Pharmacogenetics place in modern medical science and practice

Pharmacogenetic evidence-based treatment strategies will have major implications for all aspects of the product pipeline, including drug discovery, high throughput target screening protocols, lead optimization, and drug formulation to produce series of medicines for a particular disease which will meet the efficacy needs of the majority of patients. The initial proof of principle experiments involves whole genome screening for DNA variants and determination of specific patterns of variants associated with adverse events of marketed products [SNP Print(sm)]. Pharmacogenetics has the potential of changing the pipeline model of drug discovery, clinical development, and mass customization marketing.     

Emergency medical services evaluations for chest pain during first COVID-19 lockdown in Hollands-Midden,the Netherlands

ObjectiveTo assess whether the COVID-19 lockdown in 2020 had negative indirect health effects, as people seem to have been reluctant to seek medical care.MethodsAll emergency medical services (EMS) transports for chest pain or out-of-hospital cardiac arrest (OHCA) in the Dutch region Hollands-Midden (population served > 800,000) were evaluated during the initial 6 weeks of the COVID-19 lockdown and during the same time period in 2019. The primary endpoint was the number of evaluated chest pain patients in both cohorts. In addition, the number of EMS evaluations of ST-elevation myocardial infarction (STEMI) and OHCA were assessed.ResultsDuring the COVID-19 lockdown period, the EMS evaluated 927 chest pain patients (49% male, age 62 ± 17 years) compared with 1041 patients (51% male, 63 ± 17 years) in the same period in 2019, which corresponded with a significant relative risk (RR) reduction of 0.88 (95% confidence interval (CI) 0.81–0.96). Similarly, there was a significant reduction in the number of STEMI patients (RR 0.52, 95% CI 0.32–0.85), the incidence of OHCA remained unchanged (RR 1.23, 95% CI 0.83–1.83).ConclusionDuring the first COVID-19 lockdown, there was a significant reduction in the number of patients with chest pain or STEMI evaluated by the EMS, while the incidence of OHCA remained similar. Although the reason for the decrease in chest pain and STEMI consultations is not entirely clear, more attention should be paid to the importance of contacting the EMS in case of suspected cardiac symptoms in possible future lockdowns.Supplementary InformationThe online version of this article (10.1007/s12471-021-01545-y) contains supplementary material, which is available to authorized users.     

Implementing voluntary medical male circumcision for HIV prevention in Nyanza Province, Kenya: lessons learned during the first year

Background

In 2007, the World Health Organization endorsed male circumcision as an effective HIV prevention strategy. In 2008, the Government of Kenya (GoK) launched the national voluntary medical male circumcision (VMMC) program in Nyanza Province, the geographic home to the Luo, the largest non-circumcising ethnic group in Kenya. Currently, several other African countries are in the early stages of implementing this intervention.

Methods and Results

This paper uses data from a health facility needs assessment (n = 81 facilities) and a study to evaluate the implementation of VMMC services in 16 GoK facilities (n = 2,675 VMMC clients) to describe Kenya''s experience in implementing the national program. The needs assessment revealed that no health facility was prepared to offer the minimum package of services as outlined by the national guidelines, and partner organizations were called upon to fill this gap. The findings concerning human resource shortages facilitated the GoK''s decision to endorse trained nurses to provide VMMCs, enabling more facilities to offer the service. Findings from the evaluation study resulted in replacing voluntary counseling and testing (VCT) with provider-initiated testing and counseling (PITC) and subsequently doubling the proportion of VMMC clients tested for HIV.

Conclusions

This paper outlines how certain challenges, like human resource shortages and low HIV test rates, were addressed through national policy changes, while other challenges, like large fluctuations in demand, were addressed locally. Currently, the program requires significant support from partner organizations, but a strategic plan is under development to continue to build capacity in GoK staff and facilities. Coordination between all parties was essential and was facilitated through the formation of national, provincial, and district VMMC task forces. The lessons learned from Kenya''s VMMC implementation experience are likely generalizable to other African countries.     

Association between virtual primary care and emergency department use during the first year of the COVID-19 pandemic in Ontario,Canada

Background:Uptake of virtual care increased substantially during the first year of the COVID-19 pandemic. The aim of this study was to evaluate whether a shift from in-person to virtual visits by primary care physicians was associated with increased use of emergency departments among their enrolled patients.Methods:We conducted an observational study of monthly virtual visits and emergency department visits from Apr. 1, 2020, to Mar. 31, 2021, using administrative data from Ontario, Canada. We used multivariable regression analysis to estimate the association between the proportion of a physician’s visits that were delivered virtually and the number of emergency department visits among their enrolled patients.Results:The proportion of virtual visits was higher among female, younger and urban physicians, and the number of emergency department visits was lower among patients of female and urban physicians. In an unadjusted analysis, a 1% increase in a physician’s proportion of virtual visits was found to be associated with 11.0 (95% confidence interval [CI] 10.1–11.8) fewer emergency department visits per 1000 rostered patients. After controlling for covariates, we observed no statistically significant change in emergency department visits per 1% increase in the proportion of virtual visits (0.2, 95% CI −0.5 to 0.9).Interpretation:We did not find evidence that patients substituted emergency department visits in the context of decreased availability of in-person care with their family physician during the first year of the COVID-19 pandemic. Future research should focus on the long-term impact of virtual care on access and quality of patient care.

Access and continuity are important health system characteristics for the prevention and management of chronic diseases and treatment of nonurgent acute concerns.^1,2 Virtual care has the potential to improve both of these characteristics. It has also been associated with improved therapeutic effects, efficiency gains, patient satisfaction and compliance.³ Despite these potential benefits, virtual care was not widely adopted in Canada before the COVID-19 pandemic. In 2018, only 4% of family physicians in Canada were offering video visits.⁴ Some prepandemic studies found reduced quality and inconsistent results regarding patient experiences with virtual care, even with improved access.^3,5 The pandemic pushed health care systems to rapidly implement virtual primary care; physicians in Canada were directed to restrict in-office visits and provide care virtually whenever possible.⁶ One Ontario-based study found a 5600% increase in virtual visits early in the pandemic, while in-office visits decreased by 79%, compared with the same period in 2019.⁷ Several Canadian studies also reported that emergency department visits declined during the first wave of the pandemic, possibly owing to avoidance of in-person urgent care from fear of contracting SARS-CoV-2.^8–10In later stages of the pandemic, questions arose about the quality of virtual care and the broader system effects of reduced access to in-person care, such as patients substituting emergency department visits when in-person care options were unavailable.^11–13 The impact of virtual care on emergency department use has been studied elsewhere, but we are not aware of published studies in the context of the COVID-19 pandemic in Ontario. Six studies found that virtual care had no impact on use of emergency departments, as described in a review article, but 1 study reported that nurse consultations via telephone were associated with increased emergency department visits.¹⁴ Observational studies found no association between virtual care and subsequent or reduced emergency department use.^15,16 Several studies found that patients self-reported that they would use the emergency department 4%–12% of the time if no virtual care options were available.^15,17,18We aimed to evaluate whether a shift from in-person to virtual visits by primary care physicians in patient enrolment practices was associated with increased use of emergency departments among their enrolled patients during the first year of the COVID-19 pandemic.     

Prospective validation of the ABCD2 score for patients in the emergency department with transient ischemic attack

Background:

The ABCD2 score (Age, Blood pressure, Clinical features, Duration of symptoms and Diabetes) is used to identify patients having a transient ischemic attack who are at high risk for imminent stroke. However, despite its widespread implementation, the ABCD2 score has not yet been prospectively validated. We assessed the accuracy of the ABCD2 score for predicting stroke at 7 (primary outcome) and 90 days.

Methods:

This prospective cohort study enrolled adults from eight Canadian emergency departments who had received a diagnosis of transient ischemic attack. Physicians completed data forms with the ABCD2 score before disposition. The outcome criterion, stroke, was established by a treating neurologist or by an Adjudication Committee. We calculated the sensitivity and specificity for predicting stroke 7 and 90 days after visiting the emergency department using the original “high-risk” cutpoint of an ABCD2 score of more than 5, and the American Heart Association recommendation of a score of more than 2.

Results:

We enrolled 2056 patients (mean age 68.0 yr, 1046 (50.9%) women) who had a rate of stroke of 1.8% at 7 days and 3.2% at 90 days. An ABCD2 score of more than 5 had a sensitivity of 31.6% (95% confidence interval [CI] 19.1–47.5) for stroke at 7 days and 29.2% (95% CI 19.6–41.2) for stroke at 90 days. An ABCD2 score of more than 2 resulted in sensitivity of 94.7% (95% CI 82.7–98.5) for stroke at 7 days with a specificity of 12.5% (95% CI 11.2–14.1). The accuracy of the ABCD2 score as calculated by either the enrolling physician (area under the curve 0.56; 95% CI 0.47–0.65) or the coordinating centre (area under the curve 0.65; 95% CI 0.57–0.73) was poor.

Interpretation:

This multicentre prospective study involving patients in emergency departments with transient ischemic attack found the ABCD2 score to be inaccurate, at any cut-point, as a predictor of imminent stroke. Furthermore, the ABCD2 score of more than 2 that is recommended by the American Heart Association is nonspecific.There are approximately 100 visits to the emergency department per 100 000 population for transient ischemic attack each year.¹ Although often considered benign, transient ischemic attack carries a risk of imminent stroke. Studies have shown that the risk of stroke is 0.2%–10% within 7 days of the first transient ischemic attack, and this risk increases to 1.2%–12% at 90 days.^2–9 Stroke continues to be the leading cause of disability among adults and the third-leading cause of death in North America.^10,11 Identifying people with transient ischemic attack who are at high risk of stroke is an opportunity to prevent stroke.^3,4 However, urgent investigation of all transient ischemic attacks would require substantial resources. Three studies have attempted to develop clinical decision rules (i.e., scores) for assessing whether a patient with transient ischemic attack is at high risk of stroke.^9,12,13 Combined, these studies led to the development of the ABCD2 (Age, Blood pressure, Clinical features, Duration of symptoms and Diabetes) score. However, despite its widespread implementation, the ABCD2 score has not yet been prospectively validated.^12,14–18 This essential step in the development of rules for making clinical predictions has recently been requested.^14,19–21The objective of this study was to externally validate the ABCD2 score as a tool for identifying patients seen in the emergency department with transient ischemic attack who are at high risk of stroke within 7 (primary outcome) and 90 days (one of the secondary outcomes).