Prevalence, Associated Risk Factors, and Adverse Cardiovascular Outcomes of Statins Discontinuation: A Systematic Review.

PURPOSE: Statins are widely prescribed for cardiovascular diseases (CVD) prevention; however, a significant proportion of users discontinue the medication for various reasons. This review aimed to determine the prevalence of statin therapy discontinuation, its associated factors, and adverse cardiovascular outcomes within the first year of discontinuation. METHODS: The PubMed, EMBASE, ScienceDirect, SCOPUS, and Google Scholar databases were systematically searched from their inception to December 2022. Manual searches were also conducted on the bibliographies of relevant articles. Studies were included for qualitative data synthesis and assessed for methodological quality. RESULTS: Fifty-two studies, predominantly cohort studies (n = 38), involving 4 277 061 participants were included. The prevalence of statin discontinuation within the first year of statin initiation ranged from 0.8% to 70.5%, which was higher for primary prevention indications. Factors frequently associated with an increased likelihood of statin discontinuation included male sex, nonWhite ethnicity, smoking status, and being uninsured. Conversely, discontinuation was less likely in patients with CVD who received secondary prevention statin therapy and in patients with polypharmacy. Furthermore, age showed diverse and inconsistent relationships with statin discontinuation among various age categories. Five studies that reported the cardiovascular risk of statin discontinuation within the first year of initiation showed significantly increased risk of discontinuation, including all-cause mortality (hazard ratio: 1.36-3.65). CONCLUSION: Our findings indicate a high prevalence of statin discontinuation and an increased likelihood of adverse cardiovascular outcomes within the first year of discontinuation, despite wide variability across published studies. This review highlights the importance of addressing the modifiable risk factors associated with statin discontinuation, such as smoking and lack of insurance coverage.

Accuracy of sonographic lower segment thickness and prediction of vaginal birth after caesarean in a resourced-limited setting; Prospective study.

OBJECTIVES: To assess the accuracy of ultrasound measurement of the lower uterine segment (LUS) thickness against findings at laparotomy, and to investigate its correlation with the success rate of vaginal birth after one previous caesarean delivery (CD) in a resource-limited setting. DESIGN: Prospective study. SETTING: Obstetrics and Gynaecology department in a tertiary hospital in Ghana. POPULATION: Women with one previous CD undergoing either a trial of labour (TOLAC) or elective CD. METHODS: Myometrial lower uterine segment thickness (mLUS) and full lower uterine segment thickness (fLUS) were measured with transvaginal ultrasound (TVUS). The women were managed according to local protocols with the clinicians blinded to the ultrasound measurements. The LUS was measured intraoperatively for comparison with ultrasound measurements. MAIN OUTCOME MEASURES: Lower uterine segment findings at laparotomy, successful vaginal birth. RESULTS: A total of 311 pregnant women with one previous CD were enrolled; 147 women underwent elective CD and 164 women underwent a TOLAC. Of the women that underwent TOLAC, 96 (58.5%) women had a successful vaginal birth. The mLUS was comparable to the intraoperative measurement in the elective CD group with LUS thickness <5 mm (bias of 0.01, 95% CI -0.10 to 0.12 mm) whereas fLUS overestimated LUS <5 mm (bias of 0.93, 95% CI 0.80-1.06 mm). Successful vaginal birth rate correlated with increasing mLUS values (odds ratio 1.30, 95% CI 1.03-1.64). Twelve cases of uterine defect were recorded. LUS measurement ≤2.0 mm was associated with an increased risk of uterine defects with a sensitivity of 91.7% (95% CI 61.5-99.8%) and specificity of 81.8% (95% CI 75.8-86.8%). CONCLUSION: Accurate TVUS measurement of the LUS is technically feasible in a resource-limited setting. This approach could help in making safer decisions on mode of birth in limited-resource settings.

Focused Ultrasound-Mediated Disruption of the Blood-Brain Barrier for AAV9 Delivery in a Mouse Model of Huntington's Disease.

Huntington's disease (HD) is a monogenic neurodegenerative disorder caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the HTT gene. There are no cures for HD, but the genetic basis of this disorder makes gene therapy a viable approach. Adeno-associated virus (AAV)-miRNA-based therapies have been demonstrated to be effective in lowering HTT mRNA; however, the blood-brain barrier (BBB) poses a significant challenge for gene delivery to the brain. Delivery strategies include direct injections into the central nervous system, which are invasive and can result in poor diffusion of viral particles through the brain parenchyma. Focused ultrasound (FUS) is an alternative approach that can be used to non-invasively deliver AAVs by temporarily disrupting the BBB. Here, we investigate FUS-mediated delivery of a single-stranded AAV9 bearing a cDNA for GFP in 2-month-old wild-type mice and the zQ175 HD mouse model at 2-, 6-, and 12-months. FUS treatment improved AAV9 delivery for all mouse groups. The delivery efficacy was similar for all WT and HD groups, with the exception of the zQ175 12-month cohort, where we observed decreased GFP expression. Astrocytosis did not increase after FUS treatment, even within the zQ175 12-month group exhibiting higher baseline levels of GFAP expression. These findings demonstrate that FUS can be used to non-invasively deliver an AAV9-based gene therapy to targeted brain regions in a mouse model of Huntington's disease.

Focused ultrasound-mediated delivery of viral neuronal tracers in marmosets.

In this issue of Cell Reports Methods, Parks et al. present an approach to non-invasively deliver adeno-associated viruses in a marmoset model using focused ultrasound (FUS) for neuronal tracing. The optimization of this technique in this non-human primate model is highly valuable for future FUS-mediated drug delivery studies.

Absence of abnormal vascular changes on prenatal imaging aids in differentiating simple uterine scar dehiscence from placenta accreta spectrum: a case series.

Accurate prenatal discrimination between a simple, non-adherent uterine scar dehiscence with an underlying placenta and the severe end of the placenta accreta spectrum is problematic as the two can appear similar on prenatal imaging. This may lead to the false diagnosis of placenta accreta spectrum resulting obstetric anxiety, overtreatment and potential iatrogenic morbidity. Despite potential similarities in the etiology, the manifestation and management of these two conditions is very different. The prenatal sonographic features of seven confirmed cases of simple uterine scar dehiscence with an underlying placenta previa were examined. The common sonographic features found for scar dehiscence was a thinned myometrium (<1 mm) overlying a generally homogenous placenta and a placental bulge. There was absence of lacunae and features of hypervascularity including bridging vessels. Our findings suggest accurate discrimination between a simple scar dehiscence with the placenta underlying it and placenta accreta spectrum can be made on prenatal ultrasound if the placenta is carefully examined for the vascular features unique to PAS.

Assessment of Qatar community pharmacists' competence and practices related to renal and gastrointestinal adverse effects of nonprescription NSAIDs.

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently dispensed nonprescription drugs in community pharmacies. However, inappropriate use of NSAIDs by consumers has been associated with development of gastrointestinal (GI) injuries and renal injuries. Community pharmacists' education of consumers on proper use of NSAIDs and their associated adverse effects has been shown to reduce the GI and renal injuries. In Qatar, no studies have been done to assess the community pharmacists' knowledge, attitude, and practices related to renal and GI adverse effects of NSAIDs. Therefore, this study aimed to assess Qatar community pharmacists' knowledge, attitude, and practices on the safe use of nonprescription NSAIDs to reduce the risk of kidney and GI injuries. Methods: A cross-sectional web-based survey was conducted among community pharmacists in Qatar. A pre-tested 28-item questionnaire that was developed through a multi-phase iterative process was administered to a convenient sample of community pharmacists in Qatar. Data were analyzed using descriptive and inferential statistics with statistical significance set at p < 0.05. Results: Overall, 114 community pharmacists responded to the online questionnaire (response rate 15.2%). Approximately 90% of the community pharmacists demonstrated from good to excellent knowledge on the renal and GI adverse effects of NSAIDs, with none of their sociodemographic and professional characteristics having a significant effect on their knowledge scores. More than half of the pharmacists reported that they always or usually educated patients on the dosage (98.6%), administration (95.8%), side effects and precautions (78%), and contraindications (71.2%) of NSAIDs during their routine practices. The majority of the pharmacists had positive attitude towards educating patients about adverse effects of NSAIDs, as well as identifying high-risk patients who should avoid nonprescription NSAIDs. However, 45.7% of the pharmacists strongly agreed or agreed that educating patients about NSAIDs can be time consuming. Conclusion: Community pharmacists in Qatar demonstrated good knowledge of the renal and GI adverse effects of NSAIDs with some obvious areas of improvement, and this can be reinforced through continuing professional development. They also showed positive attitudes towards protecting patients against the renal and GI adverse effects of NSAID. However, a significant proportion of the pharmacists admitted that educating patients on NSAIDs was time consuming, which is a cause of concern warranting further investigation. Community pharmacy managers should provide community pharmacists adequate time and support to educate individuals at risk of renal and GI injuries who obtain NSAIDs from their pharmacies. Also, the Ministry of Public Health of Qatar should consider making counseling on high-risk medications (e.g., NSAIDs and insulin) by community pharmacists mandatory so that measures can be put in place in the pharmacies to free the pharmacist for education and counseling.

Adherence as a Predictor of Glycemic Control Among Adolescents With Type 1 Diabetes: A Retrospective Study Using Real-world Evidence.

PURPOSE: Metabolic control among adolescents with type 1 diabetes mellitus (T1DM) is generally poor. Nonadherence is a contributor to this poor glycemic control, leading to adverse outcomes. The findings of studies reporting the association between adherence and glycemic control are conflicting. This study aimed to assess the level of adherence among adolescents with T1DM and its relationship with glycemic control. METHODS: This was a retrospective, cross-sectional study that was conducted at Sidra Medicine, a state-of-the-art tertiary health care facility for women and children in Qatar. Mean blood or interstitial glucose monitoring frequency (BGMF) was used to assess adherence level among adolescents with T1DM, whereas glycemic control was assessed via documented glycated hemoglobin A1c (HbA1c). Adolescents who had a mean BGMF of ≥4 checks per day were considered adherent, and those who had an HbA1c level of <7% were considered as having controlled diabetes. Correlational and logistic regression analyses were performed to assess the relationship between adherence and glycemic control, incorporating other covariates into the model. FINDINGS: The rate of adherence among adolescents with T1DM in Qatar was 40.9%. Adherent adolescents had significantly lower median HbA1c levels compared with nonadherent adolescents (9.0% vs. 9.7%; P = 0.002). A significant negative correlation was found between BGMF and HbA1c level (correlation coefficient rs = -0.325; P < .001). Approximately 97% of nonadherent adolescents compared with 87% of adherent adolescents had suboptimal diabetes control (HbA1c ≥7%) (P = .016). Furthermore, nonadherent adolescents were 78% less likely to have controlled diabetes compared with adherent adolescents (adjusted odds ratio = 0.221; 95% CI, 0.063-0.778; P = 0.019). The combined effect of the determinants of glycemic control among adolescents with T1DM that were included in the multiple regression model was able to explain approximately 9% of the variances in glycemic control (Cox and Snell R2 = 0.092). IMPLICATIONS: The current findings suggest that nonadherence was highly prevalent among adolescents with T1DM and was a significant independent predictor of glycemic control, explaining 9% of the variability. This finding warrants further exploration of other possible predictors of poor glycemic control among the adolescent population. Comprehensive interventions, including educational, technological, and health service delivery aspects, aimed at improving adherence and ultimately optimizing glycemic control are warranted in adolescents with T1DM.

Determination of potential drug-drug interactions in prescription orders dispensed in a community pharmacy setting using Micromedex® and Lexicomp®: a retrospective observational study.

Background Community pharmacists have a role in identifying drug-drug interactions (DDIs) when processing prescription orders and dispensing medications to patients. The harmful effects of DDIs can be prevented or minimized by using an electronic DDI checker to screen for potential DDIs (pDDIs). However, different DDI checkers have variable rates of detecting pDDIs. Aim To estimate the prevalence of pDDIs in prescriptions dispensed in a community pharmacy setting using two electronic DDI databases and to evaluate the association between the pDDIs and contributory factors. Method Eligible prescription orders dispensed by a community pharmacy chain in Qatar from January to July 2020 were included in this retrospective observational study. For each prescription, Micromedex® and Lexicomp® were simultaneously used to identify pDDIs, and the interactions categorized based on severity and risk rating. Results Seven hundred-twenty prescriptions met the inclusion criteria, of which Micromedex® and Lexicomp® respectively identified 125 prescriptions (17.4%) and 230 prescriptions (31.9%) as having at least one pDDI. Moderate strength of agreement was found between Lexicomp® and Micromedex® in identifying pDDIs (Cohen's Kappa = 0.546). Micromedex® classified 61.6% of DDIs as major severity, while Lexicomp® classified 30.8% as major severity. The number of concurrent medications per prescription was significantly and positively associated with pDDI. Conclusion This study demonstrates a high prevalence of pDDIs among prescriptions dispensed in a community pharmacy setting. It is advisable that community pharmacists in Qatar, who typically do not have access to computerized patient profiles, use these DDI checkers to ensure all pDDIs are communicated to respective prescribers for appropriate action.

Evaluation of patient safety culture in community pharmacies in Qatar.

INTRODUCTION: Patient safety culture is a key contributor to medication safety globally. However, the perspective of pharmacists and other personnel in community pharmacy regarding patient safety culture may vary from one country to another. OBJECTIVE: The aim of this study was to determine the perspectives of community pharmacy personnel in Qatar about patient safety culture in community pharmacy setting. METHODS: A cross-sectional web-based survey utilising the Agency for Healthcare Research and Quality Community Pharmacy Survey on Patient Safety Culture was conducted. Participants included community pharmacy personnel practicing in Qatar. Both descriptive and inferential statistics were applied for data analyses, with statistical significance set at ≤ 0.05. RESULTS: Two hundred and forty participants completed the survey. A large proportion of the respondents (52.5%) reported an "excellent" overall rating of patient safety in their respective community pharmacies. Patient counselling and teamwork composites of patient safety culture were associated with the highest positive responses (95% and 93.7%, respectively). The "staffing, work pressure and pace" composite demonstrated the lowest positive response (50.6%) among the 11 composites. Inferential analysis revealed that working in chain pharmacies was significantly associated with positive responses related to "teamwork" (P = .019). Furthermore, working for more than 40 hours per week had a significant positive influence on the overall perceptions of patient safety (P = .025). CONCLUSION: There was an overall positive perception towards patient safety culture among the surveyed community pharmacy personnel in Qatar. Superiority was observed with patient counselling and teamwork, while staffing, work pressure and pace were judged poorly, warranting further investigations and potential targeting for interventions.

Evidence of community pharmacists' response preparedness during COVID-19 public health crisis: A cross-sectional study.

INTRODUCTION: Community pharmacists are often the first point of contact for the public, especially during pandemics. As outlined by the International Pharmaceutical Federation, community pharmacists have an important public health role during this Coronavirus Disease 2019 (COVID-19) public health emergency. We therefore investigated the current practices, response preparedness and professional development needs of community pharmacists in Qatar. METHODOLOGY: A descriptive cross-sectional online 38-item questionnaire-based survey constructed on evidence-based public health roles of pharmacists was conducted between 28 May and 18 June 2020. Questions related to current practices required responses on a 5-point Likert-type scale ranging from "always" to "never". The questionnaire was evaluated for validity and the reliability analysis showed a Cronbach's alpha coefficient of 0.921. RESULTS: The response (n = 311) rate for the survey was 34.2%. More than 75% of pharmacists "always" encouraged and practiced hygiene and social distancing measures. On the other hand, the proportion of pharmacists "always" involved in patient assessment, education or providing information related to COVID-19 and application of evidence-based protocol ranged from 32 to 73%. The vast majority (87-96%) of pharmacists indicated that they needed professional development related to COVID-19. Overall, 77% of pharmacists either "strongly agreed" or "agreed" that they have all the necessary COVID-19 related emergency response preparedness and training. Country from which pharmacists obtained their first degree, and the type of pharmacy where they practice influenced their overall perception toward emergency response preparedness. CONCLUSIONS: Community pharmacists in Qatar are willing to receive additional training related to COVID-19 public health crisis despite being prepared to engage with patients.

Barriers to Diabetes Adherence: Translation and Cultural Adaptation of the Instrument Into Arabic Context.

OBJECTIVES: Barriers to Diabetes Adherence (BDA) instrument is a measure developed in English to assess barriers to adherence in adolescents with type 1 diabetes (T1DM). The main objectives of the present study were to translate and culturally adapt the BDA tool into Arabic for the assessment of barriers to adherence in adolescents with T1DM in Arabic-speaking populations. METHODS: The International Society for Pharmacoeconomics and Outcomes Research guidelines for the translation and cultural adaptation of patient-reported outcome measures were used for the process. Permission to use the instrument was obtained from the developers. This was followed by 2 forward translations of the tool into Arabic. The 2 Arabic versions were combined into a reconciled Arabic version that was then back-translated into English. This was then tested against the original tool. The resultant Arabic version underwent a cognitive debriefing process to assess its comprehension and appropriateness among potential users, and this resulted in further refinements, leading to the final Arabic version of the tool. RESULTS: The translation and cognitive debriefing processes revealed issues related to the cultural or conceptual equivalence of the tool that were addressed and resolved by rewording, restructuring, or addition or elimination of words or phrases that in certain circumstances necessitated communications with the developers for further clarifications of the intended meaning of relevant items. This process generated an easy, comprehensive, clear, and culturally acceptable tool as proven by the cognitive debriefing and clinical review processes. CONCLUSION: A culturally acceptable Arabic translation of the BDA tool was developed to be used in adolescent Arabic population with T1DM.

Relationship between Stages of Change and Glycemic Control in Patients with Type 2 Diabetes Mellitus in a Primary Health-care Setting.

INTRODUCTION: Advanced stages of change (SOC) are usually associated with lower glycated hemoglobin (HbA1c) scores in patients with type 2 diabetes mellitus (T2DM). Additionally, these patients' adherence to antidiabetic medications is crucial to achieve controlled HbA1c scores. The purpose of this study was to determine the relationship between SOC and HbA1c as well as between medication adherence and HbA1c in patients with T2DM in a primary health-care setting in Qatar. MATERIALS AND METHODS: A cross-sectional observational study was conducted in patients with T2DM at the noncommunicable diseases clinics at Mesaimeer Healthcare Center and West Bay Health Care Center. Medication adherence was assessed using the Morisky Medication Adherence Scale (MMAS-8), whereas a two-item SOC questionnaire was used to measure the SOC. HbA1c values were obtained from the electronic database at the clinic. Spearman rank correlations were performed, with the significance level set at α < 0.05. RESULTS: A total of 387 patients were included in the analysis. More than 75% of them reported that they were in the maintenance stage, and 35.4% of them had a controlled diabetes status. There was no significant correlation between SOC and HbA1c or between medication adherence and HbA1c. CONCLUSIONS: There was no relationship between SOC and HbA1c or between medication adherence and HbA1c in patients with T2DM, indicating that in this study, self-reported measures are not associated with the HbA1c scores of patients.

Using the transtheoretical model's stages of change to predict medication adherence in patients with type 2 diabetes mellitus in a primary health care setting.

BACKGROUND: Qatar is currently experiencing a worrying increase in the prevalence of diabetes mellitus (DM). One of the most common reasons for uncontrolled DM is non-adherence to medications. The socio-behavioral intervention has proven effective in some chronic illnesses. OBJECTIVES: To assess the stages of change (SOC) and medication adherence scores of type 2 diabetes mellitus (T2DM) patients visiting primary healthcare institutions in Qatar, and to evaluate the cause and effect relationship between SOC and adherence to antidiabetic medications. METHODS: The 8-item Morisky Medication Adherence Scale (MMAS-8) was used to assess medication adherence, and a 2-item SOC questionnaire was utilized to classify the SOC. The analysis to determine if the SOC could predict medication adherence while controlling for demographic characteristics, total number of prescribed medications and disease duration was done using hierarchical multiple regression. RESULTS: The final analysis included 387 patients. In relation to medication adherence, majority of the patients were in the maintenance stage (76.7%), followed by the preparation stage (14.7%), the action stage (3.9%), the contemplation stage (3.4%) and the precontemplation stage (1.3%). Most of the patients were in high adherence towards antidiabetic medications (50.3%) followed by low level (26.4%) and medium level (23.3%). SOC was significant and positively predicted medication adherence, which accounted for around 58 to 60% (p < 0.001) while controlling for covariates. CONCLUSIONS: SOC was significant and positively predicted medication adherence. The study recommends that the SOC questionnaire could potentially be used to identify patients at risk for low adherence.

Assessment of a Statistical Algorithm for the Prediction of Benign Paroxysmal Positional Vertigo.

Importance: Benign paroxysmal positional vertigo (BPPV) is an otologic pathologic condition defined as a sensation of spinning triggered by changes in head position relative to gravity and caused by an entrapment of fragmented endolymph debris most commonly in the posterior semicircular canal. Confirmation of diagnosis requires experience with procedures that are poorly known by those other than practitioners with advanced otologic training. The complexity in the diagnosis of BPPV inspired the design of a questionnaire-based algorithm that would be useful for determining a vestibular diagnosis and treatment options. Objective: To assess a statistical algorithm for the diagnosis of BPPV in a busy tertiary care setting, with the long-term goal of implementing a clinical pathway to efficiently diagnose and treat patients with dizziness. Design, Setting, and Participants: In this retrospective case series, 200 patients who visited the Department of Otolaryngology-Head and Neck Surgery at Johns Hopkins University School of Medicine for their initial vertigo symptoms from September 1, 2016, to December 31, 2016, were assessed. Interventions: Use of a validated patient questionnaire as a tool to differentiate patients with dizziness in an electronic medical record review. Main Outcomes and Measures: Linear predictor (LP) value based on the questionnaire for the diagnosis of BPPV. Results: Of the 200 patient visits reviewed (132 [66%] female), 106 (53.0%; 68 [64%] female) had the information necessary to calculate the LP value and had a confirmed final diagnosis. On the basis of an LP value of 0.2 or greater, the sensitivity for a diagnosis of BPPV was 0.75 and the specificity was 1.0. The positive predictive value was 1.0, whereas the negative predictive value was 0.96. Patients with BPPV had a statistically significantly different LP value (odds ratio, 5.92; 95% CI, 2.73-12.83) than did patients without BPPV. Conclusions and Relevance: The findings of this study suggest that the algorithm is efficient for the diagnosis of BPPV in a clinical care setting.

Direct Oral Anticoagulant Use in Atypical Thrombosis-Related Conditions.

OBJECTIVE: To review the published literature for evidence of the efficacy and safety of direct oral anticoagulants (DOACs) when used in the management of atypical thrombosis-related conditions. DATA SOURCES: A comprehensive MEDLINE database search (1948 to July 2017) and EMBASE search (1980 to July 2017) were conducted using the search terms direct oral anticoagulant in combination with acute coronary syndrome (ACS), antiphospholipid antibody syndrome (APLAS), and cancer-associated thrombosis (CAT). STUDY SELECTION AND DATA EXTRACTION: The literature search was limited to studies that were conducted in humans and published in English. Clinical trials, observational studies, and case series were selected. DATA SYNTHESIS: A total of 20 published studies were selected from the literature. Only 1 randomized controlled study showed a significant reduction in cardiovascular outcomes on DOAC use in ACS patients but at the expense of increased bleeding. For the use of DOACs in APLAS, the evidence from case series seems to suggest low incidence of thromboembolic events or recurrent thrombosis in low-risk patients. Finally, in cancer patients, DOACs were comparable to warfarin in preventing CAT in 8 studies of different designs. Major bleeding with DOACs was not significantly lower than in patients who received an enoxaparin/warfarin regimen. CONCLUSIONS: Until more evidence from the ongoing clinical trials is available, DOACs may not be favorable add-on therapy in ACS patients receiving standard antiplatelet therapy but may be alternative to warfarin in preventing or treating thrombosis in low-risk APLAS patients as well as in cases of CAT in which patients have to be managed with warfarin.

Emigration of skilled healthcare workers from developing countries: can team-based healthcare practice fill the gaps in maternal, newborn and child healthcare delivery?

BACKGROUND AND INTRODUCTION: Emigration of healthcare workers from developing countries is on the rise and there is an urgent need for policies that increase access to and continuity of healthcare. In this commentary, we highlight some of the negative impacts of emigration on maternal and child health and discuss whether team-based healthcare delivery could possibly mitigate the shortfall of maternal and child health professionals in developing countries. METHODOLOGY: We cross-examine the availability of supporting structures to implement team-based maternal and child healthcare delivery in developing countries. We briefly discuss three key supporting structures: culture of sharing, telecommunication, and inter-professional education. Supporting structures are examined at system, organizational and individual levels. We argue that the culture of sharing, limited barriers to inter-professional education and increasing access to telecommunication will be advantageous to implementing team-based healthcare delivery in developing countries. CONCLUSION AND GLOBAL HEALTH IMPLICATIONS: Although most developing countries may have notable supporting structures to implement team-based healthcare delivery, the effectiveness of such models in terms of cost, time and infrastructure in resource limited settings is still to be evaluated. Hence, we call on usual stakeholders, government, regulatory colleges and professional associations in countries with longstanding emigration of maternal and child healthcare workers to invest in establishing comprehensive models needed to guide the development, implementation and evaluation of team-based maternal and child healthcare delivery.

Progress in the discovery of treatments for C. difficile infection: A clinical and medicinal chemistry review.

Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality. The incidence of C. difficile infection in developed countries has become increasingly high due to the emergence of newer epidemic strains, a growing elderly population, extensive use of broad spectrum antibiotics, and limited therapies for this diarrheal disease. Because treatment options currently available for C. difficile infection have some drawbacks, including cost, promotion of resistance, and selectivity problems, new agents are urgently needed to address these challenges. This review article focuses on two parts: the first part summarizes current clinical treatment strategies and agents under clinical development for C. difficile infection; the second part reviews newly reported anti-difficile agents that have been evaluated or reevaluated in the last five years and are in the early stages of drug discovery and development. Antibiotics are divided into natural product inspired and synthetic small molecule compounds that may have the potential to be more efficacious than currently approved treatments. This includes potency, selectivity, reduced cytotoxicity, and novel modes of action to prevent resistance.

A training program for pharmacy students on providing diabetes care.

OBJECTIVE: To compare second- and third-year pharmacy students' competence, attitudes, and self-confidence in providing diabetes care before and after completing a hand-on diabetes training program and to determine if the program had an impact on students' attitude and self-confidence based on their year in the curriculum. DESIGN: The program included classroom lectures and hands-on learning sessions in 5 facets of diabetes care. Pre- and post-test instruments measured students' competence, attitudes, and confidence in diabetes care. ASSESSMENT: Students' competence and the mean overall confidence score significantly improved after completing the program, while mean overall attitude score did not. Third-year students had significantly higher confidence scores than did second-year students on both pre- and post-program tests. No significant difference was found for attitude scores between second- and third-year students. CONCLUSION: The hands-on learning program was an effective approach to training pharmacy students in diabetes care, improving both their competence and confidence.

Effects of lesions of the optic nerve, optic tectum and nervus terminalis on rod precursor proliferation in the goldfish retina.

Teleost retinas grow throughout life by proliferation of neuroblasts at the retinal margin and dedicated rod precursors in the outer nuclear layer. Mechanisms regulating this proliferation are largely unknown. Previous investigators observed that rod precursor replication, as detected by incorporation of radioactive thymidine into cells of the outer nuclear layer, is enhanced after optic nerve crush. We attempted to determine whether this was due to severing of the retinopetal (nervus terminalis, n.t.) or retinofugal (retinal ganglion cell) axons in the optic nerve of the goldfish, Carassius auratus. In the first series of experiments, we ablated unilaterally the optic nerve, olfactory bulb (containing n.t. ganglia), or optic tectum (containing retinal ganglion cell axons and n.t. collaterals). Rod precursor proliferation increased dramatically in both retinas as soon as 5 days after surgery; in addition, the numbers of dividing cells were greater in the ipsilateral retina 10-15 days after optic nerve crush or tectal ablation and in the contralateral retina 20-25 days after olfactory bulb ablation. These observations are not accounted for by the known projections of retinal ganglion cells, but are consistent with the projections of the n.t. In the second series of experiments, n.t. projections to the brain and retina were severed bilaterally 7-8 weeks before the unilateral optic nerve crush or hemitectal ablation. Rod precursor proliferation increased as before, but the quantities of dividing cells were always equal in both retinas. We conclude that the n.t. may modulate rod proliferation locally and that injury to (some) brain regions may cause release of mitogens that affect rod precursors in both retinas.

Induction of proliferating cell nuclear antigen (PCNA)-immunoreactive cells in goldfish retina following intravitreal injection with 6-hydroxydopamine.

1. The dopaminergic neurotoxin, 6-hydroxydopamine (6-OHDA), was injected intravitreally into the eyes of juvenile (5- to 6-cm) goldfish. 2. Proliferation of rod neuroblasts caused by 6-OHDA (2 micrograms in 2 microliters saline) was detected in retinal wholemounts by immunofluorescence for proliferating cell nuclear antigen (PCNA) 3, 7, 14, 20, or 30 days after injection. 3. The injected dose of 6-OHDA was sufficient to cause permanent loss of dopaminergic interplexiform and serotonergic amacrine cells in the injected eye but not in the contralateral control eye. 4. 6-OHDA increased the density (mm-2) of PCNA-ir cells in the outer nuclear layer (ONL) of the injected eye to 2.65 times the initial density 20-30 days after injection, and it increased the density of PCNA-ir cells in the ONL of the contralateral, untreated eye, equally but after a delay of less than or equal to 7 days with respect to the injected eye. 5. 6-OHDA also increased the density of PCNA-ir cells in the inner nuclear layer (INL) to greater than 20 times the initial density 7 days after injection, followed by a rapid decline almost to control levels by 14 days after injection. 6. The sequence of responses to 6-OHDA, with PCNA-ir cells first scattered in the ONL and then clustered in the INL, suggests that neuroblasts from the ONL migrate to the INL to compensate for toxin-induced cell loss. 7. Double staining for 5-bromodeoxyuridine (BrUdR; a thymidine analogue) and PCNA, carried out on 7 days after intravitreal injection with 6-OHDA, showed that 77% of all PCNA-ir cells in the outer nuclear layer had been in S phase during the previous 24 hr. 8. Immunoreactivity for PCNA was found to be a valid marker for rod neuroblasts which have entered S phase within 1-2 days before sampling and was shown to be especially convenient for investigating the distribution of proliferating cells in whole mounts. 9. In controls injected unilaterally with saline or saline plus 1% dimethyl sulfoxide (DMSO), the differences in densities of PCNA-ir rod precursor nuclei 2-30 days after injection vs. day 0 (uninjected) were statistically insignificant in both injected and uninjected eyes (Negishi et al., 1991). Therefore the local effect of injecting 6-OHDA was due to 6-OHDA itself, not to mechanical damage or nonspecific actions of foreign substances.(ABSTRACT TRUNCATED AT 400 WORDS)