A prospective, randomized, parallel group, double blind, multicenter study to compare the efficacy, safety and immunogenicity of Lupin's Ranibizumab with Lucentis® in patients with neovascular age-related macular degeneration.

Purpose: The present study compares the efficacy, safety, and immunogenicity of Lupin's biosimilar ranibizumab with that of Lucentis® in patients with neovascular age-related macular degeneration. Methods: This prospective, double-blind, multi-centric phase-III study was conducted across 19 centers in India. A total of 202 patients with neovascular age-related macular degeneration were randomized (1:1) to receive either Lupin's biosimilar ranibizumab or Lucentis®, 0.5 mg, as an intravitreous injection once every month for 3 months. The primary efficacy endpoint was the proportion of patients who lost fewer than 15 letters from baseline in best-corrected visual acuity. The safety profile included assessment of adverse events, ophthalmic examination, physical and systemic examination, and vital parameters. The immunogenicity assessment was based on evaluation of anti-drug antibodies. Results: Overall, 174 patients (87 [86.14%] in each group) completed the study. The demographics and baseline characteristics were comparable between the treatment groups. The proportion of patients losing fewer than 15 letters from baseline best corrected visual acuity score in the study eye was comparable between two groups. The difference between Lupin's ranibizumab and Lucentis® for the proportion of patients who lost fewer than 15 letters was within the predefined equivalence margin (intention-to-treat population: 1.0%; 95% confidence interval [CI], -3.3% to 5.4% and per protocol population: 1.2%; 95% CI, -3.2% to 6.4%). The incidence of treatment-emergent adverse events was comparable, and 11 (10.89%) patients in Lupin's ranibizumab and 19 (18.81%) patients in Lucentis® group had at least one treatment-emergent adverse event. The immunogenicity incidence as assessed by proportion of patients with positive anti-drug antibodies was numerically lower in Lupin's ranibizumab (4.95%) than Lucentis® (12.87%). Conclusion: Lupin's biosimilar ranibizumab demonstrated therapeutic equivalence, desirable safety, and favorable immunogenicity profile compared to Lucentis®.

Piperine exhibits preventive and curative effect on erythrocytes membrane modifications and oxidative stress against in vitro albumin glycation.

Inhibition of non-enzymatic glycation processes is an essential aspect of treating type 2 diabetes and related complications. In this study, piperine's preventative, simultaneous and curative effect in glucose-induced albumin glycation was examined by analyzing the structural and functional markers of albumin. The protective and antioxidant influence of piperine on erythrocytes was assessed by examining cellular membrane modifications with antioxidant status. Albumin glycation was performed in three different experimental sets of 21 days at 37°C in dark conditions-using different piperine concentrations (250, 500, and 1,000 µM) and time of addition of glucose (30 mM)/piperine (1,000 µM) in a respective solution at 10th day. Piperine with glycated albumin leads to decreased fructosamine, carbonyl group, and protein-bound glucose. It had protected free amino groups, thiol group, and reduced beta-amyloid, protein aggregates formation. The presence of piperine with glycated albumin prevented erythrocytes hemolysis, membrane modifications, and maintained the antioxidant status. Piperine showed the antiglycation effects in a dose-dependent manner, additionally, its pre-treatment exhibited maximum attenuation by manifesting its primarily preventive role. PRACTICAL APPLICATIONS: Piperine is a natural alkaloid compound found in pepper, has been reported to possess anti-cancer, anti-microbial, and anti-inflammatory properties. The present study evaluated the antiglycation potential of piperine in albumin's glycation and it displayed preventive action, protected erythrocytes from oxidative damage induced by glycated albumin. We concluded that the daily intake of piperine can be adequate to prevent glycation-induced diabetic complications development in hyperglycemic conditions.

The feasibility of online video calling to engage patients with cystic fibrosis in exercise training.

INTRODUCTION: Physical activity, including structured exercise, is an essential component in the management of cystic fibrosis. The use of telehealth such as video-calling may be a useful method for the delivery of exercise and physical activity interventions, though the feasibility of this remains unknown. METHODS: Nine patients with cystic fibrosis (three female, six male, 30.9 ± 8.7 years) volunteered to participate. Participants completed an eight-week exercise training intervention conducted via Skype, using personalised exercises, with all sessions supervised by an exercise therapist. Feasibility was assessed by demand, implementation, practicality and acceptability. Changes in anthropometric, pulmonary, physical activity and quality of life variables were also assessed. RESULTS: Two male participants withdrew from the study, citing lack of available time. The remaining participants found use of Skype useful, with a mean satisfaction rating of 9/10, and three participants requesting to continue the sessions beyond the duration of the study. Mean compliance with sessions was 68%, with mean duration of sessions being 20 min. A total of 25% of calls suffered from technical issues such as video or audio lags. Anthropometric, pulmonary, physical activity and quality of life variables remained unchanged over the course of the study period. DISCUSSION: The use of Skype to deliver an exercise intervention to patients withcystic fibrosis was found to be technologically feasible, and acceptable among participants. Findings have implications for clinical practice and could allow care teams to engage patients remotely in exercise. Further research is required to assess the efficacy of this modality on increasing physical activity and associated health outcomes.

Exploring NursEs lived Experience of Discussions about Sexual health, with kidney patients in Devon (NEEDS).

AIM: The aim of the study is to gain a better understanding about the complexities of discussing sexuality with patients. DESIGN: The study will explore how nurses understand the phenomenon by using an Interpretive Phenomenological Approach; the technique encourages deep reflection and rich descriptions about lived experience. METHODS: Six nurses will be interviewed using iterative, open-ended questions with prompts to illicit rich data. PREDICTED RESULTS: Understand the support required to enable nurses to engage in deeper, more fulfilling conversations with patients about sexuality.

Pilot parallel randomised controlled trial of protective socks against usual care to reduce skin tears in high risk people: 'STOPCUTS'.

BACKGROUND: Skin tears are common in older adults and those taking steroids and warfarin. They are traumatic, often blunt injuries caused by oblique knocks to the extremities. The epidermis may separate from the dermis or both layers from underlying tissues leaving a skin flap or total loss of tissue, which is painful and prone to infection. 'Dermatuff™' knee-length socks containing Kevlar fibres (used in stab-proof vests and motorcyclists' clothing) aim to prevent skin tears. The acceptability of the socks and the feasibility of a randomised controlled trial (RCT) had not been explored. METHODS: In this pilot parallel group RCT, 90 people at risk of skin-tear injury from Devon care homes and primary care were randomised to receive the socks or treatment as usual (TAU). The pilot aimed to estimate parameters to inform the design of a substantive trial and record professionals' views and participants' acceptability of the intervention and of study participation. RESULTS: Participants were randomised from July 2013 and followed up until February 2015. Community participants were easier to recruit than care homes residents but were 10 years younger on average and more active. To recruit 90 participants, 395 had to be approached overall as 77% were excluded or declined. Seventy-nine participants (88%) completed the trial and 27/44 (61%) wore the socks for 16 weeks. There were 31 skin tear injuries affecting 18 (20%) of the 90 participants. The TAU group received more injuries, more repeated episodes, and larger tears with greater severity. Common daily diary reasons for not wearing the socks included perceived warmth in hot weather or not being available (holiday, in hospital, bed rest). Resource use data were obtainable and indicated that sock wearing gave a reduction in treatment costs whilst well-completed questionnaires showed improvements in secondary outcomes. CONCLUSIONS: This pilot trial has successfully informed the design and conduct of a future definitive cost-effectiveness RCT. It would need to be conducted in primary care with 880 active at-risk, elderly patients (440 per arm). Skin tear incidence and quality of life (from EQ5D5L) over a 4-month period would be the primary and secondary outcomes respectively. TRIAL REGISTRATION: ISRCTN, ISRCTN96565376.

Does treatment by a specialist physiotherapist change pain and function in young adults with symptoms from femoroacetabular impingement? A pilot project for a randomised controlled trial.

AIM: Femoroacetabular impingement (FAI) is recognised as a source of hip pain but the effect of conservative treatment remains untested. This pilot study aimed to inform and evaluate the methods required to conduct a substantive trial comparing the effect of treatment by a physiotherapist versus routine care on the symptoms of FAI. DESIGN: A parallel group, pilot randomised controlled trial (RCT). SETTING: A single NHS acute hospital trust, Devon, England. PARTICIPANTS: 30 adults with symptomatic FAI were recruited. 23 (77%) completed the study. INTERVENTIONS: Intervention was 3 months of treatment by a specialist physiotherapist. The control group received routine care. MAIN OUTCOMES: Change in pain and function was measured using a Visual Analogue Scale, Non Arthritic Hip Score (NAHS), Lower Extremity Functional Score (LEFS) and Hip Outcome Score. RESULTS: Participants in the intervention arm undertook a personalised exercise programme to improve pelvic and femoral control plus advice on posture, activity pacing and pain relief. The mean change in NAHS for the intervention group was 12.7 (95% CI 4.7 to 20.7) and 1.8 (95% CI -5.3 to 9.0) in the control group; Median change in LEFS was 11.5 (95% CI 5.0 to 26.0) versus -1.0 (95% CI -7.0 to 4.0). This improvement in LEFS was beyond minimal clinically important difference in the intervention group. Pain scores improved marginally in both groups. CONCLUSIONS: Methodological strengths and weaknesses were successfully identified for a substantive study. Further research is needed to evaluate the relative influence of structural and neuromuscular features on symptoms of FAI and the role of conservative treatment.

Pilot randomised controlled trial of protective socks against usual care to reduce skin tears in high risk people "STOPCUTS": study protocol.

BACKGROUND: Skin tears are traumatic injuries occurring mostly on the extremities due to shearing and friction forces that separate the epidermis and the dermis from underlying tissues. They are common and occur mostly in older adults and those taking medications that compromise skin integrity. Pretibial skin tears can develop into leg ulcers, which require lengthy, expensive treatment to heal. Traumatic injuries are the second most common type of wounds after pressure ulcers in care homes and are the commonest reason for older adults to require the attention of a community nurse. Common causes of skin tear injuries are bumping into furniture and other obstacles, using mobility aids, transfer to/from wheelchairs, getting in and out of bed and falls. No effective preventative measures currently exist but knee-length, protective socks are now available that contain impact-resistant Kevlar fibres (of the type used in stab-proof vests) and cushioning layers underneath. METHODS/DESIGN: In this pilot parallel group, randomised controlled trial, 90 people at risk of skin-tear injury will be randomised with equal allocation to receive the intervention or usual care. They will be recruited from care homes and from the community via general practices and a research volunteer database. Pilot outcomes include recruitment, eligibility, attrition, ascertainment of injuries and completion of outcome measures. Acceptability of the intervention and of study participation will be explored using semi-structured interviews. The proposed primary outcome for the future definitive trial is skin tear-free days. Secondary outcomes are skin tear severity, health status, specific skin-tears quality of life, capability and fear of falling, measured at baseline and the end of the study and in the event of a skin tear. DISCUSSION: The results of this study will be used to inform the development and design of a future randomised controlled trial to assess the effectiveness and cost-effectiveness of a unique and innovative approach to skin tear prevention. Approval was granted by the NRES - Cornwall and Plymouth Research Ethics Committee (13/SW/013). Dissemination will include publication of quantitative and qualitative findings, and experience of public involvement in peer-reviewed journals. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN96565376.

Phase 1 pilot study of e-mail support for people with long term conditions using the Internet.

BACKGROUND: Use of the Internet for people with Long Term Conditions (LTCs) can have a positive effect on knowledge, social support, behavioural and clinical outcomes, yet there is concern that a 'digital divide' prevents some patients from benefitting. While some patients do not have access to the Internet, others that do may still lack expertise or the confidence to make full use of it. The aim of this pilot study was to develop an intervention and test methods for a definitive randomised controlled trial (RCT) of anonymous personal online email support for patients in this latter group. METHODS: Recruitment success was evaluated by the number and appropriateness of participants recruited. A personalised e-health support intervention was developed. The provisional primary outcome was the extent to which the Internet affected the participants' confidence in dealing with their LTC. Primary outcome, seven process measures and two secondary outcomes measures were evaluated for completeness of data and sensitivity to detect changes. RESULTS: Thirty nine participants were recruited, 29 after personally receiving a leaflet, seven via email advertising, and three via leaflets left in waiting areas. Most participants (61%) were aged over 60. The majority (21/38) rated themselves as experienced Internet users although only 5/38 had used discussion forums for their LTC. Piloting the intervention identified support needed as: (i) technical help with some websites, (ii) advice about issues such as anonymity, (iii) help in judging information quality, (iv) identification of relevant information (via 'Information Prescriptions'), (v) motivational support to try new sites. Attrition was fairly high: 20/39 completed follow up questionnaires. Three process measures showed ceiling effects and two had too many missing values to be useable. CONCLUSION: E-health support is a promising way of addressing the problems faced by older generation e-health seekers. Face-to-face leaflet distribution recruited sufficient numbers but additional locations other than hospital should be tried to recruit Internet novices with LTCs. An RCT is feasible and necessary to evaluate the potential benefits of anonymous email support. Our methods could be used by other researchers studying Internet use by people with LTCs.

Asylum seekers' expectations of and trust in general practice: a qualitative study.

BACKGROUND: The UK has substantial minority populations of short-term and long-term migrants from countries with various types of healthcare systems. AIM: This study explored how migrants' previous knowledge and experience of health care influences their current expectations of health care in a system relying on clinical generalists performing a gatekeeping role. DESIGN OF STUDY: Two qualitative methods. SETTING: Glasgow, UK. METHOD: Focus groups or semi-structured interviews were conducted with 52 asylum seekers. Analyses identified several areas where previous experience affected current expectations. An overview of health systems in each country of origin was established by combining responders' accounts with World Health Organization statistics. RESULTS: Asylum seekers had previous experience of a diverse range of healthcare systems, most of which were characterised by a lack of GPs and direct access to hospital-based specialists. For some responders, war or internal conflict resulted in a complete breakdown of healthcare systems. Responders' accounts also highlighted the difficulties that marginalised groups had in accessing health care. Although asylum seekers were generally pleased with the care they received from the NHS, there were areas where they experienced difficulties: confidence in their GP and access to hospital-based specialists and medication. These difficulties encountered might be explained by previous experience. CONCLUSION: GPs and other healthcare professionals need to be aware that experience of different systems of care can have an impact on individuals' expectations in a GP-led system. If these are not acknowledged and addressed, a lack of confidence and trust in the GP may undermine the effectiveness of the clinical consultation.

"They think we're OK and we know we're not". A qualitative study of asylum seekers' access, knowledge and views to health care in the UK.

BACKGROUND: The provision of healthcare for asylum seekers is a global issue. Providing appropriate and culturally sensitive services requires us to understand the barriers facing asylum seekers and the facilitators that help them access health care. Here, we report on two linked studies exploring these issues, along with the health care needs and beliefs of asylum seekers living in the UK. METHODS: Two qualitative methods were employed: focus groups facilitated by members of the asylum seeking community and interviews, either one-to-one or in a group, conducted through an interpreter. Analysis was facilitated using the Framework method. RESULTS: Most asylum seekers were registered with a GP, facilitated for some by an Asylum Support nurse. Many experienced difficulty getting timely appointments with their doctor, especially for self-limiting symptoms that they felt could become more serious, especially in children. Most were positive about the health care they received, although some commented on the lack of continuity. However, there was surprise and disappointment at the length of waiting times both for hospital appointments and when attending accident and emergency departments. Most had attended a dentist, but usually only when there was a clinical need. The provision of interpreters in primary care was generally good, although there was a tension between interpreters translating verbatim and acting as patient advocates. Access to interpreters in other settings, e.g. in-patient hospital stays, was problematic. Barriers included the cost of over-the-counter medication, e.g. children's paracetamol; knowledge of out-of-hours medical care; and access to specialists in secondary care. Most respondents came from countries with no system of primary medical care, which impacted on their expectations of the UK system. CONCLUSION: Most asylum seekers were positive about their experiences of health care. However, we have identified issues regarding their understanding of how the UK system works, in particular the role of general practitioners and referral to hospital specialists. The provision of an Asylum Support nurse was clearly a facilitator to accessing primary medical care. Initiatives to increase their awareness and understanding of the UK system would be beneficial. Interpreting services also need to be developed, in particular their role in secondary care and the development of the role of interpreter as patient advocate.