Clinical Relevant Improvement Research Articles

Recompensation of cirrhosis in candidates of transplant: Tips and tricks for delisting.

Liver transplantation (LT) is the most successful treatment for patients with decompensated cirrhosis. The availability of effective and safe etiological treatments has altered the natural history of decompensated cirrhosis. Recently, the concept of recompensation has been defined. Patients who achieve recompensation may be removed from the waiting list for LT. Therefore, achieving an etiological cure is the cornerstone in the treatment of patients with decompensated cirrhosis. However, most patients improve their liver function after an etiologic cure, and only a proportion of patients achieve true recompensation after an etiological cure. Some patients maintain a condition of "MELD purgatory," that is, an improvement in the Model for End-Stage Liver Disease score without relevant clinical improvement that prevents delisting and may be even detrimental because lower Model for End-Stage Liver Disease score delays LT. Herein, we review the available evidence regarding recompensation and the management of recompensated patients on the waiting list for LT.

Improvement in functional outcome 1 year after nonsurgical multidisciplinary treatmentfor chronic pain after total knee arthroplasty: Aprospective cohort study.

The purpose of this study was to evaluate a multidisciplinary intervention developed for patients with debilitating chronic pain after total knee arthroplasty (TKA) unresponsive to existing treatment options. A treatment-based prospective cohort study was caried out in 30 TKA patients with debilitating chronic pain at least 1 year after TKA. The treatment was a multidisciplinary intervention. Main inclusion criteria: no indication for surgery. Primary outcome was function measured by KOOS-PS, OKS, OKS-APQand WORQ. Secondary outcome measures were pain, fear of movement, self-efficacy, quality of life (QoL), health care and pain medication use, work rehabilitationand patient satisfaction. The assessments took place pre- and directly posttreatment, at 1, 3and 12 months follow-up. The clinical relevance was assessed by predefined minimal important clinical change (MCIC). At baseline patients were on average 64.7 (±7.9) years old, 67% were female, and they had knee pain for 42 (10-360) months. The results at 12-month follow-up: first, a significant improvement was shown in function, pain, fear of movement, self-efficacy and QoL. Second, in 38.5%-69.2% of patients clinical relevant improvement was shown for functional outcome, 31% for pain,and 50% for self-efficacy. Third, 42% of patients reported 'no healthcare use in the past three months'. One year after a multidisciplinary treatment a clinically relevant improvement was shown in terms of function, pain, self-efficacy and QoL. It seems to be a promising treatment option in this difficult-to-treat patient group with debilitating chronic pain after TKA. Future research should examine the effect of the treatment in a larger study population, considering a control group, and focusing on the working population and evaluating cost-efficacy. Level II.

Pseudoarthrosis after anterior cervical discectomy and fusion: rate of occult infections and outcome of anterior revision surgery

BackgroundPseudoarthrosis after anterior cervical discectomy and fusion (ACDF) is relatively common and can result in revision surgery. The aim of the study was to analyze the outcome of patients who underwent anterior revision surgery for pseudoarthrosis after ACDF.MethodsFrom 99 patients with cervical revision surgery, ten patients (median age: 48, range 37–74; female: 5, male: 5) who underwent anterior revision surgery for pseudoarthrosis after ACDF with a minimal follow up of one year were included in the study. Microbiological investigations were performed in all patients. Computed tomography (CT) scans were used to evaluate the radiological success of revision surgery one year postoperatively. Clinical outcome was quantified with the Neck Disability Index (NDI), the Visual Analog Scale (VAS) for neck and arm pain, and the North American Spine Society Patient Satisfaction Scale (NASS) 12 months (12–60) after index ACDF surgery. The achievement of the minimum clinically important difference (MCID) one year postoperatively was documented.ResultsOccult infection was present in 40% of patients. Fusion was achieved in 80%. The median NDI was the same one year postoperatively as preoperatively (median 23.5 (range 5–41) versus 23.5 (7–40)), respectively. The MCID for the NDI was achieved 30%. VAS-neck pain was reduced by a median of 1.5 points one year postoperatively from 8 (3–8) to 6.5 (1–8); the MCID for VAS-neck pain was achieved in only 10%. Median VAS-arm pain increased slightly to 3.5 (0–8) one year postoperatively compared with the preoperative value of 1 (0–6); the MCID for VAS-arm pain was achieved in 14%. The NASS patient satisfaction scale could identify 20% of responders, all other patients failed to reach the expected benefit from anterior ACDF revision surgery. 60% of patients would undergo the revision surgery again in retrospect.ConclusionOccult infections occur in 40% of patients who undergo anterior revision surgery for ACDF pseudoarthrosis. Albeit in a small cohort of patients, this study shows that anterior revision surgery may not result in relevant clinical improvements for patients, despite achieving fusion in 80% of cases.Level of evidenceRetrospective study, level III.

Full-Endoscopic Lumbar Discectomy vs Standard Discectomy: A Noninferiority Study on Clinically Relevant Changes.

Surgery for lumbar disc herniation (LDH) has had a remarkable technological development during the past 20 years. Microscopic discectomy has traditionally been the gold standard method to treat symptomatic LDH before the introduction of full-endoscopic lumbar discectomy (FELD). The FELD procedure allows unsurpassed magnification and visualization and is currently the most minimally invasive surgical technique. In this study, FELD was compared with standard surgery for LDH, with a focus on medically relevant changes in patient-reported outcome measures (PROMs). The purpose of this study was to investigate whether FELD is noninferior to other surgical methods for LDH surgery in the most common PROMs, including postoperative leg pain and disability, while still reaching the necessary thresholds for relevant clinical and medical improvements. Patients undergoing a FELD procedure at the Sahlgrenska University Hospital, Gothenburg, Sweden, between 2013 to 2018 were included. A total of 80 (41 men and 39 women) patients were enrolled. The FELD patients were matched 1:5 to controls from the Swedish spine register (Swespine) who had a standard microscopic or mini-open discectomy surgery. PROMs, including the Oswestry Disability Index (ODI) and the Numerical Rating Scale (NRS), as well as the patient acceptable symptom states (PASS) and the minimal important change (MIC), were used to compare the efficacy of the 2 surgical approaches. The FELD group achieved medically relevant and significant improvements noninferior to standard surgery within the predefined thresholds of MIC and PASS. No differences could be found in disability measured by ODI FELD -28.4 (SD 19.2) vs standard surgery -28.7 (SD 18.9) or leg pain NRSLeg FELD -4.35 (SD 2.93) vs standard surgery -4.99 (SD 3.12). All intragroup score changes were significant. The FELD results are not inferior to standard surgery 1 year postoperatively after LDH surgery. There were no medically significant differences regarding MIC achieved or final PASS in any of the measured PROMs, including leg pain, back pain, or disability (ODI) between the surgical methods. The present study highlights that FELD is noninferior to standard surgery in clinically relevant PROMs.

A collaborative approach to engaging undergraduate students in learning and developing evidence-based practice

Background: Students often have difficulty engaging with evidenced-based practice (EBP) courses that are largely theoretical and lack clinical relevance. This may result in graduates lacking vital skills to critique practice and participate in quality improvement. Approach: This paper describes the development and implementation of a collaborative academic and healthcare industry-based course that linked theoretical aspects of EBP. Students undertook a quality improvement project during clinical practice experience. Course assessments were designed to provide feedback on the progression of projects, the integration of theoretical and practical aspects of EBP and dissemination of findings. Conclusions: The course required substantial collaboration between the university and industry partners to identify clinically relevant projects and coordinate academic and clinical mentorship to support the students. The course demonstrated a significant level of clinical and academic partnership that resulted in relevant clinical quality improvements and increased student engagement with learning about, producing and implementing EBP.

Brexpiprazole augmentation in a clozapine-resistant young schizophrenic patient: a successful case report.

IntroductionAlthough clozapine is considered the most effective drug for Treatment Resistant Schizophrenia (TRS), only 40% of patients treated will meet clinical response. Literature reviews and meta-analytic data offer no definite conclusions about the most effective clozapine augmentation strategies. Nevertheless, it has been suggested that the lack of evidence should not discourage clinicians from trying out new strategies in individual patients. Brexpiprazole is a novel 5-HT and DA modulator antipsychotic that exhibits partial agonism to D2/D3 and 5HT1A receptors, antagonism to 5HT2A and α-1B/2C receptors and represents a promising new drug in the pharmacotherapy of schizophrenia for both acute and maintenance treatment. In current literature there is no evidence of experiences in brexpiprazole augmentation for clozapine resistant patients.ObjectivesThis case report describes a successful clinical experience of brexpiprazole augmentation in a complicated case of clozapine resistant paranoid schizophrenia with consistent negative symptoms, the clinical evolution and metabolic improvement consequent to this therapy combination.MethodsIn a 27 male TRS patient, sequentially treated with adequate doses of risperidone, cariprazine, aripiprazole and olanzapine monotherapy, prescribed for adequate time, clozapine treatment was started, with a gradual titration from 25 to 300 mg/day, without significant clinical response on both positive and negative symptoms. Successively was introduced fluoxetine, from 10 to 30 mg/day, with no relevant clinical improvement. After 2 months of pharmacological stabilization with clozapine and fluoxetine described dosages, brexpiprazole was introduced starting from 1 mg/day and rapidly increasing till 4 mg/day.ResultsAfter 6 weeks of treatment, PANSS positive and negative subscales showed a significant decrease, respectively from 28 to 17 and from 42 to 20, while general psychopathology subscale decreased from 66 to 34. Negative sub-items with major improvement were those regarding blunted affect, emotional withdrawal, poor rapport, and passive/apathetic social withdrawal. Brexpiprazole augmentation also allowed to slowly decrease (in 6 months) clozapine dose till actual 150 mg/day, with a significant improvement in general tolerability and a slow decline in metabolic parameters (BMI from 36.5 to 30.3; fasting glucose from 112 to 92 mg/dL; total cholesterol from 248 to 182 mg/dL; total triglycerides from 392 to 198 mg/dL).ConclusionsIn this case report brexpiprazole augmentation in a clozapine resistant young schizophrenic patient was an effective strategy with significant symptoms improvement, in particular in PANSS general psychopathology and PANSS negative subscales. The consequent clozapine dose reduction contribute to the slow decrease in metabolic parameters considered.Disclosure of InterestNone Declared

Changes in functional capacity after a cardiac rehabilitation program in Spain: defining the profile of those who improve

Abstract Background Improvement in functional capacity (FC) is one of the most notable benefits patients experience after cardiac rehabilitation (CR) and it is highly important as low levels of FC are associated with a high risk of cardiovascular (CV) disease and all cause mortality. Purpose To study the changes in FC after a CR program in Spain and to define the profile of those patients that improve. Methods Single-centre observational study from 793 patients with ischaemic heart disease (15.3% women, age 61.79±10.70 years), participating in a CR program from 2015 to 2020 with a stress test performed, both at beginning of CR (conventional stress test, n=436; CPET, n=340; imaging stress test, n=17) and at end of CR (conventional stress test, n=468; CPET, n=322; imaging stress test, n=3). A comparative analysis of patients with “improved FC” and “non-improved FC” at end of CR, was performed. Relevant clinical improvement was defined as a 10% increase of VO2, in accordance with reviewed literature. Additionally, a descriptive analysis of patient exercise capacity parameters was performed at beginning of CR and at end CR, for the complete sample. Results A total of 1586 exercise tests were analysed. All exercise capacity parameters analysed showed significant improvement at end of CR, with p values <0.01, (Graph 1). Clinically relevant FC improvement was observed in 54.2% of patients that participated in CR; 45.5% of all women and 55.8% of all men. Patients that improved FC completed significantly more CR training sessions (p<0.05) than those who did not improve FC (21.39±4.53, 20.37±5.84). Those who improved FC were significantly older (62.74±10.90), presented with significantly more STEMI (n=197, 45.8%), and achieved significantly less METS (7.42±3.01) at baseline, (p<0.05, Table 1). Conclusions Our CR rehabilitation program improves patient's functional capacity significantly. Patients with clinically relevant functional capacity improvement, are significantly older patients with STEMI as diagnosis at CV event, complete significantly more CR training sessions and showed significantly worst physical performance (METS) at baseline. Funding Acknowledgement Type of funding sources: None.

Evaluation of functional outcome measures after fampridine treatment in patients with multiple sclerosis - An interventional follow-up study

ObjectiveThe purpose of this interventional study on participants with multiple sclerosis (MS) with walking disability was to evaluate changes in functional hand and walking measurements after fampridine treatment, after stratifying by the Expanded Disability Status Scale (EDSS). We furthermore wanted to investigate different functional measurements to evaluate their ability to detect responders to fampridine with a clinically relevant improvement. MethodsPatients were recruited from the MS Clinic at Odense University Hospital and were classified into two disability groups based on their EDSS score (moderate EDSS (EDSSMod) 4.5–5.5 [n = 19] and severe EDSS (EDSSSev) 6.0–7.0 [n = 14]). At baseline (visit 1) they completed the Timed 25-Foot Walk (T25FW), 2-Minute Walk Test (2MWT), Nine Hold Peg Test (9HPT), 12-item Multiple Sclerosis Walking Scale (MSWS-12), and the Six Spot Step Test (SSST). Participants were given 10 mg twice daily fampridine for 14 days before retested (visit 2). For each measurement, cut-off values were used to define responders with a clinically relevant improvement to treatment. The measurements were evaluated separately and in combination. ResultsOf the 33 participants, 25 (75.8%) were identified as having a clinically relevant improvement (CRI). For all patients combined (EDSSAll), all five measurements showed significant functional improvement after treatment. For the individual measurements, the highest participant response rates after 14 days of fampridine treatment were seen on the MSWS-12 (57.6%) and 2MWT (42.4%). The 2MWT also showed the largest performance improvement (18.5%) from visit 1 to visit 2. For patients with severe disability (EDSSSev), no significant improvement was seen after fampridine treatment on the T25FW, and most of the responders to T25FW had moderate disability (EDSSMod, 71.5%). Conversely for the SSST, most responders were EDSSSev (83.3%). No participants had a clinically relevant improvement on the 9HPT. The combination of T25FW, SSST, and MSWS-12 was less sensitive in distinguishing responders from non-responders, whereas the combination of 2MWT and MSWS-12 identified the same responders and could better distinguish fampridine responders from non-responders. ConclusionEDSS level did not influence the effect of fampridine treatment on functional hand and walking measures and the responsiveness of the measurements differed only a little between moderate and severe EDSS levels. The combination of self-reported walking capacity (MSWS-12) and walking endurance (2MWT) was better than T25FW, SSST, and MSWS-12 at detecting clinically meaningful improvement after fampridine treatment, which could prove useful in the clinical monitoring of walking disabilities in MS during fampridine treatment.

Exploratory insights into novel prehabilitative neuromuscular exercise-conditioning in total knee arthroplasty

BackgroundContemporary strategies for prehabilitation and rehabilitation associated with total knee arthroplasty (TKA) surgery have focused on improving joint range-of-motion and function with less emphasis on neuromuscular performance beneficially affecting joint stability. Furthermore, prehabilitation protocols have been found to be too long and generic-in-effect to be considered suitable for routine clinical practice.MethodsA pragmatic exploratory controlled trial was designed to investigate the efficacy of a novel, acute prehabilitative neuromuscular exercise-conditioning (APNEC) in patients electing TKA. Adults electing unilateral TKA were assessed and randomly allocated to exercise-conditioning (APNEC, n = 15) and usual care (Control, n = 14) from a specialised orthopaedic hospital, in the United Kingdom. APNEC prescribed nine stressful exercise-conditioning sessions for the knee extensors of the surgery leg, accrued over one week (3 sessions·week−1; 36 exercise repetitions in total; machine, gravity-loaded) and directly compared with usual care (no exercise). Prescribed exercise stress ranged between 60%—100% of participant’s daily voluntary strength capacity, encompassing purposefully brief muscular activations (≤ 1.5 s). Baseline and follow-up indices of neuromuscular performance focusing on muscle activation capacity (electromechanical delay [EMD], rate of force development [RFD] and peak force [PF]) were measured ipsilaterally using dynamometry and concomitant surface electromyography (m. rectus femoris[RF] and m. vastus lateralis[VL]).ResultsGroup mean ipsilateral knee extensor muscular activation capacity (EMDRF [F(3,57) = 53.5; p < 0.001]; EMDVL [F(3,57) = 50.0; p < 0.001]; RFD [F(3,57) = 10.5; p < 0.001]) and strength (PF [F(3,57) = 16.4; p < 0.001]) were significantly increased following APNEC (Cohen’s d, 0.5—1.8; 15% to 36% vs. baseline), but unchanged following no exercise control (per protocol, group by time interaction, factorial ANOVA, with repeated measures), with significant retention of gains at 1-week follow-up (p < 0.001).ConclusionsThe exploratory APNEC protocol elicited significant and clinically-relevant improvement and its retention in neuromuscular performance in patients awaiting TKA.Trial registration(date and number): clinicaltrial.gov: NCT03113032 (4/04/2017) and ISRCTN75779521 (3/5/2017).

A Randomised, Comparative, Effectiveness Trial Evaluating Low- versus High-Level Supervision of an Exercise Intervention for Women with Breast Cancer: The SAFE Trial.

Simple SummaryThe compelling evidence demonstrating the benefits of exercise to cancer survivors is biased towards ‘more well’ patients undertaking exercise interventions in tightly controlled (highly supervised) conditions. The aim of this trial was to evaluate the safety, feasibility, and effect of a 12-week exercise intervention delivered under ‘real-world’ conditions (that is, with low-level supervision, defined as five sessions across 12 weeks) compared with the same exercise intervention delivered under high-level supervision (20 sessions across 12 weeks). The understudied, less well women with breast cancer were the target population; that is, women with stage II or higher disease at diagnosis, and at least one comorbidity or treatment-related side-effect. The results showed that exercise was safe and feasible for this understudied breast cancer subgroup, and, while women who received the exercise intervention with low-level supervision experienced improvements in quality of life and physical function, greater gains in strength and exercise self-efficacy were observed for women who had the exercise intervention delivered via high-level supervision. Future research will determine whether the extra benefit gained through higher supervision levels lead to longer term quality of life and survival benefits.The aim of this comparative, effectiveness trial was to evaluate the safety, feasibility and effect of an exercise intervention delivered via low-level versus high-level supervision. The target population were women who were diagnosed with ≥stage II breast cancer, had ≥ one comorbidity and/or persistent treatment-related side-effects, and were insufficiently physically active. Sixty women (50 ± 9 years) were randomized to the low-supervision group (n = 30) or high-supervision group (n = 30). The low-supervision group participated in a 12-week, individually-tailored exercise intervention supported by five supervised sessions with an exercise professional. The high-supervision group participated in the same exercise intervention but received 20 supervised sessions across the 12-week period. The target weekly dosage of 600 metabolic equivalent minutes of exercise per week (MET-mins/wk) and the session content, such as safety and behaviour change topics, were standardized between the groups. The primary outcomes were intervention safety, defined as the number, type, and severity of exercise-related adverse events (e.g., musculoskeletal injury or exacerbated treatment-related side effects), and feasibility, which was defined as compliance to target exercise dosage. The effect of the intervention on quality of life, physical activity, self-efficacy, fitness, and strength was also assessed (pre- and post-intervention, and at 12-week follow-up). The intervention was safe, with no exercise-related adverse events of grade 3 or above in either group. Both groups reported high compliance to the target exercise dosage (median MET-mins/wk: High = 817; Low = 663), suggesting the exercise intervention was feasible, irrespective of supervision level. Improvements in quality of life, physical activity and fitness were observed post-intervention and maintained at follow-up for both groups (p < 0.05). Only the high-supervision group showed clinically-relevant improvements in strength and self-efficacy at post-intervention (p < 0.05). Individually-targeted exercise delivered under high- or low-levels of supervision is safe, feasible and beneficial for women with stage II+ breast cancer. Future research needs to assess whether the greater gains observed in the group who received higher supervision may contribute to longer term maintenance of physical activity levels and overall health benefits. Australian and New Zealand Clinical Trials Registry: ACTRN12616000547448.

Balneotherapy in spondyloarthropathy: A systematic review

To evaluate the effectiveness of balneotherapy on spondyloarthritis. Two authors independently searched the CENTRAL, MEDLINE, SCOPUS, EMBASE and WEB OF SCIENCE databases until July 2017, for randomized controlled trials published in French or English, that included participants, and interventions: adults with spondyloarthritis, treated by balneotherapy program or one of its components and compared with any other intervention or no treatment. Internal validity, external validity, quality of the statistical analysis, and publication bias were systematically evaluated. We report the best level of evidence. Nine articles were selected; the internal validity was high in two studies, average in one study, and low in six studies. With high internal validity, one study found a difference for pain between immersion in radon-rich water and tap water for the whole population or rheumatic disease, but the BASFI is not improved for the subgroup of patients with spondyloarthritis. The other study with high validity reported a significant 28-week improvement in quality of life and a composite index. In a study with moderate internal validity involving ankylosing spondylitis patients with associated with inflammatory bowel disease, a balneotherapy program demonstrated a relevant clinical improvement when compared to patients on waiting list. With low internal validity, TNFa inhibitors+spa therapy were found to be superior to a treatment with TNFa inhibitors alone in patients with psoriatic arthritis. Two trials with high validity demonstrated improvements, but this systematic review is not sufficient to prove the efficacy of balneotherapy in spondyloarthritis. More trials are needed with larger sample size to confirm the preliminary results observed and conclusively determine the benefits of balneotherapy.

Investigation of the efficacy and safety of ultrasoundstandardized autologous blood injection as treatment for lateral epicondylitis.

BackgroundThere are various conservative treatment options for lateral epicondylitis (LE). The aim is to evaluate pain, daily functioning, and complications after ultrasound-standardized autologous blood injections in patients with LE.MethodsFor this prospective cohort study, consecutive patients (>18 years) diagnosed with LE were included. Autologous blood was injected using a medical device containing an injection disposable with 12 small needles (Instant Tennis Elbow Cure [ITEC]) device. Patient-Rated Tennis Elbow Evaluation (PRTEE), subjective elbow score (SES), palpation and provocation pain, satisfaction, and complications of treatment were measured at baseline and two months after treatment. Paired t-tests and Fisher’s exact tests were used for calculating the difference between pre- and post-treatment outcomes.ResultsFifty-five elbows were analyzed. Mean time between pre- and post-treatment was 11.1 weeks (standard deviation [SD], 8.9 weeks). The mean PRTEE score decreased from 68.2 (SD, 15.7) before surgery to 53.2 (SD, 25.9; p<0.001) after. The mean SES improved from 36.9 (SD, 20.8) to 51.7 (SD, 27.4; p<0.001). Despite this improvement, only 44.7% of patients showed relevant clinical improvement in PRTEE, and 37.3% showed significant clinical improvement based on SES. Four patients reported a complication and the injection disposable failed three times.ConclusionsUltrasound-standardized autologous blood injection using the ITEC device is not an effective tool in reducing symptoms related to LE. This study showed that only half of all patients experienced a positive effect. In this heterogeneous cohort of patients, we showed no added value of ultrasound standardization.

Appraisal of vitreous syphilis antibody as a novel biomarker for the diagnosis of syphilitic uveitis: a prospective case-control study.

To determine the sensitivity and specificity of syphilis antibody tests in vitreous samples and to propose an algorithm using vitreous syphilis antibody as a supplementary test to confirm syphilitic uveitis (SU). A prospective case-control study was conducted at the Retina and Uveitis Clinic from May 2017 to January 2020. Initially, patients were classified based on syphilis serology into group 1 (positive testing) and group 2 (negative testing). Group 1 was further divided into 2 subgroups (group 1A and 1B) depending on their relevant clinical manifestations and clinical improvement. Group 2 served as a control group. Thirty-eight patients were enrolled in the study: 14 in group 1A, 5 in group 1B, and 19 in group 2B. No patient was assigned to group 2A. All patients in group 1A, representing definite SU, completed syphilis test (rapid plasma reagin [RPR], enzyme immunoassay [EIA], and fluorescent treponemal antibody-absorption [FTA-ABS]) for vitreous, and all vitreous samples yielded positive results. Of the 5 subjects in group 1B, 3 cases were considered to be not SU with different conditions, and 2 were indeterminate for SU. They presented with different features not typical of SU, and they had variable and fewer positive syphilis antibody responses. The most sensitive test for detecting syphilis antibodies in vitreous was EIA (90.9%), followed by RPR (80.0%) and FTA-ABS IgG (78.9%). EIA and FTA-ABS had the highest specificity, detecting 100% of the syphilis antibody. Vitreous analysis of syphilis antibody can serve as a supplementary test to confirm SU in selected cases as the proposed algorithm.

The REPAIR Study: Effects of Macitentan on RV Structure and Function in Pulmonary Arterial Hypertension

ObjectivesThe REPAIR (Right vEntricular remodeling in Pulmonary ArterIal hypeRtension) study evaluated the effect of macitentan on right ventricular (RV) and hemodynamic outcomes in patients with pulmonary arterial hypertension (PAH), using cardiac magnetic resonance (CMR) and right heart catheterization (RHC). BackgroundRV failure is the primary cause of death in PAH. CMR is regarded as the most accurate noninvasive method for assessing RV function and remodeling and CMR measures of RV function and structure are strongly prognostic for survival in patients with PAH. Despite this, CMR is not routinely used in PAH clinical trials. MethodsREPAIR was a 52-week, open-label, single-arm, multicenter, phase 4 study evaluating the effect of macitentan 10 mg, with or without phosphodiesterase type-5 inhibition, on RV remodeling and function and cardiopulmonary hemodynamics. Primary endpoints were change from baseline to week 26 in RV stroke volume, determined by CMR; and pulmonary vascular resistance, determined by RHC. Efficacy measures were assessed for all patients with baseline and week 26 data for both primary endpoints. ResultsAt a prespecified interim analysis in 42 patients, both primary endpoints were met, enrollment was stopped, and the study was declared positive. At final analysis (n = 71), RV stroke volume increased by 12 mL (96% confidence level: 8.4-15.6 mL; P < 0.0001) and pulmonary vascular resistance decreased by 38% (99% confidence level: 31%-44%; P < 0.0001) at week 26. Significant positive changes were also observed in secondary and exploratory CMR (RV and left ventricular), hemodynamic, and functional endpoints at week 26. Improvements in CMR RV and left ventricular variables and functional parameters were maintained at week 52. Safety (n = 87) was consistent with previous clinical trials. ConclusionsIn the context of this study, macitentan treatment in patients with PAH resulted in significant and clinically-relevant improvements in RV function and structure and cardiopulmonary hemodynamics. At 52 weeks, improvements in RV function and structure were sustained. (REPAIR: Right vEntricular remodeling in Pulmonary ArterIal hypeRtension [REPAIR]; NCT02310672)

The effectiveness of the information-motivation model and domestic brushing with a hypochlorite-based formula on peri-implant mucositis: A randomized clinical study.

ObjectiveManagement of mucositis is essential for the long‐term maintenance of dental implants. This study determined the efficacy, in terms of clinical parameters, of an adjunctive domiciliary agent paired with non‐surgical periodontal therapy (NSPT) for patients with peri‐implant mucositis.Materials and methodsPatients involved in a periodontal maintenance program were randomly distributed to the domestic use of a chlorhexidine toothpaste and mouthwash (control) or a hypochlorite‐based formula brushing solution (test) after diagnosis of peri‐implant mucositis. A modified approach towards NSPTwas performed after 10 days of domestic use of the assigned maintenance product in both groups. Clinical and patient‐related outcomes were recorded during a 90‐day follow‐up period.ResultsForty patients completed the three‐month study (20 patients per group). Both groups showed relevant clinical and patient outcome improvements after the NSPT (T2) and between T1 and T2 (p < 0 0.01), except for PPD. For the test group, the clinical improvement was significantly greater than that for the control group at the seventh‐day evaluation (T1) in the gingival index (0–3) and FMBS (%). Favorable outcomes were maintained during the entire follow‐up period.ConclusionThe present study showed that the modified NSPT paired with the domestic use of nitradine‐based formula helps resolve peri‐implant mucositis and that nitradine might represent an alternative to chlorhexidine in these cases.Clinical relevanceThe gold standard for nonsurgical maintenance is full‐mouth disinfection. A previous decontamination of the oral cavity with chlorhexidine or nitradine domiciliary for 10 days could reduce plaque and inflammation, resulting in a painless operative session. This protocol may help reduce airborne contamination and the risk of cross‐infection, and during the pandemic, the protocol is safer for clinicians. In the same clinical cases, nitradine may be more efficient than chlorhexidine, and the former has no side effects such as discolouration.

Repeated greater occipital nerve injections with corticosteroids in medically intractable chronic cluster headache: a retrospective study

IntroductionCurrent prophylactic drugs for cluster headache are associated with limited efficacy, serious side effects and poor tolerability. Greater occipital nerve injection (GON-injection) has been proven effective and safe as a single, one-time injection in episodic (ECH), and to a lesser extent, chronic cluster headache (CCH). We aim to analyse the effectiveness and safety of repeated GON-injections in medically intractable chronic cluster headache (MICCH).MethodsClinical data of all cluster headache patients who had received at least one GON-injection between 2014 and 2018 in our tertiary headache centre were retrieved from patients’ medical records. Clinical history was taken as part of routine care shortly before and 6 weeks after GON-injection.ResultsWe identified 47 MICCH patients (79 injections), and compared results with 22 non-MI CCH patients (30 injections) and 50 ECH patients (63 injections). Nineteen MICCH patients received repeated injections (32 in total, range 2–8). Rates of clinical relevant improvement to a first injection were similar in all groups (MICCH: 60%, non-MICCH 73%, ECH 76%; attack freedom: MICCH: 30%, non-MICCH 32%, ECH 43%). Furthermore, no difference in response to the first and second injection was shown between groups (all p > 0.29). Median effect duration in MICCH was 6 weeks (IQR 2.8–12 weeks). Side effects were only mild and local.ConclusionIn this retrospective analysis, first and repeated GON-injections were well-tolerated and equally effective in MICCH as in non-MICCH, and ECH.

Weight Loss Maintenance With Once-Weekly Semaglutide 2.4 MG in Adults With Overweight or Obesity Reaching Maintenance Dose (STEP 4)

Background: In people with overweight or obesity, long-term maintenance of weight loss is challenging. Subcutaneous (s.c.) semaglutide, a glucagon-like peptide-1 analogue, has shown clinically-relevant weight loss in a phase 2 trial in people with obesity. STEP 4 investigated the impact of continued semaglutide 2.4 mg treatment, vs switching to placebo, on maintenance of weight loss in participants who reached 2.4 mg of semaglutide during a run-in period. Methods: This was a 68-week withdrawal trial (NCT03548987) in 902 subjects aged ≥18 years with body mass index (BMI) ≥30 kg/m2 (or BMI ≥27 kg/m2 with ≥1 weight-related comorbidity), without diabetes. Following a 20 week run-in period, 803 subjects who reached the maintenance dose of once-weekly (OW) s.c. semaglutide 2.4 mg were randomized 2:1 to continue treatment with semaglutide 2.4 mg or switch to placebo for 48 weeks, both as adjunct to lifestyle intervention. The primary endpoint was percentage change in body weight between randomization (week 20) and week 68. Confirmatory secondary endpoints included change in waist circumference and systolic blood pressure. Two estimands were defined: treatment policy and trial product; results are presented for the treatment policy estimand, unless stated otherwise. Results: Mean body weight (±SD) was 107.2 ±22.7 kg at week 0 and 96.1 ±22.6 kg at randomization (week 20; mean change -10.6%). Randomized participants were mostly female (79%) and white (84%); mean age was 46 years and mean BMI was 34.4 kg/m2. Between weeks 20–68, estimated mean body weight change was −7.9% vs +6.9% for semaglutide 2.4 mg vs placebo (estimated treatment difference [ETD]: −14.8%; 95% confidence interval [CI]: −16.0, −13.5; p<0.0001), and -8.8% vs 6.5%, respectively, for the trial product estimand (ETD: -15.3%; 95% CI: -16.5, -14.1; p<0.0001). For participants randomized to continue semaglutide, the estimated change in body weight from week 0–68 was -17.4% (-18.2% for trial product estimand). Continued semaglutide treatment (weeks 20–68) led to clinically-relevant improvements in waist circumference, systolic blood pressure, BMI, HbA1c, FPG, and lipids (total cholesterol, LDL, VLDL, and triglycerides) vs switching to placebo (p<0.0001 for all). During the run-in period, 5.3% of participants discontinued treatment due to adverse events; during the randomized period, 2.4% (semaglutide) and 2.2% (placebo) discontinued. Nausea, diarrhea and constipation (mostly transient and mild-to-moderate) were the most frequent adverse events with semaglutide. Conclusion: In adults with overweight or obesity, continued treatment after dose escalation with OW s.c. semaglutide 2.4 mg until week 68 led to clinically-relevant weight loss, while switching to placebo led to significant weight regain; these data underscore the chronicity and relapsing nature of obesity, and the need for continued treatment.

Impact of effective regurgitant orifice area on outcome of secondary mitral regurgitation transcatheter repair

ObjectivesTo assess the value of effective regurgitant orifice (ERO) in predicting outcome after edge-to-edge transcatheter mitral valve repair (TMVR) for secondary mitral regurgitation (SMR) and identify the optimal cut-off for patients’ selection.MethodsUsing the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) registry, that included patients undergoing edge-to-edge TMVR for SMR between November 2008 and January 2019 in 8 experienced European centres, we assessed the optimal ERO threshold associated with mortality in SMR patients undergoing TMVR, and compared characteristics and outcomes of patients according to baseline ERO.ResultsAmong 1062 patients with severe SMR and ERO quantification by proximal isovelocity surface area method in the registry, ERO was < 0.3 cm2 in 575 patients (54.1%), who were more symptomatic at baseline (NYHA class ≥ III: 91.4% vs. 86.9%, for ERO < vs. ≥ 0.3 cm2; P = 0.004). There was no difference in all-cause mortality at 2-year follow-up according to baseline ERO (28.3% vs. 30.0% for ERO < vs. ≥ 0.3 cm2, P = 0.585). Both patient groups demonstrated significant improvement of at least one NYHA class (61.7% and 73.8%, P = 0.002), resulting in a prevalence of NYHA class ≤ II at 1-year follow-up of 60.0% and 67.4% for ERO < vs. ≥ 0.3 cm2, respectively (P = 0.05).ConclusionAll-cause mortality at 2 years after TMVR does not differ if baseline ERO is < or ≥ 0.3 cm2, and both groups exhibit relevant clinical improvements. Accordingly, TMVR should not be withheld from patients with ERO < 0.3 cm2 who remain symptomatic despite optimal medical treatment, if TMVR appropriateness was determined by experienced teams in dedicated valve centres.

UNISON - nivolumab then ipilimumab + nivolumab in advanced non-clear cell renal cell carcinoma (ANZUP 1602): Part 1—Nivolumab monotherapy.

325 Background: Immune checkpoint inhibitors (ICI) are active in many cancers, but people with rare variant, non clear-cell renal cell carcinoma (nccRCC) have been excluded from most clinical trials in RCC. UNISON (NCT03177239) aimed to test 2 hypotheses; the activity of nivolumab in nccRCC (Part 1), and the benefit of adding ipilimumab to nivolumab, in people whose cancers progress on nivolumab (Part 2). Methods: 83 participants (pts) with advanced nccRCC with good (ECOG0/1) performance status, were enrolled including papillary type 1 (17%), papillary type 2 (28%), chromophobe (18%), Xp11 translocation (6%), hereditary leiomyomatosis renal cell carcinoma syndrome-associated renal cell carcinoma (6%), RCC unclassified (10%) and other (15%) histological subtypes. Participants took nivolumab (N) 240mg every two weeks in Part 1 in total. If they experienced progression and remained eligible they could take N (3mg/kg) plus ipilimumab (I; 1mg/kg) every 3 weeks for up to 4 doses (Part 2). Pts with disease control after N or N + I could continue N for up to 1 year. UNISON was powered to distinguish a clinically-relevant improvement in objective tumor response rate (OTRR) from 15% to 30% in people taking N+I in Part 2 in pts whose cancers were refractory to single-agent first-line N. Here we report results of Part 1. Results: Pts experience of N appeared similar to previous reports, with most experiencing mild adverse events. 12 treatment related SAE occurred in 11 patients (13%). 14 pts (17%) experienced treatment delays, or permanent treatment discontinuation (10%). The median time on treatment was 5.1 months. The OTRR was 17% with 3 complete responses and 11 partial responses. The median duration of response was 21 months. Stable disease occurred in 49% of pts and disease progression in 34%. The disease control rate at 6 months was 45% (95% CI: 34%, 56%). The median PFS was 4.0 months (95% CI: 3.6, 7.4). The 6 month progression-free survival (PFS) was 45% (95% CI: 34-55) and the 12 months PFS was 30% (95% CI: 21%, 40%). Conclusions: Pts with nccRCC treated with N experience similar adverse events compared to pts with other cancers. A substantial minority of people with nccRCC derive benefit, but many pts have cancers refractory to anti-PD1, similar to other reports. The activity of I and N in this PD1-refractory population is of considerable interest and will be reported at a later date. Clinical trial information: NCT03177239 .

Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).

Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).