Evaluating the impact of trigeminal neuralgia

Patients with idiopathic trigeminal neuralgia (TN) were categorised into 3 subtypes (n 5 225). Group 1 (n 5 155, 68.9%) had TN without concomitant pain, group 2 (n532, 14.2%) had TN with intermittent concomitant pain, and group 3 (n539, 16.9%) had TN with autonomic symptoms. We tested 2 hypotheses: (1) that different pain profiles would be associated with the different groups; (2) that the severe pain associated with TN would impact negatively on activities of daily living and thereby result in disability as defined by the World Health Organisation. A different pain profile was found across the groups. We obtained unequivocal evidence that TN causes disability with up to 45% of patients being absent from usual daily activities 15 days or more in the past 6 months. On the Hospital Anxiety and Depression Scale, 35.7% patients had mild-to-severe depression and over 50% were anxious. The Pain Catastrophizing Scale showed that 78% of patients had considerable negative thoughts with scores.20 and a mean score of 36.4. Prior to referral, only 54% had been prescribed carbamazepine while opioids had been prescribed in 14.6% of the patients. Prior to referral, over 80% had already been to 1 specialist centre which had not provided appropriate management. Patients with TN report varied characteristics but all result in some degree of psychosocial disability especially before adequate therapy is attained

Cognitive and sensorimotor function in participants being treated for trigeminal neuralgia pain

Background Trigeminal neuralgia (TN) is an orofacial condition defined by reoccurring, spontaneous, short-lived but excruciating stabbing pain. Pharmacological interventions constitute the first-line treatment for TN, with antiepileptic drugs commonly prescribed. People treated for TN pain with antiepileptic drugs describe cognitive and motor difficulties affecting activities of daily living, and report poorer quality of life. We undertook the first comprehensive objective evaluation of sensorimotor and cognitive performance in participants being treated for TN pain with antiepileptic drugs relative to age-matched controls. Methods Participants (43 TN, 41 control) completed a battery of sensorimotor (steering, aiming and tracking) and cognitive (working memory, processing speed, inhibition) tasks. Results The TN group performed significantly worse than controls on the sensorimotor tracking and aiming tasks and across all cognitive measures. Conclusions The data explain why patients treated with antiepileptic drugs report impairment when conducting activities of daily living (given the need for cognitive and motor capability within most of these). The study is an important first step in: (i) ensuring there is adequate information on the impact of pharmacological treatment; (ii) identifying measures to determine optimal medication dosage and track change over time; (iii) creating an evidence base that could allow scientific justification of alternative pain treatment options for TN (e.g. the costs/benefits of surgery)

‘Warning: allergic to penicillin’: association between penicillin allergy status in 2.3 million NHS general practice electronic health records, antibiotic prescribing and health outcomes

Background The prevalence of reported penicillin allergy (PenA) and the impact these records have on health outcomes in the UK general population are unknown. Without such data, justifying and planning enhanced allergy services is challenging. Objectives To determine: (i) prevalence of PenA records; (ii) patient characteristics associated with PenA records; and (iii) impact of PenA records on antibiotic prescribing/health outcomes in primary care. Methods We carried out cross-sectional/retrospective cohort studies using patient-level data from electronic health records. Cohort study: exact matching across confounders identified as affecting PenA records. Setting: English NHS general practices between 1 April 2013 and 31 March 2014. Participants: 2.3 million adult patients. Outcome measures: prevalence of PenA, antibiotic prescribing, mortality, MRSA infection/colonization and Clostridioides difficile infection. Results PenA prevalence was 5.9% (IQR = 3.8%–8.2%). PenA records were more common in older people, females and those with a comorbidity, and were affected by GP practice. Antibiotic prescribing varied significantly: penicillins were prescribed less frequently in those with a PenA record [relative risk (RR)  = 0.15], and macrolides (RR = 4.03), tetracyclines (RR = 1.91) nitrofurantoin (RR = 1.09), trimethoprim (RR = 1.04), cephalosporins (RR = 2.05), quinolones (RR = 2.10), clindamycin (RR = 5.47) and total number of prescriptions were increased in patients with a PenA record. Risk of re-prescription of a new antibiotic class within 28 days (RR = 1.32), MRSA infection/colonization (RR = 1.90) and death during the year subsequent to 1 April 2013 (RR = 1.08) increased in those with PenA records. Conclusions PenA records are common in the general population and associated with increased/altered antibiotic prescribing and worse health outcomes. We estimate that incorrect PenA records affect 2.7 million people in England. Establishing true PenA status (e.g. oral challenge testing) would allow more people to be prescribed first-line antibiotics, potentially improving health outcomes

Patient perspective on decisions to switch disease-modifying treatments in relapsing-remitting multiple sclerosis

Background: There are now large cohorts of people with relapsing-remitting multiple sclerosis (pwRRMS) who have taken several Disease-Modifying Treatments (DMTs). Studies about switching DMTs mostly focus on clinical outcomes rather than patients' decision-making. Neurologists are now required to support decisions at various times during the relapsing disease course and they do so with concerns about DMTs risks. This qualitative study investigates how pwRRMS weigh up the pros and cons of DMTs, focusing on perceptions of effectiveness and risks when new treatments are considered. / Objective: To increase understanding of people's experiences of decision-making when switching DMTs. / Methods: 30 semi-structured interviews were conducted with pwRRMS in England. 16 participants had switched DMT and their experiences were compared with those who had only taken one DMT. Interviews were analysed thematically to answer: what main factors influence people's decision-making to switch DMTs and why? / Results: Of the 16 participants with experience of switching DMT, eight had taken two or more DMTs; eight had taken three or more. Two was the DMT median. This study demonstrated that despite the term "switching" implying that similar treatments are inter-changeable, for pwRRMS taking new treatments involves different emotions, routines, risks, prognosis and communication experiences. Two meta themes identified were: 1) A distinctive, rapid and emotional decision-making process where old emotions related to MS prognosis are revisited. 2) Switching has a different impact on communication for escalation or de-escalation processes. / Conclusion: Switching DMT involves different routines, risks, prognosis and communication experiences. These decisions are emotionally difficult because of the fear about transitioning to secondary progressive MS, and DMT effectiveness uncertainty. Patient centred decision aids should include information about first and consecutive treatment decisions

Outcome measures in facial prosthesis research: a systematic review

Statement of problem Facial prosthesis research uses a wide variety of outcome measures, which results in challenges when comparing the effectiveness of interventions among studies. Consensus is lacking regarding the most appropriate and meaningful outcome measures to use in facial prosthesis research to capture important perspectives. Purpose The purpose of the systematic review was to identify and synthesize outcome measures used in facial prosthesis research. Material and methods Electronic searches were performed in 11 databases (including nonpeer-reviewed literature). The citations were searched, and expert societies were contacted to identify additional studies. Inclusion criteria comprised studies of participants with facial defects who required or had received prosthetic rehabilitation with an external facial prosthesis. Exclusion criteria comprised participants with ocular prostheses, case reports, case series with fewer than 5 participants, laboratory-based studies, and studies published before 1980. Study selection was performed independently by 2 reviewers. Discrepancies were resolved through discussion or by a third reviewer. Outcome measures were synthesized with a categorization approach based on the perspective, theme, and subtheme of the outcome measures. Quality assessment was performed with an appraisal tool that enabled evaluation of studies with diverse designs. Results Database searching identified 13 058 records, and 7406 remained after duplications were removed. After initial screening, 189 potentially relevant records remained, and 186 full texts were located (98% retrieval rate). After full-text screening, 124 records were excluded. Citation searches and contact with expert societies identified 4 further records. In total, 69 articles (grouped into 65 studies) were included. Studies were categorized as per the perspective of their outcome measures, with the following findings: patient-reported (74% of studies), clinical indicators (34%), clinician-reported (8%), multiple viewpoints (6%), and independent observer-reported (3%). Patient-reported outcome measures included tools to assess satisfaction, quality of life, and psychologic health. Variability in the choice of outcome measures was evident among the studies, with many self-designed, unvalidated, condition-specific questionnaires reported. A greater number of outcome measure themes emerged over time; themes such as service delivery and health state utility have recently been evaluated. Conclusions Over the past 40 years, facial prosthesis research has focused on patient-reported outcome measures. Outcome measures relating to other perspectives have been used less frequently, although new themes appear to be emerging in the literature. Future research should use outcome measures with appropriate measurement properties for use with facial prosthetics

Patient and prescriber views of penicillin-allergy testing and subsequent antibiotic use: a rapid review

About 10% of U.K. patients believe that they are allergic to penicillin and have a "penicillin allergy label" in their primary care health record. However, around 90% of these patients may be mislabelled. Removing incorrect penicillin allergy labels can help to reduce unnecessary broad-spectrum antibiotic use. A rapid review was undertaken of papers exploring patient and/or clinician views and experiences of penicillin allergy testing (PAT) services and the influences on antibiotic prescribing behaviour in the context of penicillin allergy. We reviewed English-language publications published up to November 2017. Limited evidence on patients' experiences of PAT highlighted advantages to testing as well as a number of concerns. Clinicians reported uncertainty about referral criteria for PAT. Following PAT and a negative result, a number of clinicians and patients remained reluctant to prescribe and consume penicillins. This appeared to reflect a lack of confidence in the test result and fear of subsequent reactions to penicillins. The findings suggest lack of awareness and knowledge of PAT services by both clinicians and patients. In order to ensure correct penicillin allergy diagnosis, clinicians and patients need to be supported to use PAT services and equipped with the skills to use penicillins appropriately following a negative allergy test result

Organizational Barriers to Oral Health Conversations Between Health Visitors and Parents of Children Aged 9–12 Months Old

Background: Dental caries is the most prevalent preventable childhood disease and a major public health priority. Local authorities in England have a statutory responsibility to improve child health, including oral health, through the “Healthy Child Programme.” The “Healthy Child Programme,” which includes the provision of oral health advice is delivered by health visitors to parents of young children. To date, research has mainly concentrated on individual interactions between health visitors and parents, with less attention given to the broader context in which these oral health conversations between health visitor and parents take place. Objective: Our study explored the organizational factors that obstruct health visitors from engaging in meaningful conversations with parents about young children's oral health. Methods: Qualitative interviews and focus groups were held with health visiting teams (n = 18) conducting home visits with parents of 9–12-month olds in a deprived, urban area in England. Results: The study revealed the wide variation in what and how oral health advice is delivered to parents at home visits. Several barriers were identified and grouped into four key themes: (1) Priority of topics discussed in the home visits; (2) Finance cuts and limited resources; (3) Oral health knowledge and skills; and (4) Collaborative working with other professionals. It was evident that organizational factors in current public health policy and service provision play an important role in shaping oral health practices and opportunities for behavior change. Conclusion: Organizational practices and procedures play an important role in creating interaction patterns between health visiting teams and parents of young children. They often limit effective engagement with and positive change in oral health. For future oral health interventions to be effective, awareness of these barriers is essential alongside them being founded on evidence-based advice and underpinned by appropriate theory

The 'Switch' study protocol: a randomised-controlled trial of switching to an alternative tumour-necrosis factor (TNF)-inhibitor drug or abatacept or rituximab in patients with rheumatoid arthritis who have failed an initial TNF-inhibitor drug

Background: Rheumatoid Arthritis (RA) is one of the most common autoimmune diseases, affecting approximately 1% of the UK adult population. Patients suffer considerable pain, stiffness and swelling and can sustain various degrees of joint destruction, deformity, and significant functional decline. In addition, the economic burden due to hospitalisation and loss of employment is considerable, with over 50% of patients being work-disabled within 10 years of diagnosis. Despite several biologic disease modifying anti-rheumatic drugs (bDMARD) now available, there is a lack of data to guide biologic sequencing. In the UK, second-line biologic treatment is restricted to a single option, rituximab. The aim of the SWITCH trial is to establish whether an alternative-mechanism-TNF-inhibitor (TNFi) or abatacept are as effective as rituximab in patients with RA who have failed an initial TNFi drug. Methods/Design: SWITCH is a pragmatic, phase IV, multi-centre, parallel-group design, open-label, randomised, controlled trial (RCT) comparing alternative-mechanism-TNFi and abatacept with rituximab in patients with RA who have failed an initial TNFi drug. Participants are randomised in a 1:1:1 ratio to receive alternative mechanism TNFi, (monoclonal antibodies: infliximab, adalimumab, certolizumab or golimumab or the receptor fusion protein, etanercept), abatacept or rituximab during the interventional phase (from randomisation up to week 48). Participants are subsequently followed up to a maximum of 96 weeks, which constitutes the observational phase. The primary objective is to establish whether an alternative-mechanism-TNFi or abatacept are non-inferior to rituximab in terms of disease response at 24 weeks post randomisation. The secondary objectives include the comparison of alternative-mechanism-TNFi and abatacept to rituximab in terms of disease response, quality of life, toxicity, safety and structural and bone density outcomes over a 12-month period (48 weeks) and to evaluate the cost-effectiveness of switching patients to alternative active therapies compared to current practice. Discussion: SWITCH is a well-designed trial in this therapeutic area that aims to develop a rational treatment algorithm to potentially inform personalised treatment regimens (as opposed to switching all patients to only one available (and possibly unsuccessful) therapy), which may lead to long-term improved patient outcomes and gains in population health

Amiloride, fluoxetine or riluzole to reduce brain volume loss in secondary progressive multiple sclerosis: the MS-SMART four-arm RCT

Background: Neuroprotective drugs are needed to slow or prevent neurodegeneration and disability accrual in secondary progressive multiple sclerosis. Amiloride, fluoxetine and riluzole are repurposed drugs with potential neuroprotective effects. Objectives: To assess whether or not amiloride, fluoxetine and riluzole can reduce the rate of brain volume loss in people with secondary progressive multiple sclerosis over 96 weeks. The secondary objectives that were assessed were feasibility of a multiarm trial design approach, evaluation of anti-inflammatory effects, clinician- and patient-reported efficacy and three mechanistic substudies. Design: A multicentre, multiarm, randomised, double-blind, placebo-controlled, parallel-group Phase IIb trial with follow-up at 4, 8, 12, 24, 36, 48, 72 and 96 weeks. Patients, investigators (including magnetic resonance imaging analysts), and treating and independent assessing neurologists were blinded to the treatment allocation. The target sample size was 440 patients. Setting: Thirteen UK clinical neuroscience centres. Participants: Participants were aged 25–65 years, had secondary progressive multiple sclerosis with evidence of disease progression independent of relapses in the previous 2 years, and had an Expanded Disability Status Scale score of 4.0–6.5. Patients were ineligible if they could not have a magnetic resonance imaging scan; had a relapse or steroids in the previous 3 months; or had epilepsy, depression, bipolar disorder, glaucoma, bleeding disorders or significant organ comorbidities. Exclusion criteria were concurrent disease-modified treatments, immunosuppressants or selective serotonin reuptake inhibitors. Interventions: Participants received amiloride (5 mg), fluoxetine (20 mg), riluzole (50 mg) or placebo (randomised 1 : 1 : 1 : 1) twice daily. Main outcome measures: The primary end point was magnetic resonance imaging-derived percentage brain volume change at 96 weeks. Secondary end points were new/enlarging T2 lesions, pseudoatrophy, and clinician- and patient-reported measures (including the Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, Symbol Digit Modalities Test, low-contrast letter visual acuity, Multiple Sclerosis Impact Scale 29 items, version 2, Multiple Sclerosis Walking Scale, version 2, and questionnaires addressing pain and fatigue). The exploratory end points included measures of persistent new T1 hypointensities and grey matter volume changes. The substudies were advanced magnetic resonance imaging, optical coherence tomography and cerebrospinal fluid analyses. Results: Between December 2014 and June 2016, 445 patients were randomised (analysed) to amiloride [n = 111 (99)], fluoxetine [n = 111 (96)], riluzole [n = 111 (99)] or placebo [n = 112 (99)]. A total of 206 randomised patients consented to the advanced magnetic resonance imaging substudy, 260 consented to the optical coherence tomography substudy and 70 consented to the cerebrospinal fluid substudy. No significant difference was seen between the active drugs and placebo in percentage brain volume change at week 96 as follows (where negative values mean more atrophy than placebo): amiloride minus placebo 0.0% (Dunnett-adjusted 95% confidence interval –0.4% to 0.5%), fluoxetine minus placebo –0.1% (Dunnett-adjusted 95% confidence interval –0.5% to 0.3%); riluzole minus placebo –0.1% (Dunnett-adjusted 95% confidence interval –0.6% to 0.3%). There was good adherence to study drugs. The proportion of patients experiencing adverse events was similar in the treatment and placebo groups. There were no emergent safety issues. Limitations: There was a lower than expected uptake in the cerebrospinal fluid substudy. Conclusions: A multiarm Phase II paradigm is efficient in determining which neuroprotective agents to take through to Phase III trials. Amiloride, fluoxetine and riluzole were not effective in reducing the brain atrophy rate in people with secondary progressive multiple sclerosis. Mechanistic pathobiological insight was gained. Future work: To use the information gained from the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) to inform future trial design as new candidate agents are identified. Trial registration: Current Controlled Trials ISRCTN28440672, NCT01910259 and EudraCT 2012-005394-31. Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 3. See the NIHR Journals Library website for further project information. This trial also received funding from the UK MS Society and the US National Multiple Sclerosis Society