Widespread Vascularization and Correlation of Glycosaminoglycan Accumulation to Tendon Pain in Human Plantar Fascia Tendinopathy.

BACKGROUND: Plantar fasciitis is a painful tendinous condition (tendinopathy) with a high prevalence in athletes. While a healthy tendon has limited blood flow, ultrasound has indicated elevated blood flow in tendinopathy, but it is unknown if this is related to a de facto increase in the tendon vasculature. Likewise, an accumulation of glycosaminoglycans (GAGs) is observed in tendinopathy, but its relationship to clinical pain is unknown. PURPOSE: To explore to what extent vascularization, inflammation, and fat infiltration were present in patients with plantar fasciitis and if they were related to clinical symptoms. STUDY DESIGN: Descriptive laboratory study. METHODS: Biopsy specimens from tendinopathic plantar fascia tissue were obtained per-operatively from both the primary site of tendon pain and tissue swelling ("proximal") and a region that appeared macroscopically healthy at 1 to 2 cm away from the primary site ("distal") in 22 patients. Biopsy specimens were examined with immunofluorescence for markers of blood vessels, tissue cell density, fat infiltration, and macrophage level. In addition, pain during the first step in the morning (registered during an earlier study) was correlated with the content of collagen and GAGs in tissue. RESULTS: High vascularization (and cellularity) was present in both the proximal (0.89%) and the distal (0.96%) plantar fascia samples, whereas inconsistent but not significantly different fat infiltration and macrophage levels were observed. The collagen content was similar in the 2 plantar fascia regions, whereas the GAG content was higher in the proximal region (3.2% in proximal and 2.8% in distal; P = .027). The GAG content in the proximal region was positively correlated with the subjective morning pain score in the patients with tendinopathy (n = 17). CONCLUSION: In patients with plantar fasciitis, marked tissue vascularization was present in both the painful focal region and a neighboring nonsymptomatic area. In contrast, the accumulation of hydrophilic GAGs was greater in the symptomatic region and was positively correlated with increased clinical pain levels in daily life. CLINICAL RELEVANCE: The accumulation of GAGs in tissue rather than the extent of vascularization appears to be linked with the clinical degree of pain symptoms of the disease.

To allow or avoid pain during shoulder rehabilitation exercises for patients with chronic rotator cuff tendinopathy-Study protocol for a randomized controlled trial (the PASE trial).

BACKGROUND: Rotator cuff (RC) tendinopathy is the most reported shoulder disorder in the general population with highest prevalence in overhead athletes and adult working-age population. A growing body of evidence support exercise therapy as an effective intervention, but to date there are no prospective randomized controlled trials addressing pain as an intervention variable. METHODS: A single-site, prospective, pragmatic, assessor-blinded randomized controlled superiority trial. Eighty-four patients aged 18-55 years with chronic (symptom duration over 3 months) RC tendinopathy are randomized 1:1 to receive shoulder exercise during which pain is either allowed or avoided. The intervention period lasts 26 weeks. During that period, participants in both groups are offered 8 individual on-site sessions with an assigned sports physiotherapist. Participants perform home exercises and are provided with a pain and exercise logbook and asked to report completed home-based exercise sessions and reasons for not completing sessions (pain or other reasons). Patients are also asked to report load and the number of sets and repetitions per sets for each exercise session. The logbooks are collected continuously throughout the intervention period. The primary and secondary outcomes are obtained at baseline, 6 weeks, 26 weeks, and 1 year after baseline. The primary outcome is patient-reported pain and disability using the Shoulder PAin and Disability Index (SPADI). Secondary outcomes are patient-reported pain and disability using Disability Arm Shoulder and Hand short-form (Quick DASH), and shoulder pain using Numeric Pain Rating Scale. Objective outcomes are shoulder range of motion, isometric shoulder muscle strength, pain sensitivity, working ability, and structural changes in the supraspinatus tendon and muscle using ultrasound. DISCUSSION: The results of this study will contribute knowledge about the treatment strategies for patients with RC tendinopathy and help physiotherapists in clinical decision-making. This is the first randomized controlled trial comparing the effects of allowing pain versus avoiding pain during shoulder exercises in patients with chronic RC tendinopathy. If tolerating pain during and after exercise proves to be effective, it will potentially expand our understanding of "exercising into pain" for this patient group, as there is currently no consensus. TRIAL REGISTRATION: ClinicalTrials.gov NCT05124769. Registered on August 11, 2021.

Incidence and Characteristics of the Hyperosmolar Hyperglycemic State: A Danish Cohort Study.

OBJECTIVE: The hyperosmolar hyperglycemic state (HHS) is a rare and life-threatening complication of diabetes. We aimed to estimate the incidence of HHS and describe the clinical and biomarker profiles of patients with HHS, including subgroups with acidosis and acute kidney injury. RESEARCH DESIGN AND METHODS: This nationwide, descriptive cohort study used Danish registry data during years 2016-2018 to identify acutely admitted patients fulfilling the hyperglycemia and hyperosmolarity criteria of HHS (glucose ≥33 mmol/L and osmolarity [2 × sodium + glucose] ≥320 mmol/L). RESULTS: We identified 634 patients (median age, 69 years (first quartile; third quartile: 58; 79) who met the criteria of HHS among 4.80 million inhabitants aged ≥18 years. The incidence rates were 16.5 and 3.9 per 10,000 person-years among people with known type 1 (n = 24,196) and type 2 (n = 251,357) diabetes, respectively. Thirty-two percent of patients with HHS were not previously diagnosed with diabetes. Patients were categorized as pure HHS (n = 394) and combined HHS and diabetic ketoacidosis (HHS-DKA; n = 240). The in-hospital mortality rate for pure HHS was 17% and 9% for HHS-DKA. CONCLUSIONS: The incidence of HHS was higher among patients with type 1 diabetes compared with type 2 diabetes. HHS is a spectrum of hyperglycemic crises and can be divided in pure HHS and HHS-DKA. In one-third of patients, HHS was the debut of their diabetes diagnosis.

Physiological and clinical effects of low-intensity blood-flow restricted resistance exercise compared to standard rehabilitation in adults with knee osteoarthritis-Protocol for a randomized controlled trial.

INTRODUCTION: Osteoarthritis (OA) is a common disease with high socioeconomical costs. In Denmark, standard rehabilitation (SR) consists of a combination of patient education and supervised physical exercise involving a standardized neuromuscular training program. As an evidence-based alternative, high-load (>70% 1RM) resistance training (HIRT) has shown positive rehabilitation effects in knee-OA but may not be tolerated in all patients (~25%) due to knee joint pain. However, low-load resistance training (20-40% 1RM) with concurrent partial blood-flow restriction (BFR) appears to produce effects similar to HIRT yet involving reduced joint pain during and after exercise. The aim is to examine the effect of low-load BFR training compared to SR on pain, thigh muscle mass and muscle function in adults with knee-OA. We hypothesize that 12 weeks of BFR will lead to superior improvements in pain, muscle mass and mechanical muscle function compared to SR. METHODS AND ANALYSIS: 90 participants diagnosed with radiographic knee-OA will be randomized to either BFR or SR twice a week for 12 weeks. BFR will consist of two selected lower limb strength exercises performed with an inflated pneumatic occlusion cuff. Intervention procedures in SR consist of a full 8 weeks GLA:D course followed by 4 weeks of team group training. Primary outcome variable is the change in KOOS-Pain subscale from baseline to 12 weeks. Secondary outcome variables are changes in pain sensitivity, functional performance, muscle mass and mechanical muscle function. Intention-to-treat and per-protocol analyses will be conducted. One-way analysis of variance will be performed to evaluate between-group changes. Pre-to-post intervention comparisons will be analyzed using a mixed linear model. Regression analysis will be performed to evaluate potential associations between selected outcome variables.

Correction: von Eyben et al. A Risk Model for Patients with PSA-Only Recurrence (Biochemical Recurrence) Based on PSA and PSMA PET/CT: An Individual Patient Data Meta-Analysis. Cancers 2022, 14, 5461.

In the original publication [...].

Epigenetic Regulation of Driver Genes in Testicular Tumorigenesis.

In testicular germ cell tumor type II (TGCT), a seminoma subtype expresses an induced pluripotent stem cell (iPSC) panel with four upregulated genes, OCT4/POU5F1, SOX17, KLF4, and MYC, and embryonal carcinoma (EC) has four upregulated genes, OCT4/POU5F1, SOX2, LIN28, and NANOG. The EC panel can reprogram cells into iPSC, and both iPSC and EC can differentiate into teratoma. This review summarizes the literature on epigenetic regulation of the genes. Epigenetic mechanisms, such as methylations of cytosines on the DNA string and methylations and acetylations of histone 3 lysines, regulate expression of these driver genes between the TGCT subtypes. In TGCT, the driver genes contribute to well-known clinical characteristics and the driver genes are also important for aggressive subtypes of many other malignancies. In conclusion, epigenetic regulation of the driver genes are important for TGCT and for oncology in general.

A Risk Model for Patients with PSA-Only Recurrence (Biochemical Recurrence) Based on PSA and PSMA PET/CT: An Individual Patient Data Meta-Analysis.

An individual patient meta-analysis followed 1216 patients with PSA-only recurrence (biochemical recurrence, BCR) restaged with [68Ga]Ga-PSMA-11 PET/CT before the salvage treatment for median 3.5 years and analyzed the overall survival (OS). A new risk model included a good risk group with a prescan PSA < 0.5 ng/mL (26%), an intermediate risk group with a prescan PSA > 0.5 ng/mL and a PSMA PET/CT with 1 to 5 positive sites (65%), and a poor risk group with a prescan PSA > 0.5 ng/mL and a PSA PET/CT with > 5 positive sites (9%) (p < 0.0001, log rank test). The poor risk group had a five-year OS > 60%. Adding a BCR risk score by the European Association of Urology did not significantly improve the prediction of OS (p = 0.64). In conclusion, the restaging PSMA PET/CT markedly predicted the 5-year OS. The new risk model for patients with PSA-only relapse requires a restaging PSMA PET/CT for patients with a prescan PSA > 0.5 ng/mL and has a potential use in new trials aiming to improve the outcome for patients with PSA-only recurrence who have polysites prostate cancer detected on PSMA PET/CT.

Profiling Bispebjerg Acute Cohort: Database Formation, Acute Contact Characteristics of a Metropolitan Hospital, and Comparisons to Urban and Rural Hospitals in Denmark.

Purpose: To present a metropolitan cohort, Bispebjerg acute cohort (BAC), and compare patient characteristics and outcomes with patients from urban and rural hospitals in Denmark. Patients and Methods: We linked data from seven Danish nationwide registries and included all acute contacts to non-psychiatric hospitals in the years 2016-2018. Acute hospital contacts to Bispebjerg and Frederiksberg Hospital constituted BAC, representing a solely metropolitan/urban catchment area. Patient characteristics and outcomes were compared to the rest of Denmark in an urban cohort (UrC) and a rural cohort (RuC), stratified by visit and hospitalization contact types. Results: We identified 4,063,420 acute hospital contacts in Denmark and BAC constituted 8.4% (n=343,200) of them. BAC had a higher proportion of visits (65.1%) compared with UrC (52.1%) and RuC (45.3%). Patients in BAC more often lived alone (visits: BAC: 34.8%, UrC: 30.6%, RuC: 29.2%; hospitalizations: BAC: 50.8%, UrC: 36.7%, RuC: 37.2%) and had temporary CPR number (visits: BAC: 4.4%, UrC: 1.9%, RuC: 1.6%; hospitalizations: BAC: 1.5%, UrC: 0.9%, RuC: 0.8%). Visit patients in BAC were younger (BAC: 36, UrC: 42, RuC: 45 years, median), more often students (BAC: 18.0%, UrC: 14.0%, RuC: 12.5%), and had more contacts due to infectious diseases (BAC: 19.8%, UrC: 14.1%, RuC: 6.2%) but less due to injuries (BAC: 40.0%, UrC: 43.8%, RuC: 60.7%). Hospitalized patients in BAC had higher median age (BAC: 64, UrC: 61, RuC: 64 years) and fewer were in employment than in UrC (BAC: 26.1%, UrC: 32.1%, RuC: 28.1%). BAC Hospitalizations had a lower death rate within 30 days than in RuC (BAC: 3.0% [2.9-3.1%], UrC: 3.1% [3.0-3.1%], RuC: 3.4% [3.3-3.4%]), but a higher readmission-rate (BAC: 20.5% [20.3-20.8%], UrC: 17.3% [17.2-17.4%], RuC: 17.5% [17.5-17.6%]). Conclusion: Significant differences between BAC, urban, and rural cohorts may be explained by differences in healthcare structure and sociodemographics of the catchment areas.

Unpacking the behavioural components and delivery features of early childhood obesity prevention interventions in the TOPCHILD Collaboration: a systematic review and intervention coding protocol.

INTRODUCTION: Little is known about how early (eg, commencing antenatally or in the first 12 months after birth) obesity prevention interventions seek to change behaviour and which components are or are not effective. This study aims to (1) characterise early obesity prevention interventions in terms of target behaviours, delivery features and behaviour change techniques (BCTs), (2) explore similarities and differences in BCTs used to target behaviours and (3) explore effectiveness of intervention components in preventing childhood obesity. METHODS AND ANALYSIS: Annual comprehensive systematic searches will be performed in Epub Ahead of Print/MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, as well as clinical trial registries. Eligible randomised controlled trials of behavioural interventions to prevent childhood obesity commencing antenatally or in the first year after birth will be invited to join the Transforming Obesity in CHILDren Collaboration. Standard ontologies will be used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials provided by trialists. Narrative syntheses will be performed to summarise intervention components and compare applied BCTs by types of target behaviours. Exploratory analyses will be undertaken to assess effectiveness of intervention components. ETHICS AND DISSEMINATION: The study has been approved by The University of Sydney Human Research Ethics Committee (project no. 2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). The study's findings will be disseminated through peer-reviewed publications, conference presentations and targeted communication with key stakeholders. PROSPERO REGISTRATION NUMBER: CRD42020177408.

Transforming Obesity Prevention for CHILDren (TOPCHILD) Collaboration: protocol for a systematic review with individual participant data meta-analysis of behavioural interventions for the prevention of early childhood obesity.

INTRODUCTION: Behavioural interventions in early life appear to show some effect in reducing childhood overweight and obesity. However, uncertainty remains regarding their overall effectiveness, and whether effectiveness differs among key subgroups. These evidence gaps have prompted an increase in very early childhood obesity prevention trials worldwide. Combining the individual participant data (IPD) from these trials will enhance statistical power to determine overall effectiveness and enable examination of individual and trial-level subgroups. We present a protocol for a systematic review with IPD meta-analysis to evaluate the effectiveness of obesity prevention interventions commencing antenatally or in the first year after birth, and to explore whether there are differential effects among key subgroups. METHODS AND ANALYSIS: Systematic searches of Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo and trial registries for all ongoing and completed randomised controlled trials evaluating behavioural interventions for the prevention of early childhood obesity have been completed up to March 2021 and will be updated annually to include additional trials. Eligible trialists will be asked to share their IPD; if unavailable, aggregate data will be used where possible. An IPD meta-analysis and a nested prospective meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome will be body mass index z-score at age 24±6 months using WHO Growth Standards, and effect differences will be explored among prespecified individual and trial-level subgroups. Secondary outcomes include other child weight-related measures, infant feeding, dietary intake, physical activity, sedentary behaviours, sleep, parenting measures and adverse events. ETHICS AND DISSEMINATION: Approved by The University of Sydney Human Research Ethics Committee (2020/273) and Flinders University Social and Behavioural Research Ethics Committee (HREC CIA2133-1). Results will be relevant to clinicians, child health services, researchers, policy-makers and families, and will be disseminated via publications, presentations and media releases. PROSPERO REGISTRATION NUMBER: CRD42020177408.

Iridium thin-film coatings for the BabyIAXO hybrid X-ray optic.

Reflective coatings are an essential feature of X-ray telescopes. Their overall performance relies heavily on substrate compatibility and how well they conform to the optics assembly processes. We use X-ray reflectometry (XRR) to demonstrate the compatibility of shaping flat substrates coated with iridium, and show that specular and nonspecular reflectance before and after shaping is on par with traditional hot-slumped coated substrates. From 1.487 and 8.048keV measurements, we find that the substrates have rms roughness of 0.38nm and magnetron sputtered iridium deposits with rms surface roughness of 0.27-0.35nm. A hydrocarbon overlayer from atmospheric contamination is present with a thickness of 1.4-1.6nm and a density of 1.2-1.6g/cm3. Both the traditional hot slumped and the flat substrates undergoing post-coating shaping have a similar characteristic surface morphology and are equally well-suited for use with X-ray optics. Finally, we demonstrate by simulation the improved effective area achieved by using a low-Z overlayer, and illustrate the performance of a hybrid optic coated with optimized bilayers for a Primakoff axion spectrum emitted by the sun.

177Lu-PSMA Radioligand Therapy Is Favorable as Third-Line Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer. A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

In this systematic review and network meta-analysis (NMA), we aimed to assess the benefits and harms of third-line (L3) treatments in randomized controlled trials (RCTs) of patients with metastatic castration-resistant prostate cancer (mCRPC). Two reviewers searched for publications from 1 January 2006 to 30 June 2021. The review analyzed seven RCTs that included 3958 patients and eight treatments. Treatment with prostate-specific membrane antigen (PSMA)-based radioligand therapy (PRLT) resulted in a 1.3-times-higher rate of median PSA decline ≥50% than treatment with abiraterone, enzalutamide, mitoxantrone, or cabazitaxel (p = 0.00001). The likelihood was 97.6% for PRLT to bring about the best PSA response, out of the examined treatments. PRLT resulted in a 1.1-times-higher six-month rate of median radiographic progression-free survival. Treatment with PRLT in the VISION trial resulted in 1.05-times-higher twelve-month median overall survival than L3 treatment with cabazitaxel in other RCTs. PRLT more often resulted in severe thrombocytopenia and less often in severe leukopenia than did cabazitaxel. In conclusion, for patients with mCRPC, L3 treatment with PRLT is highly effective and safe.

Specimen-Specific Finite Element Models for Predicting Fretting Wear in Total Hip Arthroplasty Tapers.

Products from fretting wear and corrosion in the taper junction of total hip arthroplasty (THA) devices can lead to adverse local tissue reactions. Predicting damage as a function of design parameters would aid in the development of more robust devices. The objectives of this study were to develop an automated method for identifying areas of fretting wear on THA taper junctions, and to assess the predictive ability of a finite element model to simulate fretting wear in THA taper junctions. THA constructs were fatigue loaded, thus inducing damage on the stem taper. An automated imaging and analysis algorithm quantified fretting wear on the taper surfaces. Specimen-specific finite element models were used to calculate fretting work done (FWD) at the taper junction. Simulated FWD was correlated to imaged fretting wear. Results showed that the automated imaging approach identified fretting wear on the taper surface. Additionally, finite element models showed the greatest predictive ability for tapers exhibiting distal contact. Finite element models predicted an average of 30.3% of imaged fretting wear. With additional validation, the imaging and finite element techniques may be useful to manufacturers and regulators in the development and review of new THA devices.

Maternal age and risk of cesarean section in women with induced labor at term-A Nordic register-based study.

INTRODUCTION: Over the last decades, induction of labor has increased in many countries along with increasing maternal age. We assessed the effects of maternal age and labor induction on cesarean section at term among nulliparous and multiparous women without previous cesarean section. MATERIAL AND METHODS: We performed a retrospective national registry-based study from Denmark, Finland, Iceland, Norway, and Sweden including 3 398 586 deliveries between 2000 and 2011. We investigated the impact of age on cesarean section among 196 220 nulliparous and 188 158 multiparous women whose labor was induced, had single cephalic presentation at term, and no previous cesarean section. Confounders comprised country, time-period, and gestational age. RESULTS: In nulliparous women with induced labor the rate of cesarean section increased from 14.0% in women less than 20 years of age to 39.9% in women 40 years and older. Compared with women aged 25-29 years, the corresponding relative risks were 0.60 (95% confidence interval [95% CI] 0.57 to 0.64) and 1.72 (95% CI 1.66 to 1.79). In multiparous induced women the risk of cesarean section was 3.9% in women less than 20 years rising to 9.1% in women 40 years and older. Compared with women aged 25-29 years, the relative risks were 0.86 (95% CI 0.54 to 1.37) and 1.98 (95% CI 1.84 to 2.12), respectively. There were minimal confounding effects of country, time-period, and gestational age on risk for cesarean section. CONCLUSIONS: Advanced maternal age is associated with increased risk of cesarean section in women undergoing labor induction with a single cephalic presentation at term without a previous cesarean section. The absolute risk of cesarean section is 3-5 times higher across 5-year age groups in nulliparous relative to multiparous women having induced labor.

Parasite specific 7SL-derived small RNA is an effective target for diagnosis of active trypanosomiasis infection.

Human and animal African trypanosomiasis (HAT & AAT, respectively) remain a significant health and economic issue across much of sub-Saharan Africa. Effective control of AAT and potential eradication of HAT requires affordable, sensitive and specific diagnostic tests that can be used in the field. Small RNAs in the blood or serum are attractive disease biomarkers due to their stability, accessibility and available technologies for detection. Using RNAseq, we have identified a trypanosome specific small RNA to be present at high levels in the serum of infected cattle. The small RNA is derived from the non-coding 7SL RNA of the peptide signal recognition particle and is detected in the serum of infected cattle at significantly higher levels than in the parasite, suggesting active processing and secretion. We show effective detection of the small RNA in the serum of infected cattle using a custom RT-qPCR assay. Strikingly, the RNA can be detected before microscopy detection of parasitaemia in the blood, and it can also be detected during remission periods of infection when no parasitaemia is detectable by microscopy. However, RNA levels drop following treatment with trypanocides, demonstrating accurate prediction of active infection. While the small RNA sequence is conserved between different species of trypanosome, nucleotide differences within the sequence allow generation of highly specific assays that can distinguish between infections with Trypanosoma brucei, Trypanosoma congolense and Trypanosoma vivax. Finally, we demonstrate effective detection of the small RNA directly from serum, without the need for pre-processing, with a single step RT-qPCR assay. Our findings identify a species-specific trypanosome small RNA that can be detected at high levels in the serum of cattle with active parasite infections. This provides the basis for the development of a cheap, non-invasive and highly effective diagnostic test for trypanosomiasis.

The retropubic tension-free vaginal tape procedure-Efficacy, risk factors for recurrence and long-term safety.

INTRODUCTION: The retropubic tension-free vaginal tape has been the preferred method for primary surgical treatment of stress urinary incontinence and stress-dominated mixed urinary incontinence in women for more than 20 years. This study presents long-term safety and efficacy data and assesses risk factors for long-term recurrence. MATERIAL AND METHODS: In a case-series design we assessed a historical cohort of primary surgeries performed with the tension-free vaginal tape procedure in 596 women from 1998 to 2012 with follow up through 2015. Information from the medical records was transferred to a case report form comprising data on early and late complications and recurrence of urinary incontinence defined as bothersome stress urinary incontinence symptoms. All analyses were performed with SPSS using Pearson chi-square, survival and Cox regression analyses. RESULTS: After a 10-year follow up, mixed urinary incontinent women (hazard ratio 2.1, 95% confidence interval [CI] 1.4-3.0) had a significantly increased risk of recurrence of stress urinary incontinence symptoms compared with women with pure stress urinary incontinence as the indication for surgery. Overall cumulative cure rates after 1, 5 and 10 years were 92% (95% CI; 90%-94%), 79% (95% CI; 75%-83%) and 69% (95% CI; 63%-75%), respectively. Recurrent surgery (0.3%) and serious tape complications needing major surgical treatment (0.3%) were rare. Six patients (1.0%) had the tape cut due to urinary retention, and nine patients (1.5%) reported urinary retention more than 3 months after surgery. CONCLUSIONS: The tension-free vaginal tape procedure has a high long-term durability. Mixed urinary incontinence as an indication for surgery predicted long-term recurrence. Long-term complications were rare.

Corticosteroid injection is the best treatment in plantar fasciitis if combined with controlled training.

PURPOSE: Plantar fasciitis is a very common (lifetime incidence ~ 10%) and long-lasting injury with major impact on daily function. Combining corticosteroid injection and physical training (strength training and stretching) was hypothesized to result in a superior effect compared to each treatment separately. METHODS: A single blinded randomized controlled superiority trial conducted in 2013-2014 with a 2-year follow-up (end Sept 2016). 123 consecutive patients (20-65 years) referred to two study centers in Denmark: Institute of Sports Medicine, Bispebjerg Hospital, University of Copenhagen and a private rheumatology clinic with symptoms of plantar fasciitis, and ultrasound measured thickness above 4.0 mm were invited. 25 did not fulfill the inclusion criteria (mainly ultrasound criteria) and 8 refused participation. 90 patients were randomized (pulling sealed envelopes) to 3 groups: (1) 3 months strength training and stretching (n = 30), (2) corticosteroid injections with monthly intervals until thickness < 4.0 mm (maximum 3 injections) (n = 31), (3) combination of the two treatments (n = 29). During the 3 months intervention period load reduction was recommended (cushioning shoes and insoles and abstaining from running and jumping). The main outcome was improvement in Pain at function on a 100-mm VAS score and in Foot Function Index (FFI, range 0-230) at 6 months (Clinicaltrials.gov Identifier: NCT01994759). RESULTS: All groups improved significantly over time, but the combination of corticosteroid injection and training (strength training and stretching) had a superior effect at all time points. The mean difference between the combined treatment and training was 40 points in FFI (95% confidence interval (CI) 63-17 points, p < 0.001) and 20 mm for VAS function pain (CI 35-5 mm, p < 0.01). The mean difference between the combined treatment and corticosteroid injections only was 29 points in FFI (CI 52-7 points, p < 0.01) and 17 mm for VAS function pain (CI 32-2 mm, p < 0.05). All differences were clinically relevant. CONCLUSION: The best treatment for plantar fasciitis is the combination of corticosteroid injections and training (strength training and stretching). This combined treatment is superior both in the short- and in the longterm. Corticosteroid injections combined with controlled training are recommended as first line treatment in patients with plantar fasciitis. LEVEL OF EVIDENCE: 1.

Kinetics and tissue distribution of bismuth, tin and lead after implantation of miniature shotgun alloy pellets in rats.

INTRODUCTION: Shotgun pellets containing bismuth (Bi) as substitute for lead (Pb) are increasingly being used due to environmental concerns. Information on toxicokinetics of Bi is lacking for the assessment of humans accidentally shot by Bi-containing shotgun alloy pellets. METHODS: Male Wistar rats were exposed to miniature alloy pellets containing Bi, tin (Sn) and minor amounts of Pb by implantation in muscle tissues of the hind legs. RESULTS: The concentrations of Bi in whole blood and urine increased up to 53 weeks after implantation. The highest concentrations of Sn in whole blood were observed three weeks after implantation, then declining to background levels 53 weeks after implantation. Lead in whole blood increased up to 13 weeks of exposure, and declined for the remaining observation period. Bismuth and Sn accumulated mainly in kidney, but also in liver, testicle and brain. Analytical field emission scanning electron microscopy of post-implant pellets showed depletion of Pb towards the pellet surface. Oxygen and chlorine accumulated in Sn rich lamellas in areas next to the pellet surface. The distribution of Bi remained visually unaffected as compared to pre-implant pellets. CONCLUSION: The concentration of Bi increased during the whole observation period in blood, urine, kidney, brain, testicle and liver. The decline in the concentrations of Pb and Sn in blood and urine after reaching the peak concentration may be related to alterations in the chemical composition and element distribution of the implanted alloy pellets.

Can oxytocin augmentation modify the risk of epidural analgesia by maternal age in cesarean sections?

INTRODUCTION: Maternal age is an established risk factor for cesarean section; epidural analgesia and oxytocin augmentation may modify this association. We investigated the effects and interactions of oxytocin augmentation, epidural analgesia and maternal age on the risk of cesarean section. MATERIAL AND METHODS: In all, 416 386 nulliparous women with spontaneous onset of labor, ≥37 weeks of gestation and singleton infants with a cephalic presentation during 2000-2011 from Norway and Denmark were included [Ten-group classification system (Robson) group 1]. In this case-control study the main exposure was maternal age; epidural analgesia, oxytocin augmentation, birthweight and time period were explanatory variables. Chi-square test and logistic regression were used to estimate associations and interactions. RESULTS: The cesarean section rate increased consistently with advancing maternal age, both overall and in strata of epidural analgesia and oxytocin augmentation. We observed strong interactions between maternal age, oxytocin augmentation and epidural analgesia for the risk of cesarean section. Women with epidural analgesia generally had a reduced adjusted odds ratio when oxytocin was used compared with when it was not used. In Norway, this applied to all maternal age groups but in Denmark only for women ≥30 years. Among women without epidural, oxytocin augmentation was associated with an increased odds ratio for cesarean section in Denmark, whereas no difference was observed in Norway. CONCLUSIONS: Oxytocin augmentation in nulliparous women with epidural analgesia is associated with a reduced risk of cesarean section in labor with spontaneous onset.