The Composite Hypothesis Contrast Procedure: A Novel Sequential Multiple-Comparison Approach

The sequential composite hypothesis contrast multiple-comparison procedure is introduced for comparing two treatment conditions with one or two control conditions on one or two outcome measures. The procedure deserves consideration insofar as its power advantage over other commonly applied multiple-comparison methods can be sizable

Development of International Learning Outcomes for Shelter Medicine in Veterinary Education: A Delphi Approach

Shelter medicine is a veterinary discipline of growing importance. Formally accepted as a clinical specialty in the USA in 2014, the practice of shelter medicine worldwide is expanding. As a topic in veterinary pre-registration (undergraduate) education, it is frequently used as an opportunity to teach primary care skills, but increasingly recognized as a subject worthy of teaching in its own right. The aim of this study was to use a Delphi consensus methodology to identify learning outcomes relevant to shelter medicine education. Shelter medicine educators worldwide in a variety of settings, including universities, non-governmental organisations and shelters were invited to participate. Participants were initially invited to share shelter medicine teaching materials. These were synthesised and formatted into Learning Outcomes (LOs) based on Bloom’s taxonomy and organised into five subject-specific domains. Participants were then asked to develop and evaluate the identified LOs in two rounds of online surveys. Consensus was determined at >80% of panellists selecting “agree” or “strongly agree” in response to the statement “please indicate whether you would advise that it should be included in a shelter medicine education program” for each LO. In the second survey, where re-wording of accepted LOs was suggested, preference was determined at >50% agreement. Through this method, 102 agreed LOs have been identified and refined. These LOs, as well as those which did not reach consensus, are presented here. These are intended for use by shelter medicine educators worldwide, to enable and encourage the further development of this important veterinary discipline

Opioids Switching with Transdermal Systems in Chronic Cancer Pain

<p>Abstract</p> <p>Background</p> <p>Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy</p> <p>Objective</p> <p>To assess the efficacy and tolerability of an alternative transdermally applied (TDS) opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment.</p> <p>Methods</p> <p>A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks</p> <p>Results</p> <p>Pain relief as assessed by VAS, PPI, and PRI significantly improved (p < 0.0001) in all patients at all 3 follow up visits. After 3 weeks of treatment, the reduction in the mean VAS, PPI, and PRI scores in the fentanyl and buprenorphine groups was 68, 77, 74, and 69, 79, and 62%, respectively. Over the same time period the use of oral morphine as rescue medication was reduced from 27.5 ± 20.5 (mean ± SD) to 3.75 ± 8.06, and 33.8 ± 18.9 to 3.75 ± 10.9 mg/day in the fentanyl and buprenorphine groups, respectively. There was no significant difference in either pain relief or rescue medication use between the two patient groups The number of patient with adverse events fell during the study. After the third week of the treatment the number of patients with constipation was reduced from 11 to 5, and 10 to 4 patients in the fentanyl and buprenorphine groups, respectively. There was a similar reduction in the incidence of nausea and vomiting. No sedation was seen in any patient after one week of treatment.</p> <p>Conclusion</p> <p>Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.</p

Razvoj i vrednovanje dvoslojnih tableta propranolol hidroklorida

The objective of the present research was to develop a bilayer tablet of propranolol hydrochloride using superdisintegrant sodium starch glycolate for the fast release layer and water immiscible polymers such as ethyl cellulose, Eudragit RLPO and Eudragit RSPO for the sustaining layer. In vitro dissolution studies were carried out in a USP 24 apparatus I. The formulations gave an initial burst effect to provide the loading dose of the drug followed by sustained release for 12 hrs from the sustaining layer of matrix embedded tablets. In vitro dissolution kinetics followed the Higuchi model via a non-Fickian diffusion controlled release mechanism after the initial burst release. FT-IR studies revealed that there was no interaction between the drug and polymers used in the study. Statistical analysis (ANOVA) showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p 0.005) in the amount of drug released after 12 h from optimized formulations was observed.U radu je opisan razvoj dvoslojnih tableta propranolol hidroklorida, koristeći superdezintegrator škrob glikolat natrij u sloju za brzo oslobađanje i polimere koji se ne miješaju s vodom (etil celuloza, Eudragit RLPO i Eudragit RSPO) u sloju za usporeno oslobađanje. In vitro oslobađanje praćeno je u USP aparatu I te je uočeno početno naglo oslobađanje ljekovite tvari iza kojeg slijedi polagano oslobađanje tijekom 12 sati. In vitro kinetika oslobađanja prati Higouchijev model, dok mehanizam kontroliranog oslobađanja ne slijedi Fickov zakon poslije početnog naglog oslobađanja. FT-IR studije ukazuju da nema interakcije između ljekovite tvari i polimera upotrebljenih u oblikovanju. Statistička analiza (ANOVA) nije pokazala značajne razlike u kumulativnoj količini oslobođenog lijeka iz optimiranih formulacija poslije 15 minuta i polije 12 h

Cutpoints for mild, moderate and severe pain in patients with osteoarthritis of the hip or knee ready for joint replacement surgery

<p>Abstract</p> <p>Background</p> <p>Cutpoints (CPs) for mild, moderate and severe pain are established and used primarily in cancer pain. In this study, we wanted to determine the optimal CPs for mild, moderate, and severe pain in joint replacement surgery candidates with osteoarthritis (OA) of the hip or knee, and to validate the different CPs.</p> <p>Methods</p> <p>Patients (n = 353) completed the Brief Pain Inventory (BPI), the WOMAC Arthritis Index, and the SF-36 health status measure. Optimal CPs for categorizing average pain with three severity levels were derived using multivariate analysis of variance, using different CP sets for average pain as the independent variable and seven interference items from the BPI as the dependent variable. To validate the CPs, we assessed if patients in the three pain severity groups differed in pain as assessed with WOMAC and SF-36, and if BPI average pain with the optimal CPs resulted in higher correlation with pain dimensions of the WOMAC and SF-36 than other CPs.</p> <p>Results</p> <p>The optimal CPs on the 0–10 point BPI scale were CP (4,6) among hip patients and CP (4,7) among knee patients. The resulting pain severity groups differed in pain, as assessed with other scales than those used to derive the CPs. The optimal CPs had the highest association of average pain with WOMAC pain scores.</p> <p>Conclusion</p> <p>CPs for pain severity differed somewhat for patients with OA of the hip and knee. The association of BPI average pain scores categorized according to the optimal CPs with WOMAC pain scores supports the validity of the derived optimal CPs.</p

A study of young peoples' attitudes to opportunistic Chlamydia testing in UK general practice

<p>Abstract</p> <p>Objective</p> <p>The objective of this study was to assess young people's perceptions of being offered a chlamydia screening test in United Kingdom (UK) general practice.</p> <p>Methods</p> <p>This is qualitative study that uses focus groups and individual interviews with young adults (age 16 – 18) to assess their views.</p> <p>Results</p> <p>These young adults were a difficult group to gain access to. Two focus groups, one in a school, the other in a general practice (family practice), and 2 individual interviews were undertaken (total sample 18). Respondents were unfamiliar with Chlamydia, but broadly aware of sexually transmitted infections. General practice (family practice) was perceived as an acceptable place to deliver opportunistic screening, but participants felt that tests should not be initiated by GP receptionists. Novel delivery routes such as schools and "Pub"/Bar dispensing machines were discussed. Issues around stigma and confidentiality were also raised.</p> <p>Conclusion</p> <p>Opportunistic Chlamydia screening in UK general practice (family practic seems acceptable to young adults. While this is a difficult group to gain access to for research, attempts need to made to ensure acceptability to users of this programme.</p

Interference with work in fibromyalgia - effect of treatment with pregabalin and relation to pain response

BACKGROUND: Clinical trials in chronic pain often collect information about interference with work as answers to component questions of commonly used questionnaires but these data are not normally analysed separately. METHODS: We performed a meta-analysis of individual patient data from four large trials of pregabalin for fibromyalgia lasting 8-14 weeks. We analysed data on interference with work, inferred from answers to component questions of Fibromyalgia Impact Questionnaire (FIQ), Short Form 36 Health Survey, Sheehan Disability Scale, and Multidimensional Assessment of Fatigue, including "How many days in the past week did you miss work, including housework, because of fibromyalgia?" from FIQ. Analyses were performed according to randomised treatment group (pregabalin 150-600 mg daily or placebo), pain improvement (0-10 numerical pain rating scale scores at trial beginning vs. end), and end of trial pain state (100 mm visual analogue pain scale [VAS]). RESULTS: Comparing treatment group average outcomes revealed modest improvement over the duration of the trials, more so with active treatment than with placebo. For the 'work missed' question from FIQ the change for patients on placebo was from 2.2 (standard deviation [SD] 2.3) days of work lost per week at trial beginning to 1.9 (SD 2.1) days lost at trial end (p &lt; 0.01). For patients on 600 mg pregabalin the change was from 2.1 (SD 2.2) days to 1.6 (SD 2.0) days (p &lt; 0.001). However, the change in days of work lost was substantial in patients with a good pain response: from 2.0 (SD 2.2) days to 0.97 (SD 1.6) days (p &lt; 0.0001) for those experiencing &gt;/= 50% pain improvement and from 1.9 (SD 2.2) days to 0.73 (SD 1.4) days (p &lt; 0.0001) for those achieving a low level of pain at trial end (&lt;30 mm on the VAS). Patients achieving both &gt;/= 50% pain improvement and a pain score &lt;30 mm on the VAS had the largest improvement, from 2.0 (SD 2.2) days to 0.60 (SD 1.3) days (p &lt; 0.0001). Analysing answers to the other questions yielded qualitatively similar results. CONCLUSIONS: Effective pain treatment goes along with benefit regarding work. A reduction in time off work &gt;1 day per week can be achieved in patients with good pain responses