The proximal hamstring avulsion clinical trial (PHACT)-a randomised controlled non-inferiority trial of operative versus non-operative treatment of proximal hamstrings avulsions: study protocol.

INTRODUCTION: The treatment of proximal hamstring avulsions is controversial. While several trials have investigated the outcome for patients treated surgically, there is today no prospective trial comparing operative treatment with non-operative treatment. This protocol describes the design for the proximal hamstring avulsion clinical trial (PHACT)-the first randomised controlled trial of operative versus non-operative treatment for proximal hamstring avulsions. METHODS AND ANALYSIS: PHACT is a multicentre randomised controlled trial conducted across Sweden, Norway and Finland. Eligible patients (60 participants/treatment arm) with a proximal hamstring avulsion of at least two of three tendons will be randomised to either operative or non-operative treatment. Participants allocated to surgery will undergo reinsertion of the tendons with suture anchors. The rehabilitation programme will be the same for both treatment groups. When patient or surgeon equipoise for treatment alternatives cannot be reached and randomisation therefore is not possible, patients will be invited to participate in a parallel observational non-randomised cohort. The primary outcome will be the patient-reported outcome measure Perth hamstring assessment tool at 24 months. Secondary outcomes include the Lower Extremity Functional Score, physical performance and muscle strength tests, patient satisfaction and MR imaging. Data analysis will be blinded and intention-to-treat analysis will be preformed. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Ethical Committee of Uppsala University (DNR: 2017-170) and by the Norwegian ethical board (REC: 2017/1911). The study will be conducted in agreement with the Helsinki declaration. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03311997.

Similar outcome of femoral neck fractures treated with Pinloc or Hansson Pins: 1-year data from a multicenter randomized clinical study on 439 patients.

Background and purpose - There are few reports on the efficiency of the Hansson Pinloc System (Pinloc) for fixation of femoral neck fractures. We compare Pinloc with the commonly used Hansson Pin System in a randomized clinical trial. The primary outcome measure is non-union or avascular necrosis within 2 years. We now report fracture failures and reoperations within the first year.Patients and methods - Between May 2014 and February 2017, 439 patients were included in the study. They were above 50 years of age and treated for a femoral neck fracture at 9 orthopedic departments in Sweden. They were randomized to either Pinloc or Hansson pins. The fractures were grouped as (a) non-displaced regardless of age, (b) displaced in patients < 70 years, or (c) ≥ 70 years old, but deemed unfit to undergo arthroplasty. Follow-up with radiographs and outpatient visits were at 3 and 12 months. Failure was defined as early displacement/non-union, symptomatic segmental collapse, or deep infection.Results - 1-year mortality was 11%. Of the 325 undisplaced fractures, 12% (21/169) Pinloc and 13% (20/156) Hansson pin patients had a failure during the first year. The reoperation frequencies were 10% (16/169) and 8% (13/156) respectively. For the 75 patients 50-69 years old with displaced fractures, 11/39 failures occurred in the Pinloc group and 11/36 in the Hansson group, and 8/39 versus 9/36 patients were reoperated. Among those 39 patients ≥ 70 years old, 7/21 failures occurred in the Pinloc group and 4/18 in the Hansson group. Reoperation frequencies were 4/21 for Pinloc and 3/18 for the Hansson pin patients. No statistically significant differences were found in any of the outcomes between the Pinloc and Hansson groups.Interpretation - We found no advantages with Pinloc regarding failure or reoperation frequencies in this 1-year follow-up.

Women do not fare worse than men after lumbar fusion surgery: Two-year follow-up results from 4,780 prospectively collected patients in the Swedish National Spine Register with lumbar degenerative disc disease and chronic low back pain.

BACKGROUND CONTEXT: Proper patient selection is of utmost importance in the surgical treatment of degenerative disc disease (DDD) with chronic low back pain (CLBP). Among other factors, gender was previously found to influence lumbar fusion surgery outcome. PURPOSE: This study investigates whether gender affects clinical outcome after lumbar fusion. STUDY DESIGN: This is a national registry cohort study. PATIENT SAMPLE: Between 2001 and 2011, 2,251 men and 2,521 women were followed prospectively within the Swedish National Spine Register (SWESPINE) after lumbar fusion surgery for DDD and CLBP. OUTCOME MEASURES: Patient-reported outcome measures (PROMs), visual analog scale (VAS) for leg and back pain, Oswestry Disability Index (ODI), quality of life (QoL) parameter EQ5D, and labor status and pain medication were collected preoperatively, 1 and 2 years after surgery. METHODS: Gender differences of baseline data and PROM improvement from baseline were analyzed. The effect of gender on clinically important improvement of PROM was determined in a multivariate logistic regression model. Furthermore, gender-related differences in return-to-work were investigated. RESULTS: Preoperatively, women had worse leg pain (p<.001), back pain (p=.002), lower QoL (p<.001), and greater disability than men (p=.001). Postoperatively, women presented greater improvement 2 years from baseline for pain, function, and QoL (all p<.01). Women had better chances of a clinically important improvement than men for leg pain (odds ratio [OR]=1.39, 95% confidence interval [CI]: 1.19-1.61, p<.01) and back pain (OR=1.20,95% CI:1.03-1.40, p=.02) as well as ODI (OR=1.24, 95% CI:1.05-1.47, p=.01), but improved at a slower pace in leg pain (p<.001), back pain (p=.009), and disability (p=.008). No gender differences were found in QoL and return to work at 2 years postoperatively. CONCLUSIONS: Swedish women do not have worse results than men after spinal fusion surgery. Female patients present with worse pain and function preoperatively, but improve more than men do after surgery.

Long-term dietary vitamin D intake and risk of fracture and osteoporosis: a longitudinal cohort study of Swedish middle-aged and elderly women.

CONTEXT: The importance of dietary vitamin D for osteoporotic fracture prevention is uncertain. OBJECTIVE: Our objective was to investigate associations between dietary vitamin D intake with risk of fracture and osteoporosis. DESIGN AND PARTICIPANTS: In the population-based Swedish Mammography Cohort (including 61 433 women followed for 19 years), diet was assessed by repeated food frequency questionnaires. SETTING: The study was conducted in 2 municipalities in central Sweden. MAIN OUTCOME MEASURE: Incident fractures were identified from registry data. In a subcohort (n = 5022), bone mineral density was determined by dual-energy x-ray absorptiometry and serum 25-hydroxyvitamin D was measured using HPLC-tandem mass spectrometry. RESULTS: A total of 14 738 women experienced any type of first fracture during follow-up, and 3871 had a hip fracture. Multivariable-adjusted hazard ratio (HR) for any first fracture was 0.96 (95% confidence interval, 0.92-1.01) for the lowest (mean, 3.1 µg/d) and 1.02 (0.96-1.07) for the highest (mean, 6.9 µg/d) quintile compared with the third quintile of vitamin D intake. The corresponding HR for a first hip fracture was 1.02 (0.96-1.08) for the lowest and 1.14 (1.03-1.26) for the highest quintile. Intakes >10 µg/d, compared with <5 µg/d, conferred an HR of 1.02 (0.92-1.13) for any fracture and an HR of 1.27 (1.03-1.57) for hip fracture. The intake of vitamin D did not affect the odds for osteoporosis, although higher levels were associated with higher bone mineral density (0.3%-2%, P < .0001). A positive association was observed between vitamin D intake and serum 25-hydroxyvitamin D. CONCLUSIONS: Dietary intakes of vitamin D seem of minor importance for the occurrence of fractures and osteoporosis in community-dwelling Swedish women.

Plasma vitamin D and mortality in older men: a community-based prospective cohort study.

BACKGROUND: Vitamin D status is known to be important for bone health but may also affect the development of several chronic diseases, including cancer and cardiovascular diseases, which are 2 major causes of death. OBJECTIVE: We aimed to examine how vitamin D status relates to overall and cause-specific mortality. DESIGN: The Uppsala Longitudinal Study of Adult Men, a community-based cohort of elderly men (mean age at baseline: 71 y; n = 1194), was used to investigate the association between plasma 25-hydroxyvitamin D [25(OH)D] and mortality. Total plasma 25(OH)D was determined with HPLC atmospheric pressure chemical ionization mass spectrometry. Proportional hazards regression was used to compute hazard ratios (HRs). RESULTS: During follow-up (median: 12.7 y), 584 (49%) participants died. There was a U-shaped association between vitamin D concentrations and total mortality. An approximately 50% higher total mortality rate was observed among men in the lowest 10% (<46 nmol/L) and the highest 5% (>98 nmol/L) of plasma 25(OH)D concentrations compared with intermediate concentrations. Cancer mortality was also higher at low plasma concentrations (multivariable-adjusted HR: 2.20; 95% CI: 1.44, 3.38) and at high concentrations (HR: 2.64; 95% CI: 1.46, 4.78). For cardiovascular death, only low (HR: 1.89; 95% CI: 1.21, 2.96) but not high (HR: 1.33; 95% CI: 0.69, 2.54) concentrations indicated higher risk. CONCLUSIONS: Both high and low concentrations of plasma 25(OH)D are associated with elevated risks of overall and cancer mortality. Low concentrations are associated with cardiovascular mortality.

Determining vitamin D status: a comparison between commercially available assays.

BACKGROUND: Vitamin D is not only important for bone health but can also affect the development of several non-bone diseases. The definition of vitamin D insufficiency by serum levels of 25-hydroxyvitamin D depends on the clinical outcome but might also be a consequence of analytical methods used for the definition. Although numerous 25-hydroxyvitamin D assays are available, their comparability is uncertain. We therefore aim to investigate the precision, accuracy and clinical consequences of differences in performance between three common commercially available assays. METHODOLOGY/PRINCIPAL FINDINGS: Serum 25-hydroxyvitamin D levels from 204 twins from the Swedish Twin Registry were determined with high-pressure liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLC-APCI-MS), a radioimmunoassay (RIA) and a chemiluminescent immunoassay (CLIA). High inter-assay disagreement was found. Mean 25-hydroxyvitamin D levels were highest for the HPLC-APCI-MS technique (85 nmol/L, 95% CI 81-89), intermediate for RIA (70 nmol/L, 95% CI 66-74) and lowest with CLIA (60 nmol/L, 95% CI 56-64). Using a 50-nmol/L cut-off, 8% of the subjects were insufficient using HPLC-APCI-MS, 22% with RIA and 43% by CLIA. Because of the heritable component of 25-hydroxyvitamin D status, the accuracy of each method could indirectly be assessed by comparison of within-twin pair correlations. The strongest correlation was found for HPLC-APCI-MS (r = 0.7), intermediate for RIA (r = 0.5) and lowest for CLIA (r = 0.4). Regression analyses between the methods revealed a non-uniform variance (p<0.0001) depending on level of 25-hydroxyvitamin D. CONCLUSIONS/SIGNIFICANCE: There are substantial inter-assay differences in performance. The most valid method was HPLC-APCI-MS. Calibration between 25-hydroxyvitamin D assays is intricate.

Plasma 25-hydroxyvitamin D levels and fracture risk in a community-based cohort of elderly men in Sweden.

CONTEXT: Blood levels of 25-hydroxyvitamin D [25(OH)D] is the generally accepted indicator of vitamin D status, but no universal reference level has been reached. OBJECTIVE: The objective of the study was to determine the threshold at which low plasma 25(OH)D levels are associated with fractures in elderly men and clarify the importance of low levels on total fracture burden. DESIGN AND PARTICIPANTS: In the Uppsala Longitudinal Study of Adult Men, a population-based cohort (mean age, 71 yr, n = 1194), we examined the relationship between 25(OH)D and risk for fracture. Plasma 25(OH)D levels were measured with high-pressure liquid chromatography-mass spectrometry. SETTING: The study was conducted in the municipality of Uppsala in Sweden, a country with a high fracture incidence. MAIN OUTCOME MEASURE: Time to fracture was measured. RESULTS: During follow-up (median 11 yr), 309 of the participants (26%) sustained a fracture. 25(OH)D levels below 40 nmol/liter, which corresponded to the fifth percentile of 25(OH)D, were associated with a modestly increased risk for fracture, multivariable-adjusted hazard ratio 1.65 (95% confidence interval 1.09-2.49). No risk difference was detected above this level. Approximately 3% of the fractures were attributable to low 25(OH)D levels in this population. CONCLUSIONS: Vitamin D insufficiency is not a major cause of fractures in community-dwelling elderly men in Sweden. Despite the fact that cutaneous synthesis of previtamin D during the winter season is undetectable at this northern latitude of 60 degrees, only one in 20 had 25(OH)D levels below 40 nmol/liter, the threshold at which the risk for fracture started to increase. Genetic adaptations to limited UV light may be an explanation for our findings.

Seasonal genetic influence on serum 25-hydroxyvitamin D levels: a twin study.

BACKGROUND: Although environmental factors, mainly nutrition and UV-B radiation, have been considered major determinants of vitamin D status, they have only explained a modest proportion of the variation in serum 25-hydroxyvitamin D. We aimed to study the seasonal impact of genetic factors on serum 25-hydroxyvitamin D concentrations. METHODOLOGY/PRINCIPAL FINDINGS: 204 same-sex twins, aged 39-85 years and living at northern latitude 60 degrees, were recruited from the Swedish Twin Registry. Serum 25-hydroxyvitamin D was analysed by high-pressure liquid chromatography and mass spectrometry. Genetic modelling techniques estimated the relative contributions of genetic, shared and individual-specific environmental factors to the variation in serum vitamin D. The average serum 25-hydroxyvitamin D concentration was 84.8 nmol/l (95% CI 81.0-88.6) but the seasonal variation was substantial, with 24.2 nmol/l (95% CI 16.3-32.2) lower values during the winter as compared to the summer season. Half of the variability in 25-hydroxyvitamin D during the summer season was attributed to genetic factors. In contrast, the winter season variation was largely attributable to shared environmental influences (72%; 95% CI 48-86%), i.e., solar altitude. Individual-specific environmental influences were found to explain one fourth of the variation in serum 25-hydroxyvitamin D independent of season. CONCLUSIONS/SIGNIFICANCE: There exists a moderate genetic impact on serum vitamin D status during the summer season, probably through the skin synthesis of vitamin D. Further studies are warranted to identify the genes impacting on vitamin D status.