Treatment outcome at 1 year did not differ between use of cast or walker in the first 3 weeks after an acute Achilles tendon rupture. A registry study of 1304 patients from the Danish Achilles tendon database.

BACKGROUND: The best choice of orthosis in the treatment of acute Achilles tendon rupture is still under debate. OBJECTIVE: To investigate if choice of orthosis in the first 3 weeks of treatment affected patient reported outcome (Achilles tendon Total Rupture Score (ATRS)), tendon elongation (Achilles Tendon Resting Angle (ATRA) and Heel Rise Height (HRH)) and re-rupture. METHODS: Registry study in the Danish Achilles tendon Database. Patients treated with cast and patients treated with walker in the first 3 weeks of treatment were compared using a linear mixed-effects model adjusted for potential confounders. RESULTS: 1304 patients were included in the study. No clinically relevant difference was found: Adjusted mean difference (using walker the whole period as reference)(95% CI) ATRS after 1 year = 0.1(-3.0; 4.1), ATRS after 6 months = 2.0(-4.5; 5.8), ATRS after 2 years = 3.0(-0.7; 7.0), HRH difference = 0.6(-6.6; 8.2), ATRA difference = 0.03°(-1.5; 1.6), re-rupture(odds ratio) = 0.812(0.4; 1.61). CONCLUSION: Patients treated with cast the first 3 weeks after acute Achilles tendon rupture did not have better treatment outcome than patients treated with walker.

Patient-reported experience and outcome measures during treatment for gastroesophageal cancer.

OBJECTIVE: Gastroesophageal cancer has high mortality, and continuous assessment of patient-reported data is salient for optimisation of supportive care. We aimed to evaluate our multidisciplinary concept with respect to patient-reported variables. METHODS: At diagnosis and later during the treatment, three areas of patient-reported measures were evaluated: the given information and care, fatigue (Multidimensional Fatigue Inventory [MFI-20]), dysphagia (Ogilvie dysphagia score) and weight loss. RESULTS: Of 130 outpatients, planned for a surgical procedure and given a contact nurse (CN), 106 responded. During treatment, 81% of the patients were satisfied with their CN. The given information was considered very good or good by >90% and easily understood. Half of the patients reported need for supportive care, which was rated good by 85%. All dimensions of the MFI-20 test, except mental fatigue, worsened during the treatment period. At diagnosis, 61% of the patients experienced eating problems, leading to 7% weight loss. Although dysphagia improved, weight loss reached 13% at the end of treatment. CONCLUSION: A multidisciplinary concept can be of value in giving appropriate and understandable information, leading to high satisfaction with the provided care. However, as fatigue and weight loss increased during the treatment period, patients need structured multidisciplinary support.

Interaction profiling identifies the human nuclear exosome targeting complex.

The RNA exosome is a conserved degradation machinery, which obtains full activity only when associated with cofactors. The most prominent activator of the yeast nuclear exosome is the RNA helicase Mtr4p, acting in the context of the Trf4p/Air2p/Mtr4p polyadenylation (TRAMP) complex. The existence of a similar activator(s) in humans remains elusive. By establishing an interaction network of the human nuclear exosome, we identify the trimeric Nuclear Exosome Targeting (NEXT) complex, containing hMTR4, the Zn-knuckle protein ZCCHC8, and the putative RNA binding protein RBM7. ZCCHC8 and RBM7 are excluded from nucleoli, and consistently NEXT is specifically required for the exosomal degradation of promoter upstream transcripts (PROMPTs). We also detect putative homolog TRAMP subunits hTRF4-2 (Trf4p) and ZCCHC7 (Air2p) in hRRP6 and hMTR4 precipitates. However, at least ZCCHC7 function is restricted to nucleoli. Our results suggest that human nuclear exosome degradation pathways comprise modules of spatially organized cofactors that diverge from the yeast model.

Achilles tendon Total Rupture Score at 3 months can predict patients' ability to return to sport 1 year after injury.

PURPOSE: To investigate how the Achilles tendon Total Rupture Score (ATRS) at 3 months and 1 year after injury is associated with a patient's ability to return to work and sports as well as to investigate whether sex and age influence ATRS after 3 months and 1 year. METHOD: This is a retrospective study analysing the data from the Danish Achilles tendon Database. A total of 366 patients were included. Logistic regression was conducted to describe the effect of ATRS on return to work and sports. The effect of age and sex on ATRS was analysed by linear regression. RESULTS: Three months after injury patients had a significantly increased chance of return to sport after 1 year with an increased ATRS (OR 1.06, p = 0.001) but a non-significant effect on return to work. After 1 year, patients had a significantly increased probability of having returned to sport (OR 1.11, p < 0.001) and also having returned to work (OR 1.05, p = 0.007) with an increased ATRS. Men had an average 7 (p = 0.006) points higher ATRS at 3 months and an average 22 (p = 0.006) points higher at 1 year. CONCLUSION: ATRS is associated with patients' ability to return to sports and work. ATRS at 3 months can be used as a predictor of the patient's ability to return to sports after 1 year. Hereby, ATRS might help to individualise rehabilitation by identifying patients who do not respond adequately to the chosen treatment. LEVEL OF EVIDENCE: II.

Feasibility of an early progressive resistance exercise program for acute Achilles tendon rupture.

BACKGROUND: Long-term strength deficits are common after Achilles tendon ruptures. Early use of progressive resistance exercises may help reduce strength deficits, but the feasibility of this approach is unknown. The aim was to investigate the feasibility of early progressive resistance exercises regarding patient acceptability and compliance with the intervention. METHODS: We recruited patients with an acute Achilles tendon rupture treated non-surgically. During 9 weeks of immobilisation with a walking boot, participants attended weekly supervised physiotherapy sessions of progressive resistance exercises and performed home exercises, consisting of isometric ankle plantarflexion, seated heel-rise, and elastic band exercises. Acceptability was evaluated using a 7-point Likert scale (1 = very unacceptable and 7 = very acceptable) with feasibility threshold at 80% of the participants rating ≥ 4. Adherence to the exercises was defined as 80% of the participants performing at least 50% of the home exercises. During the intervention, tendon healing and adverse events were monitored. RESULTS: Sixteen participants (mean age 46 (range 28-61), male/female = 13/3) completed the intervention. Pre-injury Achilles tendon total rupture score was 98 (SD 8). All participants rated the acceptability of the exercises ≥ 5 (moderate acceptable to very acceptable) at 9- and 13-week follow-up and 9/16 rated 7 points (very acceptable). Participants performed 74% (range 4-117) of the total prescribed home exercises and 15/16 performed > 50%. One participant was not compliant with the home exercises due to feeling uncomfortable performing these independently. There were no re-ruptures, but one case of deep venous thrombosis. CONCLUSIONS: The early progressive resistance exercise program for treatment of non-surgically treated Achilles tendon rupture was feasible. Future studies should investigate the efficacy of the progressive intervention. TRIAL REGISTRATION: The study was registered at Clinical Trials (NCT04121377) on 29 September 2019. CLINICALTRIALS: NCT04121377 .

PROMoter uPstream Transcripts share characteristics with mRNAs and are produced upstream of all three major types of mammalian promoters.

PROMoter uPstream Transcripts (PROMPTs) were identified as a new class of human RNAs, which are heterologous in length and produced only upstream of the promoters of active protein-coding genes. Here, we show that PROMPTs carry 3'-adenosine tails and 5'-cap structures. However, unlike mRNAs, PROMPTs are largely nuclear and rapidly turned over by the RNA exosome. PROMPT-transcribing DNA is occupied by RNA polymerase II (RNAPII) complexes with serine 2 phosphorylated C-terminal domains (CTDs), mimicking that of the associated genic region. Thus, the inefficient elongation capacity of PROMPT transcription cannot solely be assigned to poor CTD phosphorylation. Conditions that reduce gene transcription increase RNAPII occupancy of the upstream PROMPT region, suggesting that they reside in a common transcription compartment. Surprisingly, gene promoters that are actively transcribed by RNAPI or RNAPIII also produce PROMPTs that are targeted by the exosome. RNAPIII PROMPTs bear hallmarks of RNAPII promoter-associated RNAs, explaining the physical presence of RNAPII upstream of many RNAPIII-transcribed genes. We propose that RNAPII activity upstream gene promoters are wide-spread and integral to the act of gene transcription.

Long-term follow-up after acute achilles tendon rupture - Does treatment strategy influence functional outcomes?

BACKGROUND: Patients struggle to fully recover after an Achilles tendon rupture. Although several studies has investigated surgical and non-surgical treatment, the best treatment is still uncertain. The aim of this study was to investigate long-term patient-reported outcomes and objective measures 4 years after acute Achilles tendon rupture and compare whether outcomes differed between patients treated on basis of the previous regimen preferring surgical treatment and the new regimen preferring functional rehabilitation. METHODS: Achilles tendon Total Rupture Score (ATRS), number of re-ruptures and the objective measures; Achilles tendon resting angle, calf circumference, heel-rise height, and muscle endurance were measured at a 4-year follow-up. Patients were recruited from Aalborg University Hospital. RESULTS: Seventy-six patients were included (29% female). The mean ATRS was 71.4 (95% CI: 65.8 to 77.1) at 4 years follow-up. No difference in ATRS was observed between Previous regimen and New regimen at any timepoint (time x group interaction, (p=0.851). The injured side was still significantly impaired compared with the non-injured side in terms of all objective measures. Impairments in objective measures were not dependent on the preferred treatment strategy. CONCLUSIONS: Patient reported impairments and objective functional deficits persist 4 years after an acute Achilles tendon rupture. No differences in patient reported outcome or objective measures at the 4 years follow-up was observed between the old treatment regimen preferring surgery compared with the new treatment regimen preferring functional rehabilitation.

Resistance Exercises in Early Functional Rehabilitation for Achilles Tendon Ruptures Are Poorly Described: A Scoping Review.

OBJECTIVES: To (1) describe which resistance exercises are used in the first 8 weeks of treatment for acute Achilles tendon rupture and (2) assess the completeness of reporting of the exercise descriptions. DESIGN: Scoping review. LITERATURE SEARCH: We searched the MEDLINE, Embase, CINAHL, Cochrane Library, and Physiotherapy Evidence Database (PEDro) databases. STUDY SELECTION CRITERIA: Randomized controlled trials, cohort studies, and case series (10 or more participants) that reported using resistance exercise in the immobilization period in the first 8 weeks of treatment for acute Achilles tendon rupture were included. DATA SYNTHESIS: Completeness of exercise description was assessed with the Consensus on Exercise Reporting Template (CERT) and the Toigo and Boutellier exercise descriptor framework. RESULTS: Thirty-eight studies were included. Fifty-one resistance exercises were extracted and categorized as isometric exercises (n = 20), heel raises (n = 6), strengthening with external resistance (n = 13), or unspecified (n = 12). A median of 8 (interquartile range, 6-10) of a possible 19 CERT items was reported. The amount of items described of the 13 Toigo and and Boutellier exercise descriptors ranged from 0 to 11. CONCLUSION: A variety of resistance exercises targeted at the ankle plantar flexors were used as part of early functional rehabilitation after Achilles tendon rupture. However, most studies provided inadequate description of resistance exercise interventions. J Orthop Sports Phys Ther 2020;50(12):681-691. Epub 23 Oct 2020. doi:10.2519/jospt.2020.9463.

Using Real-Life Data to Strengthen the Education of Pharmacy Technician Students: From Student to Research Assistant.

This commentary is based on the experience of teaching and observations of how pharmacy technician students can expand their perspective on patient safety by using real-life student-gathered patient data collected from community pharmacies. Pharmacy technicians in Denmark work extensively with counselling on the safe and efficient use of medications. Final-year pharmacy technician students can take the elective course in Clinical Pharmacy in Community Pharmacy, which targets the students who wish to work in depth with patient communication and quality assurance in counselling. One assignment that forms part of the course is for students to collect data about patients' beliefs about medications. Teachers' observations suggest that when students gather and work with their own data, they change their perspective on patients' beliefs about medications. It also strengthens the students' awareness of their responsibility for ensuring patient safety and contributes valid data to research in pharmacy practice.

Defining Components of Early Functional Rehabilitation for Acute Achilles Tendon Rupture: A Systematic Review.

BACKGROUND: Early functional rehabilitation is frequently discussed in treating Achilles tendon rupture. A consistent definition of what constitutes early functional rehabilitation has not been established across the literature, despite studies supporting its efficacy. A standardized definition would be helpful to pool data across studies, allow for between-study comparisons, and ultimately work toward developing clinical guidelines. PURPOSE: To define early functional rehabilitation (including when it is initiated and what it entails) when used to treat Achilles tendon rupture and to identify outcome measures for evaluating the effect of treatment. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: Ovid MEDLINE, EMBASE, PEDro, CINAHL, and Cochrane databases were searched for relevant studies. Eligibility criteria for selecting studies consisted of randomized controlled trials, cohort studies, and case series (≥10 participants) including weightbearing or exercise-based interventions within 8 weeks after Achilles tendon rupture. RESULTS: A total of 174 studies published between 1979 and 2018 were included. Studies were rated a median (interquartile range [IQR]) of 17 (15-20) on the Downs & Black checklist and included 9098 participants. Early functional rehabilitation incorporated weightbearing (95%), range of motion (73%), and isometric/strengthening exercises (50%). Weightbearing was initiated within the first week, whereas exercise (eg, ankle range of motion, strengthening, whole-body conditioning) was initiated in the second week. Initiation of exercises varied based on whether treatment was nonsurgical (mean, 3.0 weeks; IQR, 2.0-4.0 weeks) or simple (mean, 2.0 weeks; IQR, 0.0-2.3 weeks) or augmented surgical repair (mean, 0.5 weeks; IQR, 0.0-2.8 weeks) (P = .017). Functional outcomes including ankle range of motion (n = 84) and strength (n = 76) were reported in 130 studies. Other outcome domains included patient-reported outcomes (n = 89), survey-based functional outcomes (n = 50), and tendon properties (n = 53). CONCLUSION: Early functional rehabilitation includes weightbearing and a variety of exercise-based interventions initiated within the first 2 weeks after acute Achilles tendon rupture/repair. Because early functional rehabilitation has lacked a standardized definition, interventions and outcome measures are highly variable, and pooling data across studies should be done with attention paid to what was included in the intervention and how treatment was assessed.

Completeness and data validity in the Danish Achilles tendon Database.

INTRODUCTION: Acute Achilles tendon rupture is a severe injury causing functional deficits and sick leave. Data from the Danish Achilles tendon Database (DADB) can help us monitor and optimise treatment. The aim of this study was to investigate the completeness and data validity in the DADB. METHODS: The study was performed as a registry study comparing data in the DADB with data from patient records. Data were collected from three of 11 hospitals registered in the DADB. The study was conducted from 1 January to 31 December 2016. A completeness of 80% was considered satisfactory, and a parameter was valid if there was agreement between the DADB and the patient record in 80% of the cases. RESULTS: Overall, completeness was 77% (155/201); for the non-operated patients 81% (150/185) and the operated patients 31% (5/16). The seven investigated parameters all showed a validity of 83-100%. CONCLUSIONS: This study documented a satisfactory completeness of data on the non-operated patients registered in the DADB and an unsatisfactory completeness of data on operated patients. All investigated parameters were valid. These results suggest that data in the DADB on non-operated patients can contribute to research within the field. Due to a limited sample on operated patients, conclusions should be made with caution. The logistics concerning data collection among operated patients warrants optimisation. FUNDING: not relevant. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency and the Danish Patient Safety Authority.

Requirements for chromatin reassembly during transcriptional downregulation of a heat shock gene in Saccharomyces cerevisiae.

Heat shock genes respond to moderate heat stress by a wave of transcription. The induction phase is accompanied by the massive eviction of histones, which later reassemble with DNA during the ensuing phase of transcription downregulation. In this article, we identify determinants of this reassembly throughout the heat shock protein 104 gene (HSP104) transcription unit. The results show that, although histone H3 lacking amino acids 4-30 of its N-terminal tail (H3Delta4-30) is normally deposited, reassembly of H3Delta4-40 is obliterated with an accompanying sustained transcription. On mutation of the histone chaperones Spt6p and Spt16p, but not Asf1p, reassociation of H3 with DNA is compromised. However, despite a lasting open chromatin structure, transcription ceases normally in the spt6 mutant. Thus, transcriptional downregulation can be uncoupled from histone redeposition and ongoing transcription is not required to prevent chromatin reassembly.

Shockwave therapy for chronic Achilles tendinopathy: a double-blind, randomized clinical trial of efficacy.

BACKGROUND AND PURPOSE: Chronic Achilles tendinopathy is a painful condition and there are often unsatisfactory results with conservative treatment. Extracorporal shock-wave therapy (ESWT) has been introduced for the management of various soft tissue conditions. The objective of the study was to compare the effect of supplementing conservative treatment of chronic Achilles tendinopathy with ESWT or placebo. PATIENTS AND METHODS: This was a randomized, double-blind, placebo-controlled trial. Patients assigned to nonoperative treatment of chronic achilles tendinopathy were randomized to receive either active ESWT or sham ESWT over 4 weeks. There were 48 patients (28 men) with a mean age of 47 (19-80) years. American Orthopaedic Foot and Ankle Society (AOFAS) score and pain were assessed before treatment, during the 4-week treatment period, and at 4, 8, and 12 weeks of follow-up. RESULTS: Both groups improved during the treatment and follow-up period. The mean AOFAS score increased from 74 (SD 12) to 81 (16) in the placebo group and from 70 (6.8) to 88 (10) in the intervention group (p = 0.05). Better results were seen in the intervention group at 8 and 12 weeks of follow-up (p = 0.01 and p = 0.04, respectively). Interpretation Extracorporal shock-wave therapy appears to be a supplement for the treatment of chronic Achilles tendinopathy.

Foot exercises and foot orthoses are more effective than knee focused exercises in individuals with patellofemoral pain.

OBJECTIVES: To examine the effect of knee targeted exercises compared to knee targeted exercises combined with foot targeted exercises and foot orthoses in patients with patellofemoral pain. DESIGN: Forty adult individuals (28 women, 12 men) diagnosed with patellofemoral pain and screened for excessive calcaneal eversion were randomized to knee targeted exercises or knee targeted exercises combined with foot targeted exercise and orthoses. METHODS: The knee targeted exercises were prescribed during three supervised consultations. Individuals were instructed to perform the exercises 3 times per week during a 12-week period. The foot targeted exercises were prescribed for 2 times per week for 12 weeks with one session per week being supervised by a physiotherapist. The primary outcome was the subscale "pain" in the Knee Injury and Osteoarthritis Outcome Score (KOOS) at 4 months. RESULTS: Individuals randomized to knee targeted exercises combined with foot targeted exercises and foot orthoses had 8.9 points (95%CI: 0.4; 17.4) - NNT=3 (2-16) larger improvement in KOOS pain at the primary endpoint. CONCLUSIONS: The addition of foot targeted exercises and foot orthoses for 12 weeks was more effective than knee targeted exercises alone in individuals with patellofemoral pain. The effect was apparent after 4 months, but not significantly different after 12 months.

No serological evidence for rickettsial diseases among Danish elite orienteerers.

A series of sudden unexpected cardiac deaths among Swedish elite orienteerers in the 1980s have resulted from the combination of infectious diseases and physical exercise. Studies in the late 1990s have pointed to Chlamydia and Barontella, which both had a high seroprevalence among Swedish elite orienteerers. We conducted a case-control study aimed to elucidate the serologic prevalence of rickettsial diseases among Danish elite orienteerers. Ticks are known as vectors for some rickettsial diseases. None of the orienteerers had a positive antibody titer against any of the tested Rickettsia despite a very high frequency of tick bites in this group.

Higher rate of serious perinatal events in non-Western women in Denmark.

INTRODUCTION: To elucidate possible mechanisms behind the increased risk of stillbirth and infant mortality among migrants in Denmark, this study aimed to analyse characteristics of perinatal deaths at Hvidovre Hospital 2006-2010 - -according to maternal country of origin. METHODS: We identified children born at Hvidovre Hospital who died perinatally and included the patient files in a series of case studies. Our data were linked to data from population-covering registries in Statistics Denmark. Timing, causes of death as well as social, medical and obstetric characteristics of the parents were described according to maternal country of origin. RESULTS: This study included 125 perinatal deaths. The data indicated that intrapartum death, death caused by maternal disease, lethal malformation and preterm birth may be more frequent among non-Western than among Danish-born women. Obesity and disposition to diabetes may also be more prevalent among the non-Western women. CONCLUSIONS: The role of obesity, gestational diabetes, preeclampsia and severe congenital anomalies should be a main focus in improving our understanding the increased risk of perinatal death among non-Western migrant women in Denmark. Six of 28 perinatal deaths in the non-Western group were intrapartum deaths and warrants further concern. FUNDING: This project was funded by the Danish Council for Strategic Research as part of the SULIM project. TRIAL REGISTRATION: The linkage of data from patient files to data from Statistics Denmark was approved by the Danish Data Protection Agency. Only anonymised data were used.

Exercise therapy and custom-made insoles are effective in patients with excessive pronation and chronic foot pain--a randomized controlled trial.

BACKGROUND: Excessive foot pronation is a causal mechanisms described in relation to injuries of the lower extremities. Evidence to support an effective treatment is insufficient. OBJECTIVE: To investigate the effect of exercise and custom-made insoles to patients with excessive pronation and chronic pain conditions in the foot at short and long term follow-up. METHODS: Single blinded Randomized Controlled Trial with 80 subjects randomized: (1) Standard Intervention, (2) Insole, (3) Exercise, and (4) Insole+Exercise. Exercise - 12 week supervised program. Insoles - individually molded and posted. Pain was measured during walking, resting and running. Static and dynamic foot postures were measured as calcaneal angle, navicular drift, drop and height. RESULTS: The average duration of foot pain was 7.3 years. There was a significant pain reduction during walking within all groups at 4 and 12 months follow-up. No differences were seen between groups in any of the pain parameters. Weak correlations between changes in pain and foot postures were observed at baseline and one-year follow-up. CONCLUSION: A significant pain reduction was seen in all groups, none of the treatment modalities seem to be superior with the number of patients included. Compliance in the standard intervention group was a concern at 12 months.

[Patient safety in a health technology assessment perspective]. / Patientsikkerhed i medicinsk teknologivurderingsperspektiv.

The Danish Act of Patient Safety entered into force in 2004. This paper studies the consequences of the Act for the health care system and its users by a literature evaluation and an interview study with key persons. Despite the substantial resources spent on the reporting system, no evidence is found that the Act has an improved effect on patient safety. One of the biggest barriers for reporting adverse events is a lack of follow-up and feedback. Research into the patient's role on preventing adverse events is limited. The possibilities created by the Act should be utilized to their full potential.

RNA exosome depletion reveals transcription upstream of active human promoters.

Studies have shown that the bulk of eukaryotic genomes is transcribed. Transcriptome maps are frequently updated, but low-abundant transcripts have probably gone unnoticed. To eliminate RNA degradation, we depleted the exonucleolytic RNA exosome from human cells and then subjected the RNA to tiling microarray analysis. This revealed a class of short, polyadenylated and highly unstable RNAs. These promoter upstream transcripts (PROMPTs) are produced approximately 0.5 to 2.5 kilobases upstream of active transcription start sites. PROMPT transcription occurs in both sense and antisense directions with respect to the downstream gene. In addition, it requires the presence of the gene promoter and is positively correlated with gene activity. We propose that PROMPT transcription is a common characteristic of RNA polymerase II (RNAPII) transcribed genes with a possible regulatory potential.

[Tibialis posterior tendon dysfunction. An often neglected cause of painful adult flatfoot]. / Tibialis posterior-seneinsufficiens. En ofte overset årsag til smertefuld platfod hos voksne.

The posterior tibialis tendon is the most important dynamic stabilizer of the medial longitudinal arch of the foot. Posterior tibial tendon dysfunction (PTTD) may result from an acute trauma or a progressive degeneration of the tendon and should be suspected in painful flatfoot. The diagnosis is largely clinical, based on pain, tenderness and swelling along the tendon underneath the medial malleolus, the too-many-toes sign and persistant hindfoot valgus during heel rise. Untreated PTTD often results in total collapse of the longitudinal arch and severe osteoarthritis of the ankle or hindfoot. In traumatic cases acute repair of the tendon should be considered.