Effects of Cognitive Behavioral Therapy and Cash Transfers on Older Persons Living Alone in India : A Randomized Trial.

BACKGROUND: A growing number of older persons in developing countries live entirely alone and are physically, mentally, and financially vulnerable. OBJECTIVE: To determine whether phone-based cognitive behavioral therapy (CBT) or a cash transfer reduce functional impairment, depression, or food insecurity in this population. DESIGN: Randomized controlled trial. (ClinicalTrials.gov: NCT04225845; American Economic Association RCT Registry: AEARCTR-0007582). SETTING: Tamil Nadu, India, 2021. PARTICIPANTS: 1120 people aged 55 years and older and living alone. INTERVENTIONS: A 6-week, phone-based CBT and a 1-time cash transfer of 1000 rupees (U.S. $12 at market exchange rates) were evaluated in a factorial design. MEASUREMENTS: The World Health Organization Disability Assessment Schedule (WHODAS), the Geriatric Depression Scale, and food security, all measured 3 weeks after CBT for 977 people and 3 months after for 932. Surveyors were blind to treatment assignment. RESULTS: The WHODAS score (scale 0 to 48, greater values representing more impairment) decreased between baseline and the 3-week follow-up by 2.92 more (95% CI, -5.60 to -0.23) in the group assigned cash only than in the control group, and the depression score (ranging from 0 to 15, higher score indicating more depressive symptoms) decreased by 1.01 more (CI, -2.07 to 0.06). These effects did not persist to the 3-month follow-up, and CBT alone and the 2 together had no significant effects. There were no effects on food security. LIMITATIONS: The study cannot say whether more sustained or in-person therapy would have been effective, how results would translate outside of the COVID-19 period, or whether results in the consented sample differ from those in a larger population. Primary outcomes were self-reported. CONCLUSION: Among older people living alone, a small cash transfer was effective in alleviating short-term (3 weeks) functional impairment, produced a small but not clinically or statistically significant reduction in depression, and had no effect on food security. There were no short-term effects from CBT or the 2 interventions together. None of the interventions showed any effect at 3 months. PRIMARY FUNDING SOURCE: National Institute on Aging (NIA).

Weak acids as an alternative anti-microbial therapy.

Weak acids such as acetic acid and N-acetyl cysteine (NAC) at pH less than their pKa can effectively eradicate biofilms due to their ability to penetrate the biofilm matrix and the cell membrane. However, the optimum conditions for their activity against drug resistant strains, and safety, need to be understood for their application to treat infections or to inactivate biofilms on hard surfaces. Here, we investigate the efficacy and optimum conditions at which weak acids can eradicate biofilms. We compared the efficacy of various mono and triprotic weak acids such as N-acetyl cysteine (NAC), acetic acid, formic acid and citric acid, in eradicating biofilms. We found that monoprotic weak acids/acid drugs can kill mucoid P. aeruginosa mucA biofilm bacteria provided the pH is less than their pKa, demonstrating that the extracellular biofilm matrix does not protect the bacteria from the activity of the weak acids. Triprotic acids, such as citric acid, kill biofilm bacteria at pH â€‹< â€‹pKa1. However, at a pH between pKa1 and pKa2, citric acid is effective in killing the bacteria at the core of biofilm microcolonies but does not kill the bacteria on the periphery. The efficacy of a monoprotic weak acid (NAC) and triprotic weak acid (citric acid) were tested on biofilms formed by Klebsiella pneumoniae KP1, Pseudomonas putida OUS82, Staphylococcus aureus 15981, P. aeruginosa DK1-NH57388A, a mucoid cystic fibrosis isolate and P. aeruginosa PA_D25, an antibiotic resistant strain. We showed that weak acids have a broad spectrum of activity against a wide range of bacteria, including antibiotic resistant bacteria. Further, we showed that a weak acid drug, NAC, can kill bacteria without being toxic to human cells, if its pH is maintained close to its pKa. Thus weak acids/weak acid drugs target antibiotic resistant bacteria and eradicate the persister cells in biofilms which are tolerant to other conventional methods of biofilm eradication.

On-Demand Manufacturing of Direct Compressible Tablets: Can Formulation Be Simplified?

PURPOSE: Oral direct compressible tablets are the most frequently used drug products. Manufacturing of tablets requires design and development of formulations, which need a number of excipients. The choice of excipients depends on the concentration, manufacturability, stability, and bioavailability of the active pharmaceutical ingredients (APIs). At MIT, we developed a miniature platform for on-demand manufacturing of direct compressible tablets. This study investigated how formulations could be simplified to use a small number of excipients for a number of different API's in which long term stability is not required. METHOD: Direct compressible tablets of five pharmaceutical drugs, Diazepam, Diphenhydramine HCl, Doxycycline Monohydrate, Ibuprofen, and Ciprofloxacin HCl, with different drug loadings, were made using direct compression in an automated small scale system.. The critical quality attributes (CQA) of the tablets were assessed for the quality standards set by the United States Pharmacopeia (USP). RESULTS: This miniature system can manufacture tablets - on-demand from crystalline API using the minimum number of excipients required for drug product performance. All drug tablets met USP quality standards after manufacturing and after 2 weeks of accelerated stability test, except for slightly lower drug release for Ibuprofen. CONCLUSIONS: On-demand tablets manufacturing where there is no need for long term stability using a flexible, miniature, automated (integrated) system will simplify pharmaceutical formulation design compared to traditional formulations. This advancement will offer substantial economic benefits by decreasing product time-to-market and enhancing quality.