Acute Kidney Injury in COVID-19.

COVID-19 is mainly considered a respiratory illness, but since SARS-CoV-2 uses the angiotensin converting enzyme 2 receptor (ACE2) to enter human cells, the kidney is also a target of the viral infection. Acute kidney injury (AKI) is the most alarming condition in COVID-19 patients. Recent studies have confirmed the direct entry of SARS-CoV-2 into the renal cells, namely podocytes and proximal tubular cells, but this is not the only pathomechanism of kidney damage. Hypovolemia, cytokine storm and collapsing glomerulopathy also play an important role. An increasing number of papers suggest a strong association between AKI development and higher mortality in COVID-19 patients, hence our interest in the matter. Although knowledge about the role of kidneys in SARS-CoV-2 infection is changing dynamically and is yet to be fully investigated, we present an insight into the possible pathomechanisms of AKI in COVID-19, its clinical features, risk factors, impact on hospitalization and possible ways for its management via renal replacement therapy.

A Digital Intervention for Primary Care Practitioners to Support Antidepressant Discontinuation (Advisor for Health Professionals): Development Study.

BACKGROUND: The number of people receiving antidepressants has increased in the past 3 decades, mainly because of people staying on them longer. However, in many cases long-term treatment is not evidence based and risks increasing side effects. Additionally, prompting general practitioners (GPs) to review medication does not improve the rate of appropriate discontinuation. Therefore, GPs and other health professionals may need help to support patients discontinuing antidepressants in primary care. OBJECTIVE: This study aims to develop a digital intervention to support practitioners in helping patients discontinue inappropriate long-term antidepressants (as part of a wider intervention package including a patient digital intervention and patient telephone support). METHODS: A prototype digital intervention called Advisor for Health Professionals (ADvisor HP) was planned and developed using theory, evidence, and a person-based approach. The following elements informed development: a literature review and qualitative synthesis, an in-depth qualitative study, the development of guiding principles for design elements, and theoretical behavioral analyses. The intervention was then optimized through think-aloud qualitative interviews with health professionals while they were using the prototype intervention. RESULTS: Think-aloud qualitative interviews with 19 health professionals suggested that the digital intervention contained useful information and was readily accessible to practitioners. The development work highlighted a need for further guidance on drug tapering schedules for practitioners and clarity about who is responsible for broaching the subject of discontinuation. Practitioners highlighted the need to have information in easily and quickly accessible formats because of time constraints in day-to-day practice. Some GPs felt that some information was already known to them but understood why this was included. Practitioners differed in their ideas about how they would use ADvisor HP in practice, with some preferring to read the resource in its entirety and others wanting to dip in and out as needed. Changes were made to the wording and structure of the intervention in response to the feedback provided. CONCLUSIONS: ADvisor HP is a digital intervention that has been developed using theory, evidence, and a person-based approach. The optimization work suggests that practitioners may find this tool to be useful in supporting the reduction of long-term antidepressant use. Further quantitative and qualitative evaluation through a randomized controlled trial is needed to examine the feasibility, effectiveness, and cost-effectiveness of the intervention.

REDUCE (Reviewing long-term antidepressant use by careful monitoring in everyday practice) internet and telephone support to people coming off long-term antidepressants: protocol for a randomised controlled trial.

BACKGROUND: Around one in ten adults take antidepressants for depression in England, and their long-term use is increasing. Some need them to prevent relapse, but 30-50% could possibly stop them without relapsing and avoid adverse effects and complications of long-term use. However, stopping is not always easy due to withdrawal symptoms and a fear of relapse of depression. When general practitioners review patients on long-term antidepressants and recommend to those who are suitable to stop the medication, only 6-8% are able to stop. The Reviewing long-term antidepressant use by careful monitoring in everyday practice (REDUCE) research programme aims to identify safe and cost-effective ways of helping patients taking long-term antidepressants taper off treatment when appropriate. METHODS: Design: REDUCE is a two-arm, 1:1 parallel group randomised controlled trial, with randomisation clustered by participating family practices. SETTING: England and north Wales. POPULATION: patients taking antidepressants for longer than 1 year for a first episode of depression or longer than 2 years for repeated episodes of depression who are no longer depressed and want to try to taper off their antidepressant use. INTERVENTION: provision of 'ADvisor' internet programmes to general practitioners or nurse practitioners and to patients designed to support antidepressant withdrawal, plus three patient telephone calls from a psychological wellbeing practitioner. The control arm receives usual care. Blinding of patients, practitioners and researchers is not possible in an open pragmatic trial, but statistical and health economic data analysts will remain blind to allocation. OUTCOME MEASURES: the primary outcome is self-reported nine-item Patient Health Questionnaire at 6 months for depressive symptoms. SECONDARY OUTCOMES: depressive symptoms at other follow-up time points, anxiety, discontinuation of antidepressants, social functioning, wellbeing, enablement, quality of life, satisfaction, and use of health services for costs. SAMPLE SIZE: 402 patients (201 intervention and 201 controls) from 134 general practices recruited over 15-18 months, and followed-up at 3, 6, 9 and 12 months. A qualitative process evaluation will be conducted through interviews with 15-20 patients and 15-20 practitioners in each arm to explore why the interventions were effective or not, depending on the results. DISCUSSION: Helping patients reduce and stop antidepressants is often challenging for practitioners and time-consuming for very busy primary care practices. If REDUCE provides evidence showing that access to internet and telephone support enables more patients to stop treatment without increasing depression we will try to implement the intervention throughout the National Health Service, publishing practical guidance for professionals and advice for patients to follow, publicised through patient support groups. TRIAL REGISTRATION: ISRCTN:12417565. Registered on 7 October 2019.

Supporting antidepressant discontinuation: the development and optimisation of a digital intervention for patients in UK primary care using a theory, evidence and person-based approach.

OBJECTIVES: We aimed to develop a digital intervention to support antidepressant discontinuation in UK primary care that is scalable, accessible, safe and feasible. In this paper, we describe the development using a theory, evidence and person-based approach. DESIGN: Intervention development using a theory, evidence and person-based approach. SETTING: Primary Care in the South of England. PARTICIPANTS: Fifteen participants with a range of antidepressant experience took part in 'think aloud' interviews for intervention optimisation. INTERVENTION: Our digital intervention prototype (called 'ADvisor') was developed on the basis of a planning phase consisting of qualitative and quantitative reviews, an in-depth qualitative study, the development of guiding principles and a theory-based behavioural analysis. Our optimisation phase consisted of 'think aloud' interviews where the intervention was iteratively refined. RESULTS: The qualitative systematic review and in-depth qualitative study highlighted the centrality of fear of depression relapse as a key barrier to discontinuation. The quantitative systematic review showed that psychologically informed approaches such as cognitive-behavioural therapy were associated with greater rates of discontinuation than simple advice to reduce. Following a behavioural diagnosis based on the behaviour change wheel, social cognitive theory provided a theoretical basis for the intervention. The intervention was optimised on the basis of think aloud interviews, where participants suggested they like the flexibility of the system and found it reassuring. Changes were made to the tone of the material and the structure was adjusted based on this qualitative feedback. CONCLUSIONS: 'ADvisor' is a theory, evidence and person-based digital intervention designed to support antidepressant discontinuation. The intervention was perceived as helpful and reassuring in optimisation interviews. Trials are now needed to determine the feasibility, clinical and cost-effectiveness of this approach.

Feasibility and Preliminary Effectiveness of the Homework Intervention Strategy (eHIS) Program to Enhance Male Condom Use: Research Protocol.

BACKGROUND: Although condoms are effective in reducing the risk of sexually transmitted infections (STIs) and unintended pregnancy, they are still often not used consistently and correctly. Negative impact on sensation and pleasure, ruining the mood, causing problems with maintaining erection, and condom slippage or breakage are some of the reasons given by men explaining why they do not want to use condoms. Although many interventions promoting condom use exist, some of them delivered online are complex and time- and resource-intensive. The Homework Intervention Strategy (eHIS) program, adapted from the existing face-to-face Kinsey Institute Homework Intervention Strategy (KIHIS) program, aims to address these issues by encouraging men to focus on sensation and pleasure when trying different types of condoms and lubricants in a low-pressure situation (on their own, without a partner present). OBJECTIVE: The objectives of this study are to assess the feasibility, acceptability, and users' engagement with the eHIS program, its preliminary effectiveness in increasing condom use frequency and consistency, as well as the feasibility of the program's evaluation approach, including choice of measures and participant recruitment and retaining strategies (primary outcomes). Secondary outcomes include condom use experience, condom use attitudes, condom use self-efficacy, condom use errors and problems, and condom fit-and-feel. All of these will be analyzed in the context of participants' demographics, sexual history, and previous condom use. METHODS: The study has a pre-post-test, within-subjects design. Men aged 18 to 69 and living in the United Kingdom are recruited through posters, leaflets, social media, and emails. Study participants are asked to complete T1 (baseline) measures before entering the eHIS website. After completing the T1 measures, they can order a free condoms and lubricants kit and have access to the eHIS website for 4 weeks. During that time they are asked to practice using different types of condoms and lubricants on their own in a no-pressure situation. Following T1, participants are asked to complete the T2 and T3 measures at 4 and 10 weeks, respectively. RESULTS: Data collection for the study is completed. Data analysis is in progress and is expected to be completed by February 2018. CONCLUSIONS: This brief, home-based, self-guided program may lead to increased consistent and correct condom use. Online delivery can make the program an easily accessible and low-cost health promotion intervention, which has the potential to reach a wide and diverse audience. If results of the current study show the program's feasibility and preliminary effectiveness in changing condom use related outcomes, a larger scale randomized controlled trial (RCT) will be conducted. TRIAL REGISTRATION: Research Registry: researchregistry2325; http://www.researchregistry.com/browse-the-registry.html# home/registrationdetails/58da6cad1d7ab0314337d076/ (Archived by WebCite at http://www.webcitation.org/6vXs6S9XW).

Ultrasonic vocalizations (USV) in the three standard laboratory mouse strains: developmental analysis.

Mice, similarly to some other rodent species, communicate with specialized sounds in the ultrasonic range called ultrasonic vocalizations (USV). Evaluation of this behavioral activity enables estimation of the social interactions in animal models of autistic spectrum disorders (ASD). Because transgenic mouse models are generated, in most cases, on the mixed 129SV/C57BL6 genetic background, we were interested if parameters that characterize USV differ between these two mouse strains. In addition, we wanted to compare these strains with the BALB/c line. In order to analyze USV, we applied the standard isolation test to newborn animals and compared standard parameters. Obtained results indicate clear differences between the 129SV and C57BL6 strains in respect to all analyzed USV parameters. Both strains behave also differently when compared with the BALB/c strain. For this reason in experiments utilizing transgenic animals, contribution of various genetic backgrounds has to be carefully considered.

Molecular diagnostics of families with long-QT syndrome.

The Department of Pediatric Cardiology, Medical University of Silesia in Katowice-Ligota, studied 24 patients with clinically diagnosed (using ECG) long-QT syndrome (LQTS) in 18 cases. Nine patients were diagnosed with LQT1 and nine with LQT2. The other six individuals were healthy, with no symptoms characteristic for prolonged QT syndrome, but came from families with confirmed disease occurrence. The study was conducted on members of four families. In order to search for mutations (using mSSCP and sequencing), genomic DNA was obtained from patients to determine the expression levels of the genes KCNQ1 and KCNH2 (HERG), involved in the occurrence of clinical signs of disease. Total RNA was extracted from peripheral blood. Consent to the use of blood samples of patients had been given by the Bioethics Commission of the Medical University of Silesia. mSSCP analysis and sequencing did not confirm the occurrence of mutations in KCNQ1 and HERG associated with the occurrence of LQTS. Analysis of gene expression profile of KCNQ1 and HERG confirmed the presence of disease in people with a known clinical diagnosis. Overexpression, as well as reduced expression, was observed for the examined genes. KCNQ1 was inhibited in two families, whereas HERG was reduced in one and overexpressed in the other. Gene expression profile analysis showed abnormal expressions of KCNQ1 and HERG in healthy subjects, which may be a sign of predisposition to develop the disease. The novelty of our study involved the use of total mRNA isolated from human peripheral blood, and the very limited evidence in the literature to date regarding the assessment of gene expression profile of HERG and KCNQ1 in relation to the presence of prolonged QT syndrome.