Trust in the approval process of medicines mediates the effect of an educational intervention on the pain relief induced by a generic analgesic

BackgroundGeneric medicines have been associated with less efficacy compared to originator products. Educational videos explaining generic medicines can have a positive effect on perceptions of generic drugs and their pain-relieving effect.The central aim of the current study was to examine whether trust in the governmental approval process of medicines mediates the effect of educational video interventions on the pain-relieving effect induced by a generic medicine and whether trust can be built by improving individuals’ understanding of generic medication.MethodsThis is a secondary analysis of a randomized controlled trial where participants with frequent tension headaches were randomly assigned to either watching a video explaining generic drugs (n = 69) or a video informing about headaches (control group: n = 34). After watching the video, participants took an originator and a generic pain analgesic in a randomized order to treat their next two consecutive headaches. Pain severity was measured before and 1 h after taking the medicine.ResultsA multiple serial mediator model showed that improving individuals' understanding of generic medicines is associated with increased trust in medicines. Both factors together, understanding and trust, significantly mediated the effect of the video education about generic drugs on the generic's pain-relieving effect (total indirect effect: coefficient: 0.20, 95% CI: 0.42, −0.0001).ConclusionResults of this study show that improving individuals’ understanding of generic medication and trust in the process of approving medicines should be considered as important mechanisms of future educational interventions about generic medicines.     

Greater occipital and supraorbital nerve blockade for the preventive treatment of migraine: a single-blind,randomized, placebo-controlled study

Objective: Nerve injections have been used for the acute and preventive treatment of migraine in recent decades. Most of these injections focused on greater occipital nerve (GON) blockade. However, few studies were placebo controlled, and only a few of them investigated GON and supraorbital nerve (SON) blockade together. This study aimed to evaluate the efficacy of GON and SON blockade with local anesthetics for the preventive treatment of migraine without aura.

Methods: Eighty-seven patients diagnosed with migraine without aura were included in the study. Patients were divided randomly. One group was injected with 1% lidocaine, the other group was injected with 0.9% saline. GON and SON injections were done bilaterally. The injections were repeated weekly for 3 weeks. Patients were followed up for 2 months to assess clinical response.

Results: Seventy-one patients completed the study. After 2 months, the number of headache days decreased significantly from 12.8?±?10.9 to 5.3?±?7.4, and VAS decreased from 8.3?±?1.0 to 5.5?±?1.9 in the blockade group. The number of headache days decreased from 12.4?±?10.3 to 7.5?±?7.2 and VAS decreased from 8.2?±?1.1 to 7.4?±?1.3 in the placebo group. Response was seen in 65.1% of the patients in the blockade group (65.4% for episodic migraine, 64.7% for chronic migraine) and 28.6% of the patients in the placebo group. The difference was significant.

Conclusions: The results suggest that GON and SON blockade with lidocaine was more effective than the placebo in the prophylactic treatment of both episodic and chronic migraine.     

Efficacy and comfort of olopatadine versus ketotifen ophthalmic solutions: a double-masked,environmental study of patient preference

SUMMARY

Background: Ocular allergies cause itching, redness, chemosis, tearing, and swelling of the eyelids in sensitized individuals. The options available for treatment of ocular allergy include olopatadine 0.1% (Opatanol; Patanol [US]*) and ketotifen 0.025% (Zaditen; Zaditor [US]?). Patient preference for an eye drop can often be a primary factor in determining the level of compliance and satisfaction with any given therapy.

Objective: This study sought patient perspective on eye drop efficacy in controlling signs and symptoms of allergic conjunctivitis and eye drop comfort. Also evaluated were the factors considered by patients when making decisions of preference.

Methods: One hundred patients with previous history and current symptoms of seasonal or perennial allergic conjunctivitis were enrolled at two centers (Athens, Greece, N = 50; Padova, Italy, N = 50) for this two visit, double-masked study. Qualified patients received two masked bottles of medication (one olopatadine, one ketotifen) and were asked to use both medications as needed over the course of four weeks, but not to exceed usage of two drops of medication per eye per day. At the second visit, patients answered five questions comparing the two masked medications in terms of preference, drop comfort, and efficacy in treatment of signs and symptoms. Patients also defined the factors upon which they based these decisions.

Results: A significantly greater percentage of patients (81%) selected olopatadine when asked which medication they preferred; which they found more comfortable; which they found more efficacious in reducing symptoms of allergy; and which they would select if visiting the doctor's office (P < 0.0001). Seventy-six percent (76%) of patients considered both efficacy and comfort when making their preference decisions (P < 0.0001). No adverse events were volunteered or elicited.

Conclusion: In this study, patients preferred to use the anti-allergy eye drop olopatadine over ketotifen after using both drops and evaluating relative efficacy and comfort during the course of four weeks. A significantly greater percentage of the patients preferred to use olopatadine during the study period, found it more efficacious and comfortable, and would select olopatadine if visiting their doctor's office during allergy season.     

Perioperative use of etoricoxib reduces pain and opioid side-effects after total abdominal hysterectomy: a double-blind,randomized, placebo-controlled phase III study

Abstract

Objective:

To evaluate the effects of two different doses of etoricoxib delivered perioperatively compared with placebo and standard pain management on pain at rest, pain with mobilization, and use of additional morphine/opioids postoperatively.     

心理护理干预对胃癌患者疼痛、情绪及睡眠的影响

目的：探讨心理护理干预对胃癌患者疼痛、情绪及睡眠的影响。方法选取本院2012年2月∽2014年2月收治的50例胃癌患者作为观察组,所有患者均接受胃癌根治术的相关治疗,并于术后开展有效的心理干预,选取同期50例根治术治疗的胃癌患者作为对照组,仅给予临床常规护理。结果两组患者护理前焦虑抑郁心理、疼痛评分以及睡眠时间比较差异均无统计学意义（P〉0.05）,护理后观察组患者的抑郁情绪评分、焦虑情绪评分、疼痛评分、睡眠时间均显著好于对照组,差异有统计学意义（P〈0.05）。结论胃癌患者术后疼痛、不良情绪及睡眠障碍情况多由于对疾病的恐惧所引起,手术后给予不同方向的心理护理干预,可显著降低各种不良事件的发生率,促进术后恢复,提高手术实际效果。     

Radiotherapy plus either transdermal fentanyl or paracetamol and codeine for painful bone metastases: a randomised study of pain relief and quality of life

SUMMARY

Objective: To compare the effects of providing analgesia with either transdermal fentanyl (TTS-fentanyl) or paracetamol and codeine (P/C) in addition to radiotherapy in patients with metastatic bone pain.

Methods: In a prospective study, 26 patients with radiologically confirmed bony metastases received radiotherapy (R/T). They were randomised to receive either 500?mg paracetamol and 30?mg codeine four times per day (P/C group), or transdermal fentanyl patches delivering 25|ig fentanyl/h (TTS-fentanyl group). Pain was assessed using visual analogue pain ratings (VAS) and the Greek Brief Pain Inventory (G-BPI) questionnaire administered before R/T and after 3 months.

Results: Data were available from 24 eligible patients. Use of TTS-fentanyl was associated with significantly superior pain relief. Mean VAS fell from 7.0 to 1.1 with TTS-fentanyl and from 8.3 to 4.3 with P/C, p?<?0.01. The TTS-fentanyl group also showed significantly greater improvements of important G-BPI domains including global quality of life, pain, and physical, cognitive, and role functioning, than the P/C group (p?<?0.01). Four patients receiving TTS-fentanyl and three receiving P/C reported severe nausea/vomiting.

Conclusions: Transdermal fentanyl combined with R/T was more effective in reducing metastatic bone pain and resulted in greater improvements in quality of life than paracetamol and codeine.     

Efficacy and safety of tapentadol prolonged release for moderate-to-severe chronic osteoarthritis knee pain: a pooled analysis of two double-blind,randomized, placebo- and oxycodone controlled release-controlled studies

Objective: To compare efficacy and safety of tapentadol prolonged-release (PR) and oxycodone-controlled release (CR) in moderate-to-severe chronic osteoarthritis knee pain.

Methods: Data from two double-blind, randomized, placebo- and oxycodone CR-controlled phase 3 studies with a 3-week titration period and 12-week controlled dose adjustment maintenance period were pooled. Primary efficacy end-points were change from baseline in average pain intensity at week 12 (US end-point) and over the entire maintenance period (non-US end-point).

Results: A total of 2,010 patients were assessed. For both primary end-points, tapentadol PR was significantly more effective than oxycodone CR (LS mean difference of –0.41 [95% CI?=?–0.65, –0.16; p?=?0.001] at week 12 and –0.35 [95% CI?=?–0.58, –0.12; p?=?0.003] over 12 weeks of maintenance [last observation carried forward]). Significantly better outcomes than for oxycodone CR were also observed for patient global impression of change, both Short Form-36 component scores, and EuroQoL-5Dimensions health status index (all p?p?Conclusions: The analyses suggest that tapentadol PR provided superior pain relief and a more improved overall health status than oxycodone CR in a large patient population with moderate-to-severe chronic osteoarthritis pain. Compared to oxycodone CR, tapentadol PR showed a more favorable tolerability profile with better gastrointestinal tolerability.     

Efficacy and safety of tapentadol prolonged release formulation in the treatment of elderly patients with moderate-to-severe chronic osteoarthritis knee pain: a pooled analysis of two double-blind,randomized, placebo-, and active-controlled trials

Objective: To compare efficacy and safety of tapentadol prolonged release (PR) vs oxycodone controlled release (CR) in younger patients (<65?years of age) and in elderly patients (≥65 and ≥75 years of age) in the treatment of moderate-to-severe chronic osteoarthritis (OA) knee pain.

Methods: Data from two double-blind, randomized, placebo-, and oxycodone CR-controlled phase 3 trials were pooled and stratified by age. Primary efficacy end-points were change from baseline in average pain intensity at week 12 (US end-point) and over the entire maintenance period (non-US end-point).

Results: A total of 1357 patients <65?years, 653 patients ≥65?years, and 176 patients ≥75?years of age were assessed. The comparison between tapentadol PR and oxycodone CR showed numerically better pain relief under tapentadol PR for both primary end-points in all three age groups. More favorable improvements were also observed for patient global impression of change, the Short Form-36 physical component score, and EuroQoL-5Dimensions health status index. In the elderly, incidences of dizziness and somnolence were comparable between active treatments, but incidences of nausea, vomiting, and constipation were considerably lower under tapentadol PR. Treatment completion rates were lowest under oxycodone CR;?>?50% of elderly oxycodone CR patients named side-effects as the main reason for discontinuation.

Conclusions: Tapentadol PR was effective in the treatment of moderate-to-severe chronic OA pain in elderly and younger patients. Compared to oxycodone CR, the overall and the gastrointestinal tolerability profile in particular were better in all tapentadol PR groups, regardless of age.     

Fentanyl buccal tablet (FBT) for relief of breakthrough pain in opioid-treated patients with chronic low back pain: a randomized,placebo-controlled study

ABSTRACT

Background: Short-acting opioids are commonly used to treat breakthrough pain (BTP) and rapid-onset formulations are being developed to improve the effectiveness of this approach. Fentanyl buccal tablet (FBT) is a new formulation of fentanyl that enhances transbuccal drug delivery via an effervescent reaction and may provide relatively rapid-onset analgesia. FBT was evaluated for BTP in opioid-treated patients with chronic low back pain – the first such study in a population with chronic non-cancer pain.

Design: Randomized, double-blind, placebo-controlled.

Patients and setting: Patients with chronic low back pain receiving long-term opioid therapy at 16 pain treatment centers in the United States.

Procedures: Following open-label titration to identify an effective FBT dose, patients were randomly assigned to one of three double-blind dose sequences (six doses of FBT, three placebo) to treat nine BTP episodes. Pain intensity (PI), measured on an 11-point scale (0 = no pain; 10 = worst pain), and other outcomes were assessed for 2?h after dosing.

Data analysis: The primary efficacy measure was the sum of pain intensity differences (PIDs) for the first 60?min (SPID₆₀); secondary efficacy measures included PIDs at other time points, pain relief (PR), meaningful PR, time to meaningful PR, use of supplementary BTP medication, and self/investigator-reported adverse events.

Results: Of the 124 patients screened, 105 patients were enrolled, 84 identified an effective FBT dose, and 77 entered the double-blind phase. SPID₆₀ significantly favored FBT (?p < 0.0001). All secondary measures also favored FBT, with PIDs and PR showing significant differences versus placebo as early as 10 and 15?min, respectively. An improvement in PI score of ≥ 33% occurred in a significantly larger proportion of FBT-treated episodes versus placebo from 15?min (20% vs. 11%, p < 0.01) through 2?h (65% vs. 28%, p < 0.0001). Patients were approximately four times more likely to require supplemental opioids for BTP episodes following administration of placebo compared with episodes treated with FBT. AEs were typical for opioids, and were mostly reported during dose titration. Limitations of this study may be related to its open-label dose-titration phase (which has the potential to compromise blinding) and the recruitment of patients from pain clinics, which could potentially yield a study population that is not representative of the general population with BTP.

Conclusions: FBT was efficacious and well tolerated in the treatment of BTP in opioid-treated patients with chronic low back pain.     

Informing a collaborative-care model for delivering medication assisted treatment for opioid dependence (MATOD): An analysis of pharmacist,prescriber and patient perceptions

BackgroundDemand for medication assisted treatment for opioid dependence (MATOD) in Australia exceeds capacity, particularly in rural and regional areas. There is increasing recognition that community pharmacists are well-positioned to take on expanded roles in MATOD delivery, however there has been limited Australian research exploring attitudes of pharmacists, prescribers, and patients to collaborative models of care.Objective(s)This study aimed to better understand enablers and barriers to a collaborative model for MATOD, to inform implementation in regions where increases in treatment capacity are urgently needed.MethodsSemi-structured telephone interviews were conducted with pharmacists (n = 11), prescribers (n = 6), and patients (n = 8) recruited from the Frankston-Mornington Peninsula region in Victoria, Australia, where transport and access to services have impacts on health care utilisation. The COM-B model was used to explore perceptions of pharmacists’ capability, opportunity, and motivations for delivering collaborative care.ResultsThere was strong motivation among healthcare professionals to participate in a collaborative model of care, with the main perceived benefits including improvements in accessibility, convenience, and continuity of care, and leverage of pharmacists’ high level of patient engagement. Key barriers identified by both pharmacists and prescribers included a perceived lack of pharmacist skills in some areas (capability) and resources (opportunity) to deliver collaborative care in a community pharmacy setting. Established relationships between all stakeholders (social opportunity) and communication between pharmacists and prescribers were identified as facilitators. Barriers and facilitators aligned with seven key areas: skills, confidence, relationships, patient selection, protocols, communication and resources.ConclusionsFindings informed the development of a collaborative model that was individualised, protocol based, and supported by training and clear processes.Project impactThis study identifies specific barriers and facilitators to a pharmacist-prescriber collaborative model of care for MATOD. The resulting model will be tested in a hybrid implementation-effectiveness trial in the Frankston-Mornington Peninsula region.     

An oral yohimbine/L-arginine combination (NMI 861) for the treatment of male erectile dysfunction: a pharmacokinetic, pharmacodynamic and interaction study with intravenous nitroglycerine in healthy male subjects

AIMS: Interaction of phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction with organic nitrates could lead to severe hypotension. NMI 861 is a combination of 7.7 mg yohimbine tartrate and 6 g l-arginine glutamate. A similar oral combination, which contains the same amount of yohimbine and L-arginine, has been shown to improve erectile function in previous studies. METHODS: In two placebo-controlled, randomized, double-blind, two-way crossover design studies we aimed to assess first the pharmacokinetics and pharmacodynamics of a single oral dose of NMI 861 administered in 16 healthy male subjects, and then the pharmacodynamics of orally administered NMI 861 in combination with intravenous nitroglycerine (GTN) in 12 healthy male subjects. Systolic (SBP) and diastolic (DBP) blood pressures, pulse rate and adverse events were measured in each study. RESULTS: NMI 861 was well tolerated by all subjects with no significant adverse reactions reported. For L-arginine, mean C(max) +/- SEM (range) was 42 +/- 2.2 (28-63) microg ml(-1) and t(max) (range) was 0.88 (0.50-1.5) h. AUC and t(1/2) were not calculated for L-arginine because of the presence of endogenous concentrations and the contribution from food sources. For yohimbine, mean C(max) was 42 +/- 11 (2.8-128) ng ml(-1); t(max) was 0.57 (0.25-1.0) h; mean AUC(0,8 h) was 65 +/- 24 (5.4-332), ng ml(-1) h and t(1/2) was 1.0 +/- 0.34 (0.40-6.0) h. There was a small but significant difference in the mean change from baseline for SBP from 0 to 6 h after NMI 861 treatment compared with placebo (0.8 +/- 1.4 vs-4.1 +/- 2.1 mmHg, respectively; 95% CI 0.0, 9.8 mmHg (P = 0.047)). There was no significant difference in SBP between treatments for the studied periods 6-12 h and 12-24 h. There was no significant difference in DBP or pulse between NMI 861 and placebo treatments for the three studied time periods. In the study designed to investigate the interaction of organic nitrate with NMI 861, subjects were infused intravenously with increasing doses of GTN (15 min each dose) at 2.5, 5, 10, 20 and 40 microg min(-1) starting 40 min after a single oral dose of either NMI 861 or placebo. There was no significant difference in the hypotensive response induced by GTN between the NMI 861 and placebo treatments. The mean maximum changes from baseline during GTN infusion for subjects administered with either NMI 861 or placebo were a decrease of 16.9 +/- 3.4 vs 13.6 +/- 2.4 mmHg (mean difference between treatments -3.3 mmHg, 95% CI -12.7, 6.0 mmHg (P = 0.460)) for SBP, a decrease of 14.7 +/- 2.0 vs 14.0 +/- 2.0 mmHg for DBP (mean difference -0.7 mmHg, 95% CI -8.2, 6.8 mmHg (P = 0.835)), and an increase of 11.8 +/- 1.9 vs 14.1 +/- 2.4 beats min(-1) for pulse, respectively (mean difference -2.3 beats min(-1), 95% CI -9.3, 4.5 beats min(-1) (P = 0.464)). CONCLUSIONS: Acute oral administration of NMI 861 was found to be well tolerated and bioavailable in healthy male subjects and no significant hypotensive interaction with intravenous GTN was detected at the doses investigated.