A systematic review of qualitative evidence: Perspectives of fathers whose partner experienced postpartum psychosis.

AIMS: This study aimed to systematically identify, appraise and synthesize qualitative evidence which explored fathers' experiences and perspectives of their partners' postpartum psychosis. DESIGN: Qualitative evidence synthesis (QES). DATA SOURCES: Seven databases (CINAHL, PsycINFO, Medline, Scopus, Google Scholar, ProQuest Dissertations and Open Grey) were systematically searched for qualitative studies from each database's inception to the 17th of February 2022. REVIEW METHODS: Studies that utilized a qualitative research design to explore fathers' experiences and perspectives of their partners' postpartum psychosis were included. Studies were appraised using the Critical Appraisal Skills Programme to determine their methodological quality. Qualitative data were extracted and synthesized using the process of thematic synthesis to form analytical themes. RESULTS: Eleven reports (seven journal articles and four theses), representing six unique qualitative studies were included in the review. Two analytical themes and eight subthemes were identified. The analytical themes were 'a sense of loss across multiple domains of their lives', and 'informational and emotional support needs'. CONCLUSION: Postpartum psychosis is a severe mental health condition which also impacts the woman's partner. Fathers experienced an array of emotions which they attributed to a lack of knowledge and understanding of postpartum psychosis. The development of appropriate support structures is needed to better support fathers in supporting their partners. REPORTING METHOD: This review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement and ENTREQ reporting guidelines. PATIENT OR PUBLIC CONTRIBUTION: There was no patient or public contribution. IMPACT: WHAT PROBLEM DID THIS STUDY ADDRESS?: Fathers play a pivotal role in supporting their partner who has postpartum psychosis, and a supportive father has a positive impact on the mental health of the mother. Several qualitative studies have explored fathers' experiences of their partners' psychosis. This QES integrated findings from these studies to gain a deeper understanding and knowledge of the father's experience. WHAT ARE THE MAIN FINDINGS?: Fathers reported a significant sense of loss across multiple domains of their lives, from a perceived loss of their relationship with their partner to a loss of the future they had planned together. Fathers experienced an array of emotions, such as fear and shock which they attributed to their lack of knowledge and awareness of postpartum psychosis. WHERE AND ON WHOM WILL THIS RESEARCH HAVE AN IMPACT?: This review provides a deeper insight and understanding into the father's experiences and perspectives of their partners' postpartum psychosis. This insight can inform healthcare professionals and policymakers in the development of appropriate support structures which meet the needs of this population. The provision of appropriate support structures could have a positive impact on the father's well-being and ability to support their partner.

Nonpharmacological Interventions for Management of Behavioral and Psychological Symptoms of Dementia in Long-Term Care Facilities by Direct Caregivers: A Systematic Review.

Behavioral and psychological symptoms of dementia (BPSD) are a worldwide problem. Estimates indicate approximately 96% of persons with dementia (PWD) exhibit BPSD that are directly associated with long-term care (LTC) placement and approximately one half of these persons experience symptoms classified as severe. BPSD are associated with lost days of work, high turnover, and poor job satisfaction for direct caregivers. Nonpharmacological interventions (NPIs) are effective for management of BPSD when used properly. NPIs are more likely to be used by direct caregivers who are knowledgeable about and have confidence in BPSD effectiveness. Various training techniques promote development of this self-efficacy. The current systematic review synthesizes evidence concerning the use of NPIs for management of BPSD by direct caregivers in LTC settings. Gaps in the literature include evaluation of positive impact of NPIs on PWD and behavior precedent factors. This review emphasizes the need for development and provision of quality NPI education for direct caregivers in LTC settings. [Journal of Gerontological Nursing, 48(7), 18-23.].

Exploiting structural analysis, in silico screening, and serendipity to identify novel inhibitors of drug-resistant falciparum malaria.

Plasmodium falciparum thymidylate synthase-dihydrofolate reductase (TS-DHFR) is an essential enzyme in folate biosynthesis and a major malarial drug target. This bifunctional enzyme thus presents different design approaches for developing novel inhibitors against drug-resistant mutants. We performed a high-throughput in silico screen of a database of diverse, drug-like molecules against a non-active-site pocket of TS-DHFR. The top compounds from this virtual screen were evaluated by in vitro enzymatic and cellular culture studies. Three compounds active to 20 microM IC(50)'s in both wildtype and antifolate-resistant P. falciparum parasites were identified; moreover, no inhibition of human DHFR enzyme was observed, indicating that the inhibitory effects appeared to be parasite-specific. Notably, all three compounds had a biguanide scaffold. However, relative free energy of binding calculations suggested that the compounds might preferentially interact with the active site over the screened non-active-site region. To resolve the two possible modes of binding, co-crystallization studies of the compounds complexed with TS-DHFR enzyme were performed. Surprisingly, the structural analysis revealed that these novel, biguanide compounds do indeed bind at the active site of DHFR and additionally revealed the molecular basis by which they overcome drug resistance. To our knowledge, these are the first co-crystal structures of novel, biguanide, non-WR99210 compounds that are active against folate-resistant malaria parasites in cell culture.

Evaluation of a venous-return assist device to treat severe post-thrombotic syndrome (VENOPTS). A randomized controlled trial.

Severe post-thrombotic syndrome (PTS) is responsible for considerable disability, reduced quality of life and increased health care costs. Current therapies are limited and often ineffective. We performed a two-centre, randomized, cross-over controlled trial to evaluate Venowave, a novel lower-limb venous-return assist device, for the treatment of severe PTS. Eligible subjects were allocated to receive, in randomized order, Venowave for eight weeks and a control device for eight weeks. The eight-week treatment periods were separated by a four-week period when no device was used (i.e. wash-out period). The primary outcome measure was a 'clinical success' defined as: i) reported benefit from the device; and ii) moderate or greater improvement in symptoms of PTS; and iii) willingness to continue using the device. Secondary outcome measures included quality of life (QOL) as measured by VEINES-QOL questionnaire (higher scores indicate better QOL), and PTS severity as measured by the Villalta PTS scale (higher scores indicate more severe PTS). The study was registered with Clinical Trials. gov (NCT00182208). Thirty-two patients were enrolled. Of these, 26 (80%) were also using graduated compression stockings. Twenty-six participants completed both trial periods. Clinical success occurred in 10 (31%) participants receiving Venowave and four (13%) participants receiving the control device, with two (6%) participants reporting a clinical success with both devices (P = 0.11). Mean VEINES-QOL score at the end of study period was significantly greater (P = 0.004) for Venowave (52.5; SD 5.8) compared to control (50.2; SD 6.2). Mean Villalta scale score at the end of study period was significantly decreased (P = 0.004) for Venowave (12.2; SD 6.3) compared to control (15.0; SD 6.1). In conclusion, Venowave appears to be a very promising new therapy for patients with severe PTS, which may be used alone or in combination with graduated compression stockings.

Search for non-nucleoside inhibitors of HIV-1 reverse transcriptase using chemical similarity, molecular docking, and MM-GB/SA scoring.

A virtual screening protocol has been applied to seek non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) and its K103N mutant. First, a chemical similarity search on the Maybridge library was performed using known NNRTIs as reference structures. The top-ranked molecules obtained from this procedure plus 26 known NNRTIs were then docked into the binding sites of the wild-type reverse transcriptase (HIV-RT) and its K103N variant (K103N-RT) using Glide 3.5. The top-ranked 100 compounds from the docking for both proteins were post-scored with a procedure using molecular mechanics and continuum solvation (MM-GB/SA). The validity of the virtual screening protocol was supported by (i) testing of the MM-GB/SA procedure, (ii) agreement between predicted and crystallographic binding poses, (iii) recovery of known potent NNRTIs at the top of both rankings, and (iv) identification of top-scoring library compounds that are close in structure to recently reported NNRTI HTS hits. However, purchase and assaying of selected top-scoring compounds from the library failed to yield active anti-HIV agents. Nevertheless, the highest-ranked database compound, S10087, was pursued as containing a potentially viable core. Subsequent synthesis and assaying of S10087 analogues proposed by further computational analysis yielded anti-HIV agents with EC50 values as low as 310 nM. Thus, with the aid of computational tools, it was possible to evolve a false positive into a true active.