Impact of a Collaborative Pharmaceutical Care Service for Patients With Parkinson’s Disease

Objective: To identify the impact of a collaborative pharmaceutical care service (CPCS) on medication safety and establish the impact of the CPCS on patient reported outcomes for Parkinson’s disease (PD) patients.Methods: Initially, PD outpatients receiving the CPCS between March 2017 and March 2019 were compared with PD patients receiving standard of care to identify differences in management. Pharmacist interventions data were coded and patients with PD receiving the CPCS were compared with those receiving standard of care to determine differences in medicines prescribed and dosage associated with these. Following this, data of patients receiving CPCS at baseline and 3-months follow-up were collected using a questionnaire consisting of validated measures of two patient-reported outcomes [adherence and quality of life (QoL)]. Mean scores for continuous variables were calculated, with descriptive analysis of categorical variables consisting of frequency counts and percentages. Change in adherence score before and after CPCS was investigated using a Wilcoxon sign rank sum test, spearman correlation analysis was used to correlate the changes in QoL before and after CPCS with the number of interventions, and p < 0.05 indicates that the difference is statistically significant.Results: A total of 331 PD outpatients received CPCS over 490 outpatient visits with an average age of 71.83 (±12.54). Five hundred and forty-five drug related problems were recorded as pharmacist interventions, of which most involved change to dosage (n = 226, 41.47%), adverse drug reactions (n = 135, 24.77%), and change in a medication (n = 102, 18.72%). Compared with those receiving standard of care, patients receiving CPCS were significantly less likely to have been prescribed pramipexole (18.52 versus 23.77%, p < 0.001) and more likely to have been prescribed amantadine (5.40 versus 3.70%, p = 0.02) and selegiline (17.36 versus 11.64%, p < 0.001). Lower dosages of levodopa/benserazide (0.51 ± 0.31 g versus 0.84 ± 0.37 g, p < 0.001), levodopa/carbidopa (0.33 ± 0.23 g versus 0.66 ± 0.47 g, p < 0.001), pramipexole (1.14 ± 1.63 mg versus 1.27 ± 0.69 mg, p = 0.01), and entacapone (130.00 ± 79.76 mg versus 173.09 ± 97.86 mg, p < 0.001) were also recorded. At baseline 119 PD outpatients with an average age of 69.98 (±9.90) were recruited for the longitudinal study. At 3-month follow-up, participants reported improvement in bodily pain subscale (baseline versus 3-months follow-up, 30.04 ± 22.21 versus 23.01 ± 20.98, p = 0.037) and medication adherence (6.19 ± 1.50 versus 6.72 ± 1.73, p = 0.014). Frequency of CPCS use was related to activity of daily living subscale (p = 0.047), the bodily pain subscale (p = 0.026), and medication adherence (p = 0.011). Total score of PDQ-39 was associated with patient education (p = 0.005) and usage and dosage combined with patient education (p = 0.006), while medication adherence score was associated with usage and dosage (p = 0.005).Conclusion: The CPCS was effective in resolving drug-related problems and in improving patients’ medication regimens, medication adherence, and QoL through patient education and dosage adjustments. This is the first step in the development and feasibility testing of pharmacy services for PD patients in China.

Depression and Anxiety as Mediators of PTSD Symptom Clusters and Pain in Treatment-Seeking Canadian Forces Members and Veterans

ABSTRACT Introduction Chronic pain (CP) commonly presents alongside psychiatric conditions such as depression, PTSD, and generalized anxiety. The current study sought to better understand this complex relationship by determining whether anxiety and depression symptom severity mediated the relationship between DSM-5 PTSD symptom clusters and pain symptoms in a sample of 663 Canadian Armed Forces (CAF) personnel and veterans seeking treatment for mental health conditions. Materials and Methods Generalized anxiety disorder, depression, and PTSD symptom severity were measured using self-report scales provided as part of a standard intake protocol. Pain symptoms were measured using the Bodily Pain subscale of the SF-36 (SF-36 BPS). Linear regressions were used to explore the relationship between PTSD symptom clusters, depression, anxiety, and pain. Bootstrapped resampling analyses were employed to test mediation effects. Results The average SF-36 BPS score in this sample was 36.6, nearly 1.5 SDs below the population health status, enforcing the salience of pain symptoms as a concern for veterans and CAF seeking treatment for military-related psychiatric conditions. The effects of PTSD symptom clusters avoidance, negative mood and cognitions, and arousal on pain were fully mediated by anxiety and depression severity. However, the effect of intrusion on pain was not mediated by depression and only partly mediated by anxiety. Conclusion Findings emphasize the importance of including anxiety and depression in models of PTSD and pain, particularly in samples where psychiatric comorbidity is high. Clinically, results highlight the need for improved treatment regimens that address pain symptoms alongside common psychiatric comorbidities.

Effect of a Single-Shot of a High-Density Viscoelastic Solution of Hyaluronic Acid in Patients with Symptomatic Primary Knee Osteoarthritis: The No-Dolor Study

Background Pronolis®HD mono 2.5% is a novel, one-shot, high-density sterile viscoelastic solution, recently available in Spain, which contains a high amount of intermediate molecular weight hyaluronic acid (HA), highly concentrated (120 mg in 4.8 mL solution: 2.5%). The objective of the study was to analyze the efficacy and safety of this treatment in symptomatic primary knee osteoarthritis (OA). Methods This observational, prospective, multicenter, single-cohort study involved 166 patients with knee OA treated with a single-shot of Pronolis®HD mono 2.5% and followed up as many as 24 weeks. Results Compared with baseline, the score of the Western Ontario and McMaster Universities Arthritis Osteoarthritis Index (WOMAC) pain subscale significantly reduced at the 12-week visit (primary endpoint, median: 9 interquartile range [IQR]: 7-11 versus median: 4; IQR: 2-6). The percentage of patients achieving >50% improvement in the pain subscale increased progressively from 37.9% (at 2 weeks) to 66.0% (at 24 weeks). Similarly, WOMAC scores for pain on movement, stiffness subscale, and functional capacity subscale showed significant reductions at the 12-week visit which were maintained up to the 24-week visit. The EuroQol visual analog scale score significantly increased after 12 weeks (median: 60 versus 70). The need for rescue medication (analgesics/nonsteroidal anti-inflammatory drugs) also significantly decreased in all post-injection visits. Three patients (1.6%) reported local adverse events (joint swelling) of mild intensity. Conclusions In conclusion, a single intra-articular injection of the high-density viscoelastic gel of HA is effective and safe for the relief of symptoms in patients with knee OA. Trial registration: ClinicalTrial# NCT04196764

Nutraceuticals for Knee Osteoarthritis Pain Relief. Results from a Preliminary Randomised Clinical Trial

Osteoarthritis is the most common inflammation-based joint disease. Polyphenols are plant secondary metabolites with established antioxidant and anti-inflammatory properties. Recognizing the need for holistic approaches in the management of knee osteoarthritis, we designed a two-arm, randomised clinical trial to evaluate the efficacy of a supplement rich in phenolic compounds in OA. Primary outcomes included changes in Visual Analog Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain subscale. Secondary outcome measures were the changes in WOMAC stiffness and functionality subscales. Patients were randomised (1:1) to receive a mixture of phenolic compounds and ascorbic acid (PhAA,) or ascorbic acid (AA). Μedical history, biochemical profile and anthropometric measurements were obtained. Eighty-six patients were screened and 25 were randomly allocated in a pilot study to receive a mixture of phenolic compounds and ascorbic acid (PhAA,) or ascorbic acid (AA) adjunct to stable medical treatment. The nutraceutical supplements were well tolerated and no adverse events were reported. VAS decreased in the PhAA group (p < 0.001). Additionally, WOMAC composite score decreased significantly only in the PhAA group (p < 0.05). The WOMAC subscale of pain decreased in both treatment groups (p = 0.001 for the PhAA group, p < 0.05 for the AA group). The decrease in the subscales of stiffness and physical function was not significant for either group. A possible improvement in the quality of life of these patients using nutraceutical supplements is apparent. Although preliminary, our positive results support the hypothesis that treatment with nutraceuticals may be effective for pain relief in osteoarthritis. ClinicalTrials.gov Identifier: NCT04783792.

Exercise and education versus saline injections for knee osteoarthritis: a randomised controlled equivalence trial

ObjectiveTo compare the efficacy of an exercise and education programme with open-label placebo given as intra-articular injections of inert saline on pain and function in individuals with knee osteoarthritis (OA).MethodsIn this open-label, randomised controlled trial, we recruited adults aged ≥50 years with symptomatic and radiographically confirmed knee OA in Denmark. Participants were randomised 1:1 to undergo an 8-week exercise and education programme or four intra-articular saline injections over 8 weeks. Primary outcome was change from baseline to week 9 in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire pain subscale (range 0 (worst)–100 (best)). Prespecified equivalence margins of ±8 KOOS pain points were chosen for the demonstration of comparable efficacy. Key secondary outcomes were the KOOS function and quality of life subscales, and patients’ global assessment of disease impact.Results206 adults were randomly assigned: 102 to exercise and education and 104 to intra-articular saline injections. For the primary outcome, the least squares mean changes in KOOS pain were 10.0 for exercise and education and 7.3 for saline injections (difference 2.7 points, 95% CI −0.6 to 6.0; test for equivalence p=0.0008). All group differences in the key secondary outcomes respected the predefined equivalence margins. Adverse events and serious adverse events were similar in the two groups.ConclusionIn individuals with knee OA, an 8-week exercise and education programme provided efficacy for symptomatic and functional improvements equivalent to that of four open-label intra-articular saline injections over 8 weeks.Trial registration numberNCT03843931.

IMMEDIATE EFFECTS OF SEMI-CUSTOM INSOLES AND STRUCTURED KNEE SLEEVES ON LOWER EXTREMITY KINETICS AND KINEMATICS IN RECREATIONAL MALE ATHLETES WITH PATELLOFEMORAL PAIN

The aim of this experiment was to provide insight into the immediate influence of both semi-custom insoles and knee sleeves in recreational male runners/athletes suffering from patellofemoral pain and also to explore the association between the extent of patellofemoral pain and psychological wellbeing. Experiment 1 examined 17 male recreational runners with patellofemoral pain, in semi-custom insole and no-insole conditions. Experiment 2 examined 13 male recreational athletes with patellofemoral pain, undertaking run, [Formula: see text] cut and single-leg hop movements in knee sleeve and no-sleeve conditions. In both experiments, motion capture and ground reaction forces were collected, allowing kinetics and three-dimensional kinematics to be calculated alongside patellofemoral joint loading quantified using musculoskeletal modeling. In both experiments, patellofemoral pain symptoms were examined using the KOOS patellofemoral pain subscale and psychological wellbeing using the COOP-WONCA questionnaire. The findings from both experiments showed that pain symptoms significantly predicted psychological wellbeing ([Formula: see text] in experiment 1 and [Formula: see text] in experiment 2). Experiment 1 showed that orthoses significantly reduced tibial internal rotation range of motion (no-[Formula: see text] and [Formula: see text]) whilst also increasing the peak knee adduction moment (no-[Formula: see text][Formula: see text]N[Formula: see text]m/kg and [Formula: see text][Formula: see text]N[Formula: see text]m/kg). The findings from experiment 2 revealed that the knee sleeve reduced the peak patellofemoral force (no-[Formula: see text][Formula: see text]BW and [Formula: see text][Formula: see text]BW) in the run movement and the patellofemoral load rate in the cut movement (no-[Formula: see text][Formula: see text]BW/s and [Formula: see text][Formula: see text]BW/s). Overall, the findings confirm that pain symptoms are predictive of psychological wellbeing in recreational male athletes with patellofemoral pain. Furthermore, the findings suggest that both insoles and knee sleeves may provide immediate biomechanical benefits in recreationally active individuals with patellofemoral pain, although when wearing insoles this may be at the expense of an increased knee adduction moment during running.

Effect of low-dose amitriptyline on reducing pain in clinical knee osteoarthritis compared to benztropine: study protocol of a randomised, double blind, placebo-controlled trial

Background Knee osteoarthritis is a major cause of pain and disability. Pain control is poor, with most patients remaining in moderate to severe pain. This may be because central causes of pain, a common contributor to knee pain, are not affected by current treatment strategies. Antidepressants, such as amitriptyline, have been used to treat chronic pain in other conditions. The aim of this randomised, double blind, controlled trial, is to determine whether low dose amitriptyline reduces pain in people with painful knee osteoarthritis over 3 months compared to benztropine, an active placebo. Methods/design One hundred and sixty people with painful radiographic knee osteoarthritis will be recruited via clinicians, local and social media advertising. Participants will be randomly allocated in a 1:1 ratio to receive either low dose amitriptyline (25 mg) or active placebo (benztropine mesylate, 1 mg) for 3 months. The primary outcome is change from baseline in knee pain (WOMAC pain subscale) at 12 weeks. Secondary outcomes include change in function (total WOMAC) and the proportion of individuals achieving a substantial response (≥ 50% reduction in pain intensity, measured by Visual Analog Scale, VAS, from no pain to worst pain imaginable, 0-100 mm) and moderate response (≥ 30% reduction in pain intensity, measured by VAS) at 12 weeks. Intention to treat analyses will be performed. Subgroup analyses will be done. Discussion This study will provide high level evidence regarding the effectiveness of low dose amitriptyline compared to benztropine in reducing pain and improving function in knee OA. This trial has the potential to provide an effective new therapeutic approach for pain management in knee osteoarthritis, with the potential of ready translation into clinical practice, as it is repurposing an old drug, which is familiar to clinicians and with a well described safety record. Trial registration Australian New Zealand Clinical Trials Registry prior to recruitment commencing (ACTRN12615000301561, March 31, 2015, amended 14 December 2018, February 2021). Additional amendment requested 18 July 2021.

Effectiveness of non-pharmacological interventions on sleep characteristics among adults with musculoskeletal pain and a comorbid sleep problem: a systematic review

Sleep problems are common and may be associated with persistent pain. It is unclear whether non-pharmacological interventions improve sleep and pain in adults with comorbid sleep problems and musculoskeletal (MSK) pain. We conducted a systematic review on the effectiveness of non-pharmacological interventions on sleep characteristics among adults with MSK pain and comorbid sleep problems. We searched MEDLINE, EMBASE, CINAHL, Cochrane Central and PsycINFO from inception to April 2, 2021 for randomized controlled trials (RCTs), cohort, and case-control studies. Pairs of independent reviewers critically appraised and extracted data from eligible studies. We synthesized the findings qualitatively. We screened 8459 records and identified two RCTs (six articles, 467 participants). At 9 months, in adults with insomnia and osteoarthritis pain, cognitive behavioral therapy for pain and insomnia (CBT-PI) was effective at improving sleep (Insomnia Severity Index, ISI) when compared to education (OR 2.20, 95% CI 1.25, 3.90) or CBT for pain (CBT-P) (OR 3.21, 95% CI 1.22, 8.43). CBP-P vs. education was effective at increasing sleep efficiency (wrist actigraphy) in a subgroup of participants with severe pain at baseline (mean difference 5.45, 95% CI 1.56, 9.33). At 18 months, CBT-PI, CBT-P and education had similar effectiveness on sleep and pain or health outcomes. In adults with insomnia and knee osteoarthritis, CBT-I improved some sleep outcomes including sleep efficiency (diary) at 3 months (Cohen’s d 0.39, 95% CI 0.24, 1.18), and self-reported sleep quality (ISI) at 6 months (Cohen’s d − 0.62, 95% CI -1.01, − 0.07). The intervention was no better than placebo (behavioural desensitization) for improving other sleep outcomes related to sleep onset or pain outcomes. Short-term improvement in sleep was associated with pain reduction at 6 months (WOMAC pain subscale) (sensitivity 54.8%, specificity 81.4%). Overall, in two acceptable quality RCTs of adults with OA and comorbid insomnia, CBT-PI/I may improve some sleep outcomes in the short term, but not pain outcomes in the short or long-term. Clinically significant improvements in sleep in the short term may improve longer term pain outcomes. Further high-quality research is needed to evaluate other non-pharmacological interventions for people with comorbid sleep problems and a range of MSK conditions.

The Minimal Clinically Important Difference (MCID) for the WOMAC and Factors Related to Achievement of the MCID After Medial Opening Wedge High Tibial Osteotomy for Knee Osteoarthritis

Background: Many approaches have been used to determine the minimal clinically important difference (MCID) in patients undergoing total knee arthroplasty, but the MCID for outcome measures after medial opening wedge high tibial osteotomy (MOWHTO) for the treatment of medial compartment knee osteoarthritis (OA) has not been reported. Purpose: To define the MCID for the Western Ontario and McMaster Universities Arthritis Index (WOMAC) after MOWHTO and to identify risk factors for not achieving the MCID. Study Design: Case-control study; Level of evidence, 3. Methods: Among patients with medial compartment knee OA who underwent MOWHTO, 174 patients who were followed for 2 years were included in the study. The MCID and substantial clinical benefit (SCB) for the WOMAC were determined using the anchor-based method with a 15-item questionnaire. Preoperative OA severity was measured by the Kellgren-Lawrence (K-L) grading system, and the acceptable range of the postoperative weightbearing line ratio was 50% to 70%. Patients were divided into 2 groups based on whether the MCID and SCB were achieved, and then factors related to failure to achieve the MCID and SCB were analyzed using multivariate logistic regression analysis. Results: The MCID for the WOMAC was 4.2 points for the pain subscale, 1.9 points for the stiffness subscale, 10.1 points for the function subscale, and 16.1 points for the total. Additionally, the SCB for the WOMAC was 6.4 for pain, 2.6 for stiffness, 16.4 for function, and 25.3 for the total. Overall, 116 (66.7%), 99 (56.9%), 127 (73.0%), and 128 (73.6%) patients achieved the MCID for the WOMAC pain, stiffness, function, and total, respectively, after MOWHTO. The odds of not achieving the MCID for the WOMAC total were 1.09 times greater (95% CI, 1.05-1.13; P < .001) in patients with a low preoperative WOMAC total score (cutoff values: 10.5 for pain, 3.5 for stiffness, 34.5 for function, and 51.0 for the total), 11.77 times greater (95% CI, 3.68-37.70; P < .001) in patients with K-L grade 4 OA compared with K-L grades 2 or 3 OA, and 8.39 times greater (95% CI, 2.98-23.63; P < .001) in patients with undercorrection or overcorrection. A low preoperative WOMAC score, K-L grade 4 OA, and undercorrection or overcorrection were also associated with not achieving the SCB for the WOMAC total (all P < .05). Conclusion: Patients treated with a MOWHTO require a 16.1-point improvement in the WOMAC total score to achieve a MCID from the procedure. Low preoperative WOMAC scores, severe OA, and undercorrection or overcorrection were related to failure to achieve the MCID.

Autologous semitendinosus tendon graft could function as a meniscal transplant

Purpose Meniscectomy results in poor knee function and increased risk for osteoarthritis. Meniscal allograft transplantation is not widely used due to costs and availability. The semitendinosus tendon (ST) has the potential to remodel and revascularize in an intraarticular environment, such as ACL reconstruction. The objective for this pilot study was to investigate whether the ST graft could function as a meniscal transplant. Methods The ST was doubled and sutured with running sutures and pull-out sutures in each end. Bone tunnels were used for root anchorage and the graft was sutured with allinside, inside-out and outside-in technique. The pull-out sutures were fixed over a button. Partial weight bearing was allowed with limited range of motion in a brace for the first 6 weeks. Evaluation was assessed using clinical examination, radiology and patient reported outcome. Results A total of seven patients have been included between January 2018 and June 2020. Six medial transplants and one lateral transplant were performed. Mean age was 29 years. Four patients had completed the 12-month follow-up. Improvements were noted for IKDC Global Score, KOOS pain subscale and Lysholm. MRI indicated that the transplant become more wedge-like with visible roots and minor protrusion. Conclusions Even though this is primarily a technical report the follow-up data indicate that the transplant survives and adapts in shape and capabilities to an original meniscus. There were no adverse events and the patients seem to improve in terms of pain and quality of life.