Drug dosing during pregnancy—opportunities for physiologically based pharmacokinetic models

Drugs can have harmful effects on the embryo or the fetus at any point during pregnancy. Not all the damaging effects of intrauterine exposure to drugs are obvious at birth, some may only manifest later in life. Thus, drugs should be prescribed in pregnancy only if the expected benefit to the mother is thought to be greater than the risk to the fetus. Dosing of drugs during pregnancy is often empirically determined and based upon evidence from studies of non-pregnant subjects, which may lead to suboptimal dosing, particularly during the third trimester. This review collates examples of drugs with known recommendations for dose adjustment during pregnancy, in addition to providing an example of the potential use of PBPK models in dose adjustment recommendation during pregnancy within the context of drug-drug interactions. For many drugs, such as antidepressants and antiretroviral drugs, dose adjustment has been recommended based on pharmacokinetic studies demonstrating a reduction in drug concentrations. However, there is relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Examples of using pregnancy PBPK models to predict feto-maternal drug exposures and their applications to facilitate and guide dose assessment throughout gestation are discussed

Validation Of Mannheim Peritonitis Index (A Nigerian Study)

Peritonitis is a serious intra-abdominal infection with poor prognosis despite application of aggressive surgical techniques like laparostomy, on-demand reoperations, and irrigations with/without antibiotics. There is need to categorise patients to select those who will benefit from these aggressive surgical techniques and to help compare results from different centers. We studied and assessed the Mannheim Peritonitis Index as a reliable and achievable technique in our environment. Sixty-seven consecutive patients with generalized peritonitis were studied. The clinical data and Mannheim Peritonitis Index score for each patient was collated manually after surgery. The Mannheim Peritonitis Index was graded into 3 categories: I = MPI 30. These were related to mortality; and length of in-hospital stay was used as a test of morbidity for survivors. The mean MPI score for non-survivors was 30.6 and survivors 19.7. There was 92.3% mortality in MPI >30. MPI score of 25 gave the highest degree of accuracy and should be used as a cut-off mark for assessment of poor prognosis in our environment. The Mannheim Peritonitis Index (MPI) is an easy and reliable scoring system that can be used in our environment. The score of 25 is an acceptable cut-off above which we should expect severe peritonitis. Keywords: Mannheim, Peritonitis, mortality, prognosis Ebonyi Medical Journal Vol. 6 (1) 2007 pp. 3-

Prognostic factors in generalized peritonitis in Lagos University Teaching Hospital (LUTH).

Generalised peritonitis is a more severe form of intra-abdominal infection with mortality rates of 30 – 50%. We studied the prognostic factors in generalized peritonitis with a view to documenting the current pattern of peritonitis and to determine the parameters affecting morbidity and mortality in all cases of peritonitis in LUTH. Sixty-seven consecutive patients with generalized peritonitis were recruited into the study. The biodata, clinical data, and intra-operative findings were manually collated in a proforma and subsequently analysed using EPI-INFO 2002. Forty-five patients were below the age of 30 years. Typhoid ileal perforation and ruptured appendicitis were the commonest causes accounting for 17.9% each. The most important independent prognostic factors were age, malignancy, colonic involvement, pre-operative duration of illness, characteristics of exudates and organ failures. Infective causes like typhoid ileal perforation and ruptured appendicitis are still the highest causes of generalized peritonitis in our environment. Age, malignancy, colonic involvement, pre-operative duration of illness, character of exudates and organ failure are the main prognostic factors in our study. Keywords: Generalised,Peritonitis, Secondary, Prognosis, Lagos Ebonyi Medical Journal Vol. 6 (1) 2007 pp. 37-4

Analysis of the Effects of Climate Change on Crop Output in Nigeria

This study investigates the effects of climate change factors and non-climate change factors on crop output in Nigeria. Empirical research approach was adopted with the use of secondary sources of time series annual data obtained from reputable sources for the period 1980-2013. Error Correction Mechanism was used for the analysis. It was found that in the short run, only rainfall tested significantly positive to crop output among the climate change factors but there is evidence of significant effects of all climate change factors on crop output in the long-run. For example, temperature, carbon dioxide emission, carbon emission and rainfall were tested significantly to crop output. Furthermore, non-climate change factors like economically active population, gross capital formation, and land area equipped for irrigation were significantly positive to crop output. To forestall the effects of climate change on crop output, the study recommends that policy makers should formulate policies that will aid farmers towards adaptation practices in farming that can mitigate the effects of climate change. Furthermore, governments and other relevant agencies should also design programmes that can motivate the masses to increase their involvement in crop production

Physical and mechanical properties of locally fabricated geopolymer-plastic ceiling boards

The 21st century has seen a rise in the demand for building materials, which is not unconnected to the rise in population. The high demand has led to an increase in the price of such commodities as well as a strain on environmental resources and the call for more sustainable, and cost-effective alternatives to replace the conventional materials. In this study, waste glass powder was alkali-activated to produce geopolymer, which was combined with both fine and coarse waste polyethylene terephthalate (PET) pulverized plastics (aggregates). The product was then cured to form the ceiling board. The impact of the employed glass, alkaline solution, aggregate size, and aggregate content in the boards were then investigated. Board J with 92.5% PET particles (Coarse and Fine) and 7.5% Glass Particles gave the best water absorption (16.561%), thickness swelling (3.332%) and density test (0.918 g/cm3) results. It was found that the geopolymer with equal proportions of fine and coarse PET aggregates reduced the material's ability to absorb water and increased its density and swelling thickness. The modulus of rupture and modulus of elasticity of the boards were both enhanced by adding more glass powder and fine PET aggregates. However, it was discovered that the board's mechanical qualities, unlike its physical properties, were not improved by the addition of the geopolymer during manufacture

EVALUATION OF PARTICLE BOARD FROM SUGARCANE BAGASSE AND CORN COB

This article evaluates particle board using corncob (CC) particles and mixing it homogeneously in varying percentages 20%, 40%, 50%, 60% and 80% with sugarcane bagasse (SB) using Urea Formaldehyde resin as adhesive. Particleboards of 100% SB and 100% CC were also made, thereby making seven different compositions. Properties of particleboards produced such as density, water absorption, thickness swelling, modulus of rupture and modulus of elasticity were investigated. The densities of particleboards ranged from 400 Kg/m3 to 620 Kg/m3. The results of the tests also show that the particleboard with 50% CC and 50% SB using equal volume of adhesive had favorable physical properties that are recommendable for indoor uses in buildings. In contrast, the panels cannot be recommended for load bearing purposes because they exhibit poor mechanical properties, but these mechanical properties tend to improve as the composition of CC increased from 40% to 100%. The MOR and MOE results obtained in this research work lead to a conclusion that the mechanical properties of the panels were improved as the percentage of CC replacement increased but possessed poor physical properties. Within the experimental investigation and possible limitations, the panels with 50% CC and 50% SB are the most preferred since they had preferable performance for both physical and mechanical properties

A randomized double-blind clinical trial on safety and efficacy of tauroursodeoxycholic acid (TUDCA) as add-on treatment in patients affected by amyotrophic lateral sclerosis (ALS): the statistical analysis plan of TUDCA-ALS trial

Background Amyotrophic lateral sclerosis (ALS) is a highly debilitating neurodegenerative condition. Despite recent advancements in understanding the molecular mechanisms underlying ALS, there have been no significant improvements in therapeutic options for ALS patients in recent years. Currently, there is no cure for ALS, and the only approved treatment in Europe is riluzole, which has been shown to slow the disease progression and prolong survival by approximately 3 months. Recently, tauroursodeoxycholic acid (TUDCA) has emerged as a promising and effective treatment for neurodegenerative diseases due to its neuroprotective activities. Methods The ongoing TUDCA-ALS study is a double-blinded, parallel arms, placebo-controlled, randomized multicenter phase III trial with the aim to assess the efficacy and safety of TUDCA as add-on therapy to riluzole in patients with ALS. The primary outcome measure is the treatment response defined as a minimum of 20% improvement in the ALS Functional Rating Scale-Revised (ALSFRS-R) slope during the randomized treatment period (18 months) compared to the lead-in period (3 months). Randomization will be stratified by country. Primary analysis will be conducted based on the intention-to-treat principle through an unadjusted logistic regression model. Patient recruitment commenced on February 22, 2019, and was closed on December 23, 2021. The database will be locked in September 2023. Discussion This paper provides a comprehensive description of the statistical analysis plan in order to ensure the reproducibility of the analysis and avoid selective reporting of outcomes and data-driven analysis. Sensitivity analyses have been included in the protocol to assess the impact of intercurrent events related to the coronavirus disease 2019. By focusing on clinically meaningful and robust outcomes, this trial aims to determine whether TUDCA can be effective in slowing the disease progression in patients with ALS. Trial registration ClinicalTrials.gov NCT03800524. Registered on January 11, 2019