chemotherapeutic agents or radiation, was found to cause a 4-fold elevation of the two CSF-1R ligands, CSF-1 and IL-34, as quantified by QPCR. This indicates that glioma cells can recruit and stimulate microglia and macrophages, and that current standard therapies likely exacerbate this stimulation. Other cancer types that are known to form metastases to brain, including melanoma and breast cancer, show similar abilities to produce these cytokines in response to standard therapies. The rat 9L glioblastoma line forms an aggressive tumor when tested as an orthotopic model in syngeneic Fisher rats. Seven days after implantation, PLX3397 was administered via rodent chow for 14 days, reducing the tumor growth by 44% as determined by MRI. These results provide preclinical evidence that PLX3397 may show a clinical benefit in brain cancers, either as a single agent or in combination with standard chemo- or radiation therapies. PLX3397 is nearing completion of a successful Phase 1 dose-escalation safety trial in solid tumor cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 552. doi:10.1158/1538-7445.AM2011-552</jats:p

Joint Multipoint Linkage Analysis of Multivariate Qualitative and Quantitative Traits. II. Alcoholism and Event-Related Potentials

SummaryThe availability of robust quantitative biological markers that are correlated with qualitative psychiatric phenotypes can potentially improve the power of linkage methods to detect quantitative-trait loci influencing psychiatric disorders. We apply a variance-component method for joint multipoint linkage analysis of multivariate discrete and continuous traits to the extended pedigree data from the Collaborative Study on the Genetics of Alcoholism, in a bivariate analysis of qualitative alcoholism phenotypes and quantitative event-related potentials. Joint consideration of the DSM-IV diagnosis of alcoholism and the amplitude of the P300 component of the Cz event-related potential significantly increases the evidence for linkage of these traits to a chromosome 4 region near the class I alcohol dehydrogenase locus ADH3. A likelihood-ratio test for complete pleiotropy is significant, suggesting that the same quantitative-trait locus influences both risk of alcoholism and the amplitude of the P300 component