Pregabalin-Induced Parkinsonism: Case Report and Review of the Literature.

Pregabalin is an anti-epileptic drug approved for the treatment of neuropathic pain and focal-onset seizures. In a few cases, pregabalin was associated with parkinsonism. We present a case of a 48-year-old female who had hypertension and was on losartan 50 mg/daily. Her general practitioner prescribed pregabalin 150 mg/daily for fibromyalgia-related pain. The subject doubled the dosage without medical advice. After 5 days of the increased dosage, she started to experience difficulty and slowness in movement associated with resting tremors. Neuroimaging, electrodiagnostic studies, and laboratory exams were unremarkable. Secondary parkinsonism was suspected, so pregabalin was discontinued. The subject fully recovered within 7 days. To the authors' knowledge, only 6 cases of pregabalin-induced parkinsonism were reported in the literature. Pregabalin discontinuation was the most common management. All individuals fully recovered after pregabalin withdrawal. The mechanism of pregabalin-induced parkinsonism is not fully understood.

Defining digital nursing.

BACKGROUND: The use of technology in health care, including nursing, is growing, owing in part to the COVID-19 pandemic and in response to national policy. AIMS: To investigate nurses' perceptions of digital nursing (DN). METHODS: Community and primary care nurses from across Wales were recruited (n=249) through a survey comprising open and closed questions. This was supplemented with semistructured interviews (n=25). Thematic analysis was used to analyse qualitative data. FINDINGS: Nurses had a broad range of perspectives on what DN meant, with four main themes being identified: access; impact on care; technology; and digital future. The positive impacts of DN on ways of working and patient outcomes were supported by answers to closed survey questions. CONCLUSION: Many nurses understand the value of digital tools within nursing and are clear about their benefits for patients, nurses and multiprofessional teams. However, there is a need for a clear definition and increased awareness of DN.

Effectiveness of gamma knife radiosurgery in the management of trigeminal neuralgia associated with multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Trigeminal neuralgia (TN) is a chronic condition characterized by intense facial pain akin to electric shocks, often associated with the trigeminal nerve. It can be either idiopathic or secondary, with multiple sclerosis (Ms) being a significant contributing factor. Non-responsive patients may opt for minimally invasive procedures, such as gamma knife radiosurgery (GKRS), which offers precise, non-invasive treatment and is frequently chosen as a primary approach. This meta-analysis evaluates the long-term efficacy of GKRS in TN management in Ms patients. METHODS: We conducted a focused search across various databases. Inclusion criteria encompassed studies with ≥ 30 patients using GKRS for TN in Ms, reporting pertinent clinical outcomes. Primary outcomes assessed GKRS efficacy through Barrow Neurological Institute Pain scores. Secondary outcomes encompassed bothersome numbness, facial numbness, and recurrence. Data analysis employed OpenMeta, random effect models, and odds ratios with 95% confidence intervals. Heterogeneity was assessed using I2 statistics. RESULTS: Fourteen studies with 752 cases of GKRS for TN were included. Regarding the outcomes, 83% of patients experienced a positive initial pain response, while the overall treatment success rate was 51%. Additionally, 19.6% of patients reported facial numbness, 4.1% experienced bothersome numbness, and 40% faced recurrence. The odds ratio for positive initial pain response was 0.83 (95% CI, 0.76-0.89), while for treatment success, it was 0.51 (95% CI, 0.379-0.639). Facial numbness had an odds ratio of 0.196 (95% CI, 0.130-0.262), bothersome numbness had an odds ratio of 0.041 (95% CI, 0.013-0.069), and recurrence had an odds ratio of 0.403 (95% CI, 0.254-0.551). CONCLUSIONS: In conclusion, treating trigeminal neuralgia in multiple sclerosis patients remains challenging. GKRS shows promise, but customized treatment approaches tailored to individual patient characteristics are urgently needed to address the unique challenges of this condition.

Ukraine refugee health screening service in Wales Ukraine/Powys case study 2022 by Powys Teaching Health Board and technology-enabled care Cymru.

The development of the new health screening service for Ukraine Refugees put in place by Powys Teaching Health Board in 2022 has seen extensive use from Ukrainian families in need of extra support from the National Health Service (NHS) and signposting to specific NHS departments. To discuss the experiences of the staff from Powys regarding their role in setting up the screening service and working within it, Research Assistants from Technology Enabled Care, Wales conducted interviews with two staff members. These clinical leads suggested improvements for the screening service, as captured through analysing the data collected via the interviews. This included recognition of benefits, challenges and future recommendations.

Online survey and interview evaluation to explore the use of video consulting among Allied Health Professionals during the COVID-19 pandemic.

OBJECTIVES: Allied Health Professionals (AHP) consist of 13 different specialty roles in Wales, sharing the responsibility of promoting and supporting the health and well-being of the population. During the COVID-19 pandemic, there was a shift in care provision, with the increased use of online consultations, such as those using video consultation platforms. However, this shift was associated with uncertainty and hesitancy, and, thus, to understand the usage and reasons for using video consultations, this study aimed to capture the experiences of both AHP and their patients, while investigating each role individually. PARTICIPANTS: A survey was distributed to and completed by n=8928 patients and n=4974 clinicians, all AHP were included except for orthoptists and paramedics due to ambiguities in the data. A further 86 clinicians participated in phone interviews. RESULTS: All professions had a high prevention of face-to-face with the use of video consultations (68.6% overall and 81.4% of clinicians reported the prevention). However, this was lower for certain professions such as podiatrists, potentially due to the specific patient needs, such as physical assessments. Also, a range of different appointment types were being conducted, and there was a high acceptance of these alternative methods among participants. The interviews with clinicians revealed five important aspects of video consultations: the perceived benefits, the perceived challenges, technology issues and necessary improvements, clinician preference and the future of video consulting. Specifically, the future of video consulting evidenced clinicians' desire for a blended approach to working, selecting the appropriate modality depending on the situation and patient-specific needs. CONCLUSIONS: Integrating the traditional methods of service delivery (face-to-face), and novel, innovative ways, such as video consultations, can motivate positive transformations for the efficiency and efficacy of health and social care.

Benefits, challenges and sustainability of digital healthcare for NHS Wales: a qualitative study.

INTRODUCTION: Digital healthcare in the UK was adopted out of necessity rather than choice during the COVID-19 pandemic. However, as we move forward, UK governments and healthcare services have acknowledged its evident benefits for patients, staff and the National Health Service (NHS), and are keen to sustain its improvements in the long term. OBJECTIVE: To understand the benefits, challenges and sustainability of a future-proof digital healthcare. DESIGN: A semi-structured interview study was conducted. SETTING: In NHS services in Wales, UK. PARTICIPANTS: With clinical and non-clinical staff across a mix of clinical specialties. OUTCOME MEASURES: Semi-structured interviews were conducted to address benefits, challenges and sustainability of a national video consulting (VC) service, and thematically coded using a quantification method of qualitative work. RESULTS: A total of 203 interviews were conducted and 3 dominant domains emerged, with 7 themes and 26 categories. LIMITATIONS: It is important to acknowledge that these findings were captured during a pandemic. CONCLUSIONS: NHS Wales has demonstrated that currently there are an equal measure of benefits and challenges to a national digital healthcare. However, with ongoing government and service support, improvement and evaluation, it has potential for a sustainable digital future, in which the benefits can outweigh the challenges.

Exosome-Coated tPA/Catalase Nanoformulation for Thrombolytic Therapy.

Current tissue plasminogen-based therapeutic strategies for stroke suffer from systemic side effects and poor efficacy. Hence, novel drug delivery methods are needed to overcome these shortcomings. Exosome-based drug formulations have been shown to have superior therapeutic outcomes compared to conventional systemic drug delivery approaches. In this paper, we report exosome surface-coated tissue plasminogen activator (tPA)/catalase nanoformulations with improved thrombolytic efficacy compared to free tPA, which also reduce side effects. The results showed that the tPA exosome formulations retained tPA activity, improved tPA stability, exhibited significant fibrinolysis, and showed no significant toxicity effects. Further, when combined with antioxidant enzyme catalase, the formulation was able to inhibit hydrogen peroxide-mediated oxidative stress and toxicity. Hence, exosome-based tPA/catalase nanoformulations could have the potential to offer a safer and effective thrombolytic therapy.

Digital NHS Wales: a coding reliability analysis based on the voices of 22 978 patients and clinicians on the benefits, challenges and sustainability of video consulting.

INTRODUCTION: The use of video consulting (VC) in Wales UK has expanded rapidly. Previous VC evidence has been the subject of small-scale projects and evaluations. Technology Enabled Care Cymru is an all-Wales digital service and rolls out digital interventions and evaluates on large scales, thus capturing representative data sets across Wales, and therefore a wide range of National Health Service (NHS) specialties. OBJECTIVE: To extract and analyse narrative feedback from patients and clinicians using the NHS Wales VC Service for 6 months (September 2020 to March 2021). DESIGN: A coding reliability approach of a cross-sectional study was conducted. SETTING: From all health boards across Wales. PARTICIPANTS: NHS patients and clinicians across primary, secondary and community care settings in Wales. RESULTS: Data were captured on benefits, challenges and sustainability of VC. A coding reliability analysis was used with six domain summaries materialising to include: 'The Ease of VC'; 'The Personal Touches'; 'The Benefits of VC'; 'The Challenges of VC'; 'Technical Quality'; and 'Recommendations & Future Use'. An additional 17 subdomains are included. Direct quotations from patients and clinicians are provided for context. CONCLUSIONS: A total of 22 978 participants were included. These data help demonstrate that NHS remote service delivery, via the method of VC, can be highly satisfactory, well accepted and clinically suitable yielding many benefits. Despite this, the data are not without its challenges surrounding engagement and suitability for VC. The NHS Wales VC Service rolled out and evaluated at scale and demonstrates that VC has potential for long-term sustainability. For the future, use a 'blended approach' for NHS appointments that are clinically judged and centred on patient choice.

Early evidence and lessons learnt from an NHS Wales Video Consulting Service.

Background: The use of video consulting (VC) in Wales, United Kingdom (UK) has expanded rapidly during the COVID-19 pandemic. Traditionally, VC has been the subject of small-scale projects and evaluations. In response to the pandemic emergency, there was an opportunity to roll out and evaluate VC on a larger and more representative scale, across a wider range of National Health Service (NHS) specialities.Aims: This paper presents an overview of a dataset captured by the 'The NHS Wales VC Service'. The purpose of this study was to capture perspectives of healthcare professionals only (including clinicians, administration and management) on the use of VC and explore lessons learnt from the national implementation process.Methodology: Using an online, mixed methods retrospective survey capturing descriptive and narrative data.Results: A total of 1256 NHS healthcare professionals shared their VC experience. Overall, responses were positive, and healthcare professionals expressed optimistic views regarding the use, value and benefit of VC, even when faced with challenges on occasions.Conclusions: A lesson learnt, is that difference occurs in innovation, even in a small country like Wales, yet it is not necessarily a negative outcome, but rather, respecting and incorporating difference, can improve long-term sustainability.

Taming the chaos: NHS professionals' perspective of using video consulting during COVID-19 in Wales.

The use of video consulting (VC) in the UK has expanded rapidly during the COVID-19 pandemic. Technology Enabled Care (TEC) Cymru, the Welsh Government and Local Health boards began implementing the National Health Service (NHS) Wales VC Service in March 2020. This has been robustly evaluated on a large-scale All-Wales basis, across a wide range of NHS Wales specialities. AIMS: To understand the early use of VC in Wales from the perspective of NHS professionals using it. NHS professionals were approached by TEC Cymru to provide early data. METHODS: Using an observational study design with descriptive methods including a cross-sectional survey, TEC Cymru captured data on the use, benefits and challenges of VC from NHS professionals in Wales during August and September 2020. This evidence is based on the rapid adoption of VC in Wales, which mirrors that of other nations. RESULTS: A total of 1256 NHS professionals shared their VC experience. Overall, responses were positive, and professionals expressed optimistic views regarding the use and benefit of VC, even when faced with challenges on occasions. CONCLUSIONS: This study provides evidence of general positivity, acceptance and the success of the VC service in Wales. Future research studies will now be able to explore and evaluate the implementation methods used within this study, and investigate their effectiveness in being able to achieve better outcomes through VC.

Remote mental health services: a mixed-methods survey and interview study on the use, value, benefits and challenges of a national video consulting service in NHS Wales, UK.

Social distancing laws during the first year of the pandemic, and its unprecedented changes to the National Health Service (NHS) forced a large majority of services, especially mental health teams to deliver patient care remotely. For many, this approach was adopted out of necessity, rather than choice, thus presenting a true 'testing ground' for remote healthcare and a robust evaluation on a national and representative level. OBJECTIVE: To extract and analyse mental health specific data from a national dataset for 1 year (March 2020-March 2021). DESIGN: A mixed-methods study using surveys and interviews. SETTING: In NHS mental health services in Wales, UK. PARTICIPANTS: With NHS patients and clinicians across child and adolescent, adult and older adult mental health services. OUTCOME MEASURES: Mixed methods data captured measures on use, value, benefits and challenges of video consulting (VC). RESULTS: A total of 3561 participants provided mental health specific data. These data and its findings demonstrate that remote mental health service delivery, via the method of VC is highly satisfactory, well-accepted and clinically suitable for many patients, and provides a range of benefits to NHS patients and clinicians. Interestingly, clinicians working from 'home' rated VC more positively compared with those at their 'clinical base'. CONCLUSIONS: Post 1-year adoption, remote mental health services in Wales UK have demonstrated that VC is possible from both a technical and behavioural standpoint. Moving forward, we suggest clinical leaders and government support to sustain this approach 'by default' as an option for NHS appointments.

Connecting and connectivity: providing video consulting in care homes in Wales.

BACKGROUND: During the COVID-19 pandemic, care home residents and staff were identified as being at risk of infection. Their safety was important, but equally important was safe delivery of healthcare to those who needed it. The Welsh Government provided care homes with video consulting (VC) to deliver safe healthcare to the vulnerable, combat isolation and protect the residents and staff. METHODS: To understand the use, value, benefits and challenges of using VC in care homes across Wales, telephone interviews were conducted between September and November 2020. RESULTS: From 101 interviews, findings suggest that while care homes are responsive to VC, there is a need for further awareness, better training and support for care home staff. CONCLUSIONS: Interestingly, issues around connectivity, lack of equipment and technical literacy were highlighted as minimal barriers. VC should be encouraged as a long-term service to support the health and wellbeing of care home staff and residents.

Gastric balloon: A rare cause of lumbar radiculopathy.

BACKGROUND: Factors that are known to cause lumbar epidural venous plexus (EVP) engorgement include inferior vena cava (IVC) obstruction, portal hypertension, vascular agenesis, morbid obesity, and/or hypercoagulable states. Here, we present a 32-year-old female admitted with the new onset of lumbar radiculopathy attributed to a gastric balloon causing compression of the IVC and engorgement of the EVP. CASE DESCRIPTION: A 32-year-old female was admitted with a left L5 radiculopathy. She had a history of morbid obesity and had undergone intragastric balloon insertion 4 months ago. The abdominal/pelvic CT documented an intragastric balloon producing a voluminous gastric mass with resultant compression of the IVC. The lumbar MRI showed the resultant marked multilevel engorgement of the lumbar EVP. Here, following balloon removal, the patient was immediately symptom free and remained asymptomatic over the next postoperative year. CONCLUSION: An intragastric balloon can produce a voluminous gastric mass that can result in IVC occlusion and engorgement of the EVP, leading to lumbar radiculopathy. Removal of the balloon results in immediate and permanent resolution of the compressive symptoms.

Pfizer-biontech COVID-19 RNA vaccination induces phosphatidylserine autoantibodies, cryoglobulinemia, and digital necrosis in a patient with pre-existing autoimmunity.

We describe a 64-year-old Caucasian female with a history of Raynaud's disease, hand arthritis, photosensitivity, Sjogren's syndrome and leukocytoclastic vasculitis who presented with progressively worsening fingertip necrosis that began three days after receiving a first dose of Pfizer-BioNTech COVID-19 RNA vaccine. Our workup revealed cryoglobulinemia, hypocomplementemia, elevated antinuclear antibodies (ANA) and IgM antiphospholipid autoantibodies (aPL) directed against phosphatidylserine (aPL-PS), suggesting a diagnosis of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). The patient failed to develop anti-spike IgG antibodies up to two months following vaccination. Disease progression was halted by plasmapheresis, anticoagulation, and immune suppression. We conclude that the vaccine RNA moiety may induce SLE manifesting in APS, cryoglobulinemia, hypocomplementemia, and digital necrosis.

BTK inhibition ameliorates kidney disease in spontaneous lupus nephritis.

Lupus nephritis is a common disease manifestation of SLE, in which immune complex deposition and macrophage activation are important contributors to disease pathogenesis. Bruton's tyrosine kinase (BTK) plays an important role in both B cell and FcgammaR mediated myeloid cell activation. In the current study, we examined the efficacy of BI-BTK-1, a recently described irreversible BTK inhibitor, in the classical NZB × NZW F1 (NZB/W) and MRL/lpr spontaneous mouse models of SLE. NZB/W mice were randomly assigned to a treatment (0.3 mg/kg, 1 mg/kg, 3 mg/kg and 10 mg/kg) or control group and began treatment at 22 weeks of age. The experimental setup was similar in MRL/lpr mice, but with a single treated (10 mg/kg, beginning at 8-9 weeks of age) and control group. A separate experiment was performed in the MRL/lpr strain to assess the ability of BI-BTK-1 to reverse established kidney disease. Early treatment with BI-BTK-1 significantly protected NZB/W and MRL/lpr mice from the development of proteinuria, correlating with significant renal histological protection, decreased anti-DNA titers, and increased survival in both strains. BI-BTK-1 treated mice displayed a significant decrease in nephritis-associated inflammatory mediators (e.g. LCN2 and IL-6) in the kidney, combined with a significant inhibition of immune cell infiltration and accumulation. Importantly, BI-BTK-1 treatment resulted in the reversal of established kidney disease. BTK inhibition significantly reduced total B cell numbers and all B cell subsets (immature, transitional, follicular, marginal zone, and class switched) in the spleen of NZB/W mice. Overall, the significant efficacy of BI-BTK-1 in ameliorating multiple pathological endpoints associated with kidney disease in two distinct murine models of spontaneous lupus nephritis provides a strong rationale for BTK inhibition as a promising treatment approach for lupus nephritis.

Therapeutic Uses of HSP90 Inhibitors in Non-Small Cell Lung Carcinoma (NSCLC).

BACKGROUND: Non-Small Cell Lung Carcinoma is one of the major cause of morbidity and mortality worldwide with an incidence rate of 1.3 million cases per year. Heat shock protein 90 (HSP90) is a promising drug target in cancer treatment. HSP90 is required to activate numerous eukaryotic proto-oncogenic protein kinases, hence play a prominent role in cancer. METHOD: We reviewed fifty-five articles to highlight the importance of HSP90 in NSCLC and the recent developments of its inhibitors. RESULTS: This review showed that HSP90 inhibitors i.e. Ganestespib have shown great potential in the treatment of non-small cell lung carcinoma (NSCLC). Different HSP90 inhibitors has been designed till date that acts as effective drugs in tumour suppression. However, the utility of these drugs has been limited due to several drawbacks including hepato-toxicity, poor solubility, and poorly tolerated formulations. CONCLUSION: The goal of this review is to present the data in support of use of HSP90 inhibitors in NSCLC and to provide an overview of the on-going clinical trials involving new-generation HSP90 inhibitors.

Germline Mutations in DNA Repair Genes in Lung Adenocarcinoma.

INTRODUCTION: Although lung cancer is generally thought to be environmentally provoked, anecdotal familial clustering has been reported, suggesting that there may be genetic susceptibility factors. We systematically tested whether germline mutations in eight candidate genes may be risk factors for lung adenocarcinoma. METHODS: We studied lung adenocarcinoma cases for which germline sequence data had been generated as part of The Cancer Genome Atlas project but had not been previously analyzed. We selected eight genes, ATM serine/threonine kinase gene (ATM), BRCA2, DNA repair associated gene (BRCA2), checkpoint kinase 2 gene (CHEK2), EGFR, parkin RBR E3 ubiquitin protein ligase gene (PARK2), telomerase reverse transcriptase gene (TERT), tumor protein p53 gene (TP53), and Yes associated protein 1 gene (YAP1), on the basis of prior anecdotal association with lung cancer or genome-wide association studies. RESULTS: Among 555 lung adenocarcinoma cases, we detected 14 pathogenic mutations in five genes; they occurred at a frequency of 2.5% and represented an OR of 66 (95% confidence interval: 33-125, p < 0.0001 [chi-square test]). The mutations fell most commonly in ATM (50%), followed by TP53, BRCA2, EGFR, and PARK2. Most (86%) of these variants had been reported in other familial cancer syndromes. Another 12 cases (2%) carried ultrarare variants that were predicted to be deleterious by three protein prediction programs; these most frequently involved ATM and BRCA2. CONCLUSIONS: A subset of patients with lung adenocarcinoma, at least 2.5% to 4.5%, carry germline variants that have been linked to cancer risk in Mendelian syndromes. The genes fall most frequently in DNA repair pathways. Our data indicate that patients with lung adenocarcinoma, similar to other solid tumors, include a subset of patients with inherited susceptibility.