Effect of thyroid hormone replacement therapy on mortality rate in patients undergoing total or hemithyroidectomy for benign multinodular goitre.

BACKGROUND: Thyroid surgery for benign non-toxic nodular goitre is a common endocrine surgical procedure. It is not known whether thyroid hormone replacement therapy following surgery for benign thyroid disease influences mortality or morbidity rates. METHODS: A retrospective observational study was conducted using national registries in Sweden. Overall mortality and morbidity rates were compared for patients with or without thyroid hormone replacement therapy in patients operated on with hemithyroidectomy or total thyroidectomy for a diagnosis of benign non-toxic nodular goitre. RESULTS: Between 1 July 2006 and 31 December 2017, 5573 patients were included, 1644 (29.5%) patients were operated on with total thyroidectomy and 3929 patients with hemithyroidectomy. In the hemithyroidectomy group, 1369 (34.8%) patients were prescribed thyroid hormone replacement therapy in the follow-up. The patients who underwent hemithyroidectomy and did not use thyroid hormone replacement therapy in the follow-up had a standard mortality ratio of 1.31 (95% confidence interval, 1.09-1.54). The mortality ratio was not increased in patients who underwent total thyroidectomy or hemithyroidectomy and used thyroid hormone replacement therapy. The risk of death analysed by multivariable Cox regression for patients operated on with hemithyroidectomy without later thyroid hormone replacement therapy, adjusted for age and sex, showed an increased hazard ratio of 1.65 (1.19-2.30) compared with hemithyroidectomy with hormone replacement therapy. CONCLUSION: Patients subjected to hemithyroidectomy without later hormone replacement therapy had a 30% higher risk of death compared with the normal Swedish population and a 65% increased risk of death compared with patients undergoing hemithyroidectomy with postoperative hormone replacement therapy.

Early intervention with ColdZyme mouth spray after self-diagnosis of common cold: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Previous clinical and in vitro investigations have supported the efficacy of a glycerol throat spray containing cold-adapted cod trypsin (ColdZyme) against respiratory viruses causing the common cold bycreating a protective mucosal barrier shown to deactivate common cold virus in vitro and decrease pharyngeal rhinovirus load. METHODS AND FINDINGS: This was a double-blind, randomized, parallel-group, placebo-controlled study conducted at 10 German sites to evaluate the efficacy of the medical device ColdZyme, a glycerol mouth spray containing cold-adapted cod trypsin for a naturally occurring common cold versus placebo spray. Adults experiencing a minimum of three common colds during the previous year, but otherwise healthy, were enrolled to begin treatment with the mouth spray or placebo six times daily at first sign of a common cold. Jackson's symptom scale and the 9-item Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) quality of life (QoL) domain and a sore throat scale were recorded daily by subjects, as well as any use of allowed rescue treatment. Between January and April 2019, 701 subjects were enrolled and randomly assigned to the ColdZyme group (n = 351) or the placebo group (n = 350). Of the 701 subjects, 438 (62.5%) subjects developed symptoms typical of common cold, and all 438 started study treatment (n = 220 in the ColdZyme group and n = 218 in the placebo group). The demographic profile of the treatment groups were comparable with 68.1% female and almost all subjects being Caucasian (98.4%). The age ranged between 18 and 70 years with a mean age of 41.3 (±14.4) years. There were no differences between the groups in primary and major secondary endpoints, however, the assessment using the WURSS-21 QoL domain and Jackson score suggests a slightly faster recovery with ColdZyme as symptoms and complaints affecting the quality of life were shortened by about 1 day. The beneficial effect of ColdZyme was particularly noticeable on the fifth day of the common cold. A positive difference between treatment groups was also seen for the subjects' assessments of global efficacy of the investigational product A robust safety profile for ColdZyme was demonstrated throughout the study. CONCLUSION: The safety and tolerability of ColdZyme have been confirmed in a large study population and further establishes evidence of a faster recovery from common cold symptoms. Early self-diagnosis and early use of ColdZyme mouth spray is a safe alternative for treatment of naturally occurring colds.

Early intervention with a glycerol throat spray containing cold-adapted cod trypsin after self-diagnosis of common cold: A randomised trial.

BACKGROUND: A glycerol throat spray containing cold-adapted cod trypsin (GCTS) deactivates common cold virus in vitro and decreases pharyngeal rhinovirus load after inoculation in humans. We relied on early self-diagnosis and evaluated two different scales to detect a treatment effect in naturally occurring common colds. METHODS: Adults were enrolled in this randomised, prospective, parallel group, single-blind study to begin treatment six times daily at first sign of a common cold or were assigned to a non-treated group. Jackson's symptom scale and the 9-item Wisconsin Upper Respiratory Symptom Survey (WURSS)-21 quality of life (QoL) domain were recorded daily by subjects and area under the curve over 12 days (AUC1-12) calculated. RESULTS: Treatment resulted in reduced symptoms with an AUC1-12 of 45.1 ± 32.5 for Jackson scores compared to 53.8 ± 35.7 in the controls (p = 0.023). AUC1-12 for the 9-item WURSS-21 QoL domain was likewise improved, 113.6 ± 107.7 and 152.7 ± 126.3 (p = 0.006), respectively. During the first four days fewer of the treated subjects (35.3%) used rescue medication than did the control group (50.4%, p = 0.014). CONCLUSIONS: Reduction in common cold symptoms was seen with treatment with a glycerol throat spray containing cold-adapted cod trypsin. This effect was best detected with the 9-item WURSS-21 QoL domain.

Extended Follow-up of Local Steroid Injection for Carpal Tunnel Syndrome: A Randomized Clinical Trial.

Importance: Local steroid injection is commonly used in treating patients with idiopathic carpal tunnel syndrome, but evidence regarding long-term efficacy is lacking. Objective: To assess the long-term treatment effects of local steroid injection for carpal tunnel syndrome. Design, Setting, and Participants: This exploratory 5-year extended follow-up of a double-blind, placebo-controlled randomized clinical trial was conducted from November 2008 to March 2012 at a university hospital orthopedic department. Participants included patients aged 22 to 69 years with primary idiopathic carpal tunnel syndrome and no prior treatment with local steroid injections. Data were analyzed from May 2018 to August 2018. Interventions: Patients were randomized to injection of 80 mg methylprednisolone, 40 mg methylprednisolone, or saline. Main Outcomes and Measures: The coprimary outcomes were the symptom severity score and rate of subsequent carpal tunnel release surgery on the study hand at 5 years. Secondary outcomes were time from injection to surgical treatment, SF-36 bodily pain score, and score on the 11-item disabilities of the arm, shoulder, and hand scale. Results: A total of 111 participants (mean [SD] age at follow-up, 52.9 [11.6] years; 81 [73.0%] women and 30 [27.0%] men) were randomized, with 37 in the 80 mg methylprednisolone group, 37 in the 40 mg methylprednisolone group, and 37 in the saline placebo group. Complete 5-year follow-up data were obtained from all 111 participants with no dropouts (100% follow-up). At baseline, mean (SD) symptom severity scores were 2.93 (0.85) in the 80 mg methylprednisolone group, 3.13 (0.70) in the 40 mg methylprednisolone group, and 3.18 (0.75) in the placebo group, and at the 5-year follow up, mean (SD) symptom severity scores were 1.51 (0.66) in the 80 mg methylprednisolone group, 1.59 (0.63) in the 40 mg methylprednisolone group, and 1.67 (0.74) in the placebo group. Compared with placebo, there was no significant difference in mean change in symptom severity score from baseline to 5 years for the 80 mg methylprednisolone group (0.14 [95%CI, -0.17 to 0.45]) or the 40 mg methylprednisolone group (0.12 [95%CI, -0.19 to 0.43]). After injection, subsequent surgical treatment on the study hand was performed in 31 participants (83.8%) in the 80 mg methylprednisolone group, 34 participants (91.9%) in the 40 mg methylprednisolone group, and 36 participants (97.3%) in the placebo group; the number of participants who underwent surgical treatment between the 1-year and 5-year follow-ups was 4 participants (10.8%) in the 80 mg methylprednisolone group, 4 participants (10.8%) in the 40 mg methylprednisolone group, and 2 participants (5.4%) in the placebo group. All surgical procedures were conducted while participants and investigators were blinded to type of injection received. The mean (SD) time from injection to surgery was 180 (121) days in the 80 mg methylprednisolone group, 185 (125) days in the 40 mg methylprednisolone group, and 121 (88) days in the placebo group. Kaplan-Meier survival curves showed statistically significant difference in time to surgical treatment (log-rank test: 80 mg methylprednisolone vs placebo, P = .002 ; 40 mg methylprednisolone vs placebo, P = .02; methylprednisolone 80 mg vs 40 mg, P = .37). Conclusions and Relevance: These findings suggest that in idiopathic carpal tunnel syndrome, local methylprednisolone injection resulted in statistically significant reduction in surgery rates and delay in need for surgery. Trial Registration: ClinicalTrials.gov Identifiers: NCT00806871 and NCT02652390.

Impact of Adrenalectomy on Morbidity in Patients with Non-Functioning Adrenal Cortical Tumours, Mild Hypercortisolism and Cushing's Syndrome as Assessed by National and Quality Registries.

BACKGROUND: The impact of adrenalectomy on morbidity in patients with mild hypercortisolism and non-functioning adrenocortical adenoma is unclear. The present study evaluated morbidity before and after adrenalectomy in patients with benign adrenocortical tumour with Cushing´s syndrome (CS), autonomous cortisol secretion (ACS) and non-functioning adrenocortical adenoma as assessed by national and quality registries. METHODS: Patients registered in the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery (SQRTPA) 2009-2017 with CS, ACS or non-functioning adrenocortical adenoma, were included in this retrospective study and analysed with age- and sex-matched controls, 1:3. Morbidity associated with CS was assessed pre- and postoperatively by analysing data from the Swedish National Patient Register and the Swedish Prescribed Drug Register. RESULTS: Some 271 patients were included, CS (127), ACS (45) and non-functioning adrenocortical adenoma (99), with 813 matched controls. The frequency of hypertension was almost 50% in all tumour groups. Antihypertensive medication preoperatively was more frequent in all tumour groups compared with controls. No preoperative differences in medication were detected between patients with CS and ACS. A decrease in the use of hypertensive drugs was noticed annually for all patient groups after adrenalectomy. CONCLUSIONS: Hypertension is common in patients with benign adrenocortical tumours regardless of cortisol hypersecretion. The use of antihypertensive drugs in patients with CS, ACS and non-functioning adrenocortical adenoma was reduced after adrenalectomy. These findings highlight the need for a randomized controlled trial to investigate the impact of adrenalectomy on morbidity in patients with mild hypercortisolism.

Outcomes With Surgery vs Functional Bracing for Patients With Closed, Displaced Humeral Shaft Fractures and the Need for Secondary Surgery: A Prespecified Secondary Analysis of the FISH Randomized Clinical Trial.

IMPORTANCE: Existing evidence indicates that surgery fails to provide superior functional outcome over nonoperative care in patients with a closed humeral shaft fracture. However, up to one-third of patients treated nonoperatively may require secondary surgery. OBJECTIVE: To compare the 2-year outcomes of patients who required secondary surgery with the outcomes of patients with successful initial treatment. DESIGN, SETTING, AND PARTICIPANTS: This 2-year follow-up of the Finnish Shaft of the Humerus (FISH) randomized clinical trial comparing surgery with nonoperative treatment (functional brace) was completed in January 2020. Enrollment in the original trial was between November 2012 and January 2018 at 2 university hospital trauma centers in Finland. A total of 321 adult patients with closed, displaced humeral shaft fracture were assessed for eligibility. After excluding patients with cognitive disabilities, multimorbidity, or multiple trauma and those refusing randomization, 82 patients were randomized. INTERVENTIONS: Interventions were surgery with plate fixation (n = 38; initial surgery group) or functional bracing (n = 44); the latter group was divided into the successful fracture healing group (n = 30; bracing group) and the secondary surgery group (n = 14) with fracture healing problems. MAIN OUTCOMES AND MEASURES: The primary outcome was Disabilities of Arm, Shoulder and Hand (DASH) score at 2 years (range, 0 to 100 points; 0 denotes no disability, 100 extreme disability; minimal clinically important difference, 10 points). RESULTS: Of 82 randomized patients, 38 (46%) were female. The mean (SD) age was 48.9 (17.1) years. A total of 74 patients (90%) completed the 2-year follow-up. At 2 years, the mean DASH score was 6.8 (95% CI, 2.3 to 11.4) in the initial surgery group, 6.0 (95% CI, 1.0 to 11.0) in the bracing group, and 17.5 (95% CI, 10.5 to 24.5) in the secondary surgery group. The between-group difference was -10.7 points (95% CI, -19.1 to -2.3; P = .01) between the initial and secondary surgery groups and -11.5 points (95% CI, -20.1 to -2.9; P = .009) between the bracing group and secondary surgery group. CONCLUSIONS AND RELEVANCE: Patients contemplating treatment for closed humeral shaft fracture should be informed that two-thirds of patients treated with functional bracing may heal successfully while one-third may experience fracture healing problems that require secondary surgery and lead to inferior functional outcomes 2 years after the injury. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01719887.

Subacromial decompression versus diagnostic arthroscopy for shoulder impingement: a 5-year follow-up of a randomised, placebo surgery controlled clinical trial.

OBJECTIVES: To assess the long-term efficacy of arthroscopic subacromial decompression (ASD) by comparing it with diagnostic arthroscopy (primary comparison), a placebo surgical intervention, and with a non-operative alternative, exercise therapy (secondary comparison). METHODS: We conducted a multicentre, three group, randomised, controlled superiority trial. We included 210 patients aged 35-65 years, who had symptoms consistent with shoulder impingement syndrome for more than 3 months. 175 participants (83%) completed the 5 years follow-up. Patient enrolment began on 1 February 2005 and the 5-year follow-up was completed by 10 October 2018. The two primary outcomes were shoulder pain at rest and on arm activity measured with Visual Analogue Scale (VAS). Minimally important difference (MID) was set at 15. We used a mixed-model repeated measurements analysis of variance with participant as a random factor, the baseline value as a covariate and assuming a covariance structure with compound symmetry. RESULTS: In the primary intention to treat analysis (ASD vs diagnostic arthroscopy), there were no between-group differences that exceeded the MID for the primary outcomes at 5 years: the mean difference between groups (ASD minus diagnostic arthroscopy) in pain VAS were -2.0 (95% CI -8.5 to 4.6; p=0.56) at rest and -8.0 (-17.3 to 1.3; p=0.093) on arm activity. There were no between-group differences in the secondary outcomes or adverse events that exceeded the MID. In our secondary comparison (ASD vs exercise therapy), the mean differences between groups (ASD minus exercise therapy) in pain VAS were 1.0 (-5.6 to 7.6; p=0.77) at rest and -3.9 (-12.8 to 5.1; p=0.40) on arm activity. There were no significant between-group differences for the secondary outcomes or adverse events. CONCLUSIONS: ASD provided no benefit over diagnostic arthroscopy (or exercise therapy) at 5 years for patients with shoulder impingement syndrome.

Single postoperative infusion of zoledronic acid to improve patient-reported outcome after hip or knee replacement: study protocol for a randomised, controlled, double-blinded clinical trial.

INTRODUCTION: In Sweden, roughly 3000 patients are reoperated each year due to pain and loss of function related to a loosened hip or knee prosthesis. These reoperations are strenuous for the patient, technically demanding and costly for the healthcare system. Any such reoperation that can be prevented would be of great benefit. Bisphosphonates are drugs that inhibit osteoclast function. Several clinical trials suggest that bisphosphonates lead to improved implant fixation and one small study even indicates better functional outcome. Furthermore, in epidemiological studies, bisphosphonates have been shown to decrease the rate of revision for aseptic loosening by half. Thus, there are several indirect indications that bisphosphonates could improve patient-reported outcome, but no firm evidence. METHODS AND ANALYSIS: This is a pragmatic randomised, placebo-controlled, double-blinded, academic clinical trial of a single postoperative dose of zoledronic acid, in patients younger than 80 years undergoing primary total hip or knee replacement for osteoarthritis. Participants will be recruited from two orthopaedic departments. All surgeries will be performed, and study drugs given at Motala Hospital, Sweden. The primary endpoint is to investigate between-group differences in the Hip dysfunction and Osteoarthritis Outcome Score and the Knee injury and Osteoarthritis Outcome Score at 3-year follow-up. Secondary outcomes will be investigated at 1 year, 3 years and 6 years, and stratified for hip and knee implants. These secondary endpoints are supportive, exploratory or explanatory. A total of 1000 patients will be included in the study. ETHICS AND DISSEMINATION: The study has been approved by the Regional Ethical Review Board in Linköping (DNR 2015/286-31). The study will be reported in accordance with the Consolidated Standards of Reporting Trials statement for pharmacological trials. The results will be submitted for publication in peer-reviewed academic journals and disseminated to patient organisations and the media. TRIAL REGISTRATION NUMBER: EudraCT: No 2015-001200-55; Pre-results.

Finnish study of intraoperative irrigation versus drain alone after evacuation of chronic subdural haematoma (FINISH): a study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Chronic subdural haematomas (CSDHs) are one of the most common neurosurgical conditions. The goal of surgery is to alleviate symptoms and minimise the risk of symptomatic recurrences. In the past, reoperation rates as high as 20%-30% were described for CSDH recurrences. However, following the introduction of subdural drainage, reoperation rates dropped to approximately 10%. The standard surgical technique includes burr-hole craniostomy, followed by intraoperative irrigation and placement of subdural drainage. Yet, the role of intraoperative irrigation has not been established. If there is no difference in recurrence rates between intraoperative irrigation and no irrigation, CSDH surgery could be carried out faster and more safely by omitting the step of irrigation. The aim of this multicentre randomised controlled trial is to study whether no intraoperative irrigation and subdural drainage results in non-inferior outcome compared with intraoperative irrigation and subdural drainage following burr-hole craniostomy of CSDH. METHODS AND ANALYSIS: This is a prospective, randomised, controlled, parallel group, non-inferiority multicentre trial comparing single burr-hole evacuation of CSDH with intraoperative irrigation and evacuation of CSDH without irrigation. In both groups, a passive subdural drain is used for 48 hours as a standard of treatment. The primary outcome is symptomatic CSDH recurrence requiring reoperation within 6 months. The predefined non-inferiority margin for the primary outcome is 7.5%. To achieve a 2.5% level of significance and 80% power, we will randomise 270 patients per group. Secondary outcomes include modified Rankin Scale, rate of mortality, duration of operation, length of hospital stay, adverse events and change in volume of CSDH. ETHICS AND DISSEMINATION: The study was approved by the institutional review board of the Helsinki and Uusimaa Hospital District (HUS/3035/2019 §238) and duly registered at ClinicalTrials.gov. We will disseminate the findings of this study through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04203550.

Effect of Surgery vs Functional Bracing on Functional Outcome Among Patients With Closed Displaced Humeral Shaft Fractures: The FISH Randomized Clinical Trial.

Importance: Humeral shaft fractures traditionally have been treated nonsurgically, but there has been a steady increase in the rate of surgery over the past 2 decades without high-quality evidence to justify the trend. Objective: To compare the effectiveness of surgical treatment with open reduction and internal plate fixation to nonsurgical treatment with functional bracing in the treatment of closed humeral shaft fractures. Design, Setting, and Participants: Randomized clinical trial conducted at 2 university hospital trauma centers in Finland, enrollment between November 2012 and January 2018 with a final follow-up of January 2019. A total of 82 adult patients with closed, unilateral, displaced humeral shaft fracture met criteria for inclusion. Patients were excluded if they had cognitive disabilities preventing them from following the protocol or had multimorbidity or multiple trauma. Interventions: Patients were randomly assigned to surgical treatment with open reduction and internal plate fixation (n = 38) or to nonsurgical treatment with functional bracing (n = 44). Main Outcome and Measure: The primary outcome was Disabilities of Arm, Shoulder and Hand (DASH) score at 12 months (range, 0 to 100 points, 0 denotes no disability and 100 extreme disability; minimal clinically important difference, 10 points). Results: Among 82 patients who were randomized (mean age, 48.9 years; 38 women [46%]; 44 men [54%]), 78 (95%) completed the trial. Thirteen (30%) of the patients assigned to functional bracing underwent surgery during the 12-month follow-up period to promote healing of the fracture. At 12 months, the mean DASH score was 8.9 (95% CI, 4.2 to 13.6) in the surgery group and 12.0 (95% CI, 7.7 to 16.4) in the bracing group (between-group difference, -3.1 points; 95% CI, -9.6 to 3.3; P = .34). Eleven patients (25%) allocated to functional bracing developed fracture nonunion. Three patients (8%) allocated to surgery developed a temporary radial nerve palsy. Conclusions and Relevance: Among patients with closed humeral shaft fracture, internal fixation surgery, compared with nonoperative functional bracing, did not significantly improve functional outcomes at 12 months. However, the substantial amount of treatment crossover from nonoperative to surgical treatment should be considered when interpreting the trial results. Trial Registration: ClinicalTrials.gov Identifier: NCT01719887.

Education, Home Exercise, and Supervised Exercise for People With Hip and Knee Osteoarthritis As Part of a Nationwide Implementation Program: Data From the Better Management of Patients With Osteoarthritis Registry.

OBJECTIVE: To compare the effectiveness of education (ED) plus home exercise (HE) and ED plus supervised exercise (SE) according to information provided by the Better Management of Patients With Osteoarthritis (BOA) Registry, a nationally implemented rehabilitation program for patients with hip and knee osteoarthritis (OA). In addition, we investigated whether or not the effect of the treatments differed based on the joint affected by OA (hip versus knee). METHODS: We included 38,030 participants from the BOA Registry with knee or hip OA who were treated with either ED, HE, or SE. The effect of the 3 treatment options on the pain intensity reduction (range 0-10) immediately postintervention and at 12 months was estimated using a mixed-effects model adjusted for age, sex, body mass index, affected joint (hip or knee), pain at baseline, comorbidity, and level of education. RESULTS: The participants undergoing HE or SE experienced a greater pain reduction compared to participants who received ED, both after the treatment (group mean change for ED -0.91 [95% confidence interval (95% CI) -1.15, -0.68], for HE -1.06 [95% CI -1.10, -1.01], and for SE -1.12 [95% CI -1.15, -1.08]) and at 12 months (group mean change for ED -0.58 [95% CI -0.87, -0.30], for HE -0.82 [95% CI -0.87, -0.76], and for SE -0.82 [95% CI -0.86, -0.77]). Patients with knee OA who underwent HE or SE improved more compared to patients with hip OA at both follow-ups. CONCLUSION: In primary care, HE and SE lead to similar reductions in pain intensity but are more effective than ED alone. In addition, people with knee OA benefit more from HE and SE than people with hip OA.

Treatment of carpal tunnel syndrome with wrist splinting: study protocol for a randomized placebo-controlled trial.

BACKGROUND: Carpal tunnel syndrome (CTS) is a common cause of pain, weakness, sensory loss, and activity limitations. Currently, the most common initial treatment is use of a rigid splint immobilizing the wrist, usually during night-time, for several weeks. Evidence regarding the efficacy and effect durability of wrist splinting is weak. The treatment is associated with costs and may cause discomfort and limit daily and work activities. No placebo-controlled trials have been performed. METHODS: This is a randomized controlled trial designed to assess the efficacy of a rigid wrist splint compared with soft wrist bandage (placebo) in patients with primary idiopathic CTS. The trial will be conducted at an orthopedic department. Patients, 25 to 65 years old, who seek primary health-care with symptoms of CTS will be screened, and potentially eligible patients will be referred to the study center. Patients who fulfill the trial's eligibility criteria will be invited to participate. A total of 112 patients who provide informed consent will be randomly assigned to treatment with either a rigid wrist splint or a soft bandage to be used initially for 6 weeks at night and, if possible, during the day. The splints and bandages will be fitted with a temperature-monitoring device to measure the total time during which they have actually been worn. The trial participants will complete a questionnaire that includes the 6-item CTS symptoms scale (CTS-6); the 11-item disabilities of the arm, shoulder, and hand (QuickDASH) scale; and the EuroQol 5-dimension (EQ-5D) health status and quality-of-life measure at baseline and at 6, 12, 24, and 52 weeks after treatment start. The participants will undergo physical examination and nerve conduction testing at baseline and at 52 weeks. The trial's primary outcomes are the change in the CTS-6 score from baseline to 12 weeks and the rate of carpal tunnel release surgery at 52 weeks. DISCUSSION: This is the first placebo-controlled randomized trial with electronic monitoring of actual splint use and will provide evidence regarding the efficacy of wrist splinting in patients with CTS. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN81836603 . Registered on May 5, 2018.

Improper study design precludes valid effect estimates in important suicide prevention research.

The observational study design for estimating accuracy of diagnostic tests for suicide risk in clinical work is not ideal, due to the effects of directed suicide prevention to the high-risk group. This is an example of the confounding by indication and protopathic bias, which lead to misinterpretation of the accuracy terms sensitivity and specificity. The simple arithmetic mechanism presented here, forces the conclusion that the accuracy estimates sensitivity and specificity, applied in open prospective trials of surmised diagnostic tests for suicide risk, cannot be normally interpreted as accuracy estimators. Further, the related concept "prediction of suicide" is shown to be fundamentally illogical and should not be used in the present context. All these statements reveal a far-reaching problem within the suicide prevention research: Conclusions regarding the usefulness of diagnostic tests of suicide risk in the vast previous research since decades deserve reinterpretation. Diagnostic tests per se, can possess highly qualitative properties in estimating important suicidological aspects regarding a patient, but, when studied in an open design study, it cannot be demonstrated. This problem concerns rating scales and any biological and psychological tests in medicine, when confounding factors, for example, suicide prevention, influence the outcome because of the test result per se.

Evaluation of a digital platform for osteoarthritis treatment: study protocol for a randomised clinical study.

INTRODUCTION: Despite favourable results from structured face-to-face treatment of osteoarthritis (OA) in Sweden through the Better management of patients with OsteoArthritis (BOA) initiative, only around 20% of people with knee or hip OA receive the primary treatment recommended by international guidelines (ie, information, exercise, weight management). In 2014, a digital treatment programme named Joint Academy was introduced in Sweden, based on the same concept as the face-to-face BOA programme. In line with BOA, Joint Academy follows national and international guidelines and best practice for OA treatment. Results from observational studies suggest that this digital treatment is a valuable alternative to the traditional treatment approach and can positively impact patients' function and pain. However, conclusions from such studies commonly suggest that more rigorous testing is necessary to ascertain the benefits of digital treatment delivery for people with OA. METHODS AND ANALYSIS: A randomised clinical trial will be performed, comparing regular face-to-face care according to BOA with the digital version, Joint Academy. A total of 270 participants with clinically diagnosed knee OA will be recruited at primary care centres and randomised to either standard treatment (BOA) for 3 months, or the experimental group (digital intervention programme). Both groups will receive educational sessions and exercises yet with a difference in programme deliverance. The objective of the trial is to evaluate the effectiveness of the online treatment programme, in comparison with BOA. The two treatment groups will be compared with respect to the number of repetitions of the 30 s chair stand test at 3, 6 and 12 months, using a mixed model repeated measures analysis of variance. ETHICS AND DISSEMINATION: Ethical approval has been attained from the Regional Board of Ethics in Lund, Sweden (Dnr 2017/719). Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03328741.

Subacromial decompression versus diagnostic arthroscopy for shoulder impingement: randomised, placebo surgery controlled clinical trial.

OBJECTIVE: To assess the efficacy of arthroscopic subacromial decompression (ASD) by comparing it with diagnostic arthroscopy, a placebo surgical intervention, and with a non-operative alternative, exercise therapy, in a more pragmatic setting. DESIGN: Multicentre, three group, randomised, double blind, sham controlled trial. SETTING: Orthopaedic departments at three public hospitals in Finland. PARTICIPANTS: 210 patients with symptoms consistent with shoulder impingement syndrome, enrolled from 1 February 2005 with two year follow-up completed by 25 June 2015. INTERVENTIONS: ASD, diagnostic arthroscopy (placebo control), and exercise therapy. MAIN OUTCOME MEASURES: Shoulder pain at rest and on arm activity (visual analogue scale (VAS) from 0 to 100, with 0 denoting no pain), at 24 months. The threshold for minimal clinically important difference was set at 15. RESULTS: In the primary intention to treat analysis (ASD versus diagnostic arthroscopy), no clinically relevant between group differences were seen in the two primary outcomes at 24 months (mean change for ASD 36.0 at rest and 55.4 on activity; for diagnostic arthroscopy 31.4 at rest and 47.5 on activity). The observed mean difference between groups (ASD minus diagnostic arthroscopy) in pain VAS were -4.6 (95% confidence interval -11.3 to 2.1) points (P=0.18) at rest and -9.0 (-18.1 to 0.2) points (P=0.054) on arm activity. No between group differences were seen between the ASD and diagnostic arthroscopy groups in the secondary outcomes or adverse events. In the secondary comparison (ASD versus exercise therapy), statistically significant differences were found in favour of ASD in the two primary outcomes at 24 months in both VAS at rest (-7.5, -14.0 to -1.0, points; P=0.023) and VAS on arm activity (-12.0, -20.9 to -3.2, points; P=0.008), but the mean differences between groups did not exceed the pre-specified minimal clinically important difference. Of note, this ASD versus exercise therapy comparison is not only confounded by lack of blinding but also likely to be biased in favour of ASD owing to the selective removal of patients with likely poor outcome from the ASD group, without comparable exclusions from the exercise therapy group. CONCLUSIONS: In this controlled trial involving patients with a shoulder impingement syndrome, arthroscopic subacromial decompression provided no benefit over diagnostic arthroscopy at 24 months. TRIAL REGISTRATION: Clinicaltrials.gov NCT00428870.