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Relative to the numerous studies focused on mammalian schistosomes, fewer include avian schistosomatids particularly in the southern hemisphere. This is changing and current research emerging from the Neotropics shows a remarkable diversity of endemic taxa. To contribute to this effort, nine ducks (Spatula cyanoptera, S.versicolor, Netta peposaca), 12 swans (Cygnus melancoryphus) and 1,400 Physa spp. snails from Chile and Argentina were collected for adults and larval schistosomatids, respectively. Isolated schistosomatids were preserved for morphological and molecular analyses (28S and COI genes). Four different schistosomatid taxa were retrieved from birds: Trichobilharzia sp. in N. peposaca and S. cyanoptera that formed a clade; S.cyanoptera and S. versicolor hosted Trichobilharzia querquedulae; Cygnus melancoryphus hosted the nasal schistosomatid, Nasusbilharzia melancorhypha; and one visceral, Schistosomatidae gen. sp., which formed a clade with furcocercariae from Argentina and Chile from previous work. Of the physid snails, only one from Argentina had schistosomatid furcocercariae that based on molecular analyses grouped with T. querquedulae. This study represents the first description of adult schistosomatids from Chile as well as the elucidation of the life cycles of N.melancorhypha and T. querquedulae in Chile and Neotropics, respectively. Without well-preserved adults, the putative new genus Schistosomatidae gen. sp. could not be described, but its life cycle involves Chilina spp. and C. melancoryphus. Scanning electron microscopy of T. querquedulae revealed additional, undescribed morphological traits, highlighting its diagnostic importance. Authors stress the need for additional surveys of avian schistosomatids from the Neotropics to better understand their evolutionary history.
Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.
Methods
As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men.
Results
Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects.
Conclusions
Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.
This study investigated sex differences in Fe status, and associations between Fe status and endurance and musculoskeletal outcomes, in military training. In total, 2277 British Army trainees (581 women) participated. Fe markers and endurance performance (2·4 km run) were measured at the start (week 1) and end (week 13) of training. Whole-body areal body mineral density (aBMD) and markers of bone metabolism were measured at week 1. Injuries during training were recorded. Training decreased Hb in men and women (mean change (–0·1 (95 % CI –0·2, –0·0) and –0·7 (95 % CI –0·9, –0·6) g/dl, both P < 0·001) but more so in women (P < 0·001). Ferritin decreased in men and women (–27 (95 % CI –28, –23) and –5 (95 % CI –8, –1) µg/l, both P ≤ 0·001) but more so in men (P < 0·001). Soluble transferrin receptor increased in men and women (2·9 (95 % CI 2·3, 3·6) and 3·8 (95 % CI 2·7, 4·9) nmol/l, both P < 0·001), with no difference between sexes (P = 0·872). Erythrocyte distribution width increased in men (0·3 (95 % CI 0·2, 0·4)%, P < 0·001) but not in women (0·1 (95 % CI –0·1, 0·2)%, P = 0·956). Mean corpuscular volume decreased in men (–1·5 (95 % CI –1·8, –1·1) fL, P < 0·001) but not in women (0·4 (95 % CI –0·4, 1·3) fL, P = 0·087). Lower ferritin was associated with slower 2·4 km run time (P = 0·018), sustaining a lower limb overuse injury (P = 0·048), lower aBMD (P = 0·021) and higher beta C-telopeptide cross-links of type 1 collagen and procollagen type 1 N-terminal propeptide (both P < 0·001) controlling for sex. Improving Fe stores before training may protect Hb in women and improve endurance and protect against injury.
OBJECTIVES/GOALS: Supported by the State of Alabama, the Alabama Genomic Health Initiative (AGHI) is aimed at preventing and treating common conditions with a genetic basis. This joint UAB Medicine-HudsonAlpha Institute for Biotechnology effort provides genomic testing, interpretation, and counseling free of charge to residents in each of Alabama’s 67 counties. METHODS/STUDY POPULATION: Launched in 2017, as a state-wide population cohort, AGHI (1.0) enrolled 6,331 Alabamians and returned individual risk of disease(s) related to the ACMG SF v2.0 medically actionable genes. In 2021, the cohort was expanded to include a primary care cohort. AGHI (2.0) has enrolled 750 primary care patients, returning individual risk of disease(s) related to the ACMG SF v3.1 gene list and pre-emptive pharmacogenetics (PGx) to guide medication therapy. Genotyping is done on the Illumina Global Diversity Array with Sanger sequencing to confirm likely pathogenic / pathogenic variants in medically actionable genes and CYP2D6 copy number variants using Taqman assays, resulting in a CLIA-grade report. Disease risk results are returned by genetic counselors and Pharmacogenetics results are returned by Pharmacists. RESULTS/ANTICIPATED RESULTS: We have engaged a statewide community (>7000 participants), returning 94 disease risk genetic reports and 500 PGx reports. Disease risk reports include increased predisposition to cancers (n=38), cardiac diseases (n=33), metabolic (n=12), other (n=11). 100% of participants harbor an actionable PGx variant, 70% are on medication with PGx guidance, 48% harbor PGx variants and are taking medications affected. In 10% of participants, pharmacists sent an active alert to the provider to consider/ recommend alternative medication. Most commonly impacted medications included antidepressants, NSAIDS, proton-pump inhibitors and tramadol. To enable the EMR integration of genomic information, we have developed an automated transfer of reports into the EMR with Genetics Reports and PGx reports viewable in Cerner. DISCUSSION/SIGNIFICANCE: We share our experience on pre-emptive implementation of genetic risk and pharmacogenetic actionability at a population and clinic level. Both patients and providers are actively engaged, providing feedback to refine the return of results. Real time alerts with guidance at the time of prescription are needed to ensure future actionability and value.
The interaction of relativistically intense lasers with opaque targets represents a highly non-linear, multi-dimensional parameter space. This limits the utility of sequential 1D scanning of experimental parameters for the optimization of secondary radiation, although to-date this has been the accepted methodology due to low data acquisition rates. High repetition-rate (HRR) lasers augmented by machine learning present a valuable opportunity for efficient source optimization. Here, an automated, HRR-compatible system produced high-fidelity parameter scans, revealing the influence of laser intensity on target pre-heating and proton generation. A closed-loop Bayesian optimization of maximum proton energy, through control of the laser wavefront and target position, produced proton beams with equivalent maximum energy to manually optimized laser pulses but using only 60% of the laser energy. This demonstration of automated optimization of laser-driven proton beams is a crucial step towards deeper physical insight and the construction of future radiation sources.
A machine learning model was created to predict the electron spectrum generated by a GeV-class laser wakefield accelerator. The model was constructed from variational convolutional neural networks, which mapped the results of secondary laser and plasma diagnostics to the generated electron spectrum. An ensemble of trained networks was used to predict the electron spectrum and to provide an estimation of the uncertainty of that prediction. It is anticipated that this approach will be useful for inferring the electron spectrum prior to undergoing any process that can alter or destroy the beam. In addition, the model provides insight into the scaling of electron beam properties due to stochastic fluctuations in the laser energy and plasma electron density.
To document changes in evaluation protocols for acute invasive fungal sinusitis during the coronavirus disease 2019 pandemic, and to analyse concordance between clinical and histopathological diagnoses based on new practice guidelines.
Methods
Protocols for the evaluation of patients with suspected acute invasive fungal sinusitis both prior and during the coronavirus disease 2019 period are described. A retrospective analysis of patients presenting with suspected acute invasive fungal sinusitis from 1 May to 30 June 2021 was conducted, with assessment of the concordance between clinical and final diagnoses.
Results
Among 171 patients with high clinical suspicion, 160 (93.6 per cent) had a final histopathological diagnosis of invasive fungal sinusitis, concordant with the clinical diagnosis, with sensitivity of 100 per cent, positive predictive value of 93.6 per cent and negative predictive value of 100 per cent.
Conclusion
The study highlights a valuable screening tool with good accuracy, involving emphasis on ‘red flag’ signs in high-risk populations. This could be valuable in situations demanding the avoidance of aerosol-generating procedures and in resource-limited settings facilitating early referral to higher level care centres.
Milk, dairy products, and fish are the main sources of iodine in the UK. Plant-based products are increasingly popular, especially with young women, which may affect iodine intake as they are naturally low in iodine; this is concerning as iodine is required for fetal brain development. We, aimed to (i) assess the iodine fortification of products sold as alternatives to milk, yoghurt, cheese and fish through a cross-sectional survey of UK retail outlets in 2020, and (ii) model the impact of substitution with such products on iodine intake, using portion-based scenarios. We identified 300 products, including plant-based alternatives to: (i) milk (n 146); (ii) yoghurt (n 76); (iii) cheese (n 67) and (iv) fish (n 11). After excluding organic products (n 48), which cannot be fortified, only 28 % (n 29) of milk alternatives and 6 % (n 4) of yoghurt alternatives were fortified with iodine, compared with 88 % (n 92) and 73 % (n 51), respectively, with Ca. No cheese alternative was fortified with iodine, but 55 % were fortified with Ca. None of the fish alternatives were iodine fortified. Substitution of three portions of dairy product (milk/yoghurt/cheese) per day with unfortified alternatives would reduce the iodine provided by 97·9 % (124 v. 2·6 µg) and substantially reduce the contribution to the adult intake recommendation (150 µg/d; 83 v. 1·8 %). Our study highlights that the majority of plant-based alternatives are not iodine fortified and that the use of unfortified alternatives put consumers at risk of iodine deficiency.
People presenting with first-episode psychosis (FEP) have heterogenous outcomes. More than 40% fail to achieve symptomatic remission. Accurate prediction of individual outcome in FEP could facilitate early intervention to change the clinical trajectory and improve prognosis.
Aims
We aim to systematically review evidence for prediction models developed for predicting poor outcome in FEP.
Method
A protocol for this study was published on the International Prospective Register of Systematic Reviews, registration number CRD42019156897. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance, we systematically searched six databases from inception to 28 January 2021. We used the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies and the Prediction Model Risk of Bias Assessment Tool to extract and appraise the outcome prediction models. We considered study characteristics, methodology and model performance.
Results
Thirteen studies reporting 31 prediction models across a range of clinical outcomes met criteria for inclusion. Eleven studies used logistic regression with clinical and sociodemographic predictor variables. Just two studies were found to be at low risk of bias. Methodological limitations identified included a lack of appropriate validation, small sample sizes, poor handling of missing data and inadequate reporting of calibration and discrimination measures. To date, no model has been applied to clinical practice.
Conclusions
Future prediction studies in psychosis should prioritise methodological rigour and external validation in larger samples. The potential for prediction modelling in FEP is yet to be realised.
In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.
The current study argues that population prevalence estimates for mental health disorders, or changes in mean scores over time, may not adequately reflect the heterogeneity in mental health response to the COVID-19 pandemic within the population.
Methods
The COVID-19 Psychological Research Consortium (C19PRC) Study is a longitudinal, nationally representative, online survey of UK adults. The current study analysed data from its first three waves of data collection: Wave 1 (March 2020, N = 2025), Wave 2 (April 2020, N = 1406) and Wave 3 (July 2020, N = 1166). Anxiety-depression was measured using the Patient Health Questionnaire Anxiety and Depression Scale (a composite measure of the PHQ-9 and GAD-7) and COVID-19-related posttraumatic stress disorder (PTSD) with the International Trauma Questionnaire. Changes in mental health outcomes were modelled across the three waves. Latent class growth analysis was used to identify subgroups of individuals with different trajectories of change in anxiety-depression and COVID-19 PTSD. Latent class membership was regressed on baseline characteristics.
Results
Overall prevalence of anxiety-depression remained stable, while COVID-19 PTSD reduced between Waves 2 and 3. Heterogeneity in mental health response was found, and hypothesised classes reflecting (i) stability, (ii) improvement and (iii) deterioration in mental health were identified. Psychological factors were most likely to differentiate the improving, deteriorating and high-stable classes from the low-stable mental health trajectories.
Conclusions
A low-stable profile characterised by little-to-no psychological distress (‘resilient’ class) was the most common trajectory for both anxiety-depression and COVID-19 PTSD. Monitoring these trajectories is necessary moving forward, in particular for the ~30% of individuals with increasing anxiety-depression levels.
The coronavirus disease 2019 (COVID-19) emergency has led to numerous attempts to assess the impact of the pandemic on population mental health. The findings indicate an increase in depression and anxiety but have been limited by the lack of specificity about which aspects of the pandemic (e.g. viral exposure or economic threats) have led to adverse mental health outcomes.
Methods
Network analyses were conducted on data from wave 1 (N = 2025, recruited 23 March–28 March 2020) and wave 2 (N = 1406, recontacts 22 April–1 May 2020) of the COVID-19 Psychological Research Consortium Study, an online longitudinal survey of a representative sample of the UK adult population. Our models included depression (PHQ-9), generalized anxiety (GAD-7) and trauma symptoms (ITQ); and measures of COVID-specific anxiety, exposure to the virus in self and close others, as well as economic loss due to the pandemic.
Results
A mixed graphical model at wave 1 identified a potential pathway from economic adversity to anxiety symptoms via COVID-specific anxiety. There was no association between viral exposure and symptoms. Ising network models using clinical cut-offs for symptom scores at each wave yielded similar findings, with the exception of a modest effect of viral exposure on trauma symptoms at wave 1 only. Anxiety and depression symptoms formed separate clusters at wave 1 but not wave 2.
Conclusions
The psychological impact of the pandemic evolved in the early phase of lockdown. COVID-related anxiety may represent the mechanism through which economic consequences of the pandemic are associated with psychiatric symptoms.
The COVID-19 pandemic has created an unprecedented global crisis, necessitating drastic changes to living conditions, social life, personal freedom and economic activity. No study has yet examined the presence of psychiatric symptoms in the UK population under similar conditions.
Aims
We investigated the prevalence of COVID-19-related anxiety, generalised anxiety, depression and trauma symptoms in the UK population during an early phase of the pandemic, and estimated associations with variables likely to influence these symptoms.
Method
Between 23 and 28 March 2020, a quota sample of 2025 UK adults aged 18 years and older, stratified by age, gender and household income, was recruited by online survey company Qualtrics. Participants completed standardised measures of depression, generalised anxiety and trauma symptoms relating to the pandemic. Bivariate and multivariate associations were calculated for demographic and health-related variables.
Results
Higher levels of anxiety, depression and trauma symptoms were reported compared with previous population studies, but not dramatically so. Anxiety or depression and trauma symptoms were predicted by young age, presence of children in the home, and high estimates of personal risk. Anxiety and depression were also predicted by low income, loss of income and pre-existing health conditions in self and others. Specific anxiety about COVID-19 was greater in older participants.
Conclusions
This study showed a modest increase in the prevalence of mental health problems in the early stages of the pandemic, and these problems were predicted by several specific COVID-related variables. Further similar surveys, particularly of those with children at home, are required as the pandemic progresses.
Les troubles dépressifs concernent près de deux fois plus de femmes que d’hommes [1]. Cette prévalence pourrait être due à une sensibilité accrue des femmes aux émotions négatives [2]. Peu d’études d’imagerie cérébrale ont comparé l’activité cérébrale des hommes et des femmes lors de la présentation de stimuli émotionnels.
Objectif et hypothèse
Notre objectif était d’étudier les activations cérébrales des hommes et des femmes lors d’une tâche émotionnelle. Nous avons émis l’hypothèse que le pattern d’activations cérébrales diffère selon le sexe des individus et la valence des stimuli.
Méthodologie
Nous avons mené une étude en imagerie par résonance magnétique fonctionnelle (IRMf) chez 30 participants sains (15 hommes et 15 femmes). Des stimuli à valence positive, négative et neutre étaient présentés aux sujets. Les participants ont évalué subjectivement la valence et l’intensité des stimuli.
Résultats
Nous observons une activité plus importante chez les femmes que chez les hommes dans plusieurs régions clés du traitement des émotions lors de la présentation de stimuli négatifs. Aucune différence significative entre les hommes et les femmes n’a été relevée concernant l’évaluation subjective des stimuli en termes de valence et d’intensité.
Discussion
Les résultats suggèrent qu’il existe bien une différence de patterns d’activation entre les hommes et les femmes lors de la perception des émotions négatives, qui irait dans le sens d’une sensibilité accrue chez les femmes. Celle-ci pourrait expliquer leur plus grande vulnérabilité aux troubles dépressifs. Il pourrait être intéressant de répliquer cette étude chez des patients qui souffrent de troubles de l’humeur.
Partial or non-adherence to medication is high amongst patients with schizophrenia. Rates of non-adherence of up to 72% have being reported depending on the method used and the patient population. Adherence is essential for optimal long-term patient outcomes in schizophrenia and failure to adhere to medication can have a major impact on the course of illness and treatment outcomes.
Objectives
The objective of the EMEA (Europe, Middle east and Africa) ADHES survey was to collect psychiatrist's perceptions of the assessment, reasons and management of partial and non-adherence to medication.
Aims
The aim of this poster is to present psychiatrist's perceptions collected in the EMEA ADHES survey.
Methods
The survey was devised to ascertain psychiatrists’ preferred methods of assessing adherence, their perceptions of the level of adherence, reasons for non-adherence and on strategies to improve adherence.
Results
Psychiatrists estimated that during the previous month more than half of their patients (53%) were partially or non-adherent. They estimated that as few as a third of patients who deteriorated after stopping medication was able to attribute this to their non-adherence. 76% of psychiatrists assessed adherence most frequently by asking their patient explicitly. Use of long-acting treatment was the preferred choice to address adherence problems for 62% of respondents.
Discussion
This EMEA-wide survey illustrates that while respondents recognised the relevance and importance of partial and non-adherence to medication, there remains a need for more proactive management of treatment adherence of patients with schizophrenia to reduce the frequency and consequences of relapse.
Partial or non-adherence to medication is high amongst patients with schizophrenia. Many and often overlapping factors are considered to impact on treatment adherence, including: patient-related (lack of insight, psychotic, negative or cognitive symptoms), treatment-related (adverse effects, insufficient efficacy), environmental (living situation, negative attitudes of relatives/friends), and physician-related (patient-healthcare professionals relationship) factors.
Objectives
The objective of the ADHES EMEA (Europe, Middle East and Africa) survey was to collect psychiatrist's perceptions of the assessment, reasons and management of partial and non-adherence to medication.
Aims
To present psychiatrist's opinion through EMEA of potential reasons for partial or non-adherence
Methods
The ADHES survey comprised 20 questions and was conducted in 36 countries across EMEA (over 4500 psychiatrists treating patients with schizophrenia).
Results
Across EMEA 37% of psychiatrists viewed lack of insight as the most important reason for their patients stopping medication. 23% of psychiatrists viewed patient's feeling better and thinking it unnecessary to take medication as the most important reason for their patients stopping medication. 7% or less of psychiatrists viewed undesirable side effects, insufficient efficacy, cognitive impairment or drug/alcohol abuse as the most important reasons for their patients stopping medication.
Discussion
In this survey, psychiatrists estimated that patient’s lack of insight and subjective improvement could constitute the main factors explaining poor adherence. Other factors (i.e., side effects, substance abuse) were regarded as less important. Strategies aimed at raising awareness of maintaining treatment, are warranted within EMEA, with the aim of improving clinical outcomes.
Rates of non-adherence of up to 72% have being reported, in schizophrenia, depending on the method used and the patient population. Rates of approximately 59% over 1 year have been reported for individuals with a first episode. Patients who stop medication are almost five times more likely to experience relapse than adherent patients. Failure to adhere to medication can have a major impact on the course of illness and treatment outcomes.
Objectives
The EMEA (Europe, Middle East and Africa) ADHES schizophrenia survey was a survey of psychiatrists across the region, treating patients with schizophrenia, designed to canvas their perceptions of assessment, potential reasons and management for partial or non-adherence to medication amongst their patients.
Aims
To present methodology and demographics of the EMEA ADHES survey in schizophrenia.
Methods
The EMEA ADHES survey comprised 20 questions and was conducted in 36 countries across EMEA. In addition to recording the gender, age and practice setting of the respondents, questions related directly to the issue of partial-/non-adherence in patients with schizophrenia.
Results
The survey was conducted amongst psychiatrists (including neurologists with psychiatric background in Germany) from January - March 2010. Results were obtained from 4722 respondents. Psychiatrists perceived that during the previous month more than half of their patients (53%) were partially or non-adherent across all EMEA regions
Discussion
The EMEA ADHES schizophrenia survey is a large and geographically broad survey providing insight on psychiatrists’ perceptions of the assessment, causes and management of partial and non-adherence to medication.
Partial/non-adherence to medication is common amongst patients with schizophrenia. Nurses play an important role in assessing and managing mental health problems and are often involved in helping patients manage and adhere to their medication. As such, the perception of nurses regarding the burden and potential causes of non-adherence is vital in addressing the adherence problem.
Objectives
The ADHES nurses survey collected opinions of nurses across the EMEA (Europe, Middle East and Africa) region.
Aim
To ascertain nurses' perceptions of assessment, potential causes and management of partial/non-adherence to medication in patients with schizophrenia.
Methods
The survey was conducted from January-March 2010 in 29 countries across EMEA, comprising 14 questions addressing the issue of partial/non-adherence and the use of long-acting injectable (LAI) antipsychotic medication in patients with schizophrenia.
Results
Results were obtained from 4120 respondents. Nurses estimated high levels of partial/non-adherence (mean 54%) amongst patients with schizophrenia and 85% believed improving medication adherence would have a huge/sizable impact on patient outcomes. 93% believed that continuous medication with an LAI would have long-term benefits for patients with schizophrenia, and that many patients (mean 40%) would prefer LAI medication.
Conclusion
Nurses recognize the issue of partial/non-adherence to medication in patients with schizophrenia. Most nurses believe patients are well informed about LAI antipsychotics, however, approximately a third of nurses believe patients to be poorly informed. There is a need to address the problem of partial/non-adherence in clinical practice with a multidisciplinary approach to avoid suboptimal treatment outcomes in patients with schizophrenia.