The Activation of the RIG-I/MDA5 Signaling Pathway upon Influenza D Virus Infection Impairs the Pulmonary Proinflammatory Response Triggered by Mycoplasma bovis Superinfection.

Concurrent infections with multiple pathogens are often described in cattle with respiratory illness. However, how the host-pathogen interactions influence the clinical outcome has been only partially explored in this species. Influenza D virus (IDV) was discovered in 2011. Since then, IDV has been detected worldwide in different hosts. A significant association between IDV and bacterial pathogens in sick cattle was shown in epidemiological studies, especially with Mycoplasma bovis. In an experimental challenge, IDV aggravated M. bovis-induced pneumonia. However, the mechanisms through which IDV drives an increased susceptibility to bacterial superinfections remain unknown. Here, we used the organotypic lung model precision-cut lung slices to study the interplay between IDV and M. bovis coinfection. Our results show that a primary IDV infection promotes M. bovis superinfection by increasing the bacterial replication and the ultrastructural damages in lung pneumocytes. In our model, IDV impaired the innate immune response triggered by M. bovis by decreasing the expression of several proinflammatory cytokines and chemokines that are important for immune cell recruitment and the bacterial clearance. Stimulations with agonists of cytosolic helicases and Toll-like receptors (TLRs) revealed that a primary activation of RIG-I/MDA5 desensitizes the TLR2 activation, similar to what was observed with IDV infection. The cross talk between these two pattern recognition receptors leads to a nonadditive response, which alters the TLR2-mediated cascade that controls the bacterial infection. These results highlight innate immune mechanisms that were not described for cattle so far and improve our understanding of the bovine host-microbe interactions and IDV pathogenesis. IMPORTANCE Since the spread of the respiratory influenza D virus (IDV) infection to the cattle population, the question about the impact of this virus on bovine respiratory disease (BRD) remains still unanswered. Animals affected by BRD are often coinfected with multiple pathogens, especially viruses and bacteria. In particular, viruses are suspected to enhance secondary bacterial superinfections. Here, we use an ex vivo model of lung tissue to study the effects of IDV infection on bacterial superinfections. Our results show that IDV increases the susceptibility to the respiratory pathogen Mycoplasma bovis. In particular, IDV seems to activate immune pathways that inhibit the innate immune response against the bacteria. This may allow M. bovis to increase its proliferation and to delay its clearance from lung tissue. These results suggest that IDV could have a negative impact on the respiratory pathology of cattle.

Development, Quality by Design-Based Optimization, and Stability Assessment of Oral Liquid Formulations Containing Baclofen for Hospital Use.

The absence of oral liquid pharmaceutical forms appropriate for use in pediatric and adult patients with difficulty swallowing is a public health problem, especially in the hospital context. Baclofen is a muscle relaxant of choice for treating spasticity, generally marketed only in tablet form, highlighting the need for liquid formulations to facilitate dose adjustment, administration, and swallowing. The present study aimed to develop oral liquid formulations containing baclofen, optimize them through the quality by design approach, and evaluate their physicochemical and microbiological stability. Preformulation and preliminary stability studies were carried out for the development of formulations. Experimental screening and optimization designs resulted in eleven experiments for each step that were evaluated for 28 days. A stability-indicating method by high-performance liquid chromatography presented linearity, low limits of detection and quantification, precision, accuracy, and robustness. The experimental design led to two optimized formulations containing baclofen, glycerin, potassium sorbate, citric acid, ultrapure water, flavor, and sucrose syrup or sodium carboxymethylcellulose solution as a vehicle, the last one with sucralose as a sweetener. The formulations were placed in amber glass flasks and subjected to a physicochemical and microbiological stability study. Both formulations showed physicochemical and microbiological stability when stored at room temperature and refrigerated for 84 days. The results of this study may serve as a reference in the preparation of liquid oral formulations containing baclofen in the hospital routine and collaborate with the safety and adherence to the treatment of adult and pediatric patients.

Longitudinal changes in angiogenesis biomarkers within 72 h of diagnosis and time-to-delivery in early-onset preeclampsia.

OBJECTIVES: To evaluate the association between the increment of the sFlt-1/PlGF ratio within the first 72 h after the diagnosis of early-onset preeclampsia (PE) and the time-to-delivery. Secondarily we aimed to test its predictive value for maternal adverse outcomes. STUDY DESIGN: Retrospective cohort study of 155 women with early-onset PE and measurement of sFlt-1/PlGF at diagnosis and delivery from which the expected distributions of the daily increment (Δ) of sFlt-1/PlGF ratio, sFlt-1 and PlGF were obtained. Of them, in 110 a short-term evaluation at 72 +/- 24 h was available and Δ72h were calculated and compared to the expected distributions. The high-risk groups were those with Δ72h sFlt-1/PlGF and Δ72h sFlt-1 > 3rd expected quartile or Δ72h PlGF < 1st expected quartile. The low-risk groups were those with Δ72h ≤ 0 for sFlt-1/PlGF and sFlt-1 or Δ72h PlGF ≥ 0. The rest were considered intermediate risk. MAIN OUTCOME MEASURES: Time-to-delivery and maternal adverse outcomes were compared between the three groups. RESULTS: Δ72h sFlt-1/PlGF and sFlt-1 > 3rd quartile had a significant reduction of time-to-delivery when compared to increments < 3rd quartile or ≤ 0 (5 vs 11 vs 14 days, p < 0.01) and (6 vs 8 vs 15 days, p < 0.01), respectively. Both were limited for the prediction of maternal adverse outcomes. Δ72h PlGF showed no significant relation with time-to-deliver but all abruptio placentae had PlGF < 70 pg/mL at diagnosis. CONCLUSION: High Δ72h sFlt-1/PlGF and sFlt-1 are associated to a shorter time-to-delivery while low PlGF at diagnosis is associated to abruptio placentae.

[Bladder catheterization in the hospitalized elderly people]. / Empleo del sondaje vesical en el anciano hospitalizado.

OBJECTIVES: To determine the prevalence of patients with bladder catheterization in a geriatrics service and to analyze the factors associated with the use of urinary catheterization in hospitalized elderly people. MATERIAL AND METHOD: This descriptive and retrospective study (January to December 2019) included all the patients admitted to a geriatric service, with bladder catheterization during their hospital admission. Sociodemographic and clinical data were collected. RESULTS: In 2019, 10.20% of the patients admitted required urinary catheters. Most of these patients were males (60.6%), with an average age of 86.5 years (SD: 8.65). 43.4% of the urinary catheters that were placed temporarily were indicated in the geriatric unit, 28.9% in another medical service and 26.3% in the emergency department. The median of days with a urinary catheter was 7.5 days. The most common reason to indicate a urinary catheter was acute urinary retention (AUR) (67.7%). At hospital discharge, 22.3% of the patients needed to continue with a urinary catheter at home, without needing it prior to admission. CONCLUSIONS: In our study, a high percentage of bladder catheterization was needed during the hospitalization, the most common cause being AUR. The average use (in days) of urinary catheters is high, with the consequent risk of nosocomial urinary tract infections. It is necessary to improve the prescribing habits of urinary catheterization and its early withdrawal through specific educational efforts and avoiding their inappropriate use.

Development and Stability Control of Pediatric Oral Tizanidine Hydrochloride Formulations for Hospital Use.

Tizanidine hydrochloride is a centrally acting skeletal muscle relaxant used in the treatment of spasticity. This drug is sold only as tablets or capsules, which highlights the need to develop oral liquid formulations that allow administration to children and adults with impaired swallowing. This study aim was to develop and improve tizanidine hydrochloride liquid formulations from raw material and to evaluate their stability. A stability-indicating high performance liquid chromatography method was validated for two formulations developed. Fifteen formulations were developed containing syrup and fifteen containing sodium carboxymethyl cellulose as vehicles, to select the two most suitable for stability testing. The formulations were prepared in triplicate and placed in amber polyethylene terephthalate and glass bottles, which were stored under three different conditions: at room temperature (15-30°C), under refrigeration (2-8°C), and at 40°C. The physicochemical and microbiological stability of formulations were evaluated, applying high performance liquid chromatography and microbiological count. The studied formulations at 15-30°C, 2-8°C, and 40°C can be used for a period of 70 days, and all parameters are inside of recommended specifications, enough to allow its use in the context for which it was developed, the application in hospital. The formulations developed in this work have simple components to avoid adverse reactions in vulnerable populations. Results of this study could be applied as a reference for hospital use; once it demonstrated the reliability of storage time interval and proper conditions for use.

sFlt-1/PlGF ratio for the prediction of delivery within 48 hours and adverse outcomes in expectantly managed early-onset preeclampsia.

OBJECTIVE: To analyze if sFlt-1/PlGF ratio is more useful than other parameters at diagnosis of early-onset (<34 weeks) preeclampsia (PE) in the prediction of delivery within 48 h and adverse maternal and perinatal outcomes. METHOD: Observational retrospective study of a cohort of 76 singleton pregnancies with early-onset PE and expectant management. The predictive value of sFlt-1/PlGF ratio, blood pressure, proteinuria, creatinine, liver enzymes and platelets at diagnosis for delivery < 48 h and adverse outcomes was determined. RESULTS: Maternal and perinatal adverse outcomes occurred in 25/76 (32.9%) cases and 13/69 (18.8%) livebirths, respectively. Areas under the curve (AUC) for sFlt-1/PlGF ratio were 0.59 (95%CI 0.42-0.75) and 0.75 (95%CI 0.62-0.88) for maternal and perinatal complications, respectively. Mean (standard deviation) time to delivery for a sFlt-1/PlGF ratio > 655 vs. ≤ 655 was of 4.4 (7.5) vs. 12.1 (9.3) days, p < 0.01. Relative risk for delivery within 48 h for a sFlt-1/PlGF ratio > 655 was 5.3 (95% confidence interval 2.7-10.6), p < 0.01. CONCLUSIONS: sFlt-1/PlGF ratio > 655 at diagnosis was associated with a 5-fold increased risk of delivery in ≤ 48 h. None of the parameters were good predictors of adverse maternal or perinatal outcomes.

Correlation of Kryptor and Elecsys® immunoassay sFlt-1/PlGF ratio on early diagnosis of preeclampsia and fetal growth restriction: A case-control study.

OBJECTIVES: The measurement of the soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) ratio on automated platforms has improved the detection of preeclampsia and fetal growth restriction (PE/FGR). The cut-off points of >38 and ≥85 has been defined for "rule in" and "aid in diagnosis", respectively, using the Elecsys® platform. We aimed to compare the performance of these cut-offs between the Elecsys® and Kryptor platforms at 24-28 weeks. STUDY DESIGN: Observational case-control study of singleton pregnancies at high risk for PE/FGR and sFlt-1/PlGF measurement at 24-28 weeks' gestation: 21 cases (9 early PE/FGR with delivery <32 weeks) were 1:1 matched for body mass index and parity with 21 controls. Correlations of the sFlt-1, PlGF and sFlt-1/PlGF values and diagnostic accuracy of the >38 and ≥85 cutoffs for early and late PE/FGR using Elecsys® and Kryptor assays were evaluated. MAIN OUTCOME MEASURES: PE/FGR cases showed significantly higher median (IQR) sFlt-1/PlGF values at 24-28 weeks vs. controls, using both Elecsys® and Kryptor platforms: 55 (13-254) and 97 (13-530) vs. 4.1 (2.0-6.5) and 3.9 (1.8-7.7), respectively. The sFlt-1/PlGF correlation between both methods was excellent (r2 = 0.95) although lower PlGF and higher sFlt-1/PlGF values were observed with Kryptor. The higher diagnostic accuracy was obtained for early PE/FGR with the ≥85 cutoff (95.2%; 95%CI: 83.8-99.4%) in both platforms. CONCLUSION: sFlt-1/PlGF measurements correlates well between Elecsys® and Kryptor platforms, and the cutoffs of >38 and ≥85 exhibit high diagnostic accuracy for assessing early PE/FGR at 24-28 weeks with both methods.

Angiogenesis biomarkers for the prediction of severe adverse outcomes in late-preterm preeclampsia.

OBJECTIVES: The optimal timing for delivery in non-severe late-preterm (34 + 0-36 + 6 weeks) preeclampsia (PE) is uncertain. It is attempted to reach term pregnancy safely but current clinical and analytical parameters fail to determine which cases will develop severe features that require preterm delivery. We aim to establish if angiogenic biomarkers may identify cases that would benefit from earlier delivery. STUDY DESIGN: Prospective case-control study of 96 women (n = 48 controls and n = 48 cases with PE) with maternal determinations of the sFlt-1/PlGF ratio between 34 + 0 and 36 + 6 weeks. The PE group was classified in two groups based on the need (n = 26) or not (n = 22) for preterm delivery due to criteria of severity. Diagnostic accuracy of these biomarkers for predicting preterm delivery for severe PE was evaluated. MAIN OUTCOME MEASURES: Women with PE showed higher median sFlt-1/PlGF ratio than controls (122 vs 5, p < 0.01) and lower PlGF MoM (0.7 vs 1.0, p < 0.01). However, these differences did not remain when both PE subgroups were compared. Diagnostic performance of the sFlt-1/PlGF ratio and PlGF at different cut-offs was poor for detecting PE requiring delivery before term. CONCLUSIONS: Angiogenic biomarkers are not useful to predict which late-preterm PE cases will develop severe features that require preterm delivery.

Prognostic Factors of Successful Cervical Ripening and Labor Induction in Late-Onset Fetal Growth Restriction.

OBJECTIVE: The aim of this work was to identify independent risk factors influencing the achievement of vaginal delivery among women undergoing labor induction for late-onset fetal growth restriction (FGR). METHODS: This was a retrospective cohort study of 201 singleton pregnancies with late-onset FGR (diagnosed >32 + 0 weeks) that required labor induction with cervical ripening from 37 + 0 weeks, either with dinoprostone (from 2014 to 2015) or Foley balloon (from 2016 to 2018). Independent factors for successful vaginal delivery were identified. A prediction model of vaginal delivery with the identified factors was made using logistic regression and bootstrapping with 1,000 re-samples performed for bias correction. RESULTS: Perinatal results were more favorable in the vaginal delivery group, with significantly lower neonatal admission rates (4.0 vs. 13.7%) and lower composite neonatal morbidity (4.0 vs. 15.7%). The labor induction method (Foley balloon), higher cerebro-placental ratio, lower pre-gestational BMI, and absence of pre-eclampsia were identified as independent factors associated to vaginal delivery. The area under the curve of the model was of 0.75 (95% CI 0.70-0.79). CONCLUSIONS: The use of a Foley balloon is the only modifiable risk factor to improve the chances of vaginal delivery when attempting induction of labor in singleton pregnancies with late-onset FGR.

Prognostic value of the aortic isthmus Doppler assessment on late onset fetal growth restriction.

Background As conflicting results have been reported about the association of reversed flow on the aortic isthmus (AoI) and adverse perinatal results in fetal growth restriction (FGR), we aim to compare perinatal outcomes (including tolerance to labor induction) of late-onset FGR between those with anterograde and reversed AoI flow. Methods This was an observational retrospective cohort study on 148 singleton gestations diagnosed with late-onset FGR (diagnosis ≥32+0 weeks), with an estimated fetal weight (EFW) <10th centile and mild fetal Doppler alteration: umbilical artery (UA) pulsatility index (PI) >95th centile, middle cerebral artery (MCA)-PI <5th centile or cerebral-placental ratio <5th centile. Anterograde AoI flow was present in n=79 and reversed AoI flow in n=69. Delivery was recommended from 37 weeks in both groups. Perinatal results were compared between the groups. Results The global percentage of vaginal delivery of fetuses with anterograde and reversed blood flow was 55.7% vs. 66.7% (P=0.18) and the percentage of cesarean section (C-section) for non-reassuring fetal status was 12.7% vs. 15.9% (P=0.29), respectively. When evaluating those that underwent labor induction, the vaginal delivery rate was 67.9% vs. 77.2% (P=0.17), respectively. There were no significant differences regarding any other perinatal variables and there were no cases of severe morbidity or mortality. Conclusion We observed that the presence of reversed AoI flow does not worsen perinatal outcomes on fetuses with late-onset growth restriction with mild Doppler alterations. Attempt of labor induction is feasible in these fetuses regardless of the direction of AoI flow.

Labor Induction in Late-Onset Fetal Growth Restriction: Foley Balloon versus Vaginal Dinoprostone.

OBJECTIVE: To compare vaginal delivery rate and perinatal outcomes of fetuses with late-onset fetal growth restriction (FGR) undergoing labor induction, depending on the method for cervical ripening (dinoprostone vs. Foley balloon). MATERIAL AND METHODS: We conducted a retrospective cohort study of 148 consecutive singleton gestations diagnosed with stage I late-onset FGR and Bishop score < 7, in which labor induction was indicated at ≥37 + 0 weeks. Before January 2016, cervical ripening was achieved with 10 mg of vaginal dinoprostone (n = 77) and afterwards with Fo-ley balloon (n = 71). Logistic regression analysis was used to estimate the association between mode of delivery and induction method. RESULTS: Foley balloon had lower percentages of uterine tachysystole with fetal repercussion (4.2 vs. 16.9%, p = 0.01) and cesarean sections for suspected fetal distress (7.0 vs. 26.0%, p < 0.01) when compared to dino-prostone. Lower percentages of cesarean sections were found in the Foley balloon group (15.5 vs. 37.7%, p < 0.01). The odds ratio and adjusted odds ratio of cesarean section with dinoprostone were of 3.3 and 4.4, respectively. Perinatal mortality and severe morbidity were null in both groups. CONCLUSION: The use of Foley balloon resulted in a higher percentage of vaginal delivery compared to dinoprostone, with a favorable safety profile in both groups.

In vitro dissolution method fitted to in vivo absorption profile of rivaroxaban immediate-release tablets applying in silico data.

OBJECTIVE: This study aimed to develop and validate an in vitro dissolution method based on in silico-in vivo data to determine whether an in vitro-in vivo relationship could be established for rivaroxaban in immediate-release tablets. SIGNIFICANCE: Oral drugs with high permeability but poorly soluble in aqueous media, such as the anticoagulant rivaroxaban, have a major potential to reach a high level of in vitro-in vivo relationship. Currently, there is no study on scientific literature approaching the development of RIV dissolution profile based on its in vivo performance. METHODS AND RESULTS: Drug plasma concentration values were modeled using computer simulation with adjustment of pharmacokinetic properties. Those values were converted into drug fractions absorbed by the Wagner-Nelson deconvolution approach. Gradual and continuous dissolution of RIV tablets was obtained with a 30 rpm basket on 50 mM sodium acetate +0.2% SDS, pH 6.5 medium. Dissolution was conducted for up to 180 min. The fraction absorbed was plotted against the drug fraction dissolved, and a linear point-to-point regression (R2 = 0.9961) obtained. CONCLUSION: The in vitro dissolution method designed promoted a more convenient dissolution profile of RIV tablets, whereas it suggests a better relationship with in vivo performance.

Conservative management in ureteric hydronephrosis due to deep endometriosis: Could the levonorgestrel-intrauterine device be an option?

Endometriosis can affect up to 10% of women of reproductive age, in a wide range of clinical presentations that vary from mild to severe or deep endometriosis. Deep endometriosis can affect the urinary tract in 1-5% to 15-25% cases. Even though deep endometriosis' surgeries are usually complex with higher rate of complications, conservative management is not always considered as an option because of its high failure rates. This paper describes two cases of deep endometriosis with ureteric involvement (hydronephrosis) treated conservatively with a double-pigtail stent plus a Levonorgestrel intrauterine device, after conservative surgery, who remained symptom free with no evidence of recurrence at 3 years follow-up, avoiding radical high-risk surgery. Impact statement Several treatments have been described for endometriosis. From a symptomatic perspective, conservative medical management has been proposed with a variable response. Concerning deep endometriosis (affecting the urinary or digestive tract), the definitive treatment has always been thought to be radical surgery. However, this can lead to several complications. To illustrate a possible more conservative approach this paper describes two cases of deep infiltrating endometriosis affecting the ureter, treated conservatively with a temporary pigtail ureter stent plus a Levonorgestrel intrauterine device. The management demonstrates that, in a selected population, conservative treatment solves the urinary disease avoiding the surgical complications and, what is more, improving patients' symptoms in a permanent way. Further prospective studies are needed to confirm whether the introduction of this management in clinical practice would reduce the need for surgery thereby, avoiding high-risk surgery and improving the success rate of conservative management.

Angiogenesis-related biomarkers (sFlt-1/PlGF) in placental mesenchymal dysplasia.

Determination of the soluble fms-like tyrosine kinase-1 to placental growth factor ratio (sFlt-1/PlGF) in the maternal serum is expected to aid in the monitoring and decision-making process of women at risk for placental dysfunction. We report two cases of placental mesenchymal dysplasia (PMD) with sFlt-1/PlGF correlation. The first case is a dichorionic twin pregnancy with one fetus affected by PMD and Beckwith-Wiedemann syndrome in which a high value of sFlt-1/PlGF was found, coinciding with acute maternal and fetal wellbeing decline at 31 weeks. The second case corresponds to a singleton pregnancy diagnosed of PMD with normal sFlt-1/PlGF and favorable outcome.

Angiogenesis-Related Biomarkers (sFlt-1/PLGF) in the Prediction and Diagnosis of Placental Dysfunction: An Approach for Clinical Integration.

Placental dysfunction is involved in a group of obstetrical conditions including preeclampsia, intrauterine growth restriction, and placental abruption. Their timely and accurate recognition is often a challenge since diagnostic criteria are still based on nonspecific signs and symptoms. The discovering of the role of angiogenic-related factors (sFlt-1/PlGF) in the underlying pathophysiology of placental dysfunction, taking into account that angiogenesis-related biomarkers are not specific to any particular placental insufficiency-related disease, has marked an important step for improving their early diagnosis and prognosis assessment. However, sFlt-1/PlGF has not been yet established as a part of most guidelines. We will review the current evidence on the clinical utility of sFlt-1/PlGF and propose a new protocol for its clinical integration.

The GATA-type transcriptional activator Gat1 regulates nitrogen uptake and metabolism in the human pathogen Cryptococcus neoformans.

Nitrogen uptake and metabolism are essential to microbial growth. Gat1 belongs to a conserved family of zinc finger containing transcriptional regulators known as GATA-factors. These factors activate the transcription of Nitrogen Catabolite Repression (NCR) sensitive genes when preferred nitrogen sources are absent or limiting. Cryptococcus neoformans GAT1 is an ortholog to the Aspergillus nidulans AreA and Candida albicans GAT1 genes. In an attempt to define the function of this transcriptional regulator in C. neoformans, we generated null mutants (gat1Δ) of this gene. The gat1 mutant exhibited impaired growth on all amino acids tested as sole nitrogen sources, with the exception of arginine and proline. Furthermore, the gat1 mutant did not display resistance to rapamycin, an immunosuppressant drug that transiently mimics a low-quality nitrogen source. Gat1 is not required for C. neoformans survival during macrophage infection or for virulence in a mouse model of cryptococcosis. Microarray analysis allowed the identification of target genes that are regulated by Gat1 in the presence of proline, a poor and non-repressing nitrogen source. Genes involved in ergosterol biosynthesis, iron uptake, cell wall organization and capsule biosynthesis, in addition to NCR-sensitive genes, are Gat1-regulated in C. neoformans.

The vacuolar Ca²(+) exchanger Vcx1 is involved in calcineurin-dependent Ca²(+) tolerance and virulence in Cryptococcus neoformans.

Cryptococcus neoformans is an encapsulated yeast that causes a life-threatening meningoencephalitis in immunocompromised individuals. The ability to survive and proliferate at the human body temperature is an essential virulence attribute of this pathogen. This trait is controlled in part by the Ca²(+)-calcineurin pathway, which senses and utilizes cytosolic calcium for signaling. In the present study, the identification of the C. neoformans gene VCX1, which encodes a vacuolar calcium exchanger, is reported. The VCX1 knockout results in hypersensitivity to the calcineurin inhibitor cyclosporine A at 35°C, but not at 30°C. Furthermore, high concentrations of CaCl2 lead to growth inhibition of the vcx1 mutant strain only in the presence of cyclosporine A, indicating that Vcx1 acts in parallel with calcineurin. The loss of VCX1 does not influence cell wall integrity or capsule size but decreases secretion of the major capsular polysaccharide glucuronoxylomannan (GXM) in culture supernatants.Vcx1 also influences C. neoformans phagocytosis by murine macrophages and is required for full virulence in mice. Analysis of cellular distribution by confocal microscopy confirmed the vacuolar localization of Vcx1 in C. neoformans cells.

A phase IV, open-label, multi-center study to evaluate the efficacy, safety and tolerability of olanzapine in the treatment of schizophrenia or schizophreniform disorder among Filipino patients

OBJECTIVE: This open-label, multi-center, non-randomized study evaluated the efficacy, safety and tolerability of olanzapine in the treatment of schizophrenia or schizophreniform disorder among Filipino patients. METHOD: Filipino outpatients with a DSM-IV diagnosis of either schizophrenia or schizophreniform disorder (N = 382) were enrolled in this study. They were treated with an initial dose of 10 mg/day of olanzapine with eventual titration to 5 to 20 mg/day as clinically indicated and were observed for 8 weeks. Efficacy was assessed with the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression - Severity of Illness Scale (CGI-S). Safety was assessed by collecting adverse event reports and checking vital signs. RESULTS: Statistically significant reductions from baseline to endpoint in both the mean BPRS Total score (from 36.77 +/- 12.12 to 11.43 +/10.39, p0.001) and mean CGI-S score (from 4.64 +/- 0.79 to 2.61 +/- 1.06, p0.001) were seen. The proportion of patients showing 20 percent improvement based on the BPRS Total score was 93.4 percent. Only 51 (13.7 percent) patients reported at least one treatment-emergent adverse event. The most commonly reported were somnolence (3.2 percent), weight loss (2.2 percent), tachycardia (1.3 percent), and headache (1.1 percent). CONCLUSION: The study clearly demonstrates the efficacy, safety and tolerability of olanzapine in the treatment of schizophrenia and schizophreniform disorder among Filipino patients.