Pre-exposure prophylaxis (PrEP) for HIV prevention among people who inject drugs: a global mapping of service delivery.

BACKGROUND: The World Health Organization (WHO) recommends oral pre-exposure prophylaxis (PrEP) for all people at substantial risk of HIV as part of combination prevention. The extent to which this recommendation has been implemented globally for people who inject drugs is unclear. This study mapped global service delivery of PrEP for people who inject drugs. METHODS: Between October and December 2021, a desk review was conducted to obtain information on PrEP services for people who inject drugs from drug user-led networks and HIV, harm reduction, and human rights stakeholders. Websites of organizations involved in HIV prevention or services for people who inject drugs were searched. Models of service delivery were described in terms of service location, provider, and package. RESULTS: PrEP services were identified in 27 countries (15 high-income). PrEP delivery models varied within and across countries. In most services, PrEP services were implemented in healthcare clinics without direct links to other harm reduction services. In three countries, PrEP services were also provided at methadone clinics. In 14 countries, PrEP services were provided through community-based models (outside of clinic settings) that commonly involved peer-led outreach activities and integration with harm reduction services. CONCLUSIONS: This study indicates limited PrEP availability for people who inject drugs. There is potential to expand PrEP services for people who inject drugs within harm reduction programs, notably through community-based and peer-led services. PrEP should never be offered instead of evidence-based harm reduction programs for people who inject drugs; however, it could be offered as an additional HIV prevention choice as part of a comprehensive harm reduction program.

Safety and efficacy of target controlled infusion administration of propofol and remifentanil for moderate sedation in non-hospital dental practice.

Background: Fearful and anxious patients who find dental treatment intolerable without sedative and analgesic support may benefit from moderate sedation. Target controlled infusion (TCI) pumps are superior to bolus injection in maintaining low plasma and effect-site concentration variability, resulting in stable, steady-state drug concentrations. We evaluated the safety and efficacy of moderate sedation with remifentanil and propofol using TCI pumps in non-hospital dental settings. Methods: A prospective chart review was conducted on 101 patients sedated with propofol and remifentanil using TCI pumps. The charts were completed at two oral surgeons and one general dentist's office over 6 months. Hypoxia, hypotension, bradycardia, and over-sedation were considered adverse events and were collected using Tracking and Reporting Outcomes of Procedural Sedation (TROOPS). Furthermore, patient recovery time, sedation length, drug dose, and patient satisfaction questionnaires were used to measure sedation effectiveness. Results: Of the 101 reviewed sedation charts, 54 were of men, and 47 were of women. The mean age of the patients was 40.5 ±18.7 years, and their mean BMI was 25.6 ± 4.4. The patients did not experience hypoxia, bradycardia, and hypotension during the 4694 min of sedation. The average minimum Mean Arterial Pressure (MAP) and heartbeats were 75.1 mmHg and 60.4 bpm, respectively. 98% of patients agreed that the sedation technique met their needs in reducing their anxiety, and 99% agreed that they were satisfied with the sedation 24 hours later. The average sedation time was 46.9 ± 55.6 min, and the average recovery time was 12.4 ± 4.4 min. Remifentanil and propofol had mean initial effect-site concentration doses of 0.96 µ/ml and 1.0 ng/ml respectively. The overall total amount of drug administered was significantly higher in longer sedation procedures compared to shorter ones, while the infusion rate decreased as the procedural stimulus decreased. Conclusion: According to the results of this study, no patients experienced adverse events during sedation, and all patients were kept at a moderate sedation level for a wide range of sedation times and differing procedures. The results showed that TCI pumps are safe and effective for administering propofol and remifentanil for moderate sedation in dentistry.

Components of an Evidence-Based Analytic Rubric for Use in Medical School Admissions.

Attrition from medical school remains a serious cause of concern for the medical education community. Thus, there is a need to improve our ability to select only those candidates who will succeed at medical school from many highly qualified and motivated applicants. This can be achieved, in part, by reducing the reliance on cognitive factors and increasing the use of noncognitive character traits in high-stakes admissions decisions. Herein we describe an analytic rubric that combines research-derived predictors of medical school success to generate a composite score for use in admissions decisions. The analytic rubric as described herein represents a significant step toward evidenced-based admissions that will facilitate a more consistent and transparent qualitative evaluation of medical school applicants beyond their grades and Medical College Admissions Test scores and contribute to a redesigned and improved admissions process.

Hydroxycinnamic acid amide derivatives of polyamines reverse spermine-induced CNS excitation.

The aim of this study was to examine the acute effect of a range of novel hydroxycinnamic acid derivatives of spermine on the development of spermine-induced CNS excitation and convulsions in female Laca mice, and to assess the chronic adverse behavioural effect profile of these compounds over a 5day period. Four of the six novel polyamine analogues dose-dependently inhibited body tremor and tonic convulsions caused by spermine, when administered centrally (icv) or peripherally (ip). BU43b was the most potent analogue tested, but BU31b, 33b, and 36b were also effective (p<0.01, Mann-Whitney U test). A similar profile of effectiveness was seen with peripheral and central administration, indicating that the analogues may cross the blood brain barrier. More chronic investigation of the adverse effects of the compounds administered alone over 5days of observation indicated that the drugs were well tolerated, only causing reduced locomotor activity on the first day of the study and mild changes in behaviours linked to CNS and ANS function. It is likely that NMDA receptor NR2B subunit inhibition is involved in the anticonvulsant effect of these novel analogues, but other mechanisms may also be involved. These novel polyamine derivatives warrant further investigation of their therapeutic potential in treating epilepsy and CNS disorders where excitotoxicity is implicated.

Measuring teaching effectiveness--or not.

Faculty in the present-day academic medicine environment are expected to perform multiple functions, notably, the provision of high-quality teaching to the medical professionals of tomorrow. However, evaluating the effectiveness of this teaching is particularly difficult. Student evaluations of teaching, despite their many flaws, are widely used as a convenient tool to measure teaching effectiveness. Administrators continue to routinely use student evaluation of teaching surveys in faculty retention/promotion and merit pay decisions. This practice should be reevaluated since it may have unintended consequences, such as grade inflation and content debasement, and may contribute to faculty leaving the institution and even the profession. A more valid, reliable, and formative protocol for the evaluation of genuine teaching effectiveness needs to be developed as a matter of some urgency. In this review, alternatives to the student evaluation of teaching are explored to better measure true teaching effectiveness.

Can we predict 4-year graduation in podiatric medical school using admission data?

BACKGROUND: This study examined the predictive ability of educational background and demographic variables, available at the admission stage, to identify applicants who will graduate in 4 years from podiatric medical school. METHODS: A logistic regression model was used to identify two predictors of 4-year graduation: age at matriculation and total Medical College Admission Test score. The model was cross-validated using a second independent sample from the same population. Cross-validation gives greater confidence that the results could be more generally applied. RESULTS: Total Medical College Admission Test score was the strongest predictor of 4-year graduation, with age at matriculation being a statistically significant but weaker predictor. CONCLUSIONS: Despite the model's capacity to predict 4-year graduation better than random assignment, a sufficient amount of error in prediction remained, suggesting that important predictors are missing from the model. Furthermore, the high rate of false-positives makes it inappropriate to use age and Medical College Admission Test score as admission screens in an attempt to eliminate attrition by not accepting at-risk students.

Can we predict podiatric medical school grade point average using an admission screen?

BACKGROUND: Most medical school admission committees use cognitive and noncognitive measures to inform their final admission decisions. We evaluated using admission data to predict academic success for podiatric medical students using first-semester grade point average (GPA) and cumulative GPA at graduation as outcome measures. METHODS: In this study, we used linear multiple regression to examine the predictive power of an admission screen. A cross-validation technique was used to assess how the results of the regression model would generalize to an independent data set. RESULTS: Undergraduate GPA and Medical College Admission Test score accounted for only 22% of the variance in cumulative GPA at graduation. Undergraduate GPA, Medical College Admission Test score, and a time trend variable accounted for only 24% of the variance in first-semester GPA. CONCLUSIONS: Seventy-five percent of the individual variation in cumulative GPA at graduation and first-semester GPA remains unaccounted for by admission screens that rely on only cognitive measures, such as undergraduate GPA and Medical College Admission Test score. A reevaluation of admission screens is warranted, and medical educators should consider broadening the criteria used to select the podiatric physicians of the future.

The village/commune safety policy and HIV prevention efforts among key affected populations in Cambodia: finding a balance.

The Village/Commune Safety Policy was launched by the Ministry of Interior of the Kingdom of Cambodia in 2010 and, due to a priority focus on "cleaning the streets", has created difficulties for HIV prevention programs attempting to implement programs that work with key affected populations including female sex workers and people who inject drugs. The implementation of the policy has forced HIV program implementers, the UN and various government counterparts to explore and develop collaborative ways of delivering HIV prevention services within this difficult environment. The following case study explores some of these efforts and highlights the promising development of a Police Community Partnership Initiative that it is hoped will find a meaningful balance between the Village/Commune Safety Policy and HIV prevention efforts with key affected populations in Cambodia.

Changes in salivary immunoglobulin A (IgA) following match-play and training among English premiership footballers.

Decreased salivary immunoglobulin A (sIgA), a component of mucosal immunity, is associated with intensive physical activity: suggesting that sIgA may be used for the monitoring of mucosal immunity with footballers. We investigated changes in sIgA in elite footballers, in response to training and match-play. There was a decrease in sIgA following training, with a return to pre-training levels after 18 hours of rest. This return to resting levels was not observed following competitive match-play. Overnight rest was sufficient for mucosal IgA recovery following training but not following two successive matches, suggesting that sIgA may be used to monitor training in multi-sprint sports.

Non-native English language speakers benefit most from the use of lecture capture in medical school.

Medical education in the United States and Canada continues to evolve. However, many of the changes in pedagogy are being made without appropriate evaluation. Here, we attempt to evaluate the effectiveness of lecture capture technology as a learning tool in Podiatric medical education. In this pilot project, student performance in an inaugural lecture capture-supported biochemistry course was compared to that in the previous academic year. To examine the impact of online lecture podcasts on student performance a within-subjects design was implemented, a two way ANCOVA with repeated measures. The use of lecture capture-supported pedagogy resulted in significantly higher student test scores, than achieved historically using traditional pedagogy. The overall course performance using this lecture capture-supported pedagogy was almost 6% higher than in the previous year. Non-native English language speakers benefitted more significantly from the lecture capture-supported pedagogy than native English language speakers, since their performance improved by 10.0 points. Given that underrepresented minority (URM) students, whose native language is not English, makes up a growing proportion of medical school matriculates, these observations support the use of lecture capture technology in other courses. Furthermore, this technology may also be used as part of an academic enrichment plan to improve performance on the American Podiatric Medical Licensing Examination, reduce the attrition of URM students and potentially address the predicted minority physician shortage in 2020.

Current pharmacotherapeutic concepts for the treatment of cardiovascular disease in diabetics.

With the growing worldwide obesity epidemic, obesity, type 2 diabetes mellitus and hypertension leading to premature cardiovascular events, are increasingly prevalent. Diabetes mellitus is a significant public health concern and more aggressive management of the condition and its complications, particularly cardiovascular disease, is warranted. Endothelial cell dysfunction is now known to be present at the earliest stages of metabolic syndrome, and insulin resistance and may precede the clinical diagnosis of type 2 diabetes mellitus by several years. The current focus on endothelial cell function as a potential target of pharmacotherapy in the management of cardiovascular disease in diabetics seems warranted, though not all drugs currently prescribed target endothelial cell function equally. In this review, we consider the six classes of drugs currently prescribed for the treatment of hypertension as they impact endothelial cell function and advocate for the development of novel drugs that can repair the endothelium and enhance nitric oxide availability thus preventing future cardiovascular events.

Victim's profile analysis reveals homicide affinity for minorities and the youth.

BACKGROUND: In this study we have examined the risk of death by homicide in Miami-Dade County and Broward County (BC); and examined the association between socioeconomic status and homicide while describing victim's typical characteristics such as age, gender, race/ethnicity, and type of injury. METHODS: Data was collected from the County's Medical Examiner's Offices, Census Bureau, and Federal Bureau of Investigation between 2004 and 2007. RESULTS: There has been an increase in the risk of dying by homicide in the studied area; the homicide rate for the selected period was two times higher than the national average. Although Black Non-Hispanics count for 19% of the population of Miami-Dade County and 23% in Broward County, 56% and 53% of homicide victims are among this ethnic group in Miami-Dade County and Broward County respectively. Hispanics were more at risk of being a victim of homicide in 2007 than they were in 2004. CONCLUSIONS: A substantial proportion of the homicide victims were 22 years of age or younger. . In fact, the homicide victims' average age has been steadily decreasing in recent years. The drastic increase in the risk of death by gunshot among young Black non-Hispanic and Hispanic residents warrants cause for concern.

Accelerating harm reduction interventions to confront the HIV epidemic in the Western Pacific and Asia: the role of WHO (WPRO).

The epidemic of HIV/AIDS linked to injecting drug usage is one of the most explosive in recent years. After a historical epicentre in Europe, South and North America, at present it is clearly the main cause of dissemination of the epidemic in Eastern Europe and some key Asian countries. Recently, 10 African countries reported the spread of HIV through people who inject drugs (PWID), breaking one of the final geographical barriers to the globalization of the epidemic of HIV among and from PWID. Several countries of the Asia and Pacific Region have HIV epidemics that are driven by injecting drug usage. Harm reduction interventions have been implemented in many countries and potential barriers to implementation are being overcome. Harm reduction is no longer a marginal approach in the Region; instead, it is the core tool for responding to the HIV/AIDS epidemic among PWID. The development of a comprehensive response in the Region has been remarkable, including scaling up of needle and syringe programmes (NSPs), methadone maintenance treatment (MMT), and care, support and treatment for PWID. This development is being followed up by strong ongoing changes in policies and legislations. The main issue now is to enhance interventions to a level that can impact the epidemic. The World Health Organization (WHO) is one of the leading UN agencies promoting harm reduction. Since the establishment of the Global Programme on AIDS, WHO has been working towards an effective response to the HIV epidemic among PWID. WHO's work is organized into a number of components: establishing an evidence base; advocacy; development of normative standards, tools and guidelines; providing technical support to countries; ensuring access to essential medicines, diagnostics and commodities; and mobilizing resources. In this paper, we trace the course of development of the HIV/AIDS epidemic among and from PWID in the Western Pacific and Asia Region (WPRO) as well as WHO's role in supporting the response in some of the key countries: Cambodia, China, Lao PDR, Malaysia, the Philippines and Viet Nam.

The pre-ischaemic neuroprotective effects of the polyamine analogues BU43b and BU36b in permanent and transient focal cerebral ischaemia models in mice.

The present study investigated the neuroprotective potential of two novel polyamine analogues, BU43b and BU36b, when administered 30 min prior to cerebral ischaemia. Neuroprotection in a permanent and a transient focal cerebral ischaemia mouse model (induced by intraluminal middle cerebral artery occlusion (MCAO)) was investigated using a range of histological and behavioural assessments. In the permanent ischaemia model, BU43b reduced oedema and showed a trend towards reduction in %HLV (percentage hemisphere lesion volume) when administered at a dose of 30 mg/kg i.p. Following transient ischaemia, treatment with BU43b decreased the %HLV and reduced oedema when administered at 30 mg/kg. BU43b also improved the locomotor activity (LMA) in MCAO mice at both 20 mg/kg and 30 mg/kg doses. BU36b was less effective than BU43b in both the permanent and the transient models, with its most pronounced effect being a trend towards reduction in oedema in both models. These results demonstrate that BU43b administered 30 min before ischaemia provided a good level of neuroprotection in the two models of cerebral ischaemia used and may have potential as a neuroprotective treatment for stroke.

Podiatric medical students' evaluation of a computerized student-patient encounter log system.

The computerized student-patient encounter log system represents a considerable improvement in terms of efficiency and accuracy over traditional paper-based student-patient encounter reporting systems. The computerized log not only facilitates faculty monitoring of students' assessment and management of health problems at geographically disparate locations but also provides a rich resource of data for enhancing clinical teaching and learning experiences. However, little is known about podiatric medical students' experiences with Web-based computerized student-patient encounter log systems. The findings reported in this article suggest that the computerized student-patient encounter log was considered to be useful and effective by most of the podiatric medical students surveyed and represents an improvement over traditional paper-based recording systems.

Effect of spermine and N1-dansyl-spermine on epileptiform activity in mouse cortical slices.

N(1)-dansyl-spermine is a novel polyamine analogue, which has been demonstrated to have an antagonist action at the stimulatory polyamine site on the N-methyl-D-aspartate (NMDA) receptor macrocomplex. Cortical wedges from genetically epilepsy-prone DBA/2 mice demonstrate spontaneous epileptiform activity when perfused with Mg(2+)-free artificial cerebrospinal fluid (aCSF). This epileptiform activity has been demonstrated to be primarily mediated through the NMDA receptor. N(1)-dansyl-spermine reduced the spontaneous epileptiform activity at a high dose (100 microM) but had no effect at a lower dose (50 microM). The polyamine, spermine (300 microM) caused an increase in the rate of the spontaneous epileptiform discharges. This effect of spermine was antagonised by administration of the low dose of N(1)-dansyl-spermine (50 microM). This further demonstrates the role of the NMDA receptor in the production of spontaneous epileptiform discharges in the cortical wedge preparation and clearly illustrates both the facilitatory action of spermine and the polyamine antagonist action of N(1)-dansyl-spermine at the stimulatory polyamine site on the NMDA receptor.

The pre-ischaemic neuroprotective effects of N1-dansyl-spermine in a transient focal cerebral ischaemia model in mice.

The pre-ischaemic neuroprotective potential of a novel polyamine/NMDA antagonist N1-dansyl-spermine (1-5 mg kg(-1)) was studied in a transient focal cerebral ischaemia model in mice in comparison to a reference compound, MK-801 (1 or 3 mg kg(-1)). The intraluminal suture transient middle cerebral artery occlusion (MCAO) model was used. N1-dansyl-spermine and MK-801 were administered (i.p.) 30 min prior to ischaemia. A range of histological and behavioural assessments was employed. N1-dansyl-spermine had a comparable effect to MK-801 at reducing the percentage hemisphere lesion volume (%HLV) at the doses tested. Furthermore, N1-dansyl-spermine reduced the ischaemic brain oedema, which MK-801 did not. N1-dansyl-spermine significantly reversed the decrease of locomotor activity (LMA) caused by the MCAO and showed a significant effect at improving the rotarod performance impaired by MCAO. In contrast, MK-801 had no beneficial effect on sensorimotor function and even worsened the LMA. These results clearly demonstrate the pre-ischaemic neuroprotective effect of N1-dansyl-spermine in a transient focal cerebral ischaemia model.

Effect of L-type calcium channel antagonists on spermine-induced CNS excitation in vivo.

The ability of nitrendipine, nisoldipine, verapamil and gabapentin to inhibit the development of CNS excitation induced by spermine was assessed in mice. Injection of an excitotoxic dose of spermine (100 microg, i.c.v.) in mice results in worsening tremor that culminates in the development of a fatal tonic convulsion within 8 h of spermine administration. The dihydropyridines, nitrendipine and nisoldipine, which are L-type calcium channel antagonists acting at the alpha1 subunit, inhibited the development of spermine-induced effects. Verapamil, which also acts at the alpha1 subunit of the L-type calcium channel, also inhibited the development of spermine-induced CNS excitation. Gabapentin, a postulated L-type calcium channel antagonist interacting at the alpha2delta subunit, did not inhibit the development of spermine-induced effects. These results show that antagonists of the alpha1 subunit of L-type calcium channels can effectively inhibit the effects of spermine in vivo. This may highlight the importance of L-type calcium channels in spermine action.

The pre-ischaemic neuroprotective effect of a novel polyamine antagonist, N1-dansyl-spermine in a permanent focal cerebral ischaemia model in mice.

The polyamine sites on the NMDA receptor complex offer a therapeutic target for focal ischaemia, potentially devoid of most side effects associated with NMDA antagonists. In this study, we investigated the effect of a novel polyamine antagonist, N(1)-dansyl-spermine (0.5-10 mg kg(-1)) in a permanent focal cerebral ischaemia model in mice, and compared its effect to that of MK-801 (0.3-3 mg kg(-1)) following administration 30 min prior to ischaemia. A battery of histological and behavioural tests was employed following permanent middle cerebral artery occlusion to assess any neuroprotective effect. Following middle cerebral artery occlusion, N(1)-dansyl-spermine (1-5 mg kg(-1)) and MK-801 (1 or 3 mg kg(-1)) caused a comparable and significant reduction in the percentage hemisphere lesion volume. Similarly, both drugs significantly reduced oedema and neurological deficit score to a similar extent. Locomotor activity in MCAO mice was not significantly improved by MK-801 or N(1)-dansyl-spermine, although N(1)-dansyl-spermine induced a trend towards significant improvement. Significant improvement in rotarod performance was observed at neuroprotective doses with both drugs. Upon comparison of the profile of effects, N(1)-dansyl-spermine at least matched the effectiveness of MK-801 as a neuroprotective agent in this model. In addition, in sham-operated control mice, N(1)-dansyl-spermine was well tolerated, in contrast to the pronounced adverse effects of MK-801 on locomotor activity and rotarod performance. In conclusion, this study has shown that N(1)-dansyl-spermine is as effective a neuroprotective drug as MK-801 in this model. Moreover, in contrast to MK-801, N(1)-dansyl-spermine could be a promising therapeutic candidate for stroke as it is well tolerated at neuroprotective doses in sham-operated animals.