METHODS: This was a parallel, open-label randomised controlled trial with participants recruited from psychiatric outpatient services of a teaching hospital in Kuala Lumpur and a secondary hospital in Melaka. Adults (≥18 years) diagnosed with major depressive disorder; capable of reading and understanding English or Bahasa Malaysia; prescribed with at least one antidepressant and owns a smart phone were subsequently randomly assigned (1:1) to receive treatment reminders (intervention) or standard treatment without reminders (control), using a computergenerated randomisation programme. The intervention group received two reminder categories: Outpatient appointment reminders (a day before appointment); and medication reminders (weekly basis). Participants were followed-up over two months. We utilised Montgomery- Asberg Depression Rating Scale (MADRS) to measure the severity of depression; and Brief Adherence Rating Scale (BARS) to assess medication adherence. Primary outcomes were outpatient attendance rates and medication adherence assessed at two months. Secondary outcomes included changes in depression severity within each group at two months; comparison of changes in depression severity between both groups; preferences of participants towards treatment reminders, and reasons for non-attendance among participants. This trial was registered with the National Medical Research Registry, NMRR-19-3466-52001.
RESULTS: Between February and April 2020, 183 participants were randomised to each group, of whom 179 reached study endpoint (91 [98.9%] of 92 in intervention group and 88 [96.7%] of 91 in control group). All recruited participants (n=183) were analysed using intention-to-treat approach. At two months, intervention group has significantly higher outpatient attendance rates (76.8%) than control group (56.4%) (p=0.002), and reported higher medical adherence percentage (mean difference 23.1, [95%CI 0.4, 35.8]; p<0.001). There was also significant difference in the MADRS score change between both groups (mean difference 3.4, [95%CI 0.4, 6.3]; p=0.025). Treatment reminders preferences among participants varied; forgetfulness was the most commonly reported reason (53%) for missing outpatient appointments.
CONCLUSION: Reminders through mobile messaging applications significantly improved outpatient attendance and medication adherence among patients with depression. Our findings support the use of messaging apps for treatment reminders in psychiatric outpatient settings. However, concerns regarding confidentiality require careful measures to be taken.
RESULTS: Mechanical disruption by sonication, which yielded 1.99 U/mg of GAD, was by far the most effective cell disintegration method compared with the other extraction procedures examined. In contrast, the second most effective method, freeze grinding followed by 10% v/v toluene permeabilization at 25°C for 120 min, yielded only 1.17 U/mg of GAD, which is 170% lower than the sonication method. Optimized enzymatic lysis with 3 mg/ml Yatalase® at 60°C for 30 min was the least effective. It yielded only 0.70 U/mg of GAD. Extraction using sonication was further optimized using a one-variable-at-a-time approach (OVAT). Results obtained show that the yield of GAD increased 176% from 1.99 U/mg to 3.50 U/mg.
CONCLUSION: Of the techniques used to extract GAD from A. oryzae NSK, sonication was found to be the best. Under optimized conditions, about 176% of GAD was recovered compared to recovery under non optimized conditions. The high production level of GAD in this strain offers an opportunity to conduct further studies on GABA production at a larger scale.