High Mortality Rate in Oral Glucocorticoid Users: A Population-Based Matched Cohort Study.

Objective: The aim of the study was to investigate all-cause and disease-specific mortality in a large population-based cohort of oral glucocorticoid (GC) users. Methods: This was a retrospective, matched cohort study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. The cause of death was obtained from the Swedish Cause-of-Death Registry. Patients receiving prednisolone ≥5 mg/day (or equivalent dose of other GC) for ≥21 days between 2007-2014 were included. For each patient, one control subject matched for age and sex was included. The study period was divided into 3-month periods and patients were divided into groups according to a defined daily dose (DDD) of GC used per day. The groups were: Non-users (0 DDD per day), low-dose users (>0 but <0.5 DDD per day), medium-dose users (0.5-1.5 DDD per day) and high-dose users (>1.5 DDD per day). Hazard ratios (HRs), unadjusted and adjusted for age, sex and comorbidities, were calculated using a time-dependent Cox proportional hazard model. Results: Cases (n=223 211) had significantly higher all-cause mortality compared to controls (HR adjusted for age, sex and comorbidities 2.08, 95% confidence interval 2.04 to 2.13). After dividing the cases into subgroups, adjusted HR was 1.31 (1.28 to 1.34) in non-users, 3.64 (3.51 to 3.77) in low-dose users, 5.43 (5.27 to 5.60) in medium-dose users and, 5.12 (4.84 to 5.42) in high-dose users. The highest adjusted hazard ratio was observed in high-dose users for deaths from sepsis 6.71 (5.12 to 8.81) and pulmonary embolism 7.83 (5.71 to 10.74). Conclusion: Oral GC users have an increased mortality rate compared to the background population, even after adjustment for comorbidities. High-dose users have an increased risk of dying from sepsis, and pulmonary embolism compared to controls. Whether the relationship between GC exposure and the excess mortality is causal remains to be elucidated.

Risk factors, mortality trends and cardiovasuclar diseases in people with Type 1 diabetes and controls: A Swedish observational cohort study.

Background: Historically, the incidence of cardiovascular disease and mortality in persons with Type 1 diabetes (T1D) has been increased compared to the general population. Contemporary studies on time trends of mortality and cardiovascular disease are sparse. Methods: In this observational study, T1D persons were identified in the Swedish National Diabetes Registry (n=45,575) and compared with matched controls from the general population (n=220,141). Incidence rates from 2002 to 2019 were estimated with respect to mortality and cardiovascular disease in persons with T1D overall and when stratified for prevalent cardiovascular and renal disease relative to controls. Findings: Mean age in persons with T1D was 32.4 years and 44.9% (20,446/45,575) were women. Age- and sex- adjusted mortality rates declined over time in both groups but remained significantly higher in those with T1D compared to controls during 2017-2019, 7.62 (95% CI 7.16; 8·08) vs. 2.23 (95% CI 2.13; 2.33) deaths per 1,000 person years. Myocardial infarction, heart failure and stroke decreased over time in both groups, with persistent excess risks in the range of 3.4-5.0 times from 2017 to 2019 in those with T1D. T1D persons ≥45 years without previous renal or cardiovascular complications had standardized mortality rates similar or even lower than controls 5.55 (4.51; 6.60) vs.7.08 (6.75; 7.40) respectively in the last time period. Interpretation: Excess mortality persisted over time in persons with T1D, largely in patients with cardiorenal complications. Improved secondary prevention with a focus on individualized treatment is needed to close the gap in mortality for individuals with T1D. Funding: This study was financed by grants from the ALF-agreement, NovoNordisk Foundation and the Swedish Heart and Lung Foundation.

The significance of cervical sagittal alignment for nonrecovery after whiplash injury.

BACKGROUND CONTEXT: Whiplash-associated disorder is a common cause of chronic neck pain. Several radiological cervical angular variables are suggested to have constitutional characteristics, that is, them being minimally influenced by body positioning. However, the association between these variables and pain conditions remains poorly understood. To our knowledge, no previous studies have investigated the association between constitutional angular variables and the outcome after whiplash trauma. PURPOSE: Our objectives were (1) to study the inter-rater agreement of sagittal radiologic variables between 2 raters and (2) to investigate any association between these variables and self-perceived nonrecovery after whiplash injury. STUDY DESIGN: Prospective cohort study. PATIENT SAMPLE: Forty-six patients aged 16 to 70 years, attending an emergency department after a motor vehicle accident resulting in neck pain were recruited. OUTCOME MEASURES: Self-perceived nonrecovery (yes/no) was the primary outcome measure. The secondary outcome measure was pain level on a numeric rating scale. METHODS: The participants underwent computed tomography scans in a supine position. Sagittal alignment variables (T1 slope, neck tilt, thoracic inlet angle [TIA], and C2-C7 angle) on the computed tomography scans were measured by 2 independent raters. Inter-rater agreement was tested with a paired sample t test and Bland-Altman plots for each variable. The patients were followed up after 6 months. RESULTS: No systematic differences for the assessed variables were found between the 2 raters. The overall nonrecovery rate was 28%. For the group with low neck tilt, the nonrecovery rate was 50% (95% CI: 36%-78%) and for the group with high neck tilt, 8% (95% CI: 3%-25%). The nonrecovery rate for the group low TIA was 50% (95% CI 29%-72%) and for those with high TIA 14% (95% CI 4%-26%). The associations remained significant after adjustments for possible confounders. The inter-rater analysis shows satisfactory agreement without proportional bias. CONCLUSIONS: This study indicates the existence of an association between the constitutional sagittal alignment of the cervical spine and the outcome after whiplash injuries.

High prescription rate of oral glucocorticoids in children and adults: A retrospective cohort study from Western Sweden.

OBJECTIVE: Glucocorticoids (GCs) are a cornerstone in treating various common and uncommon diseases. The aim of this study was to estimate the prevalence of GC use in terms of doses associated with risk of tertiary adrenal insufficiency in adults and children, and treatment indications. METHODS: This was a retrospective cohort study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. Patients with prescriptions of prednisolone (or equivalent dose of other GCs) ≥5 mg daily for ≥21 days between 2007 and 2014 were included. Information on concurrent diseases was obtained from the Swedish National Patient Register and the Västra Götaland Regional Healthcare Database. RESULTS: Of 1 585 335 inhabitants in Västra Götaland County, 223 211 were included in the study (women 55.6%). Mean age was 48 ± 24 years. Period prevalence of oral GC use during the 8-year study period was 14.1%. The highest prevalence (27.4%) was in men aged 80-89 years and lowest (7.5%) in men 10-19 years of age. The period prevalence in children 0-9 years of age was 10.6%. COPD and asthma were the most common indications for treatment (17.2%) followed by allergy (12.5%) and malignant neoplasms (11.5%). Allergy was the most frequent indication (20.5%) in children and adolescents. CONCLUSION: Between 2007 and 2014, every seventh inhabitant in western Sweden received a GC prescription at doses associated with risk of developing tertiary adrenal insufficiency. These findings illustrate the importance of awareness of the potential development of tertiary adrenal insufficiency in both paediatric and adult patients.

Correction to: Bacteria: back pain, leg pain and Modic sign-a surgical multicenter comparative study.

Unfortunately, the 5th author name was incorrectly published in the original paper. The complete correct name is given below.

Long-term outcome of fusion for degenerative disc disease in the lumbar spine.

AIMS: Chronic low back pain due to degenerative disc disease is sometimes treated with fusion. We compared the outcome of three different fusion techniques in the Swedish Spine Register: noninstrumented posterolateral fusion (PLF), instrumented posterolateral fusion (IPLF), and interbody fusion (IBF). PATIENTS AND METHODS: A total of 2874 patients who were operated on at one or two lumbar levels were followed for a mean of 9.2 years (3.6 to 19.1) for any additional lumbar spine surgery. Patient-reported outcome data were available preoperatively (n = 2874) and at one year (n = 2274), two years (n = 1958), and a mean of 6.9 years (n = 1518) postoperatively and consisted of global assessment and visual analogue scales of leg and back pain, Oswestry Disability Index, EuroQol five-dimensional index, 36-Item Short-Form Health Survey, and satisfaction with treatment. Statistical analyses were performed with competing-risks proportional hazards regression or analysis of covariance, adjusted for baseline variables. RESULTS: The number of patients with additional surgery were 32/183 (17%) in the PLF group, 229/1256 (18%) in the IPLF group, and 439/1435 (31%) in the IBF group. With the PLF group as a reference, the hazard ratio for additional lumbar surgery was 1.16 (95% confidence interval (CI) 0.78 to 1.72) for the IPLF group and 2.13 (95% CI 1.45 to 3.12) for the IBF group. All patient-reported outcomes improved after surgery (p < 0.001) but were without statistically significant differences between the groups at the one-, two- and 6.9-year follow-ups (all p ≥ 0.12). CONCLUSION: The addition of interbody fusion to posterolateral fusion was associated with a higher risk for additional surgery and showed no advantages in patient-reported outcome Cite this article: Bone Joint J 2019;101-B:1526-1533.

Bacteria: back pain, leg pain and Modic sign-a surgical multicentre comparative study.

PURPOSE: To compare bacterial findings in pain-generating degenerated discs in adults operated on for lumbar disc herniation (LDH), and mostly also suffering from low back pain (LBP), with findings in adolescent patients with non-degenerated non-pain-generating discs operated on for scoliosis, and to evaluate associations with Modic signs on magnetic resonance imaging (MRI). Cutibacterium acnes (Propionibacterium acnes) has been found in painful degenerated discs, why it has been suggested treating patients with LDH/LBP with antibiotics. As multidrug-resistant bacteria are a worldwide concern, new indications for using antibiotics should be based on solid scientific evidence. METHODS: Between 2015 and 2017, 40 adults with LDH/LBP (median age 43, IQR 33-49) and 20 control patients with scoliosis (median age 17, IQR 15-20) underwent surgery at seven Swedish hospitals. Samples were cultured from skin, surgical wound, discs and vertebrae. Genetic relatedness of C. acnes isolates was investigated using single-nucleotide polymorphism analysis. DNA samples collected from discs/vertebrae were analysed using 16S rRNA-based PCR sequencing. MRI findings were assessed for Modic changes. RESULTS: No bacterial growth was found in 6/40 (15%) LDH patients, compared with 3/20 (15%) scoliosis patients. Most positive samples in both groups were isolated from the skin and then from subcutis or deep within the wound. Of the four disc and vertebral samples from each of the 60 patients, 235/240 (98%) were DNA negative by bacterial PCR. A single species, C. acnes, was found exclusively in the disc/vertebra from one patient in each group. In the LDH group, 29/40 (72%) patients had at least one sample with growth of C. acnes, compared to 14/20 (70%) in the scoliosis group. Bacterial findings and Modic changes were not associated. CONCLUSIONS: Cutibacterium acnes found in discs and vertebrae during surgery for disc herniation in adults with degenerated discs may be caused by contamination, as findings in this group were similar to findings in a control group of young patients with scoliosis and non-degenerated discs. Furthermore, such findings were almost always combined with bacterial findings on the skin and/or in the wound. There was no association between preoperative Modic changes and bacterial findings. Antibiotic treatment of lumbar disc herniation with sciatica and/or low back pain, without signs of clinical discitis/spondylitis, should be seriously questioned. These slides can be retrieved under Electronic Supplementary Material.

Outcomes of Posterolateral Fusion with and without Instrumentation and of Interbody Fusion for Isthmic Spondylolisthesis: A Prospective Study.

BACKGROUND: Various methods for the treatment of isthmic spondylolisthesis are available. The aim of this study was to compare outcomes after posterolateral fusion without instrumentation, posterolateral fusion with instrumentation, and interbody fusion. METHODS: The Swedish Spine Register was used to identify 765 patients who had been operated on for isthmic spondylolisthesis and had at least preoperative and 2-year outcome data; 586 of them had longer follow-up (a mean of 6.9 years). The outcome measures were a global assessment of leg and back pain, the Oswestry Disability Index (ODI), the EuroQol-5 Dimensions (EQ-5D) Questionnaire, the Short Form-36 (SF-36), a visual analog scale (VAS) for back and leg pain, and satisfaction with treatment. Data on additional lumbar spine surgery was searched for in the register, with the mean duration of follow-up for this variable being 10.6 years after the index procedure. Statistical analyses were performed with analysis of covariance or competing-risks proportional hazards regression, adjusted for baseline differences in the studied variables, smoking, employment status, and level of fusion. RESULTS: Posterolateral fusion without instrumentation was performed in 102 patients; posterolateral fusion with instrumentation, in 452; and interbody fusion, in 211. At 1 year, improvement was reported in the global assessment for back pain by 54% of the patients who had posterolateral fusion without instrumentation, 68% of those treated with posterolateral fusion with instrumentation, and 70% of those treated with interbody fusion (p = 0.009). The VAS for back pain and reported satisfaction with treatment showed similar patterns (p = 0.003 and p = 0.017, respectively), whereas other outcomes did not differ among the treatment groups at 1 year. At 2 years, the global assessment for back pain indicated improvement in 57% of the patients who had undergone posterolateral fusion without instrumentation, 70% of those who had posterolateral fusion with instrumentation, and 71% of those treated with interbody fusion (p = 0.022). There were no significant outcome differences at the mean 6.9-year follow-up interval. There was an increased hazard ratio for additional lumbar spine surgery after interbody fusion (4.34; 95% confidence interval [CI] = 1.71 to 11.03) and posterolateral fusion with instrumentation (2.56; 95% CI = 1.02 to 6.42) compared with after posterolateral fusion without instrumentation (1.00; reference). CONCLUSIONS: Fusion with instrumentation, with or without interbody fusion, was associated with more improvement in back pain scores and higher satisfaction with treatment compared with fusion without instrumentation at 1 year, but the difference was attenuated with longer follow-up. Fusion with instrumentation was associated with a significantly higher risk of additional spine surgery. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Predictive factors for the outcome of fusion in adult isthmic spondylolisthesis.

STUDY DESIGN: A prospective study on predictive factors for the outcome of 164 patients with adult isthmic spondylolisthesis operated on with fusion. OBJECTIVE: In view of the need to better select patients for fusion, we investigated the use of the pain drawing (PD) and other potential factors for predicting the outcome of fusion. SUMMARY OF BACKGROUND DATA: Results on predictive factors of outcome after spinal fusion have been contradictory and large, well-defined, patient samples with adequate observation times are lacking. METHODS: Questionnaires including possible predictive factors and PDs were obtained before surgery. Degree and level of slip were documented. Outcome was quantified by measurement of pain (VAS), Disability Rating Index, the Oswestry Disability Index, and global assessment by the patient into "much better," "better," "unchanged," or "worse." The 2-year follow-up rate was 160 of 164 (98%). RESULTS: In the total sample 49% of patients were much better, 25% better, 14% unchanged, and 12% worse. The following preoperative factors correlated to a worse outcome in the univariate analysis: not working, no regular exercise, female gender, shortness in stature, and a nonorganic PD. The multivariate regression analysis showed that work status was the main determinant of outcome. Gender and exercise had less but significant impact (P = 0.004 and 0.02, respectively). In the multivariate regression analysis the PD was not a significant predictor (P = 0.06). CONCLUSION: The present study shows that patients working before surgery have a more favorable outcome. Also male gender and regular exercise are indicators of a better outcome after fusion. Female patients not working, not exercising or, if these factors are not known, with nonorganic PDs, should be informed about their suboptimal chances of an excellent outcome after fusion.

A prospective randomised study on the long-term effect of lumbar fusion on adjacent disc degeneration.

The existence and importance of an accelerated adjacent segment disc degeneration (ASD) after lumbar fusion have previously not been demonstrated by RCTs. The objectives of this study were, to determine whether lumbar fusion in the long term accelerates degenerative changes in the adjacent disc and whether this affects the outcome, by using a prospective randomised design. A total of 111 patients, aged 18-55, with isthmic spondylolisthesis were randomised to exercise (EX, n = 34) or posterolateral fusion (PLF, n = 77), with (n = 37) or without pedicle screw instrumentation (n = 40). The minimum 10 years FU rate was 72%, with a mean FU time of 12.6 years (range 10-17 years). Three radiographic methods of ASD quantification were used, i.e. two digital radiographic measurement methods and the semi quantitative UCLA grading scale. One digital measurement method showed a mean disc height reduction by 2% in the EX group and by 15% in the PLF group (p = 0.0016), and the other showed 0.5 mm more disc height reduction in the PLF compared to the Ex group (ns). The UCLA grading scale showed normal discs in 100% of patients in the EX group, compared to 62% in the PLF group (p = 0.026). There were no significant differences between instrumented and non-instrumented patients. In patients with laminectomy we found a significantly higher incidence of ASD compared to non laminectomised patients (22/47 vs. 2/16 respectively, p = 0.015). In the longitudinal analysis, the posterior and anterior disc heights were significantly reduced in the PLF group, whereas in the EX group only the posterior disc height was significantly reduced. Except for global outcome, which was significantly better for patients without ASD, the clinical outcome was not statistically different in patients with and without ASD. In conclusion, the long-term RCT shows that fusion accelerates degenerative changes at the adjacent level compared with natural history. The study suggests that not only fusion, but also laminectomy may be of pathogenetic importance. The clinical importance of ASD seems limited, with only the more severe forms affecting the outcome.

Posterior lumbar interbody fusion versus posterolateral fusion in adult isthmic spondylolisthesis.

STUDY DESIGN: A prospective study with historical controls. OBJECTIVE: To compare the outcome of posterior lumbar interbody fusion (PLIF) and posterolateral fusion (PLF) in adult isthmic spondylolisthesis. SUMMARY OF BACKGROUND DATA: On theoretical grounds, PLIF has been suggested to result in an improved outcome compared with PLF. Data to support this view, however, are lacking. METHODS: A total of 86 patients (age range, 18-55 years) with adult isthmic spondylolisthesis were operated on with PLIF. The comparison group consisted of 77 patients operated on with PLF with iliac bone autograft, 40 with and 37 without pedicle fixation. The 2 groups had similar socioeconomic, age and sex distribution, level of pain, and disability. Inclusion criteria and outcome measurements were identical in both groups. The PLIF group was operated on with autograft and carbon fiber ramps with pedicle fixation. Before surgery and at the 2-year follow-up, pain (VAS) and functional disability were quantified by the Disability Rating Index (DRI, 0-100) and the Oswestry Disability Index (ODI). The global outcome was assessed by the patient as much better, better, unchanged, or worse. RESULTS: The follow-up rate was 98% in the PLIF group and 97% in the PLF group. In PLIF patients, pain index improved from 66 to 35 (P < 0.0001) and the DRI from 47 to 30 (P < 0.01). The levels of pain and DRI were similar to that of the PLF group (pain 37, DRI 29, not significant), and the ODI was identical in both groups (25); 74% of the patients in both groups classified the results as much better or better. CONCLUSION: Type of fusion, PLIF or PLF, does not affect the 2-year outcome of surgical treatment of adult isthmic spondylolisthesis. Despite the theoretical advantages of PLIF, no improvement on patient outcome compared with posterolateral fusion could be demonstrated, questioning the need of anterior support in short lumbar fusions.

The long-term effect of posterolateral fusion in adult isthmic spondylolisthesis: a randomized controlled study.

BACKGROUND: Today there is some evidence-based medicine support for a positive short-term treatment effect of fusion in chronic low back pain in spondylolisthesis and in nonspecific degenerative lumbar spine disorders. The long-term effect is, however, unknown. PURPOSE: To determine the long-term outcome of lumbar fusion in adult isthmic spondylolisthesis. STUDY DESIGN: Prospective, randomized controlled study comparing a 1-year exercise program with instrumented and non-instrumented posterolateral fusion with average long-term follow-up of 9 years (range, 5-13). PATIENT SAMPLE: 111 patients aged 18 to 55 years with adult lumbar isthmic spondylolisthesis at L5 or L4 level of all degrees, and at least 1-year's duration of severe lumbar pain with or without sciatica. OUTCOME MEASURES: Pain and functional disability was quantified by pain (VAS), the Disability Rating Index (DRI), the Oswestry Disability Index (ODI) work status, and global assessment of outcome by the patient into much better, better, unchanged or worse. Quality of life was assessed by the SF-36. METHODS: The patients were randomly allocated to treatment with 1) a 1-year exercise program (n=34), 2) posterolateral fusion without pedicle screw instrumentation (n=37), or 3) posterolateral fusion with pedicle screw instrumentation (n=40). Long-term follow-up was obtained in 101 (91%) patients. Nine patients in the exercise group were eventually operated on. RESULTS: Longitudinal analysis: At long-term follow-up pain and functional disability were significantly better than before treatment in both surgical groups. No significant differences were observed between instrumented and non-instrumented patients in any variable studied. In the exercise group the pain was significantly reduced but not the functional disability. Compared with the 2-year follow-up a significant increase in functional disability was observed, as measured by the DRI, but not the ODI, in the surgical group at long term. In the exercise group no significant changes were observed between the 2-year and the long-term follow-up. Cross-sectional analysis: Between the surgical and conservative group no significant differences were observed in any outcome measurement at long-term follow-up except for global assessment, which was significantly better for surgical patients. Of surgical patients 76% classified the overall outcome as much better or better compared with 50% of conservatively treated patients (p=0.015). Quality of life as estimated by the SF-36 at long term was not different between treatment groups in any of the eight domains studied but was considerably lower than for the normal population. CONCLUSIONS: Posterolateral fusion in adult lumbar isthmic spondylolisthesis results ina modestly improved long-term outcome compared with a 1-year exercise program. Although the results show that some of the previously reported short-term improvement is lost at long term, patients with fusion still classify their global outcome as clearly better than conservatively treated patients. Furthermore, because the long-term outcome of the patients conservatively treated most likely reflects the natural course, one can also conclude that no considerable spontaneous improvement should be expected over time in adult patients with symptomatic isthmic spondylolisthesis. Substantial pain, functional disability and a reduced quality of life will in most patients most likely remain unaltered over many years.