Blinded patient preference for morphine compared to placebo in the setting of chronic refractory breathlessness – an exploratory study

Context Patients’ preference for morphine therapy has received little attention in the setting of chronic refractory breathlessness. However, this is one important factor in considering longer term therapy. Objectives The aim of this secondary analysis is to explore blinded patient preference of morphine compared to placebo for this indication and to define any predictors of preference. Methods Data were pooled from three randomized, double-blind, crossover, placebo-controlled studies of morphine (four days each) in chronic refractory breathlessness. Blinded patient preferences were chosen at the end of each study. A multivariable regression model was used to establish patient predictors of preference. Results Sixty-five participants provided sufficient data (60 males; median age 74 years; heart failure 55%, chronic obstructive pulmonary disease 45%; median Eastern Cooperative Oncology Group performance status 2). Forty-three percent of participants preferred morphine (32% placebo and 25% no preference). Morphine preference and younger age were strongly associated: odds ratio = 0.85, 95% confidence interval 0.78, 0.93;

A patient preference study that evaluated fluticasone furoate and mometasone furoate nasal sprays for allergic rhinitis

Background: Corticosteroid nasal sprays are the mainstay of treatment for allergic rhinitis. These sprays have sensory attributes such as scent and/or odor, taste and aftertaste, and run down the throat and/or the nose, which, when unpleasant, can affect patient preference for, and compliance with, treatment. Objective: This study examined patient preference for fluticasone furoate nasal spray (FFNS) or mometasone furoate nasal spray (MFNS) based on their sensory attributes after administration in patients with allergic rhinitis. Methods: This was a multicenter, randomized, double-blind, cross-over study. Patient preferences were determined by using three questionnaires (Overall Preference, Immediate Attributes, and Delayed Attributes). Results: Overall, 56% of patients stated a preference for FFNS versus 32% for MFNS (p _ 0.001); the remaining 12% stated no preference. More patients stated a preference for FFNS versus MFNS for the attributes of “less drip down the throat” (p _ 0.001), “less run out of the nose” (p _ 0.05), “more soothing” (p _ 0.05), and “less irritating” (p _ 0.001). More patients responded in favor of FFNS versus MFNS for the immediate attributes, “run down the throat” (p _ 0.001), and “run out of the nose” (p _ 0.001), and, in the delayed attributes, “run down the throat” (p _ 0.001), “run out of the nose” (p _ 0.01), “presence of aftertaste” (p _ 0.01), and “no nasal irritation” (p _ 0.001). Conclusion: Patients with allergic rhinitis preferred FFNS versus MFNS overall and based on a number of individual attributes, including “less drip down the throat,” “less run out of the nose,” and “less irritating.” Greater preference may improve patient adherence and thereby improve symptom management of the patient’s allergic rhinitis

Should Aggregate Patient Preference Data Be Used to Make Decisions on Behalf of Unrepresented Patients?

Patient preference predictors aim to solve the moral problem of making treatment decisions on behalf of incapacitated patients. This commentary on a case of an unrepresented patient at the end of life considers 3 related problems of such predictors: the problem of restricting the scope of inputs to the models (the “scope” problem), the problem of weighing inputs against one another (the “weight” problem), and the problem of multiple reasonable solutions to the scope and weight problems (the “multiple reasonable models” problem). Each of these problems poses challenges to reliably implementing patient preference predictors in important, high-stakes health care decision making. This commentary also suggests a way forward

Intravenous versus subcutaneous drug administration. Which do patients prefer? A systematic review

BACKGROUND: Intravenous (IV) drug delivery is commonly used for its rapid administration and immediate drug effect. Most studies compare IV to subcutaneous (SC) delivery in terms of safety and efficacy, but little is known about what patients prefer. METHODS: A systematic review was conducted by searching seven electronic databases for articles published up to February 2014. Included studies were randomized controlled trials (RCTs) and/or crossover designs investigating patient preference for SC versus IV administration. The risk of bias in the RCTs was determined using the Cochrane Collaboration tool. Reviewers independently extracted data and assessed the risk of bias. Any discrepancies were resolved by consensus. RESULTS: The search identified 115 publications, but few (6/115) met the inclusion criteria. Patient populations and drugs investigated were diverse. Four of six studies demonstrated a clear patient preference for SC administration. Main factors associated with SC preference were time saving and the ability to have treatment at home. Only three studies used study-specific instruments to measure preference. CONCLUSIONS: Results suggest that patients prefer SC over IV delivery. Patient preference has clearly been neglected in clinical research, but it is important in medical decision making when choosing treatment methods as it has implications for adherence and quality of life. If the safety and efficacy of both administration routes are equivalent, then the most important factor should be patient preference as this will ensure optimal treatment adherence and ultimately improve patient experience or satisfaction. Future drug efficacy and safety studies should include contemporaneous, actual patient preference where possible, utilizing appropriate measures

Incorporating patient preferences in the management of multiple long-term conditions: is this a role for clinical practice guidelines?

Background: Clinical practice guidelines provide an evidence-based approach to managing single chronic conditions, but their applicability to multiple conditions has been actively debated. Incorporating patient-preference recommendations and involving consumers in guideline development may enhance their applicability, but further understanding is needed. Objectives: To assess guidelines that include recommendations for comorbid conditions to determine the extent to which they incorporate patient-preference recommendations; use consumer-engagement processes during development, and, if so, whether these processes produce more patient-preference recommendations; and meet standard quality criteria, particularly in relation to stakeholder involvement. Design: A review of Australian guidelines published from 2006 to 2014 that incorporated recommendations for managing comorbid conditions in primary care. Document analysis of guidelines examined the presence of patient-preference recommendations and the consumer-engagement processes used. The Appraisal of Guidelines for Research and Evaluation instrument was used to assess guideline quality. Results: Thirteen guidelines were reviewed. Twelve included at least one core patient-preference recommendation. Ten used consumer-engagement processes, including participation in development groups (seven guidelines) and reviewing drafts (ten guidelines). More extensive consumer engagement was generally linked to greater incorporation of patient-preference recommendations. Overall quality of guidelines was mixed, particularly in relation to stakeholder involvement. Conclusions: Guidelines do incorporate some patient-preference recommendations, but more explicit acknowledgement is required. Consumer-engagement processes used during guideline development have the potential to assist in identifying patient preferences, but further research is needed. Clarification of the consumer role and investment in consumer training may strengthen these processes.Journal of Comorbidity 2015;5(1):122–13

Patient-reported outcomes measures and patient preferences for minimally invasive glaucoma surgical devices.

BackgroundMany therapeutic options are available to glaucoma patients. One recent therapeutic option is minimally invasive glaucoma surgical (MIGS) devices. It is unclear how patients view different treatments and which patient-reported outcomes would be most relevant in patients with mild to moderate glaucoma. We developed a questionnaire for patients eligible for MIGS devices and a patient preference study to examine the value patients place on certain outcomes associated with glaucoma and its therapies.ObjectivesTo summarize the progress to date.MethodsQuestionnaire development: We drafted the questionnaire items based on input from one physician and four patient focus groups, and a review of the literature. We tested item clarity with six cognitive interviews. These items were further refined. Patient preference study: We identified important benefit and risk outcomes qualitatively using semi-structured, one-on-one interviews with patients who were eligible for MIGS devices. We then prioritized these outcomes quantitatively using best-worst scaling methods.ResultsQuestionnaire testing: Three concepts were deemed relevant for the questionnaire: functional limitations, symptoms, and psychosocial factors. We will evaluate the reliability and validity of the 52-item draft questionnaire in an upcoming field test. Patient preference study: We identified 13 outcomes that participants perceived as important. Outcomes with the largest relative importance weights were "adequate IOP control" and "drive a car during the day."ConclusionsPatients have the potential to steer clinical research towards outcomes that are important to them. Incorporating patients' perspectives into the MIGS device development and evaluation process may expedite innovation and availability of these devices

The comprehensive cohort model in a pilot trial in orthopaedic trauma

Background: The primary aim of this study was to provide an estimate of effect size for the functional outcome of operative versus non-operative treatment for patients with an acute rupture of the Achilles tendon using accelerated rehabilitation for both groups of patients. The secondary aim was to assess the use of a comprehensive cohort research design (i.e. a parallel patient-preference group alongside a randomised group) in improving the accuracy of this estimate within an orthopaedic trauma setting. Methods: Pragmatic randomised controlled trial and comprehensive cohort study within a level 1 trauma centre. Twenty randomised participants (10 operative and 10 non-operative) and 29 preference participants (3 operative and 26 non-operative). The ge range was 22-72 years and 37 of the 52 patients were men. All participants had an acute rupture of their Achilles tendon and no other injuries. All of the patients in the operative group had a simple end-to-end repair of the tendon with no augmentation. Both groups then followed the same eight-week immediate weight-bearing rehabilitation programme using an off-the-shelf orthotic. The disability rating index (DRI; primary outcome), EQ-5D, Achilles Total Rupture Score and complications were assessed ed at two weeks, six weeks, three months, six months and nine months after initial injury. Results: At nine months, there was no significant difference in DRI between patients randomised to operative or non-operative management. There was no difference in DRI between the randomised group and the parallel patient preference group. The use of a comprehensive cohort of patients did not provide useful additional information as to the treatment effect size because the majority of patients chose non-operative management. Conclusions: Recruitment to clinical trials that compare operative and non-operative interventions is notoriously difficult; especially within the trauma setting. Including a parallel patient preference group to create a comprehensive cohort of patients has been suggested as a way of increasing the power of such trials. In our study, the comprehensive cohort model doubled the number of patients involved in the study. However, a strong preference for non-operative treatment meant that the increased number of patients did not significantly increase the ability of the trial to detect a difference between the two interventions

Change in background context disrupts performance on visual paired comparison following hippocampal damage

The medial temporal lobe plays a critical role in recognition memory but, within the medial temporal lobe, the precise neural structures underlying recognition memory remain equivocal. in this study, visual paired comparison (VPC) was used to investigate recognition memory in a human patient (YR), who had a discrete lesion of the hippocampus, and a group of monkeys with neonatal hippocampal lesions, which included the dentate gyrus, and a portion of parahippocampal region. Participants were required to view a picture of an object on a coloured background. Immediately afterwards, this familiar object was shown again, this time paired with a novel object. All participants displayed a novelty preference, provided the background on which the objects were shown was the same as the one used during the learning phase. When the background of the familiar object was changed between initial familiarization and test, only the control subjects showed a novelty preference; the hippocampal-lesioned monkeys and patient YR showed null preference. The results are interpreted within Eichenbaum and Bunsey's [Eichenbaum, H., & Bunsey, M. (1995). On the binding of associations in memory: Clues from studies on the role of the hippocampal region in paired-associate learning. Current Directions in Psychological Science, 4, 19-23] proposal that the hippocampus facilitates the formation of a flexible representation of the elements that make up a stimulus whereas the parahippocampal region is involved in the formation of a fused representation. (C) 2009 Elsevier Ltd. All rights reserved

The effect of patients’ preference on outcome in the EVerT cryotherapy versus salicylic acid for the treatment of plantar warts (verruca) trial

Background Randomised controlled trials are widely accepted as the gold standard method to evaluate medical interventions, but they are still open to bias. One such bias is the effect of patient’s preference on outcome measures. The aims of this study were to examine whether patients’ treatment preference affected clearance of plantar warts and explore whether there were any associations between patients’ treatment preference and baseline variables in the EverT trial. Methods Two hundred and forty patients were recruited from University podiatry schools, NHS podiatry clinics and primary care. Patients were aged 12 years and over and had at least one plantar wart which was suitable for treatment with salicylic acid and cryotherapy. Patients were asked their treatment preference prior to randomisation. The Kruskal-Wallis test was performed to test the association between preference group and continuous baseline variables. The Fisher’s exact test was performed to test the association between preference group and categorical baseline variables. A logistic regression analysis was undertaken with verruca clearance (yes or no) as the dependent variable and treatment, age, type of verruca, previous treatment, treatment preference as independent variables. Two analyses were undertaken, one using the health professional reported outcome and one using the patient’s self reported outcomes. Data on whether the patient found it necessary to stop the treatment to which they had been allocated and whether they started another treatment were summarised by treatment group. Results Pre-randomisation preferences were: 10% for salicylic acid; 42% for cryotherapy and 48% no treatment preference. There was no evidence of an association between treatment preference group and either patient (p=0.95) or healthcare professional (p=0.46) reported verruca clearance rates. There was no evidence of an association between preference group and any of the baseline variables except gender, with more females expressing a preference for salicylic acid (p=0.004). There was no evidence that the number of times salicylic acid was applied was different between the preference groups at one week (p=0.89) or at three weeks (p=0.24). Similarly, for the number of clinic visits for cryotherapy (p=0.71) Conclusions This secondary analysis showed no evidence to suggest that patients’ baseline preferences affected verruca clearance rates or adherence with the treatment

Evaluation of behavior in transgenic mouse models to understand human congenital pain conditions

BACKGROUND: Containing a brain for signal processing and decision making, and a peripheral component for sensation and response, the nervous system provides higher organisms a powerful method of interacting with their environment. The specific neurons involved in pain sensation are known as nociceptors and are the source of normal nociceptive pain signaling to prompt appropriate responses. Though acute hypersensitization can be advantageous by encouraging an organism to allow an injured area to heal, chronic pain conditions can be pathological and can markedly reduce quality of life. While a variety of genes have been associated with congenital pain conditions, two rare cases examined in this study have not had their mutated genes identified. Potassium voltage-gated channel subfamily H member 8, or KCNH8, is involved in regulating action potential production and propagation, and has not been linked with pain processing of any kind to date. Here, a male patient evaluated at Boston Children’s Hospital contains a novel single-base KCNH8 mutation and possesses an extremely low sensitivity to cold temperatures and mechanical pain, but a higher sensitivity to warmer temperatures. A separate protein, intersectin-2, or ITSN2, normally functions in clathrin-mediated endocytosis and exocytosis. A second patient at Boston Children’s Hospital expresses a previously-unseen point mutation in ITSN2 and experiences erythromelalgia, characterized by episodes of intense pain and red, swollen limbs during ambient warm temperatures. Through the use of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome editing, this study will produce these specific genetic mutations in mouse lines to explore their effects on mammalian behavior. OBJECTIVES: This project employs two transgenic mouse models to study the behavioral phenotypes associated with rare potentially damaging mutations in KCNH8 and ITSN2 exhibited in the human patients. Through these experiments, a greater understanding of neural pain signaling and sensitivity changes can occur. METHODS: The differences in temperature preference of KCNH8 and ITSN2 mutant mice compared to wild type mice lacking these mutations was studied using thermal plates under cold and warm conditions. Direct application of acetone and von Frey filaments to mouse paws was used to study cold and mechanical sensitivity. Further testing of stamina, anxiety, coordination, and strength were also evaluated. RESULTS: A marked decrease in sensitivity to von Frey stimulation (p<0.01) and acetone administration (p<0.05) was observed in KCNH8 mutant mice. Thermal preference testing demonstrated a decreased preference for warmer temperatures as compared to wild type mice. In addition, anxiety levels were also observed to be slightly higher in these mutant KCNH8 mice (p<0.05). The mutant ITSN2 mice spent less time at cooler temperatures, though surprisingly they significantly preferred warmer conditions as compared to their wild type littermates. A full and partial reversal of these temperature preferences was demonstrated in cold and heat thermal conditions respectively after intraperitoneal gabapentin injection, which normalized the mice toward wild type behavior. CONCLUSIONS: Data from the KCNH8 mutant mouse model indicates an aversion to warmer temperatures and a decreased ability to detect cold or mechanical pressure, much like the human patient. The mutant ITSN2 mice were less likely to spend time at cooler temperatures, indicating heightened sensory sensitivity, but their preference for warmer temperatures suggests a possible desensitization of the affected nociceptors. These results often mirror the patient’s phenotype, but the preference for ambient warmer environments appears opposite to the patient. As the ITSN2 mice feel discomfort at cooler temperatures, a proposed desensitization at warmer temperatures would result in a more comfortable environment and could explain the observed preference. The trends toward normal neural firing rates achieved through gabapentin injection suggest that the aberrant responses in mutant ITSN2 mice is due to altered sensitization, but additional examination under these conditions with a larger group of mice is necessary to further unravel these signaling pathways. However, these extremely encouraging data introduce two new molecular targets for acute pain control