A generative co-design framework for healthcare innovation: development and application of an end-user engagement framework.

Background Continual improvements to health systems, products, and services are necessary for improvements in health. However, many of these improvements are not incorporated into everyday practice. When designing new health systems, products, and services, involving members of the healthcare community and the public with personal healthcare experience can help to make sure that improvements will be useful and relevant to others like them. Methods Together with healthcare workers and family members with healthcare experience, we developed and applied a step-by-step guide to involving those with personal experience in the design of health system improvements. Results Our guide has three phases- 'Pre-Design', 'Co-Design', and 'Post-Design'. This paper describes each of these phases and illustrates how we applied them to our own project, which is to use virtual healthcare methods to improve care for children with chronic healthcare conditions and their families. In our own work, we found that healthcare workers and family members with personal healthcare experiences were able to use their knowledge and creativity to help us imagine how to improve care for children with chronic healthcare conditions and their families. We have created action items from these family member- and healthcare worker-identified needs, which we will use to shape our virtual healthcare system. Conclusions This paper may be useful for those seeking to involve members of the healthcare community and the public in the creation of better healthcare systems, products, and services. Background Challenges with the adoption, scale, and spread of health innovations represent significant gaps in the evidence-to-practice cycle. In the health innovation design process, a lack of attention paid to the needs of end-users, and subsequent tailoring of innovations to meet these needs, is a possible reason for this deficit. In the creative field of health innovation, which includes the design of healthcare products, systems (governance and organization mechanisms), and services (delivery mechanisms), a framework for both soliciting the needs of end-users and translating these needs into the design of health innovations is needed. Methods To address this gap, our team developed and applied a seven-step methodological framework, called A Generative Co-Design Framework for Healthcare Innovation. This framework was developed by an interdisciplinary team that included patient partners. Results This manuscript contributes a framework and applied exemplar for those seeking to engage end-users in the creative process of healthcare innovation. Through the stages of 'Pre-Design', 'Co-Design', and 'Post-Design', we were able to harness the creative insights of end-users, drawing on their experiences to shape a future state of care. Using an expository example of our own work, the DigiComp Kids project, we illustrate the application of each stage of the Framework. Conclusions A Generative Co-Design Framework for Healthcare Innovation provides healthcare innovators, applied health science researchers, clinicians, and quality improvement specialists with a guide to eliciting and incorporating the viewpoints of end-users while distilling practical considerations for healthcare innovation and design.

The efficacy of HI-6 DMS in a sustained infusion against percutaneous VX poisoning in the guinea-pig.

Post-exposure nerve agent treatment usually includes administration of an oxime, which acts to restore function of the enzyme acetylcholinesterase (AChE). For immediate treatment of military personnel, this is usually administered with an autoinjector device, or devices containing the oxime such as pralidoxime, atropine and diazepam. In addition to the autoinjector, it is likely that personnel exposed to nerve agents, particularly by the percutaneous route, will require further treatment at medical facilities. As such, there is a need to understand the relationship between dose rate, plasma concentration, reactivation of AChE activity and efficacy, to provide supporting evidence for oxime infusions in nerve agent poisoning. Here, it has been demonstrated that intravenous infusion of HI-6, in combination with atropine, is efficacious against a percutaneous VX challenge in the conscious male Dunkin-Hartley guinea-pig. Inclusion of HI-6, in addition to atropine in the treatment, improved survival when compared to atropine alone. Additionally, erythrocyte AChE activity following poisoning was found to be dose dependent, with an increased dose rate of HI-6 (0.48mg/kg/min) resulting in increased AChE activity. As far as we are aware, this is the first study to correlate the pharmacokinetic profile of HI-6 with both its pharmacodynamic action of reactivating nerve agent inhibited AChE and with its efficacy against a persistent nerve agent exposure challenge in the same conscious animal.

Efficacy of the antinicotinic compound MB327 against soman poisoning - Importance of experimental end point.

Medical countermeasures for acute poisoning by organophosphorus nerve agents are generally assessed over 24h following poisoning and a single administration of treatment. At 24h, the antinicotinic bispyridinium compound MB327 (1,10-(propane-1,3-diyl)bis(4-tert-butylpyridinium)) dimethanesulfonate is as effective as the oxime HI-6 against poisoning by soman, when used as part of a treatment containing atropine and avizafone. In this study, we hypothesised that an earlier endpoint, at 6h, would be more appropriate for the pharmacokinetics and mechanism of action of MB327 and would therefore result in improved protection. MB327 diiodide (33.8mg/kg) or the oxime HI-6 DMS (30mg/kg), in combination with atropine and avizafone (each at 3mg/kg) was administered intramuscularly to guinea pigs 1min following subcutaneous soman and the LD50 of the nerve agent was determined at 6h after poisoning for each treatment. The treatment containing HI-6 gave a similar level of protection at 6h as previously determined at 24h (protection ratios 3.9 and 2.9, respectively). In contrast, the protection achieved by treatment containing MB327 showed a striking increase at 6h (protection ratio >15.4) compared to the 24h end point (protection ratio 2.8). The treatment gave full protection for at least 5h against doses of soman up to 525µg/kg; in contrast, mortality began in animals treated with HI-6 after 1h. This study demonstrates the importance of using an appropriate end point and has shown that treatment including MB327 was far superior to oxime-based treatment for poisoning by soman, when assessed over a pharmacologically-relevant duration. The improved outcome was seen following a single dose of treatment: it is possible that additional doses to maintain therapeutic plasma concentrations would further increase survival time. Antinicotinic compounds therefore offer a promising addition to treatment, particularly for rapidly aging or oxime-insensitive nerve agents.

Bioscavenger is effective as a delayed therapeutic intervention following percutaneous VX poisoning in the guinea-pig.

The prolonged systemic exposure that follows skin contamination with low volatility nerve agents, such as VX, requires treatment to be given over a long time due to the relatively short half-lives of the therapeutic compounds used. Bioscavengers, such as butyrylcholinesterase (BChE), have been shown to provide effective post-exposure protection against percutaneous nerve agent when given immediately on signs of poisoning and to reduce reliance on additional treatments. In order to assess the benefits of administration of bioscavenger at later times, its effectiveness was assessed when administration was delayed for 2h after the appearance of signs of poisoning in guinea-pigs challenged with VX (4×LD50). VX-challenged animals received atropine, HI-6 and avizafone on signs of poisoning and 2h later the same combination with or without bioscavenger. Five out of 6 animals which received BChE 2h after the appearance of signs of poisoning survived to the end of the study at 48h, compared with 6 out of 6 which received BChE immediately on signs. All the animals (n=6+6) that received only MedCM, without the addition of BChE, died within 10h of poisoning. The toxicokinetics of a sub-lethal challenge of percutaneous VX were determined in untreated animals. Blood VX concentration peaked at approximately 4h after percutaneous dosing with 0.4×LD50; VX was still detectable at 36h and had declined to levels below the lower limit of quantification (10pg/mL) by 48h in 7 of 8 animals, with the remaining animal having a concentration of 12pg/mL. These studies confirm the persistent systemic exposure to nerve agent following percutaneous poisoning and demonstrate that bioscavenger can be an effective component of treatment even if its administration is delayed.

The relationship of early-onset regular smoking to alcohol use, depression, illicit drug use, and other risky behaviors during early adolescence: results from the youth supplement to the third national health and nutrition examination survey.

PURPOSE: Recently we found that the early onset of regular tobacco use is as predictive of lifetime drug use and depressive disorders as it is of alcohol use disorders [Alcohol.: Clin. Exp. Res. 23 (1999) 513.]. This finding, which paralleled findings regarding early onset of alcohol use [J. Subst. Abuse 10 (1998) 59.], suggested that early regular use of any drug might simply be an indicator of risk for a constellation of problem behaviors. The purpose of the present study is to test this hypothesis as well as to study the strength and patterns of associations among these problem behaviors already present among youth. The results will permit description of more precise profiles to identify groups of children at risk. METHODS: Using data for respondents aged 12-16 from the Third National Health and Nutrition Examination Survey (NHANES III), descriptive statistics were calculated and logistic regression models were estimated. RESULTS: Descriptive analyses indicated that in comparison with those who never smoked, or who simply experimented, early-onset regular smokers, both those who began at age 13 or younger and those who did so between 14 and 16, were those most likely to use alcohol and other drugs as well as have school problems and early sexual experiences culminating in pregnancy. Multivariate logistic regression analyses were conducted to assess the associations among these high-risk behaviors. IMPLICATIONS: These results support the hypothesis that early onset of smoking is but an indicator of a syndrome of problem behaviors already in place during childhood. They also suggest that the significance of an age onset variable may differ depending on the age of the sample used. As follow-up data are collected, we expect to learn much about the natural course of the distinct risk groups identified in the analyses by studying longitudinally this nationally representative group of early adolescents.

Clinical efficacy and safety comparison of adapalene gel and tretinoin gel in the treatment of acne vulgaris: Europe and U.S. multicenter trials.

BACKGROUND: Adapalene is a new chemical entity that exhibits tretinoin-like activities in the terminal differentiation process. OBJECTIVE: We evaluated a dose range effect of two concentrations of adapalene gel as acne treatment and compared adapalene 0.1% gel with tretinoin 0.025% gel in the treatment of acne patients in two large multicenter studies. METHODS: Multicenter, investigator-masked, parallel group studies including 89 acne patients in the dose range study and 591 patients in the concurrent controlled studies were conducted. RESULTS: Adapalene gel 0.1% was significantly more effective in treating acne lesions than 0.03% adapalene gel. Adapalene gel 0.1% was significantly more effective than 0.025% or tretinoin gel in one study and of the same effectiveness in the other study. Adapalene gel was always better tolerated than tretinoin gel. CONCLUSION: Adapalene 0.1% gel is a safe and effective treatment of acne vulgaris.

A comparison of the efficacy and safety of adapalene gel 0.1% and tretinoin gel 0.025% in the treatment of acne vulgaris: a multicenter trial.

BACKGROUND: Adapalene is a new synthetic retinoid analogue developed for the topical treatment of acne vulgaris. OBJECTIVE: The study was designed to compare the efficacy and safety and adapalene gel 0.1% with tretinoin gel 0.025% in the treatment of grade II to II facial acne vulgaris. METHODS: Three hundred twenty-three patients were enrolled in this investigator-masked, randomized, parallel group, multicenter trial. Patients applied the test materials to the entire facial area daily, for a period of 12 weeks. Efficacy and cutaneous tolerance were assessed at baseline and weeks 2,4,8, and 12. Efficacy was determined by investigator counts of noninflammatory open and closed comedones, and inflammatory papules and pustules, as well as global improvement. Cutaneous tolerance was evaluated by erythema, scaling, and dryness, along with burning and pruritus. RESULTS: Staring at weeks 2 and 4, adapalene gel produced numerically greater lesion reductions than did tretinoin gel for all lesion types. At week 12, the mean percent reduction in the different lesion counts was as follow: 49% versus 37% for total lesions (p<0.01); 46% versus 33% for noninflammatory lesions (p=0.02); 48% versus 38% for inflammatory lesions (p=0.06) in adapalene and tretinoin gel treatment groups, respectively. Cutaneous side effects were limited to a mild "retinoid dermatitis" occurring in both treatment groups; however, patients treated with adapalene gel tolerated this therapy significantly better than those treated with tretinoin gel. Laboratory test evaluations (hematology, blood chemistries, urinalysis) were performed in 54 patients before and after 3 months of treatment. No clinically significant changes were observed. CONCLUSION: Adapalene gel 0.1% applied once daily was significantly more effective in reducing acne lesions and was better tolerated than tretinoin gel 0.025% in the treatment of acne vulgaris.

Comparative study of calcipotriene (MC 903) ointment and fluocinonide ointment in the treatment of psoriasis.

BACKGROUND: The topical vitamin D analogue calcipotriene has been reported to be an effective treatment for patients with psoriasis. Comparative studies with topical steroids are informative in judging this new therapy. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of calcipotriene ointment 0.005% versus fluocinonide ointment 0.05% in the treatment of plaque psoriasis. METHODS: This study was a randomized, double-blind, parallel-group, active-controlled trial in adults who had at least mild overall disease severity and plaque elevation of at least moderate severity. Treatments were applied twice daily for 6 weeks, and subjects were evaluated at weeks 0, 2, 4, and 6. Subjects were graded on a 9-point scale (0 to 8) for scaling, erythema, plaque elevation, and for overall disease severity. A physician's global assessment of improvement/worsening was performed at every visit. RESULTS: A total of 114 subjects were enrolled at six study sites. Ninety-nine subjects completed the trial. Mean scores for signs of scaling and plaque elevation in calcipotriene-treated subjects were significantly lower by week 2 than in the fluocinonide-treated subjects. These scores continued to be significantly lower than fluocinonide through week 6 (p < 0.05). Mean scores for erythema in calcipotriene-treated subjects were significantly lower than those in fluocinonide-treated subjects at weeks 4 and 6 (p < 0.05). Both the physician's global assessment and overall disease severity showed statistically significant treatment differences in favor of calcipotriene at week 4 (p < 0.05). This superior efficacy continued through week 6. Treatment-related adverse events were observed in 12 calcipotriene-treated subjects and 5 fluocinonide-treated subjects; all were considered minor. CONCLUSION: Calcipotriene was superior to fluocinonide in the treatment of plaque psoriasis.

Comparative trial of oral clotrimazole and nystatin for oropharyngeal candidiasis prophylaxis in orthotopic liver transplant patients.

A prospective randomized study was conducted to assess the effectiveness of clotrimazole troches and nystatin suspension to prevent oral candidiasis in immunosuppressed orthotopic liver transplant patients. Thirty-four patients received either clotrimazole troches, 10 mg, five times daily, or nystatin suspension, 500,000 units, four times daily. Prophylaxis was initiated after extubation after transplantation and continued throughout the hospitalization. One of 17 patients in each treatment group developed clinical and microscopic evidence of an oropharyngeal Candida infection. This gave an intragroup and an overall infection rate of 5.9%. It appears that either nystatin or clotrimazole may be used for candidiasis prophylaxis in orthotopic liver transplant patients.

Evaluation of halobetasol propionate ointment in the treatment of plaque psoriasis: report on two double-blind, vehicle-controlled studies.

The results of two studies are presented that reveal the efficacy and safety of 0.05% halobetasol ointment in the treatment of patients with plaque psoriasis of at least moderate severity. Both multicenter studies were randomized, double-blind, and vehicle controlled, and study medications were applied twice daily for 2 weeks. One study was a paired-comparison (PC); the other study was of parallel-group (PG) design. Both studies called for evaluations at entry (week 0) and after 1 and 2 weeks of treatment. The PC study enrolled 100 patients; the PG study enrolled 110 patients; 204 patients provided efficacy data over both studies. In the PC study, plaque elevation, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistical (p less than or equal to 0.0003) and clinical significance (all greater than 1-unit difference on the rating scale) favoring 0.05% halobetasol ointment over vehicle. Pruritus (initially mild) and total score also showed statistically significant treatment differences favoring halobetasol at the final evaluation. Patient global responses for "effectiveness" and "overall rating" favored 0.05% halobetasol ointment over vehicle. In the PG study, induration, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistically and clinically significant differences favoring 0.05% halobetasol ointment over vehicle. Physician's global evaluation favored 0.05% halobetasol ointment over vehicle after 2 weeks of use. No patients were released from either study because of adverse events. No systemic adverse events or findings of skin atrophy were reported in these studies. Reports of "stings" or "burns" were equally divided between halobetasol and its vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

A review of two controlled multicenter trials comparing 0.05% halobetasol propionate ointment to its vehicle in the treatment of chronic eczematous dermatoses.

The efficacy and safety of 0.05% halobetasol propionate ointment were evaluated in patients with chronic atopic or other eczematous dermatoses in two vehicle-controlled, double-blind studies: a paired-comparison study in 124 patients (study A) and a parallel-group study in 100 patients (study B). In study A, patients applied both treatments twice daily for 2 weeks and were evaluated by investigators on days 0, 7, and 14 with 0 to 3 severity scales and by self-assessment with two 5-step end-of-treatment rating scales. In study B, patients applied treatments twice daily for 2 weeks, and investigators made evaluations on days 0, 3, 7, and 14 with 0 to 6 scales and also made a 5-step end-of-treatment physician's global assessment. In study A, both severity scores and patient ratings favored halobetasol propionate significantly on days 7 (p less than or equal to 0.0013) and 14 (p less than 0.0001); in study B, severity scores on days 3 (p less than or equal to 0.045, pruritus, erythema, and overall lesion severity), 7, and 14 (p less than 0.001, all comparisons) also favored halobetasol propionate significantly, and global assessments showed complete resolution or marked improvement for 83% of patients using halobetasol propionate versus 28% of those using vehicle (p less than 0.0001). No instances of systemic effects or skin atrophy were reported in either study. We conclude that 0.05% halobetasol propionate ointment is highly effective and well tolerated in the treatment of the conditions studied, with the rapid action and high degree of clearing associated with superpotent corticosteroid formulations.

Erythromycin 2 percent gel in the treatment of acne vulgaris.

A gel formulation of erythromycin 2 percent was compared with its vehicle in a double-blind multicenter study involving patients with mild to moderate acne vulgaris. In an analysis of 187 patients treated twice daily for 8 weeks, erythromycin 2 percent gel proved to be significantly more effective than vehicle in reducing the numbers of both inflammatory and noninflammatory lesions. After 8 weeks, 60 percent of erythromycin-treated patients had good or excellent responses compared with 36 percent of those using vehicle (p = 0.001); the lesions in two patients using erythromycin were completely cleared. The majority of patients had a favorable impression of the cosmetic characteristics of the gel formulation.

Measurement of erythema and tanning responses in human skin using a tri-stimulus colorimeter.

A 'Minolta Tri-Stimulus Colorimeter II' was evaluated for obtaining objective measurements of early changes in erythema and tanning. The meter showed a subtle, continuous transition between the primary erythematous response and the delayed tanning of skin which was below the visual threshold for detection. Thereafter, the a* (redness) value of the meter showed a significant linear correlation with the dermatologist's perception of erythema while the b* (yellow) value showed a significant correlation with the perception of tanning. This capability of the tri-stimulus colorimeter to simultaneously evaluate the hue and saturation of skin color affords an improved opportunity to quantitate the transition from erythema to tanning without subjective bias.

Efficacy of Alpha Keri after showering for treatment of xerosis.

The use of Alpha Keri bath oil in a postshower therapeutic regimen was effective in reducing the severity of moderate to severe xerosis.

Chemotherapy administration precheck verification.

Inappropriate administration of antineoplastics can result in severe adverse reactions or potential therapeutic failure. This article reports the formation and evaluation of a program designed to assure appropriate antineoplastic administration and the creation of a continuous teaching document. The primary goal was to achieve and document safe and appropriate administration of antineoplastic medications. The program was organized, initiated, and evaluated by the clinical pharmacist and assistant director of nursing. Use of available resources allowed program development without additional cost to hospital departments. A teaching series and provision of reference data were made available, and completion of a chemotherapy verification form was required before the nurse administered the antineoplastic. Over 1,500 forms have been completed in a little more than 2 years. Nurses report a high level of compliance with form completion. One chemotherapy error report has been filed in the last 28 months, compared with three error reports in the 8 weeks prior to initiation of the program. Use of the chemotherapy verification form has achieved a high standard of correct administration without errors as defined by our institution and fostered continually conscientious and acceptable antineoplastic administration.

Taste potentiation of auditory aversions in rats (Rattus norvegicus): a case for spatial contiguity.

An aversion for an auditory stimulus was established in laboratory rats when a tone was spatially and temporally contiguous with a novel taste in a food conditioned stimulus compound followed by toxicosis. The procedure involved varying the location of the tone relative to a novel tasting food. During toxicosis conditioning, one group ate sweet food with a speaker located in the food, two groups ate sweet food with the speaker displaced (near or far) from the food, and a fourth group was presented with a tone without food available. It was found that the potentiation of auditory aversions required both the presence of a novel taste and spatial contiguity between the taste and the tone.

Stability of methacholine chloride in bronchial provocation test solutions.

The stability of methacholine chloride (5 mg/ml) in 0.9% sodium chloride solution was measured. A reliable colorimetric assay (530 nm) based on the formation of a hydroxamic acid-iron complex was used. At appropriate time intervals, samples were removed from solutions stored at 4, 20, 37, 60, or 80 degrees C and assayed. The degradation of methacholine chloride followed apparent first-order kinetics of methacholine chloride followed apparent first-order kinetics at all temperatures, with observed half-lives ranging from 29.3 days at 80 degrees C to 693 days 4 degrees C. Methacholine chloride in 0.9% sodium chloride solution does not degrade as rapidly as previously suggested. According to an Arrhenius plot, storage of such solutions at 30 or 4 degrees C would result in not more than 10% degradation over a period of approximately two or five months, respectively. Thus, it should be possible to prepare stock solutions of this deliquescent drug.