Survey on current practices for neurological prognostication after cardiac arrest.

PURPOSE: To investigate current practices and timing of neurological prognostication in comatose cardiac arrest patients. METHODS: An anonymous questionnaire was distributed to the 8000 members of the European Society of Intensive Care Medicine during September and October 2012. The survey had 27 questions divided into three categories: background data, clinical data, decision-making and consequences. RESULTS: A total of 1025 respondents (13%) answered the survey with complete forms in more than 90%. Twenty per cent of respondents practiced outside of Europe. Overall, 22% answered that they had national recommendations, with the highest percentage in the Netherlands (>80%). Eighty-nine per cent used induced hypothermia (32-34 °C) for comatose cardiac arrest patients, while 11% did not. Twenty per cent had separate prognostication protocols for hypothermia patients. Seventy-nine per cent recognized that neurological examination alone is not enough to predict outcome and a similar number (76%) used additional methods. Intermittent electroencephalography (EEG), brain computed tomography (CT) scan and evoked potentials (EP) were considered most useful. Poor prognosis was defined as cerebral performance category (CPC) 3-5 (58%) or CPC 4-5 (39%) or other (3%). When prognosis was considered poor, 73% would actively withdraw intensive care while 20% would not and 7% were uncertain. CONCLUSION: National recommendations for neurological prognostication after cardiac arrest are uncommon and only one physician out of five uses a separate protocol for hypothermia treated patients. A neurological examination alone was considered insufficient to predict outcome in comatose patients and most respondents advocated a multimodal approach: EEG, brain CT and EP were considered most useful. Uncertainty regarding neurological prognostication and decisions on level of care was substantial.

Tietovarastokantaa käyttävän inventaariraportin kehittäminen osaksi integroitua tietojärjestelmää, case-tutkimus

Työn tavoitteena oli kehittää uuteen integroituun tietojärjestelmään luotettava raportti, joka korvaa olemassaolevan inventaariraportin sekä taulukkolaskentaohjelmassa manuaalisesti tehtävän varaston arvostuksen. Tutkimuksen taustalla on Stora Enson Imatran tehtaille perustettu inventaariraportin kehittämisprojekti. Tutkimus on vahvasti empiriaan pohjautuva tapaustutkimus ja se seuraa toiminta-analyyttista tutkimusotetta. Työssä keskityttiin tarkastelemaan integroituja tietojärjestelmiä ja tietovarastoja sekä tähän ympäristöön luotavaa raportin kehittämisprosessia. Työssä huomioitiin käyttäjänäkökulma ja analysoitiin erityisesti raportin luotettavuutta varmistava testausvaihe. Kehittämistyön tuloksena Fenixin inventaariraportoinnin alle muodostui kolme erillistä raporttia: inventaariraportti valinnan mukaan, joka voidaan ajaa määrittäin tai arvoittain, inventaarin hinnoitteluraportti sekä inventaarikorjausraportti. Naista inventaarimääräraportti tulee korvaamaan vanhan inventaariraportin ja yhdessä näiden raporttien avulla saavutetaan työlle asetetut tavoitteet.

Brain metastases in gastro-oesophageal adenocarcinoma: insights into the role of the human epidermal growth factor receptor 2 (HER2).

BACKGROUND: Gastro-oesophageal adenocarcinomas rarely metastasize to the central nervous system (CNS). The role of the human epidermal growth factor receptor 2 (HER2) in patients with these cancers and CNS involvement is presently unknown. PATIENTS AND METHODS: A multicentre registry was established to collect data from patients with gastro-oesophageal adenocarcinomas and CNS involvement both retrospectively and prospectively. Inclusion in the study required a predefined clinical data set, a central neuro-radiological or histopathological confirmation of metastatic CNS involvement and central assessment of HER2 by immunohistochemistry (IHC) and in situ hybridisation (ISH). In addition, expression of E-cadherin and DNA mismatch repair (MMR) proteins were assessed by IHC. RESULTS: One hundred patients fulfilled the inclusion criteria. The population's median age was 59 years (interquartile range: 54-68), of which 85 (85%) were male. Twenty-five patients were of Asian and 75 of Caucasian origin. HER2 status was positive in 36% (95% CI: 26.6-46.2) of cases. Median time from initial diagnosis to the development of brain metastases (BMets) or leptomeningeal carcinomatosis (LC) was 9.9 months (95% CI: 8.5-15.0). Median overall survival from diagnosis was 16.9 months (95% CI: 14.0-20.7) and was not related to the HER2 status. E-cadherin loss was observed in 9% of cases and loss of expression in at least one DNA MMR proteins in 6%. CONCLUSIONS: The proportion of a positive HER2 status in patients with gastro-oesophageal adenocarcinoma and CNS involvement was higher than expected. The impact of anti-HER2 therapies should be studied prospectively.

Tietovaraston tietojen laatu ja arvo

Tutkielman tarkoituksena on tutkia case -organisaationa toimivan Tiehallinnon kahden tietovaraston, kuntotietorekisterin ja tiesääjärjestelmän tietojen laatua ja arvoa sekä selvittää, mitkä ominaisuudet näihin vaikuttavat ja miten nämä koetaan tällä hetkellä. Näiden ominaisuuksien tunnistaminen auttaa organisaatiota parantamaan tietovarastoidensa tietojen laatua, joka taas lisää niistä saatavaa arvoa. Tutkimus- ja tiedonkeruumenetelminä käytetään kvalitatiivista teemahaastattelua sekä kvantitatiivista web-pohjaista kyselylomaketta. Tutkimuksessa saatiin kuva kohdeorganisaation tietovarastojen tietojen koetusta laadusta ja arvosta ja siitä mistä nämä koostuvat. Tietovaraston tietojen laatuun ja arvoon vaikuttivat selvästi eri laatuominaisuudet. Tietovarastoilla on laatuominaisuuksia, joita käyttäjät pitävät tärkeinä ja joiden he kokevat korkealaatuisina tuottavan heille hyötyä. Tietovaraston käyttäjien työtehtävät, odotukset ja tarpeet määrittävät koetun laadun tason. Tietovaraston tietojen arvo muodostuu käyttäjän kokeman hyödyn ja laadun perusteella. Tietovaraston tietojen laatuominaisuuksiin, kuten esimerkiksi käytettävyyteen, virheettömyyteen ja saatavuuteen pystytään vaikuttamaan, koska nämä ovat kiinteästi tietovaraston tekniseen toteutukseen liittyviä tekijöitä. Tietovarastojen tietojen hyötyyn ja sen kautta koettuun arvoon ei pystytä suoraan vaikuttamaan, muuten kuin laatuominaisuuksia parantamalla.

An efficient total variation algorithm for super-resolution in fetal brain MRI with adaptive regularization.

Although fetal anatomy can be adequately viewed in new multi-slice MR images, many critical limitations remain for quantitative data analysis. To this end, several research groups have recently developed advanced image processing methods, often denoted by super-resolution (SR) techniques, to reconstruct from a set of clinical low-resolution (LR) images, a high-resolution (HR) motion-free volume. It is usually modeled as an inverse problem where the regularization term plays a central role in the reconstruction quality. Literature has been quite attracted by Total Variation energies because of their ability in edge preserving but only standard explicit steepest gradient techniques have been applied for optimization. In a preliminary work, it has been shown that novel fast convex optimization techniques could be successfully applied to design an efficient Total Variation optimization algorithm for the super-resolution problem. In this work, two major contributions are presented. Firstly, we will briefly review the Bayesian and Variational dual formulations of current state-of-the-art methods dedicated to fetal MRI reconstruction. Secondly, we present an extensive quantitative evaluation of our SR algorithm previously introduced on both simulated fetal and real clinical data (with both normal and pathological subjects). Specifically, we study the robustness of regularization terms in front of residual registration errors and we also present a novel strategy for automatically select the weight of the regularization as regards the data fidelity term. Our results show that our TV implementation is highly robust in front of motion artifacts and that it offers the best trade-off between speed and accuracy for fetal MRI recovery as in comparison with state-of-the art methods.

Clinico-Pathological discrepancies in the Diagnosis of Causes of Maternal Death in Sub-Saharan Africa: Retrospective Analysis

Background Maternal mortality is a major public-health problem in developing countries. Extreme differences in maternal mortality rates between developed and developing countries indicate that most of these deaths are preventable. Most information on the causes of maternal death in these areas is based on clinical records and verbal autopsies. Clinical diagnostic errors may play a significant role in this problem and might also have major implications for the evaluation of current estimations of causes of maternal death. Methods and Findings A retrospective analysis of clinico-pathologic correlation was carried out, using necropsy as the gold standard for diagnosis. All maternal autopsies (n ¼ 139) during the period from October 2002 to December 2004 at the Maputo Central Hospital, Mozambique were included and major diagnostic discrepancies were analyzed (i.e., those involving the cause of death). Major diagnostic errors were detected in 56 (40.3%) maternal deaths. A high rate of false negative diagnoses was observed for infectious diseases, which showed sensitivities under 50%: HIV/AIDS-related conditions (33.3%), pyogenic bronchopneumonia (35.3%), pyogenic meningitis (40.0%), and puerperal septicemia (50.0%). Eclampsia, was the main source of false positive diagnoses, showing a low predictive positive value (42.9%). Conclusions Clinico-pathological discrepancies may have a significant impact on maternal mortality in sub-Saharan Africa and question the validity of reports based on clinical data or verbal autopsies. Increasing clinical awareness of the impact of obstetric and nonobstetric infections with their inclusion in the differential diagnosis, together with a thorough evaluation of cases clinically thought to be eclampsia, could have a significant impact on the reduction of maternal mortality.

A new multidisciplinary home care telemedicine system to monitor stable chronic human immunodeficiency virus-infected patients: a randomized study.

Background: Antiretroviral therapy has changed the natural history of human immunodeficiency virus (HIV) infection in developed countries, where it has become a chronic disease. This clinical scenario requires a new approach to simplify follow-up appointments and facilitate access to healthcare professionals. Methodology: We developed a new internet-based home care model covering the entire management of chronic HIV-infected patients. This was called Virtual Hospital. We report the results of a prospective randomised study performed over two years, comparing standard care received by HIV-infected patients with Virtual Hospital care. HIV-infected patients with access to a computer and broadband were randomised to be monitored either through Virtual Hospital (Arm I) or through standard care at the day hospital (Arm II). After one year of follow up, patients switched their care to the other arm. Virtual Hospital offered four main services: Virtual Consultations, Telepharmacy, Virtual Library and Virtual Community. A technical and clinical evaluation of Virtual Hospital was carried out. Findings: Of the 83 randomised patients, 42 were monitored during the first year through Virtual Hospital (Arm I) and 41 through standard care (Arm II). Baseline characteristics of patients were similar in the two arms. The level of technical satisfaction with the virtual system was high: 85% of patients considered that Virtual Hospital improved their access to clinical data and they felt comfortable with the videoconference system. Neither clinical parameters [level of CD4 + T lymphocytes, proportion of patients with an undetectable level of viral load (p = 0.21) and compliance levels 90% (p = 0.58)] nor the evaluation of quality of life or psychological questionnaires changed significantly between the two types of care. Conclusions: Virtual Hospital is a feasible and safe tool for the multidisciplinary home care of chronic HIV patients. Telemedicine should be considered as an appropriate support service for the management of chronic HIV infection.

Abacavir/Lamivudine Versus Tenofovir/Emtricitabine in Virologically Suppressed Patients Switching from Ritonavir-Boosted Protease Inhibitors to Raltegravir

There are few clinical data on the combination abacavir/lamivudine plus raltegravir. We compared the outcomes of patients from the SPIRAL trial receiving either abacavir/lamivudine or tenofovir/emtricitabine at baseline who had taken at least one dose of either raltegravir or ritonavir-boosted protease inhibitors. For the purpose of this analysis, treatment failure was defined as virological failure (confirmed HIV-1 RNA ≥50 copies/ml) or discontinuation of abacavir/lamivudine or tenofovir/emtricitabine because of adverse events, consent withdrawal, or lost to follow-up. There were 143 (72.59%) patients with tenofovir/emtricitabine and 54 (27.41%) with abacavir/lamivudine. In the raltegravir group, there were three (11.11%) treatment failures with abacavir/lamivudine and eight (10.96%) with tenofovir/emtricitabine (estimated difference 0.15%; 95% CI -17.90 to 11.6). In the ritonavir-boosted protease inhibitor group, there were four (14.81%) treatment failures with abacavir/lamivudine and 12 (17.14%) with tenofovir/emtricitabine (estimated difference -2.33%; 95% CI -16.10 to 16.70). Triglycerides decreased and HDL cholesterol increased through the study more pronouncedly with abacavir/lamivudine than with tenofovir/emtricitabine and differences in the total-to-HDL cholesterol ratio between both combinations of nucleoside reverse transcriptase inhibitors (NRTIs) tended to be higher in the raltegravir group, although differences at 48 weeks were not significant. While no patient discontinued abacavir/lamivudine due to adverse events, four (2.80%) patients (all in the ritonavir-boosted protease inhibitor group) discontinued tenofovir/emtricitabine because of adverse events (p=0.2744). The results of this analysis do not suggest that outcomes of abacavir/lamivudine are worse than those of tenofovir/emtricitabine when combined with raltegravir in virologically suppressed HIV-infected adults.

Present standards and future perspectives in the treatment of metastatic non-small cell lung cancer.

The development of novel effective immunotherapeutic agents and early clinical data hinting at significant activity in non-small cell lung cancer (NSCLC) has introduced yet another player in the field of management of advanced disease. At present, first-line cytotoxic chemotherapy is generally withheld pending results of molecular testing for any actionable genetic alteration that could lead to targeted treatment, and in their absence chemotherapy is prescribed as a default therapy. Phase III trials comparing head-to-head immune checkpoint inhibitors with standard platinum-based doublet chemotherapy are underway. Second-line chemotherapy is likewise being challenged in phase III trials, one of which having recently reported positive results in advanced squamous cell carcinoma. In tumors harboring actionable transforming genetic alterations such as EGFR mutations and ALK rearrangements, second- and third-generation inhibitors allow for multiple lines of targeted treatment beyond initial resistance, postponing the use of cytotoxic chemotherapy to very late lines of therapy. Chemotherapy as a longstanding but still present standard of care capable of prolonging survival, improving quality of life, and relieving symptoms sees its role increasingly restricted to clinical, immunological, and molecular subsets of patients where its activity and efficacy have never been tested prospectively.

BRAF Alterations as Therapeutic Targets in Non-Small-Cell Lung Cancer.

BACKGROUND: Several subsets of non-small-cell lung cancer (NSCLC) are defined by molecular alterations acting as tumor drivers, some of them being currently therapeutically actionable. The rat sarcoma (RAS)-rapidly accelerated fibrosarcoma (RAF)-mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway constitutes an attractive potential target, as v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations occur in 2-4% of NSCLC adenocarcinoma. METHODS: Here, we review the latest clinical data on BRAF serine/threonine kinase inhibitors in NSCLC. RESULTS: Treatment of V600E BRAF-mutated NSCLC with BRAF inhibitor monotherapy demonstrated encouraging antitumor activity. Combination of BRAF and MEK inhibitors using dabrafenib and trametinib is under evaluation. Preliminary data suggest superior efficacy compared with BRAF inhibitor monotherapy. CONCLUSION: Targeting BRAF alterations represents a promising new therapeutic approach for a restricted subset of oncogene-addicted NSCLC. Prospect ive trials refining this strategy are ongoing. A next step will probably aim at combining BRAF inhibitors and immunotherapy or alternatively improve a multilevel mitogen-activated protein kinase (MAPK) pathway blockade by combining with ERK inhibitors.

Clinico-Pathological discrepancies in the Diagnosis of Causes of Maternal Death in Sub-Saharan Africa: Retrospective Analysis

Background Maternal mortality is a major public-health problem in developing countries. Extreme differences in maternal mortality rates between developed and developing countries indicate that most of these deaths are preventable. Most information on the causes of maternal death in these areas is based on clinical records and verbal autopsies. Clinical diagnostic errors may play a significant role in this problem and might also have major implications for the evaluation of current estimations of causes of maternal death. Methods and Findings A retrospective analysis of clinico-pathologic correlation was carried out, using necropsy as the gold standard for diagnosis. All maternal autopsies (n ¼ 139) during the period from October 2002 to December 2004 at the Maputo Central Hospital, Mozambique were included and major diagnostic discrepancies were analyzed (i.e., those involving the cause of death). Major diagnostic errors were detected in 56 (40.3%) maternal deaths. A high rate of false negative diagnoses was observed for infectious diseases, which showed sensitivities under 50%: HIV/AIDS-related conditions (33.3%), pyogenic bronchopneumonia (35.3%), pyogenic meningitis (40.0%), and puerperal septicemia (50.0%). Eclampsia, was the main source of false positive diagnoses, showing a low predictive positive value (42.9%). Conclusions Clinico-pathological discrepancies may have a significant impact on maternal mortality in sub-Saharan Africa and question the validity of reports based on clinical data or verbal autopsies. Increasing clinical awareness of the impact of obstetric and nonobstetric infections with their inclusion in the differential diagnosis, together with a thorough evaluation of cases clinically thought to be eclampsia, could have a significant impact on the reduction of maternal mortality.

How to monitor the brain in septic patients?

Brain injury is frequently observed after sepsis and may be primarily related to the direct effects of the septic insult on the brain (e.g., brain edema, ischemia, seizures) or to secondary/indirect injuries (e.g., hypotension, hypoxemia, hypocapnia, hyperglycemia). Management of brain injury in septic patients is first focused to exclude structural intracranial complications (e.g., ischemic/hemorrhagic stroke) and possible confounders (e.g., electrolyte alterations or metabolic disorders, such as dysglycemia). Sepsis-associated brain dysfunction is frequently a heterogeneous syndrome. Despite increasing understanding of main pathophysiologic determinants, therapy is essentially limited to protect the brain against further cerebral damage, by way of "simple" therapeutic manipulations of cerebral perfusion and oxygenation and by avoiding over-sedation. Non-invasive monitoring of cerebral perfusion and oxygenation with transcranial Doppler (TCD) and near-infrared spectroscopy (NIRS) is feasible in septic patients. Electroencephalography (EEG) allows detection of sepsis-related seizures and holds promise also as sedation monitoring. Brain CT-scan detects intra-cerebral structural lesions, while magnetic resonance imaging (MRI) provides important insights into primary mechanisms of sepsis-related direct brain injury, (e.g., cytotoxic vs. vasogenic edema) and the development of posterior reversible encephalopathy. Together with EEG and evoked potentials (EP), MRI is also important for coma prognostication. Emerging clinical evidence suggests monitoring of the brain in septic patients can be implemented in the ICU. The objective of this review was to summarize recent clinical data about the role of brain monitoring - including TCD, NIRS, EEG, EP, CT, and MRI - in patients with sepsis and to illustrate its potential utility for the diagnosis, management and prognostication.

Tehdasmittausten varastointi moniulotteisella tietomallilla

Tietovarastoissa moniulotteinen tietomalli on tehokkain tapa esittää tietoa päätöksentekijöille. Sen toimivuus on hyväksi havaittu monissa eri liiketoimintaympäristöissä. Tehdasympäristöissä on tuhansia mittalaitteita, joista jokainen mittaa uniikkia valmistusprosessiin liittyvää piirrettä. Tässä työssä kehitettiin tietovarasto tehdasmittausten varastointiin käyttäen moniulotteista tietomallia. Havaittiin, että moniulotteisella mallilla tehdasmittaukset voidaan tallentaa joustavalla tavalla ja esittää käyttäjälle mielekkäässä muodossa. Moniulotteinen malli antaa myös erinomaiset keinot tiedon ryhmittelyyn ja vertailuun. Sillä ei kuitenkaan saada vastaavanlaisia hyötyjä kuin klassisissa kaupanalan tietovarastointi esimerkeissä, koska eri mittaukset ovat keskenään hyvin erilaisia. Vaikka mittaukset eivät olekaan aina vertailtavissa tai summattavissa keskenään, saadaan ne moniulotteisella mallilla tallennettua ja luokiteltua loogisesti siten, että käyttäjän on helppo löytää tarvitsemansa tieto. Lisäksi yleisesti tunnettu ja paljon käytetty tietovaraston suunnittelumalli takaa sen, että markkinoilta on saatavissa työkaluja tietovaraston käyttöön. Tietokannan toteutus tehtiin vapaasti levitettävän MySQLtiedonhallintajärjestelmän avulla. Sitä ei ole suunniteltu pääasiassa tietovarastokäyttöön, mutta halpa lisenssi ja hyvä skaalautuvuus tekevät siitä mielenkiintoisen vaihtoehdon. Sitä onkin käytetty luultua enemmän tietovarastoinnissa ja myös monien nimekkäiden organisaatioiden toimesta. Myös tässä työssä todettiin, että MySQL tarjoaa riittävät välineet tietovaraston kehittämiseen.

Vähittäiskaupan tavarantoimittaja-arviointi -tapaustutkimus

Organisaatio tarvitsee työkaluja toimittajien suorituskyvyn mittaukseen ja kehittämiseen. Ilman systemaattista mittaamista ja arviointia ostajat eivät tiedä kuinka hyvin toimittajat suoriutuvat velvoitteistaan. Tutkielman tavoit-teena oli analysoida vähittäiskaupan tavarantoimittajien arviointiprosessia keskittyen päivittäistavarakaupan toimialaan ja tavarantoimittajiin sekä luoda toimittajien arviointiin pilottiraportti. Tutkielma on tehty päivittäistavarakaupan kohdeyrityksen toimeksiannosta. Tutkielman teoreettinen aineisto pohjautuu aikaisempaan kirjallisuuteen ja tutkimukseen. Tutkielman empiiriseen osaan aineistoa kerättiin kohdeyrityksen henkilöstön haastatteluilla sekä osallistuvan havainnoinnin avulla. Lisäksi tutkija perehtyi kohdeyrityksessä käytössä olevaan tietovarastointi-sovellukseen. Kirjallisen aineiston avulla rakennettu tutkimuksen teoreettinen osa perustuu aikaisempaan tutkimukseen. Empiirinen osa muodostuu neljästä teemahaastattelusta, jotka suoritettiin kohdeyrityksessä. Haastattelujen tarkoituksena oli rakentaa tutkijalle kuva kohdeyrityksen tavarantoimittaja-arvioinnin nykytilasta. Tutkielmassa havainnollistettiin yksinkertainen raportointimalli yhden tavararyhmän arviointiin ja arviointitiedon analysointiin. Raportointimallilla havainnollistetaan tavarantoimittaja-arviointidatan käyttöä toimittaja-arvioinnissa. Jatkossa on olennaista keskittyä systemaattisen raportoinnin edelleen kehittämiseen ja arviointitiedon hyväksikäyttöön neuvotteluissa toimittajan kanssa. Lisäksi toimittajien luokittelu tavararyhmien sisällä on tärkeää jotta arvioinnissa voidaan keskittyä kaikista tärkeimpiin toimittajiin.

Genetics-Based Population Pharmacokinetics and Pharmacodynamics of Risperidone in a Psychiatric Cohort.

BACKGROUND: High interindividual variability in plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, may lead to suboptimal drug concentration. OBJECTIVE: Using a population pharmacokinetic approach, we aimed to characterize the genetic and non-genetic sources of variability affecting risperidone and 9-hydroxyrisperidone pharmacokinetics, and relate them to common side effects. METHODS: Overall, 150 psychiatric patients (178 observations) treated with risperidone were genotyped for common polymorphisms in NR1/2, POR, PPARα, ABCB1, CYP2D6 and CYP3A genes. Plasma risperidone and 9-hydroxyrisperidone were measured, and clinical data and common clinical chemistry parameters were collected. Drug and metabolite concentrations were analyzed using non-linear mixed effect modeling (NONMEM(®)). Correlations between trough concentrations of the active moiety (risperidone plus 9-hydroxyrisperidone) and common side effects were assessed using logistic regression and linear mixed modeling. RESULTS: The cytochrome P450 (CYP) 2D6 phenotype explained 52 % of interindividual variability in risperidone pharmacokinetics. The area under the concentration-time curve (AUC) of the active moiety was found to be 28 % higher in CYP2D6 poor metabolizers compared with intermediate, extensive and ultrarapid metabolizers. No other genetic markers were found to significantly affect risperidone concentrations. 9-hydroxyrisperidone elimination was decreased by 26 % with doubling of age. A correlation between trough predicted concentration of the active moiety and neurologic symptoms was found (p = 0.03), suggesting that a concentration >40 ng/mL should be targeted only in cases of insufficient, or absence of, response. CONCLUSIONS: Genetic polymorphisms of CYP2D6 play an important role in risperidone, 9-hydroxyrisperidone and active moiety plasma concentration variability, which were associated with common side effects. These results highlight the importance of a personalized dosage adjustment during risperidone treatment.