The emergence, implementation, and future growth of pharmacogenomics in psychiatry: a narrative review.

Psychotropic medication efficacy and tolerability are critical treatment issues faced by individuals with psychiatric disorders and their healthcare providers. For some people, it can take months to years of a trial-and-error process to identify a medication with the ideal efficacy and tolerability profile. Current strategies (e.g. clinical practice guidelines, treatment algorithms) for addressing this issue can be useful at the population level, but often fall short at the individual level. This is, in part, attributed to interindividual variation in genes that are involved in pharmacokinetic (i.e. absorption, distribution, metabolism, elimination) and pharmacodynamic (e.g. receptors, signaling pathways) processes that in large part, determine whether a medication will be efficacious or tolerable. A precision prescribing strategy know as pharmacogenomics (PGx) assesses these genomic variations, and uses it to inform selection and dosing of certain psychotropic medications. In this review, we describe the path that led to the emergence of PGx in psychiatry, the current evidence base and implementation status of PGx in the psychiatric clinic, and finally, the future growth potential of precision psychiatry via the convergence of the PGx-guided strategy with emerging technologies and approaches (i.e. pharmacoepigenomics, pharmacomicrobiomics, pharmacotranscriptomics, pharmacoproteomics, pharmacometabolomics) to personalize treatment of psychiatric disorders.

Performance of Immunohistochemical and Molecular Methods in Detecting Microsatellite Instability in Gastric Cancer: A Multicenter Study.

INTRODUCTION: Microsatellite instability (MSI) is an important prognostic molecular biomarker for gastric cancer (GC). MSI status may be detected by immunohistochemistry (IHC) for mismatch repair (MMR) proteins and polymerase chain reaction (PCR). Idylla™ MSI assay has not been validated for GC but may prove to be a valid alternative. METHODS: In a series of 140 GC cases, MSI status was evaluated by IHC for MLH1, PMS2, MSH2, and MSH6; gold-standard pentaplex PCR panel (PPP) (BAT-25, BAT-26, NR-21, NR-24, and NR-27); and Idylla. Statistical analysis was performed using SPSS 27.0. RESULTS: PPP identified 102 microsatellite stable (MSS) cases and 38 MSI-high cases. Only 3 cases showed discordant results. Compared with PPP, the sensitivity was 100% for IHC and 94.7% for Idylla. Specificity was 99% for IHC and 100% for Idylla. MLH1 IHC alone showed sensitivity and specificity of 97.4% and 98.0%, respectively. IHC identified three indeterminate cases; all were MSS according to PPP and Idylla. CONCLUSION: IHC for MMR proteins represents an optimal screening tool for MSI status in GC. If resources are limited, isolated MLH1 evaluation may constitute a valuable option for preliminary screening. Idylla may help detect rare MSS cases with MMR-loss and define MSI status in indeterminate cases.

No reason to smile: giant internal carotid artery aneurysm.

Giant cerebral aneurysms account for approximately 5% of all intracranial aneurysms, affecting morecommonly women in the 5th to 7th decade. When untreated, giant intracranial aneurysms face a poor prognosis withan estimated 2-year mortality of 68%. We present the case of an 82-year-old woman admitted at the emergencydepartment due to two focal to bilateral tonic-clonic seizures with a giant aneurysm of the supraclinoid segment ofthe right internal carotid artery on the CT scan. We discuss different management approaches for giant internalcarotid artery aneurysms, including direct surgical clipping, reconstructive endovascular procedures (coiling, balloon-/stent-assisted coiling, and flow diversion), deconstructive endovascular techniques (parent artery occlusion), andconservative management.

Rapidly adapting primary care sentinel surveillance across seven countries in Europe for COVID-19 in the first half of 2020: strengths, challenges, and lessons learned.

As the COVID-19 pandemic began in early 2020, primary care influenza sentinel surveillance networks within the Influenza - Monitoring Vaccine Effectiveness in Europe (I-MOVE) consortium rapidly adapted to COVID-19 surveillance. This study maps system adaptations and lessons learned about aligning influenza and COVID-19 surveillance following ECDC / WHO/Europe recommendations and preparing for other diseases possibly emerging in the future. Using a qualitative approach, we describe the adaptations of seven sentinel sites in five European Union countries and the United Kingdom during the first pandemic phase (March-September 2020). Adaptations to sentinel systems were substantial (2/7 sites), moderate (2/7) or minor (3/7 sites). Most adaptations encompassed patient referral and sample collection pathways, laboratory testing and data collection. Strengths included established networks of primary care providers, highly qualified testing laboratories and stakeholder commitments. One challenge was the decreasing number of samples due to altered patient pathways. Lessons learned included flexibility establishing new routines and new laboratory testing. To enable simultaneous sentinel surveillance of influenza and COVID-19, experiences of the sentinel sites and testing infrastructure should be considered. The contradicting aims of rapid case finding and contact tracing, which are needed for control during a pandemic and regular surveillance, should be carefully balanced.

Development Technologies for the Monitoring of Six-Minute Walk Test: A Systematic Review.

In the pandemic time, the monitoring of the progression of some diseases is affected and rehabilitation is more complicated. Remote monitoring may help solve this problem using mobile devices that embed low-cost sensors, which can help measure different physical parameters. Many tests can be applied remotely, one of which is the six-minute walk test (6MWT). The 6MWT is a sub-maximal exercise test that assesses aerobic capacity and endurance, allowing early detection of emerging medical conditions with changes. This paper presents a systematic review of the use of sensors to measure the different physical parameters during the performance of 6MWT, focusing on various diseases, sensors, and implemented methodologies. It was performed with the PRISMA methodology, where the search was conducted in different databases, including IEEE Xplore, ACM Digital Library, ScienceDirect, and PubMed Central. After filtering the papers related to 6MWT and sensors, we selected 31 papers that were analyzed in more detail. Our analysis discovered that the measurements of 6MWT are primarily performed with inertial and magnetic sensors. Likewise, most research studies related to this test focus on multiple sclerosis and pulmonary diseases.

Velocity-Monitored Resistance Training in Older Adults: The Effects of Low-Velocity Loss Threshold on Strength and Functional Capacity.

ABSTRACT: Marques, DL, Neiva, HP, Marinho, DA, and Marques, MC. Velocity-monitored resistance training in older adults: the effects of low-velocity loss threshold on strength and functional capacity. J Strength Cond Res 36(11): 3200-3208, 2022-This study analyzed the effects of velocity-monitored resistance training (RT) with a velocity loss of 10% on strength and functional capacity in older adults. Forty-two subjects (79.7 ± 7.1 years) were allocated into an RT group ( n = 21) or a control group (CG; n = 21). Over 10 weeks, the RT group performed 2 sessions per week, whereas the CG maintained their daily routine. During RT sessions, we monitored each repetition's mean velocity in the leg press and chest press exercises at 40-65% of 1 repetition maximum (1RM). The set ended when a velocity loss of 10% was reached. At pretest and post-test, both groups were assessed in the 1RM leg press and chest press, handgrip strength, medicine ball throw (MBT), walking speed (T 10 ), and 5-repetition sit-to-stand (STS). After 10 weeks, the RT group significantly improved the 1RM leg press ( p < 0.001; Hedge's g effect size [ g ] = 0.55), 1RM chest press ( p < 0.001; g = 0.72), MBT 1kg ( p < 0.01; g = 0.26), T 10 ( p < 0.05; g = -0.29), and STS ( p < 0.05; g = -0.29), whereas the CG significantly increased the T 10 ( p < 0.05; g = 0.15). Comparisons between groups at post-test demonstrated significant differences in the 1RM leg press ( p < 0.001; mean difference [MD] = 14.4 kg), 1RM chest press ( p < 0.001; MD = 7.52), MBT 1kg ( p < 0.05; MD = 0.40 m), T 10 ( p < 0.001; MD = -0.60 seconds), and STS ( p < 0.001; MD = -1.85 seconds). Our data demonstrate that velocity-monitored RT with velocity loss of 10% results in a few repetitions per set (leg press: 5.1 ± 1.2; chest press: 3.6 ± 0.9) and significantly improves strength and functional capacity in older adults.

An Experimental Study on the Validity and Reliability of a Smartphone Application to Acquire Temporal Variables during the Single Sit-to-Stand Test with Older Adults.

Smartphone sensors have often been proposed as pervasive measurement systems to assess mobility in older adults due to their ease of use and low-cost. This study analyzes a smartphone-based application's validity and reliability to quantify temporal variables during the single sit-to-stand test with institutionalized older adults. Forty older adults (20 women and 20 men; 78.9 ± 8.6 years) volunteered to participate in this study. All participants performed the single sit-to-stand test. Each sit-to-stand repetition was performed after an acoustic signal was emitted by the smartphone app. All data were acquired simultaneously with a smartphone and a digital video camera. The measured temporal variables were stand-up time and total time. The relative reliability and systematic bias inter-device were assessed using the intraclass correlation coefficient (ICC) and Bland-Altman plots. In contrast, absolute reliability was assessed using the standard error of measurement and coefficient of variation (CV). Inter-device concurrent validity was assessed through correlation analysis. The absolute percent error (APE) and the accuracy were also calculated. The results showed excellent reliability (ICC = 0.92-0.97; CV = 1.85-3.03) and very strong relationships inter-devices for the stand-up time (r = 0.94) and the total time (r = 0.98). The APE was lower than 6%, and the accuracy was higher than 94%. Based on our data, the findings suggest that the smartphone application is valid and reliable to collect the stand-up time and total time during the single sit-to-stand test with older adults.

Epidemiology of Seasonal Coronaviruses: Establishing the Context for the Emergence of Coronavirus Disease 2019.

Public health preparedness for coronavirus (CoV) disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal CoVs (sCoVs) and other cocirculating viruses in the West of Scotland, United Kingdom. We analyzed routine diagnostic data for >70 000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43, and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently, and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.

The experience of point-of-care testing for influenza in Scotland in 2017/18 and 2018/19 - no gain without pain.

BackgroundDuring the 2017/18 and 2018/19 influenza seasons, molecular amplification-based point-of-care tests (mPOCT) were introduced in Scotland to aid triaging respiratory patients for hospital admission, yet communication of results to national surveillance was unaccounted for.AimThis retrospective study aims to describe steps taken to capture mPOCT data and assess impact on influenza surveillance.MethodsQuestionnaires determined mPOCT usage in 2017/18 and 2018/19. Searches of the Electronic Communication of Surveillance in Scotland (ECOSS) database were performed and compared with information stored in laboratory information management systems. Effect of incomplete data on surveillance was determined by comparing routine against enhanced data and assessing changes in influenza activity levels determined by the moving epidemic method.ResultsThe number of areas employing mPOCT increased over the two seasons (6/14 in 2017/18 and 8/14 in 2018/19). Analysis of a small number of areas (n = 3) showed capture of positive mPOCT results in ECOSS improved between seasons and remained high (> 94%). However, capture of negative results was incomplete. Despite small discrepancies in weekly activity assessments, routine data were able to identify trend, start, peak and end of both influenza seasons.ConclusionThis study has shown an improvement in capture of data from influenza mPOCT and has highlighted issues that need to be addressed for results to be accurately captured in national surveillance. With the clear benefit to patient management we suggest careful consideration should be given to the connectivity aspects of the technology in order to ensure minimal impact on national surveillance.

End of season influenza vaccine effectiveness in adults and children in the United Kingdom in 2017/18.

BackgroundIn the United Kingdom (UK), in recent influenza seasons, children are offered a quadrivalent live attenuated influenza vaccine (LAIV4), and eligible adults mainly trivalent inactivated vaccine (TIV).AimTo estimate the UK end-of-season 2017/18 adjusted vaccine effectiveness (aVE) and the seroprevalence in England of antibodies against influenza viruses cultured in eggs or tissue.MethodsThis observational study employed the test-negative case-control approach to estimate aVE in primary care. The population-based seroprevalence survey used residual age-stratified samples.ResultsInfluenza viruses A(H3N2) (particularly subgroup 3C.2a2) and B (mainly B/Yamagata/16/88-lineage, similar to the quadrivalent vaccine B-virus component but mismatched to TIV) dominated. All-age aVE was 15% (95% confidence interval (CI): -6.3 to 32) against all influenza; -16.4% (95% CI: -59.3 to 14.9) against A(H3N2); 24.7% (95% CI: 1.1 to 42.7) against B and 66.3% (95% CI: 33.4 to 82.9) against A(H1N1)pdm09. For 2-17 year olds, LAIV4 aVE was 26.9% (95% CI: -32.6 to 59.7) against all influenza; -75.5% (95% CI: -289.6 to 21) against A(H3N2); 60.8% (95% CI: 8.2 to 83.3) against B and 90.3% (95% CI: 16.4 to 98.9) against A(H1N1)pdm09. For ≥ 18 year olds, TIV aVE against influenza B was 1.9% (95% CI: -63.6 to 41.2). The 2017 seroprevalence of antibody recognising tissue-grown A(H3N2) virus was significantly lower than that recognising egg-grown virus in all groups except 15-24 year olds.ConclusionsOverall aVE was low driven by no effectiveness against A(H3N2) possibly related to vaccine virus egg-adaption and a new A(H3N2) subgroup emergence. The TIV was not effective against influenza B. LAIV4 against influenza B and A(H1N1)pdm09 was effective.

Moving epidemic method (MEM) applied to virology data as a novel real time tool to predict peak in seasonal influenza healthcare utilisation. The Scottish experience of the 2017/18 season to date.

Scotland observed an unusual influenza A(H3N2)-dominated 2017/18 influenza season with healthcare services under significant pressure. We report the application of the moving epidemic method (MEM) to virology data as a tool to predict the influenza peak activity period and peak week of swab positivity in the current season. This novel MEM application has been successful locally and is believed to be of potential use to other countries for healthcare planning and building wider community resilience.

Cyclosporiasis in travellers returning to the United Kingdom from Mexico in 2017: lessons from the recent past to inform the future.

During the summers of 2015 and 2016, the United Kingdom experienced large outbreaks of cyclosporiasis in travellers returning from Mexico. As the source of the outbreaks was not identified, there is the potential for a similar outbreak to occur in 2017; indeed 78 cases had already been reported as at 27 July 2017. Early communication and international collaboration is essential to provide a better understanding of the source and extent of this recurring situation.

Effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2014/15 end of season results.

The 2014/15 influenza season in the United Kingdom (UK) was characterised by circulation of predominantly antigenically and genetically drifted influenza A(H3N2) and B viruses. A universal paediatric influenza vaccination programme using a quadrivalent live attenuated influenza vaccine (LAIV) has recently been introduced in the UK. This study aims to measure the end-of-season influenza vaccine effectiveness (VE), including for LAIV, using the test negative case-control design. The overall adjusted VE against all influenza was 34.3% (95% confidence interval (CI) 17.8 to 47.5); for A(H3N2) 29.3% (95% CI: 8.6 to 45.3) and for B 46.3% (95% CI: 13.9 to 66.5). For those aged under 18 years, influenza A(H3N2) LAIV VE was 35% (95% CI: -29.9 to 67.5), whereas for influenza B the LAIV VE was 100% (95% CI:17.0 to 100.0). Although the VE against influenza A(H3N2) infection was low, there was still evidence of significant protection, together with moderate, significant protection against drifted circulating influenza B viruses. LAIV provided non-significant positive protection against influenza A, with significant protection against B. Further work to assess the population impact of the vaccine programme across the UK is underway.

Tapia's Syndrome: A Comprehensive Analysis of a Rare Intensive Care-Associated Complication.

Tapia's syndrome is a rare complication of airway manipulation, involving the simultaneous paralysis of the hypoglossal nerve and the recurrent laryngeal nerve. The etiological mechanism is commonly attributed to compression or stretching during airway manipulation. An efficient recognition of this condition is pivotal for a comprehensive multidisciplinary approach and optimized recovery time. The presence of persistent dysphagia and dysphonia, coupled with observable deviation or restriction of tongue movement, not only after oral endotracheal intubation for surgical interventions with general anesthesia but also after a prolonged orotracheal intubation period in the intensive care, should heighten the suspicion of this syndrome. This report details a case of Tapia's syndrome emerging as a complication of airway manipulation and prolonged intubation in the intensive care unit.

Changes in strength-related outcomes following velocity-monitored resistance training with 10 % and 20 % velocity loss in older adults.

We compared the effects of velocity-monitored resistance training with an intra-set velocity loss (i.e., the decrement in repetition velocity over the set) of 10 % vs. 20 % on strength-related outcomes in older adults. We randomly assigned eighteen older adults to a velocity loss group of 10 % (n = 10; 78 ± 12 years) or 20 % (n = 8; 73 ± 10 years) to perform a 10-week training program. The primary outcomes were the one-repetition maximum (1RM) and the average mean velocity against absolute loads associated with loads <60 % 1RM (MVlow) and ≥ 60 % 1RM (MVhigh) in the leg and chest press exercises, assessed at pre-, mid- (week 5), and post-test. Secondary outcomes included handgrip strength, 1-kg medicine ball throw distance, 10-m walking time, and five-repetition sit-to-stand time. No differences between groups were found in any outcome at any time (p > 0.05). Both groups improved the 1RM leg press from pre- to mid- and post-test and the MVlow and MVhigh from pre- to mid-test (p < 0.05). No group improved the 1RM chest press (p > 0.05), but both increased the MVlow from pre- to mid-test (p < 0.05). Furthermore, both groups improved the sit-to-stand time, while only the 20 % velocity loss group significantly improved handgrip strength and 10-m walking time (p < 0.05). The results showed that both velocity losses improved leg press strength and velocity, chest press velocity, and sit-to-stand time in older adults, although a 10 % velocity loss was more efficient as it required less volume (i.e., total repetitions) than 20 %. Nevertheless, the latter seems required to optimize handgrip strength and 10-m walking time in older people.

Manipulating the Resistance Training Volume in Middle-Aged and Older Adults: A Systematic Review with Meta-Analysis of the Effects on Muscle Strength and Size, Muscle Quality, and Functional Capacity.

BACKGROUND: Effective manipulation of the acute variables of resistance training is critical to optimizing muscle and functional adaptations in middle-aged and older adults. However, the ideal volume prescription (e.g., number of sets performed per exercise) in middle-aged and older adults remains inconclusive in the literature. OBJECTIVE: The effects of single versus multiple sets per exercise on muscle strength and size, muscle quality, and functional capacity in middle-aged and older adults were compared. Moreover, the effects of single versus multiple sets per exercise on muscular and functional gains were also examined, considering the influence of training duration. METHODS: Randomized controlled trials and non-randomized controlled trials comparing single versus multiple sets per exercise on muscle strength, muscle size, muscle quality, or functional capacity in middle-aged and older adults (aged ≥ 50 years) in the PubMed/MEDLINE, Web of Science, and Scopus databases (01/09/2021, updated on 15/05/2022) were identified. A random-effects meta-analysis was used. RESULTS: Fifteen studies were included (430 participants; 93% women; age 57.9-70.1 years). Multiple sets per exercise produced a greater effect than single sets on lower-limb strength (standardized mean difference [SMD] = 0.29; 95% confidence interval [CI] 0.07-0.51; mean difference [MD] = 1.91 kg; 95% CI 0.50-3.33) and muscle quality (SMD = 0.40; 95% CI 0.05-0.75) gains. There were no differences between single versus multiple sets per exercise for upper-limb strength (SMD = 0.13; 95% CI - 0.14 to 0.40; MD = 0.11 kg; 95% CI - 0.52 to 0.75), muscle size (SMD = 0.15; 95% CI - 0.07 to 0.37), and functional capacity (SMD = 0.01; 95% CI - 0.47 to 0.50) gains. In addition, there were no differences between single versus multiple sets on muscle strength and size gains for training durations ≤ 12 weeks or > 12 weeks. CONCLUSIONS: Multiple sets per exercise produced greater lower-limb strength and muscle quality gains than single sets in middle-aged and older adults, although the magnitude of the difference was small. In contrast, single sets per exercise were sufficient to improve upper-limb strength, muscle size, and functional capacity in these populations. Despite these findings, researchers should conduct future high-quality, pre-registered, and blinded randomized controlled trials to strengthen the scientific evidence on this topic.

The cellular mechanism of antipsychotic-induced myocarditis: A systematic review.

Antipsychotic drug-induced myocarditis is a serious and potentially fatal adverse drug reaction characterized by inflammation of the heart muscle (myocardium) that typically develops within the first month after commencing an antipsychotic drug. Although the precise mechanism of this severe adverse drug reaction is unknown, multiple theories have been proposed with varying levels of support from cellular or animal studies. We conducted a systematic review, in accordance with PRISMA guidelines, of published preclinical and clinical studies investigating the cellular mechanism by which antipsychotic drugs induce myocarditis. A literature search including all studies available before December 10, 2022, yielded 15 studies that met our inclusion criteria. Antipsychotics examined in the included studies included clozapine (n = 13), ziprasidone (n = 1), amisulpride (n = 1), haloperidol (n = 1), levomepromazine (n = 1), olanzapine (n = 1), and sertindole (n = 1). The evidence suggests several overlapping mechanistic cascades involving: (1) increased levels of catecholamines, (2) increased proinflammatory cytokines, (3) increased reactive oxygen species (ROS), (4) reduced antioxidant levels and activity, and (5) mitochondrial damage. Notable limitations such as, a focus on clozapine, sample heterogeneity, and use of supratherapeutic doses will need to be addressed in future studies. Discovery of the mechanism by which antipsychotic drugs induce myocarditis will allow the development of clinically-useful biomarkers to identify those patients at increased risk prior to drug exposure. The development or repurposing of therapeutics to prevent or treat drug-induced myocarditis will also be possible and this will enable increased and safe use of antipsychotics for those patients in need.