A randomised double-blind placebo-controlled trial of minocycline and/or Omega-3 fatty acids added to treatment as usual for At Risk Mental States (NAYAB): study protocol

Background The At Risk Mental State (ARMS) describes individuals at high risk of developing schizophrenia or psychosis. The use of antipsychotics in this population is not supported because most individuals with ARMS are unlikely to develop psychosis. Anti-inflammatory treatments and polyunsaturated fatty acids (PUFAs) may have some beneficial effects in the treatment of ARMS. There have been no controlled clinical trials that have investigated the use of minocycline for ARMS and no trials involving PUFAs in combination with other proposed treatments. There is a need to find effective, tolerable and inexpensive interventions for ARMS that are available both in high, low and middle-income countries. Methods A six-month intervention study of minocycline and/or Omega-3 fatty acids added to treatment as usual (TAU) in patients with ARMS will be conducted in Pakistan using a randomised, placebo-controlled, double-blind factorial design. 320 consenting patients with capacity will be recruited from community, general practitioner clinics and psychiatric units. Allowing for a 25% dropout rate, we will recruit 59 completing participants to each study arm, and 236 will complete in total. We will determine whether the addition of minocycline and/or Omega-3 fatty acids to TAU attenuates rate of transition from ARMS to first-episode psychosis and improves symptoms and/or level of functioning in ARMS. We will also investigate whether any candidate risk factors such as negative symptoms, influence treatment response in the ARMS group. The primary efficacy end-point is conversion to psychotic disorder at 12 months post study entry. Analysis will be by intention-to-treat, using analysis-of variance, chi-squared tests and adjusted odds ratios to assess between-group differences. Cox regression analyses will be used to analyse potential between-group differences in time-to-onset of psychosis. Discussion The outcomes of this trial will provide evidence of the potential benefits of minocycline and PUFAs in the treatment of ARMS. Both minocycline and PUFAs are inexpensive are readily available in low/middle-income countries such as Pakistan, and if evidenced, may prove to be safe and effective for treating ARMS

Economic reliability acceptance sampling plans from truncated life tests based on the Burr Type XII percentiles

In this article, economic reliability acceptance sampling plan (ERASP) is developed for the Burr type XII distribution when the life test is truncated at pre-specified designed parameters. The minimum termination time is necessary to ensure that the specified life percentile is found under a given producer's risk. The operating characteristic values of the proposed plan are presented for various parameters. A comparative study of proposed plan and existing plan developed by Lio et al. (2010) is also discussed. The result is illustrated by a real dataset example

AI-Driven Approaches to Cybersecurity: The Impact of Machine and Deep Learning

Computer Security is constantly evolving and dynamic; today, applying Artificial Intelligence techniques becomes indispensable in treating and detecting threats to which organizations are exposed. Developing information and communications technologies requires cybersecurity mechanisms that guarantee confidentiality, integrity, availability of information, and the development of skills to detect and control new threats on time

A randomised, double-blind, placebo-controlled trial of minocycline and/or omega-3 fatty acids added to treatment as usual for at-risk mental states (NAYAB): study protocol

Abstract Background The at-risk mental state (ARMS) describes individuals at high risk of developing schizophrenia or psychosis. The use of antipsychotics in this population is not supported, because most individuals with ARMS are unlikely to develop psychosis. Anti-inflammatory treatments and polyunsaturated fatty acids (PUFAs) may have some beneficial effects in the treatment of ARMS. There have been no controlled clinical trials in which researchers have investigated the use of minocycline for ARMS and no trials involving PUFAs in combination with other proposed treatments. There is a need to find effective, tolerable and inexpensive interventions for individuals with ARMS that are available in high-, low- and middle-income countries. Methods/design A 6-month intervention study of minocycline and/or omega-3 fatty acids added to treatment as usual (TAU) in patients with ARMS will be conducted in Pakistan using a randomised, placebo-controlled, double-blind factorial design. A total of 320 consenting patients with capacity will be recruited from the community, general practitioner clinics and psychiatric units. Allowing for a 25% dropout rate, we will recruit 59 completing participants into each study arm, and in total 236 will complete the study. We will determine whether the addition of minocycline and/or omega-3 fatty acids to TAU attenuates the rate of transition from ARMS to first-episode psychosis and improves symptoms and/or level of functioning in ARMS. We will also investigate whether any candidate risk factors, such as negative symptoms, influence treatment response in the ARMS group. The primary efficacy endpoint is conversion to psychotic disorder at 12 months after study entry. Analysis will be done according to the intention to treat principle using analysis of variance, chi-square tests and adjusted ORs to assess between-group differences. Cox regression analysis will be used to evaluate potential between-group differences in time to onset of psychosis. Discussion The outcomes of this trial will provide evidence of the potential benefits of minocycline and PUFAs in the treatment of ARMS. Both minocycline and PUFAs are inexpensive, are readily available in low-/middle-income countries such as Pakistan, and if proven, may be safe and effective for treating individuals with ARMS. Trial registration ClinicalTrials.gov, NCT02569307 . Registered on 3 October 2015