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Abstract Objective Underdiagnosis of female genital tuberculosis (FGTB) often leads to infertility. In this study, we aimed to determine the site and histopathologic patterns of FGTB and its correlation with clinical presentation and acid-fast bacilli (AFB) status. Methods A retrospective cross-sectional study was conducted on 122 patients with a histopathological diagnosis of FGTB at the Department of Pathology, College of Health Sciences (CHS), Tikur Anbessa Specialized Hospital (TASH), Addis Ababa University (AAU), from January 1, 2013, to August 30, 2022. Results Female genital tuberculosis was found in 0.94% of the gynecology specimens examined. The most common presentations were menstrual disturbance, abdominopelvic pain, and infertility. Among patients with FGTB, 4.6% exhibited misleading clinical and radiologic findings, leading to suspicion of malignancy and subsequent aggressive surgical management. The endometrium was the most frequently affected organ, followed by the fallopian tube, ovary, cervix, and vulva. In the majority of tuberculous endometritis cases (53.3%), histopathology revealed early-stage granulomas. Acid-fast bacilli were found in a significant proportion (42.6%) of FGTB tissues with TB histopathology. The ovary had the highest rate of AFB detection, followed by the fallopian tube, endometrium, and cervix. Conclusion Female genital tuberculosis should be considered in reproductive-age women presenting with menstrual irregularities, abdominopelvic pain, infertility, or an abdominopelvic mass. The endometrium is commonly affected, displaying early granulomas with low AFB positivity.

Objective: Smartphone devices may enable out-of-clinic assessments in chronic neurological diseases. We describe the Draw a Shape (DaS) Test, a smartphone-based and remotely administered test of Upper Extremity (UE) function developed for people with multiple sclerosis (PwMS). This work introduces DaS-related features that characterise UE function and impairment, and aims to demonstrate how multivariate modelling of these metrics can reliably predict the 9-Hole Peg Test (9HPT), a clinician-administered UE assessment in PwMS. Approach: The DaS Test instructed PwMS and healthy controls (HC) to trace predefined shapes on a smartphone screen. A total of 93 subjects (HC, n = 22; PwMS, n = 71) contributed both dominant and non-dominant handed DaS tests. PwMS subjects were characterised as those with normal (nPwMS, n = 50) and abnormal UE function (aPwMS, n = 21) with respect to their average 9HPT time (≤ or > 22.7 (s), respectively). L1-regularization techniques, combined with linear least squares (OLS, IRLS), or non-linear support vector (SVR) or random forest (RFR) regression were investigated as functions to map relevant DaS features to 9HPT times. Main results: It was observed that average non-dominant handed 9HPT times were more accurately predicted by DaS features (r2 = 0.41, 0.05; MAE: 2.08 ± 0.34 (s)) than average dominant handed 9HPTs (r2 = 0.39, 0.05; MAE: 2.32 ± 0.43 (s)), using simple linear IRLS (0.01). Moreover, it was found that the Mean absolute error (MAE) in predicted 9HPTs was comparable to the variability of actual 9HPT times within HC, nPwMS and aPwMS groups respectively. The 9HPT however exhibited large heteroscedasticity resulting in less stable predictions of longer 9HPT times. Significance: This study demonstrates the potential of the smartphone-based DaS Test to reliably predict 9HPT times and remotely monitor UE function in PwMS. [ABSTRACT FROM AUTHOR]

Eyob Alemayehu Gebreyohannes,1 Akshaya Srikanth Bhagavathula,1,2 Tadesse Melaku Abegaz,1 Tamrat Befekadu Abebe,1 Sewunet Admasu Belachew,1 Henok Getachew Tegegn,1 Sarab M Mansoor3 1Department of Clinical Pharmacy, School of Pharmacy, University of Gondar-College of Medicine and Health Sciences, Gondar, Ethiopia; 2Department of Internal Medicine, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates; 3School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, NSW, Australia Purpose: In health communication, pictogram has a comprehensive place to aid attention, memory recall, and promote adherence. This study was conducted to assess whether pictorial intervention would help to identify and improve adverse drug reactions (ADRs) reporting in an antiretroviral therapy (ART) clinic in Northwest Ethiopia.Patients and methods: A cross-sectional study on ART-naïve HIV-positive patients was conducted from July 2015 to January 2016. The patients were randomly categorized into two groups. Group A was subjected to receive pictorial medication information and a pictogram-enhanced tool to identify and report ADRs, while group B did not receive any pictogram-enhanced tool.Results: A total of 207 ART-naïve HIV-positive patients who were registered for the ART treatment attending Gondar University Hospital ART clinic were included. Bivariate analysis showed that sociodemographic characteristics, such as age, sex, education, employment, and marital status were the main predictors of identifying and reporting ADRs. Males were twice more likely to identify ADRs than females. Univariate analysis revealed that patients assigned to group A showed a significant association with the ability to identify ART medications using pictograms. Patients assigned to group A were more likely to identify lamivudine (OR [95% CI] =7.536 [4.042–14.021], P≤0.001), tenofovir (OR [95% CI] =6.250 [2.855–13.682], P≤0.001), nevirapine (OR [95% CI] =5.320 [1.954–14.484], P=0.001), efavirenz (OR [95% CI] =3.929 [1.876–8.228], P≤0.001), and zidovudine (OR [95% CI] =3.570 [1.602–7.960], P=0.002) using pictograms. Patients in group A were 4.3 times more likely to identify diarrhea as an ADR using pictogram compared with group B.Conclusion: The use of pictorial representation resulted in only slight improvement in identification and reporting of ADRs among naïve HIV-positive patients with limited literacy in Northwest Ethiopia. This representation of ADRs merits further investigation with regard to ADR identification and promoting patients’ safety, particularly for HIV-positive patients with limited educational levels. Keywords: HIV, AIDS, ADR, pictogram, Gondar, Ethiopia, HAART

Background: No clinical test is currently available and validated to measure the maximum walking speed (WS) of multiple sclerosis (MS) patients. Since the Timed 25-Foot Walk Test (T25FW) is performed with a static start, it takes a significant proportion of the distance for MS patients to reach their maximum pace. Objectives: In order to capture the maximum WS and to quantify the relative impact of the accelerating phase during the first meters, we compared the classical T25FW with a modified version (T25FW{+}) allowing a dynamic start after a 3 meters run-up. Methods: Sixty-four MS patients and 30 healthy subjects performed successively the T25FW and the T25FW{+}. Results: The T25FW{+} was performed faster than the T25FW for the vast majority of MS and healthy subjects. In the MS population, the mean relative gain of speed due to the dynamic start on T25FW{+} was independent from the EDSS and from the level of ambulation impairment. Compared to healthy subjects, the relative difference between dynamic versus static start was more important in the MS population even in patients devoid of apparent gait impairment according to the T25FW. Conclusion: The T25FW{+} allows a more accurate measurement of the maximum WS of MS patients, which is a prerequisite to reliably evaluate deceleration over longer distance tests. Indirect arguments suggest that the time to reach the maximum WS may be partially influenced by the cognitive impairment status. The maximum WS and the capacity of MS patients to accelerate on a specific distance may be independently regulated and assessed separately in clinical trials and rehabilitation programs. [ABSTRACT FROM AUTHOR]

Daniel Asfaw Erku,1,* Sewunet Admasu Belachew,1 Abebe Basazn Mekuria,2 Kaleab Taye Haile,3 Begashaw Melaku Gebresillassie,1 Henok Getachew Tegegn,1 Asnakew Achaw Ayele1,* 1Department of Clinical Pharmacy, 2Department of Pharmacology, 3Department of Pharmaceutics and Social Pharmacy, School of Pharmacy, University of Gondar, Gondar, Ethiopia *These authors contributed equally to this work Purpose: The present study aimed at evaluating the knowledge and level of involvement of community pharmacists in the provision of patient counseling and health education services for patients with DM and perceived barriers that limit the delivery of such services.Materials and methods: A self-administered questionnaire based-survey was undertaken from January to March, 2017 with 412 pharmacists working in community pharmacies in six cities of Amhara regional state of Ethiopia: Debre Markos, Gondar, Dessie, Bahir Dar, Woldya, and Debre Birhan. Descriptive statistics, ANOVA, and Student’s t-test were employed to examine different variables.Results: Community pharmacists were found to have poor knowledge and low level of involvement, with an overall mean score of 11.54 and 2.06, respectively. A significant number of community pharmacists never practiced promoting smoking cessation (45.2%), counseling on good foot care techniques (33.7%), and counseling on the potential impact of over–the-counter and herbal drugs on DM management (34%). On the other hand, describing the right time to administer antidiabetic medications (46%) and counseling on suitable administration, handling, and storage of insulin (33.7%) were done more frequently. The main reported barriers to the delivery of these services were lack of knowledge or clinical skills, lack of access to additional training programs, and lack of personnel or resources.Conclusion: The present study revealed a poor knowledge and low level of involvement in counseling and health education services for patients with DM. Lack of knowledge or clinical skills was the most commonly reported barrier for providing such services. In order to better integrate community pharmacies into future public health programs and optimize the contribution of pharmacists, interventions should focus on overcoming the identified barriers. Keywords: community pharmacy, patient counseling, diabetes mellitus, Ethiopia

1 In this study in vitro and in vivo approaches were combined in order to investigate if the anti-epileptic mechanism(s) of action of levetiracetam (LEV; Keppra*) may involve modulation of inhibitory neurotransmission. 2 GABA- and glycine-gated currents were studied in vitro using whole-cell patch-clamp techniques applied on cultured cerebellar granule, hippocampal and spinal neurons. Protection against clonic convulsions was assessed in vivo in sound-susceptible mice. The effect of LEV was compared with reference anti-epileptic drugs (AEDs): carbamazepine, phenytoin, valproate, clonazepam. pheno-barbital and ethosuximide. 3 LEV contrasted the reference AEDs by an absence of any direct effect on glycine-gated currents. At high concentrations, beyond therapeutic relevance, it induced a small reduction in the peak amplitude and a prolongation of the decay phase of GABA-gated currents. A similar action on GABA-elicited currents was observed with the reference AEDs, except ethosuximide. 4 These minor direct effects contrasted with a potent ability of LEV (EC50 =1-10 μM) to reverse the inhibitory effects of the negative allosteric modulators zinc and β-carbolines on both GABAA and glycine receptor-mediated responses. 5 Clonazepam, phenobarbital and valproate showed a similar ability to reverse the inhibition of β-carbolines on GABA-gated currents. Blockade of zinc inhibition of GABA responses was observed with clonazepam and ethosuximide. Phenytoin was the only AED together with LEV that inhibited the antagonism of zinc on glycine-gated currents and only clonazepam and phenobarbital inhibited the action of DMCM. 6 LEV (17 mg kg) produced a potent suppression of sound-induced clonic convulsions in mice. This protective effect was significantly abolished by co-administration of the β-carboline FG 7142, from a dose of 5 mg kg1. In contrast, the benzodiazepine receptor antagonist flumazenil (up to 10 mg kg 1) was without any effect on the protection afforded by LEV. 7 The results of the present study suggest that a novel ability to oppose the action of negative modulators on the two main inhibitory ionotropic receptors may be of relevance for the anti-epileptic mechanism(s) of action of LEV. [ABSTRACT FROM AUTHOR]

Sewunet Admasu Belachew,1 Daniel Asfaw Erku,2 Abebe Basazn Mekuria,3 Begashaw Melaku Gebresillassie1 1Department of Clinical Pharmacy, 2Department of Pharmaceutical Sciences, 3Department of Pharmacology, School of Pharmacy, University of Gondar, Gondar, Ethiopia Background: Adverse drug reactions (ADRs) are a global problem and constitute a major clinical problem in terms of human suffering. The high toxicity and narrow therapeutic index of chemotherapeutic agents makes oncology pharmacovigilance essential. The objective of the present study was to assess the pattern of ADRs occurring in cancer patients treated with chemotherapy in a tertiary care teaching hospital in Ethiopia.Methods: A cross-sectional study over a 2-year period from September 2013 to August 2015 was conducted on cancer patients undergoing chemotherapy at Gondar University Referral Hospital Oncology Center. Data were collected directly from patients and their medical case files. The reported ADRs were assessed for causality using the World Health Organization’s causality assessment scale and Naranjo’s algorithm. The severities of the reported reactions were also assessed using National Cancer Institute Common Terminology CTCAE version 4.0. The Pearson’s chi-square test was employed to examine the association between two categorical variables.Results: A total of 815 ADRs were identified per 203 patients included in the study. The most commonly occurring ADRs were nausea and vomiting (18.9%), infections (16.7%), neutropenia (14.7%), fever and/or chills (11.3%), and anemia (9.3%). Platinum compounds (31.4%) were the most common group of drugs causing ADRs. Of the reported ADRs, 65.8% were grades 3–4 (severe level), 29.9% were grades 1–2 (mild level), and 4.3% were grade 5 (toxic level). Significant association was found between age, number of chemotherapeutic agents, as well as dose of chemotherapy with the occurrence of grades 3–5 toxicity.Conclusion: The high incidence of chemotherapy-related ADRs among cancer patients is of concern. Setting up an effective ADR monitoring and reporting system (onco-pharmacovigilance) and creating awareness among health care professionals regarding the importance of ADR reporting may help prevent the problem. Keywords: adverse drug reactions, causality, chemotherapy, Ethiopia, pharmacovigilance

Abebe Basazn Mekuria,1 Daniel Asfaw Erku,2 Sewunet Admasu Belachew3 1Department of Pharmacology, 2Department of Pharmaceutical Chemistry, 3Department of Clinical Pharmacy, School of Pharmacy, University of Gondar, Gondar, Ethiopia Purpose: This study aimed at identifying the information needs of cancer patients, their preferences for the means of receiving health information, and the perceived level of satisfaction of existing possibilities for acquiring cancer-related information in Ethiopia.Materials and methods: An institutional-based cross-sectional survey was employed on 556 cancer patients undergoing chemotherapy in the oncology wards of Gondar University Referral Hospital and Tikur Anbesa Specialized Hospital. Data were collected through interviewer-administered questionnaire.Results: The principal information regarded as the most important by the majority of them (67.26%) concerned information on the specific type of cancer (name and stage of cancer), followed by the side effects of chemotherapy and their management (63.29%) and “prognosis (survival)” (51.8%). Doctors were the overwhelming information source about cancer (88.8%), followed by nurses (34%). The majority of respondents (70.3%) were not satisfied at all or satisfied a little, while 15.6% of respondents reported that they were “quite” or “very” satisfied with the existing possibilities for acquiring information regarding cancer.Conclusion: Medical practitioners other than doctors and nurses such as clinical pharmacists should support and identify measures that can enhance patients’ satisfaction level regarding the existing possibilities for acquiring information regarding cancer. Periodic assessment of cancer patient’s information requirements is also crucial, considering the ever-changing dynamics of priorities of such information desires. Keywords: information seeking, preference, cancer, Ethiopia

Henok Getachew, Akshaya Srikanth Bhagavathula, Tamrat Befekadu Abebe, Sewunet Admasu Belachew Department of Clinical Pharmacy, School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia Background: Inappropriate use of antiplatelets and anticoagulants among elderly patients increases the risk of adverse outcomes. The aim of this study was to assess the prevalence of inappropriate prescribing of antithrombotic therapy in hospitalized elderly patients. Methods: A retrospective cross-sectional, single-center study was conducted at the Gondar University Hospital. A total of 156 hospitalized elderly patients fulfilling the inclusion/­exclusion criteria were included in the study. The Screening Tool for Older Person’s Prescription/Screening Tool to Alert doctors to Right Treatment criteria version 2 were applied to patients’ data to identify the total number of inappropriate prescribing (IPs) including potentially inappropriate medications and potential prescribing omissions. Results: A total of 70 IPs were identified in 156 patients who met the inclusion criteria. Of these, 36 (51.4%) were identified as potentially inappropriate medications by the Screening Tool for Older Person’s Prescription criteria. The prevalence of IP per patient indicated that 58 of the 156 (37.2%) patients were exposed to at least one IP. Of these, 32 (55.2%) had at least one potentially inappropriate medication and 33 (56.9%) had at least one potential prescribing omission. Patients hospitalized due to venous thromboembolism (adjusted odds ratio [AOR] =29.87, 95% confidence interval [CI], 1.26–708.6), stroke (AOR =7.74, 95% CI, 1.27–47.29), or acute coronary syndrome (AOR =13.48, 95% CI, 1.4–129.1) were less likely to be exposed to an IP. An increase in Charlson comorbidity index score was associated with increased IP exposure (AOR =0.60, 95% CI, 0.39–0.945). IPs were about six times more likely to absent in patients prescribed with antiplatelet only therapy (AOR =6.23, 95% CI, 1.90–20.37) than those receiving any other groups of antithrombotics. Conclusion: IPs are less common in elderly patients primarily admitted due to venous thromboembolism, stroke, and acute coronary syndrome, and those elderly patients prescribed with only antiplatelet. Patients with higher Charlson comorbidity index were, however, associated with increased IPs exposure. Our study may guide further research to reduce high-risk prescription of antithrombotics in the elderly. Keywords: prevalence, inappropriate prescribing, antithrombotic, STOPP/START criteria, elderly, Ethiopia

Tadesse Melaku Abegaz,1 Sewunet Admasu Belachew,1 Tamrat Befekadu Abebe,1 Begashaw Melaku Gebresilassie,1 Fitsum Sebsibe Teni,2 Habtamu Gebremeskel Woldie3 1Department of Clinical Pharmacy, School of Pharmacy, Gondar University, Gondar, 2Department of Pharmaceutics and Social Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, 3Department of Hospital Pharmacy, Debremarkos Teaching and Referral Hospital, Debremarkos, Ethiopia Background: Acute diarrhea is the major cause of child morbidity and mortality in low-income nations. It is the second most common cause of death among children

Sewunet Admasu Belachew, Tadesse Melaku Abegaz, Akshaya Srikanth Bhagavathula, Henok Getachew, Yonas Getaya TeferaClinical Pharmacy Department, University of Gondar, Gondar, EthiopiaAim: To investigate the overall experiences of clinical pharmacy students during their clinicalattachments and to understand the breadth and depth of clinical skills provided by their preceptors.Methods: A cross-sectional study using a self-administered questionnaire containing 34 itemsto obtain feedback from the clerkship students from June to July 2015. Data analysis was performedto calculate mean, standard deviation, percentages, and multiple logistic regression usingStatistical Package for the Social Sciences (SPSS) software Version 22. Statistical significancewas set at P15% remarked thatthey did not receive enough opportunities to hone their pharmaceutical care documentationskills. A relatively high percentage of students (32.8%) strongly agreed that their preceptors hadprovided ample opportunity to discuss the patient problems at the bedside and encouraged themto express their opinions regarding patients’ drug therapeutic issues. This study also revealedthat students’ continuity in developing their therapeutic and disease process knowledge wassignificantly associated with the preceptor’s ability to provide adequate training and orientation(P =0.01), engagement in clinical pharmacy activities (P =0.01), regular review of students’ work(P =0.01), and instruction to students before entering clinical sites (P =0.00).Conclusion: The findings of this study reveal that a majority of the students were moderatelysatisfied with the clinical training program and preceptors need to demonstrate effective pharmaceutical care processes in their clinical sites.Keywords: pharmaceutical care, training, clinical skills

Background: Poor adherence to antidiabetic medications leads to a higher rate of hospital admissions and adverse health outcomes in type 2 diabetes mellitus patients. Objective: This study aims to evaluate whether a pharmacist-led medication therapy management, compared to the usual care, could enhance medication adherence and reduce hospital admission in patients with type 2 diabetes mellitus. Methods: A prospective randomized controlled study was conducted in patients with type 2 diabetes mellitus from February 1 to July 30, 2016. Patients in the control group (n=65) received the usual care while patients in the intervention group (n=62) received a personalized pharmacotherapeutic care plan and diabetes education. The two groups were compared by repeated measure ANOVA at 3 and 6‐months with medication adherence (using Morisky medication adherence scale) and number of hospital admissions as the main outcome variables. Results: A total of 127 patients were included in the study. A marked and statistically significant increase in medication adherence from baseline to 3 and 6 months were noted in the intervention group (increased from 9.2% at baseline to 61% at 6 month) compared with the control group (increased from 13.2% at baseline (to 30.2% at 6 month; p-value

The article presents a case study of a 38-year-old woman with multiple sclerosis (MS). The patient's serum hepatic enzyme tests found that she had grade 4 liver failure. She was treated with glatiramer acetate, a disease-modifying therapy approved for treatment of MS, in October 2006. She was also taking ibuprofen 400 milligram twice a day to treat her influenza. However, asthenia developed within three days.

Abstract Background Newborn granule neurons are generated from proliferating neural stem/progenitor cells and integrated into mature synaptic networks in the adult dentate gyrus of the hippocampus. Since light/dark variations of the mitotic index and DNA synthesis occur in many tissues, we wanted to unravel the role of the clock-controlled Period2 gene (mPer2) in timing cell cycle kinetics and neurogenesis in the adult DG. Results In contrast to the suprachiasmatic nucleus, we observed a non-rhythmic constitutive expression of mPER2 in the dentate gyrus. We provide evidence that mPER2 is expressed in proliferating neural stem/progenitor cells (NPCs) and persists in early post-mitotic and mature newborn neurons from the adult DG. In vitro and in vivo analysis of a mouse line mutant in the mPer2 gene (Per2Brdm1), revealed a higher density of dividing NPCs together with an increased number of immature newborn neurons populating the DG. However, we showed that the lack of mPer2 does not change the total amount of mature adult-generated hippocampal neurons, because of a compensatory increase in neuronal cell death. Conclusion Taken together, these data demonstrated a functional link between the constitutive expression of mPER2 and the intrinsic control of neural stem/progenitor cells proliferation, cell death and neurogenesis in the dentate gyrus of adult mice.

Background: Newborn granule neurons are generated from proliferating neural stem/progenitor cells and integrated into mature synaptic networks in the adult dentate gyrus of the hippocampus. Since light/dark variations of the mitotic index and DNA synthesis occur in many tissues, we wanted to unravel the role of the clock-controlled Period2 gene (mPer2) in timing cell cycle kinetics and neurogenesis in the adult DG.Results: In contrast to the suprachiasmatic nucleus, we observed a non-rhythmic constitutive expression of mPER2 in the dentate gyrus. We provide evidence that mPER2 is expressed in proliferating neural stem/progenitor cells (NPCs) and persists in early post-mitotic and mature newborn neurons from the adult DG. In vitro and in vivo analysis of a mouse line mutant in the mPer2 gene (Per2Brdm1), revealed a higher density of dividing NPCs together with an increased number of immature newborn neurons populating the DG. However, we showed that the lack of mPer2 does not change the total amount of mature adult-generated hippocampal neurons, because of a compensatory increase in neuronal cell death.Conclusion: Taken together, these data demonstrated a functional link between the constitutive expression of mPER2 and the intrinsic control of neural stem/progenitor cells proliferation, cell death and neurogenesis in the dentate gyrus of adult mice. [ABSTRACT FROM AUTHOR]

Background: B cells influence the pathogenesis of multiple sclerosis. Ocrelizumab is a humanized monoclonal antibody that selectively depletes CD20+ B cells.Methods: In two identical phase 3 trials, we randomly assigned 821 and 835 patients with relapsing multiple sclerosis to receive intravenous ocrelizumab at a dose of 600 mg every 24 weeks or subcutaneous interferon beta-1a at a dose of 44 μg three times weekly for 96 weeks. The primary end point was the annualized relapse rate.Results: The annualized relapse rate was lower with ocrelizumab than with interferon beta-1a in trial 1 (0.16 vs. 0.29; 46% lower rate with ocrelizumab; P<0.001) and in trial 2 (0.16 vs. 0.29; 47% lower rate; P<0.001). In prespecified pooled analyses, the percentage of patients with disability progression confirmed at 12 weeks was significantly lower with ocrelizumab than with interferon beta-1a (9.1% vs. 13.6%; hazard ratio, 0.60; 95% confidence interval [CI], 0.45 to 0.81; P<0.001), as was the percentage of patients with disability progression confirmed at 24 weeks (6.9% vs. 10.5%; hazard ratio, 0.60; 95% CI, 0.43 to 0.84; P=0.003). The mean number of gadolinium-enhancing lesions per T1-weighted magnetic resonance scan was 0.02 with ocrelizumab versus 0.29 with interferon beta-1a in trial 1 (94% lower number of lesions with ocrelizumab, P<0.001) and 0.02 versus 0.42 in trial 2 (95% lower number of lesions, P<0.001). The change in the Multiple Sclerosis Functional Composite score (a composite measure of walking speed, upper-limb movements, and cognition; for this z score, negative values indicate worsening and positive values indicate improvement) significantly favored ocrelizumab over interferon beta-1a in trial 2 (0.28 vs. 0.17, P=0.004) but not in trial 1 (0.21 vs. 0.17, P=0.33). Infusion-related reactions occurred in 34.3% of the patients treated with ocrelizumab. Serious infection occurred in 1.3% of the patients treated with ocrelizumab and in 2.9% of those treated with interferon beta-1a. Neoplasms occurred in 0.5% of the patients treated with ocrelizumab and in 0.2% of those treated with interferon beta-1a.Conclusions: Among patients with relapsing multiple sclerosis, ocrelizumab was associated with lower rates of disease activity and progression than interferon beta-1a over a period of 96 weeks. Larger and longer studies of the safety of ocrelizumab are required. (Funded by F. Hoffmann-La Roche; OPERA I and II ClinicalTrials.gov numbers, NCT01247324 and NCT01412333 , respectively.). [ABSTRACT FROM AUTHOR]

Background: An evolving understanding of the immunopathogenesis of multiple sclerosis suggests that depleting B cells could be useful for treatment. We studied ocrelizumab, a humanized monoclonal antibody that selectively depletes CD20-expressing B cells, in the primary progressive form of the disease.Methods: In this phase 3 trial, we randomly assigned 732 patients with primary progressive multiple sclerosis in a 2:1 ratio to receive intravenous ocrelizumab (600 mg) or placebo every 24 weeks for at least 120 weeks and until a prespecified number of confirmed disability progression events had occurred. The primary end point was the percentage of patients with disability progression confirmed at 12 weeks in a time-to-event analysis.Results: The percentage of patients with 12-week confirmed disability progression was 32.9% with ocrelizumab versus 39.3% with placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.59 to 0.98; P=0.03). The percentage of patients with 24-week confirmed disability progression was 29.6% with ocrelizumab versus 35.7% with placebo (hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.04). By week 120, performance on the timed 25-foot walk worsened by 38.9% with ocrelizumab versus 55.1% with placebo (P=0.04); the total volume of brain lesions on T2-weighted magnetic resonance imaging (MRI) decreased by 3.4% with ocrelizumab and increased by 7.4% with placebo (P<0.001); and the percentage of brain-volume loss was 0.90% with ocrelizumab versus 1.09% with placebo (P=0.02). There was no significant difference in the change in the Physical Component Summary score of the 36-Item Short-Form Health Survey. Infusion-related reactions, upper respiratory tract infections, and oral herpes infections were more frequent with ocrelizumab than with placebo. Neoplasms occurred in 2.3% of patients who received ocrelizumab and in 0.8% of patients who received placebo; there was no clinically significant difference between groups in the rates of serious adverse events and serious infections.Conclusions: Among patients with primary progressive multiple sclerosis, ocrelizumab was associated with lower rates of clinical and MRI progression than placebo. Extended observation is required to determine the long-term safety and efficacy of ocrelizumab. (Funded by F. Hoffmann-La Roche; ORATORIO ClinicalTrials.gov number, NCT01194570 .). [ABSTRACT FROM AUTHOR]