Prescribing for Patients Seeking Maternal and Child Healthcare in Sierra Leone: A Multiregional Retrospective Cross-Sectional Assessments of Prescribing Pattern Using WHO Drug Use Indicators.

PURPOSE: Rational use of medicines is a necessary constrict towards increasing access for those that desperately need them in society. In this study, we assess medicines prescribing patterns in healthcare facilities implementing free healthcare policy for pregnant women, lactating mothers and children under the age of five in Sierra Leone. MATERIALS AND METHODS: Using WHO drug use indicators, we evaluated prescription records from the pharmacies of four hospitals; one from each of the four regions in Sierra Leone. To study prescribing indicators, we systematically sampled 1200 prescriptions overall (300/hospital) retrospectively spanning a year, from June 2017 to July 2018. In evaluating patients care indicators, we randomly sampled 120 (30/hospital) patients encounter prospectively. We used MS Excel 2016 and IMB SPSS in data analysis, and p< 0.05 was considered significant for associational analysis. RESULTS: The average drug per prescription was 3.6 (SD=1.3) overall, 3.5 (1.3) for children under five and 3.4 (1.4) for pregnant women/lactating mothers. Eighty-seven percent of prescriptions for under-five children contains antibiotics as opposed to 68.4% of prescriptions for pregnant women/lactating mothers. More injections were prescribed per encounter for pregnant women/lactating mothers 23.2% than for children under five 18.1%. Overall, generic prescribing and prescribing from the National Essential Medicines List were 74.9% and 73.8%, respectively. None of the studied health facilities dispensed all of the prescribed medicines. The most prescribed pharmacological class of drugs were antibiotics, and paracetamol was the most commonly prescribed drug. CONCLUSION: Following WHO drug use indicators used in this study, drugs were irrationally prescribed within government hospitals providing free healthcare in Sierra Leone. Sustainability of the free healthcare scheme will require efficient medicine supply and management strategies. Therefore, the formulation of stewardship programs and/or an active Drug and Therapeutics Committee may be necessary to optimise drug use in these hospitals.

Sierra Leonean doctors' perceptions and expectations of the role of pharmacists in hospitals: a national cross-sectional survey.

Background The effective implementation of pharmaceutical care requires pharmacists' collaboration with other healthcare providers, especially doctors. However, doctor's perceptions and expectations may not be in line with the tasks and responsibilities of pharmacists. Objectives We aim to explore doctors' expectations and perceptions of pharmacists while working together in a multi-disciplinary team in Sierra Leone. Setting Twelve public hospitals in Sierra Leone. Method A national cross-sectional survey was conducted between July and September 2018. Anonymous self-administered questionnaires were distributed to all doctors at randomly selected public hospitals. Data were analyzed in Excel and SPSS using descriptive and inferential statistics, and a p > 0.05 was taken as statistically significant. Main outcome measure Doctors' perceptions and expectations towards pharmacists role in patient care. Results A total of 119 out of 150 questionnaires were returned. Doctors hold a mixed perception of pharmacists. The majority of medical doctors believed that pharmacists are vital (n = 98; 82.4%) as they provide services that foster better patients outcomes (n = 78; 65.6%). However, about half (n = 58; 48.8%) expressed uncertainty or perceived pharmacists as incompetent in providing clinical pharmacy services. Our findings also showed a large proportion of doctors expect pharmacists to review medication order (n = 110; 92.4%) for appropriateness and monitoring patients' response to therapy and possible adverse drug effects (n = 112; 92.2%). M ore than three quarters (n = 104, 87.4%) were in favour of collaborating with pharmacists in the process of developing patients' treatment plans. Doctors (n = 116; 97.5%) were of the view that doctor-pharmacist collaborations can be improved by developing trust relationships through dialogue. No demographic characteristics were independently associated with doubt in pharmacist clinical competence. Conclusion Reservations regarding pharmacists' clinical competency still prevail amongst medical doctors. Conversely, they view pharmacists as crucial players in the healthcare delivery system in Sierra Leone. Doctors also have high expectations of pharmacists in terms of contributing to better patient outcomes and therefore wish to collaborate. Possible interventions to settle doctors' discontent regarding pharmacists may include fostering interprofessional training, practice, and constructive dialogue.

Self-Rated Health Predicts Mortality in Very Old Men-the Manitoba Follow-Up Study.

BACKGROUND: Self-rated health (SRH) predicts death, but there are few studies over long-time horizons that are able to explore the effect age may have on the relationship between SRH and mortality. OBJECTIVES: 1. To determine how SRH evolves over 20 years; and 2. To determine if SRH predicts death in very old men. METHODS: We analyzed a prospective cohort study of men who were fit for air crew training in the Second World War. In 1996, a regular questionnaire was administered to the 1,779 surviving participants. SRH was elicited with a 5-point Likert Scale with the categories: excellent, very good, good, fair and poor/bad. We examined the age-specific distribution of SRH in these categories from the age of 75 to 95 years, to the end of the follow-up period in 2018. We constructed age-specific Cox proportional hazard models with an outcome of time to death. RESULTS: SRH declined with age. The gradient in risk of death persisted across all ages; those with poor/fair/bad SRH had consistently higher mortality rates. However, the discrimination between good and excellent was less in those aged 85+. CONCLUSIONS: SRH declines with advancing age, but continues to predict death in older men.

Inductive measurement and encoding of k-space trajectories in MR raw data.

OBJECTIVES:  The objective of this study was to concurrently acquire an inductive k-space trajectory measure and corresponding imaging data by an MR scanner. MATERIALS AND METHODS:  1D gradient measures were obtained by digital integration, regularized using measured gradient coil currents and recorded individually by the scanner concurrently with raw MR data. Gradient measures were frequency modulated into an RF signal receivable by the scanner, yielding a k-space trajectory measure from the cumulative phase of the acquired data. Generation of the gradient measure and frequency modulation was performed by previously developed custom, versatile circuitry. RESULTS:  For a normal echo planar imaging (EPI) sequence, the acquired k-space trajectory measure yielded slightly improved image quality compared to that obtained from using the scanner's estimated eddy current-compensated k-space trajectory. For a spiral trajectory, the regularized inductive k-space trajectory measure lead to a 76% decrease in the root-mean-square error of the reconstructed image. DISCUSSION:  While the proof-of-concept experiments show potential for further improvement, the feasibility of inductively measuring k-space trajectories and increasing the precision through regularization was demonstrated. The approach may offer an inexpensive method to acquire k-space trajectories concurrently with scanning.

The new plant Parinari kerstingii Engl.: Toxicity studies and anti-inflammatory properties.

ETHNOPHARMACOLOGICAL RELEVANCE: Parinari kerstingii Engl. extract is traditionally used for the treatment of inflammation, bronchopneumonia, feverish pains, and breast cancer. However, there have not been any scientific reports regarding the medicinal properties of this plant, and no experiments have been done to ascertain the safety of the extract. AIM OF THE STUDY: The objective of this work was to evaluate the toxicity of Parinari kerstingii Engl. extracts as an herbal remedy and to investigate its anti-inflammatory potential in vivo. MATERIALS AND METHODS: Sprague-Dawley albino male rats were used in these experiments. 100, 300 and 600 mg/kg of body weight doses of Parinari kerstingii Engl. water extract (PKWE) were used for a 14 day toxicity study. For the anti-inflammatory studies, the carrageenan-induced paw edema model was used to investigate the effect of four fractions of Parinari kerstingii Engl. ethanol extract [petroleum ether (fraction A), ethyl acetate (fraction B), n -butanol (fraction C) and water (fraction D)] on the paw size of rats and to investigate the inhibitory effects of Parinari kerstingii Engl. water (PKWE) and Parinari kerstingii Engl. ethanol extract (PKEE). RESULTS: The administration of 100 mg/kg and 300 mg/kg of body weight doses of Parinari kerstingii Engl. water extract showed no sign of toxicity. However, the 600 mg/kg of body weight dose showed a very significant increase in creatinine concentration. All the fractions of Parinari kerstingii Engl. extract demonstrated anti-inflammatory effects, as shown by a significant reduction in carrageenan-induced paw edema and by a significant decrease in the production of IL-1, TNF-α, COX-2, NF-кB, and PGE2. Moreover, fraction A and B showed enhanced in vivo anti-inflammatory effects compared to aspirin. Furthermore, PKEE was demonstrated to be more effective than PKWE. CONCLUSION: We present the first report on the plant Parinari kerstingii Engl. Based on our findings, PKWE at a dose of up to 300 mg/kg of body weight for 14 days is considered safe, and our anti-inflammatory results support its traditional use. Overall, Parinari kerstingii Engl. has been demonstrated to be a potential drug candidate. Thus, further experiments, such as isolation/structural elucidation of the phytochemicals and biological screening of this plant, need to be done.

Exploring the Knowledge and Perception of Generic Medicines among Final Year Undergraduate Medical, Pharmacy, and Nursing Students in Sierra Leone: A Comparative Cross-Sectional Approach.

Most low-income nations have national medicine policy that emphasized the use of generic medicines in the public health sector. However, the use of generics is often debatable as there are concerns over its efficacy, quality, and safety compared to their branded counterparts. This study was conducted to compare the knowledge and perception of generic medicines among final year undergraduate medical, pharmacy, and nursing students in Sierra Leone. We conducted a questionnaire-based cross-sectional study among these students at the College of Medicine and Allied Health Sciences University of Sierra Leone. Out of the 62 students, only two (2/62, 3.2%) knew about the acceptable bioequivalence limit. At least half of respondents in all three groups agreed that all generics are therapeutically equivalent to their innovator brand. At least half of the medicine (21/42, 50%) and nursing (6/9, 66.6%) students, compared to pharmacy students (5/11, 45.5%), believed that higher safety standards are required for proprietary medicines than for generic medicines. Most of them agreed that they need more information on the safety, quality, and efficacy aspects of generics (59/62, 95.2%). All three groups of healthcare students, despite variations in their responses, demonstrated a deficiency in knowledge and misconception regarding generic medicines. Training on issues surrounding generic drugs in healthcare training institutions is highly needed among future healthcare providers in Sierra Leone.

Important role of 5-hydroxytryptamine in glucocorticoid-induced insulin resistance in liver and intra-abdominal adipose tissue of rats.

AIM/INTRODUCTION: Both glucocorticoids and 5-hydroxytryptamine (5-HT) have been shown to induce insulin resistance (IR) in hepatocytes and adipocytes. Here, we explore whether there is a correlation between them. MATERIALS AND METHODS: Except for the control group, male rats were exposed to dexamethasone treated with or without para-chlorophenylalanine (pCPA), or carbidopa for 20 days. Except for the control group, buffalo rat liver 3A (BRL-3A) cells were exposed to dexamethasone for 24 h, treated with or without pCPA, carbidopa, or clorgiline for 48 h, or exposed to 5-HT treated with or without fluoxetine for 48 h. Whole-body IR was determined by both glucose tolerance test and measurement of fasting blood glucose and insulin, whereas hepatocytes or adipocytes IR was determined by examining either hepatic gluconeogenesis, steatosis and glucose transporter 2 expression or lipolysis. RESULTS: Dexamethasone-induced whole-body IR, liver and intraabdominal adipose IR were accompanied by upregulated expressions of tryptophan hydroxylase-1 and aromatic amino acid decarboxylase with increased 5-HT level in both tissues, which were attenuated significantly by pCPA, inhibiting tryptophan hydroxylase-1, or carbidopa, inhibiting aromatic amino acid decarboxylase. [Correction added on 22 September 2015, after first online publication: 'inhibiting aromatic amino acid decarboxylase' was duplicated and has been replaced by 'tryptophan hydroxylase-1'.] In the BRL-3A cells, dexamethasone-induced IR was also accompanied by upregulated 5-HT synthesis in dose- and time-dependent manners, and was attenuated by pCPA or carbidopa, but exacerbated by clorgiline, inhibiting monoamine oxidase-A to further increase 5-HT level. Dexamethasone also enhanced 5-HT 2A and 2B receptor expressions in both tissues and BRL-3A cells. Additionally, blocking 5-HT transporter with fluoxetine significantly suppressed 5-HT-induced IR in BRL-3A cells. CONCLUSION: Enhancement of 5-HT synthesis in liver and intra-abdominal adipose is an important reason for glucocorticoids-induced IR.

The role of monoubiquitination in endocytic degradation of human ether-a-go-go-related gene (hERG) channels under low K+ conditions.

A reduction in extracellular K(+) concentration ([K(+)](o)) causes cardiac arrhythmias and triggers internalization of the cardiac rapidly activating delayed rectifier potassium channel (I(Kr)) encoded by the human ether-a-go-go-related gene (hERG). We investigated the role of ubiquitin (Ub) in endocytic degradation of hERG channels stably expressed in HEK cells. Under low K(+) conditions, UbKO, a lysine-less mutant Ub that only supports monoubiquitination, preferentially interacted and selectively enhanced degradation of the mature hERG channels. Overexpression of Vps24 protein, also known as charged multivesicular body protein 3, significantly accelerated degradation of mature hERG channels, whereas knockdown of Vps24 impeded this process. Moreover, the lysosomal inhibitor bafilomycin A1 inhibited degradation of the internalized mature hERG channels. Thus, monoubiquitination directs mature hERG channels to degrade through the multivesicular body/lysosome pathway. Interestingly, the protease inhibitor lactacystin inhibited the low K(+)-induced hERG endocytosis and concomitantly led to an accumulation of monoubiquitinated mature hERG channels, suggesting that deubiquitination is also required for the endocytic degradation. Consistently, overexpression of the endosomal deubiquitinating enzyme signal transducing adaptor molecule-binding protein significantly accelerated whereas knockdown of endogenous signal transducing adaptor molecule-binding protein impeded degradation of the mature hERG channels under low K(+) conditions. Thus, monoubiquitin dynamically mediates endocytic degradation of mature hERG channels under low K(+) conditions.

Involvement of caveolin in low K+-induced endocytic degradation of cell-surface human ether-a-go-go-related gene (hERG) channels.

Reduction in the rapidly activating delayed rectifier K(+) channel current (I(Kr)) due to either mutations in the human ether-a-go-go-related gene (hERG) or drug block causes inherited or drug-induced long QT syndrome. A reduction in extracellular K(+) concentration ([K(+)](o)) exacerbates long QT syndrome. Recently, we demonstrated that lowering [K(+)](o) promotes degradation of I(Kr) in rabbit ventricular myocytes and of the hERG channel stably expressed in HEK 293 cells. In this study, we investigated the degradation pathways of hERG channels under low K(+) conditions. We demonstrate that under low K(+) conditions, mature hERG channels and caveolin-1 (Cav1) displayed a parallel time-dependent reduction. Mature hERG channels coprecipitated with Cav1 in co-immunoprecipitation analysis, and internalized hERG channels colocalized with Cav1 in immunocytochemistry analysis. Overexpression of Cav1 accelerated internalization of mature hERG channels in 0 mM K(+)(o), whereas knockdown of Cav1 impeded this process. In addition, knockdown of dynamin 2 using siRNA transfection significantly impeded hERG internalization and degradation under low K(+)(o) conditions. In cultured neonatal rat ventricular myocytes, knockdown of caveolin-3 significantly impeded low K(+)(o)-induced reduction of I(Kr). Our data indicate that a caveolin-dependent endocytic route is involved in low K(+)(o)-induced degradation of mature hERG channels.

Encoding of electrophysiology and other signals in MR images.

PURPOSE: To develop a gradient insensitive, generic technique for recording of non-MR signals by use of surplus scanner bandwidth. MATERIALS AND METHODS: Relatively simple battery driven hardware is used to transform one or more signals into radio waves detectable by the MR scanner. Similar to the "magstripe" technique used for encoding of soundtracks in motion pictures, the electrical signals are in this way encoded as artifacts appearing in the MR images or spectra outside the region of interest. The encoded signals are subsequently reconstructed from the signal recorded by the scanner. RESULTS: Electrophysiological (EP) eye and heart muscular recording (electrooculography [EOG] and electrocardiography [ECG]) during fast echo planar imaging (EPI) is demonstrated with an expandable, modular 8-channel prototype implementation. The gradient artifacts that would normally be dominating EOG are largely eliminated. CONCLUSION: The method provides relatively inexpensive sampling with inherent microsecond synchronization and it reduces gradient artifacts in physiological recordings significantly. When oversampling is employed, the method is compatible with all MR reconstruction and postprocessing techniques.