Surgeon variation: a south african spinal pathology treatment survey.

PURPOSE: To investigate variation in treatment decisions among spine surgeons in South Africa and the association between surgeon characteristics and the treatment they select. METHODS: We surveyed 79 South African spine surgeons. We presented four vignettes (cervical spine distractive flexion injury, lumbar disc herniation, degenerative spondylolisthesis with stenosis, and insufficiency fracture) for them to assess and select treatments. We calculated the index of qualitative variation (IQV) to determine the degree of variability within each vignette. We used Fisher's exact, and Kruskal-Wallis tests to assess the relationships between surgeons' characteristics and their responses per vignette. We compared their responses to the recommendations of a panel of spine specialists. RESULTS: IQVs showed moderate to high variability for cervical spine distractive flexion injury and insufficiency fracture and slightly lower levels of variability for lumbar disc herniation and degenerative spondylolisthesis with stenosis. This confirms the heterogeneity in South African spine surgeons' management of spinal pathologies. The surgeon characteristics associated with their treatment selection that were important were caseload, experience and training, and external funding. Also, 19% of the surgeons selected a treatment option that the Panel did not support. CONCLUSION: The findings make a case for evaluating patient outcomes and costs to identify value-based care. Such research would help countries that are seeking to contract with providers on value. Greater uniformity in treatment and easily accessible outcomes reporting would provide guidance for patients. Further investment in training and participation in fellowship programs may be necessary, along with greater dissemination of information from the literature.

Evaluation of host biomarkers for monitoring treatment response in spinal tuberculosis: A 12-month cohort study.

BACKGROUND: Monitoring treatment response is an important precaution in spinal tuberculosis (TB), particularly when the condition was clinically diagnosed rather than bacteriologically confirmed and when drug susceptibility testing was not performed. Conventional monitoring measures have limitations and there is a need for favourable alternatives. Therefore, this study aimed to investigate changes in immune biomarkers over the course of treatment for spinal TB and to compare these responses to the conventional monitoring measure, erythrocyte sedimentation rate (ESR). METHODS: Patients with spinal TB were recruited from a tertiary hospital in the Western Cape, South Africa, and provided blood samples at 0, 3, 6, 9 and 12 months of TB treatment. Blood samples were analysed for ESR, using standard techniques, and for 19 cytokines, using a multiplex platform. Changes in ESR and cytokine levels were investigated using a mixed model ANOVA and Least Significant Difference post-hoc testing. RESULTS: Twenty-six patients with spinal TB were included in the study although only fifteen remained in follow-up at 12 months. Seven biomarkers changed significantly over the course of treatment (CRP, Fibrinogen, IFN-γ, Ferritin, VEGF-A, ApoA1 and NCAM, p < 0.01) with a further three showing a strong trend towards change (CCL1, CXCL9 and GDF-15, 0.05 ≥ p ≤ 0.06). Responsive biomarkers could be approximately grouped according to patterns of progressive, initial or delayed change. ESR performed similarly to CRP, Fibrinogen and IFN-γ with all showing significant decreases between 0, 6 and 12- months of treatment. Individual ESR responses were variable. DISCUSSION: Individual ESR responses may be unreliable and support the investigation of multi-marker approaches to evaluating treatment response in spinal TB. Biomarkers of treatment response identified in the current study require validation in a larger study, which may also incorporate aspects such as evaluating biomarkers within the first week of treatment and the inclusion of a healthy control group.

HIV encephalopathy with bilateral lower limb spasticity: gross motor function and antiretroviral therapy.

AIM: To describe gross motor function in children with bilateral lower limb (BLL) spasticity due to human immunodeficiency virus encephalopathy (HIVE), and to investigate the association between age, CD4 percentage, and viral load at initiation of antiretroviral therapy (ART) and current gross motor function. METHOD: Thirty ambulant children with HIVE and BLL spasticity were recruited. Clinical parameters, including ART, were obtained from medical records. Gross motor function was assessed using the 88-item Gross Motor Function Measure (GMFM-88). RESULTS: The participant group was comprised of 14 males and 16 females (median age 8y; interquartile range [IQR] 7-11y). ART was initiated at a median age of 7 months (IQR 5-11mo) with a median CD4 percentage of 4.7% (IQR 2.3-8.0) and viral load of log10 6.0 (IQR 5.6-6.4). The median total GMFM-88 score was 89% (IQR 78-94%), with a wide range of scores in the 'Standing' domain (26-97%) and 'Walking, Running, and Jumping' domain (8-99%). No associations were detected between age at initiation of ART, CD4 percentage, or viral load and total GMFM-88 score. INTERPRETATION: Limitations in gross motor function in children with HIVE and BLL spasticity range from mild to severe. ART initiation factors were not able to predict functional status in this sample.

HIV encephalopathy with bilateral lower limb spasticity: upper limb motor function and level of activity and participation.

AIM: To describe upper limb motor function and level of activity and participation in children with HIV encephalopathy (HIVE) and bilateral lower limb (BLL) spasticity. METHOD: Thirty ambulant children with HIVE and BLL spasticity and 20 typically developing children, between 5 years and 12 years, were recruited. Upper limb motor function was assessed using the Purdue Pegboard and level of activity and participation using the Computer-Adapted Pediatric Evaluation of Disabilities Inventory (PEDI-CAT). RESULTS: The HIVE group comprised 14 males and 16 females (mean age [SD] 8y 8mo [2y 2mo], Gross Motor Function Classification System (GMFCS) level I [n=10], II [n=11], and III [n=9]) and the typically developing group comprised 11 males and 9 females (mean age 8y 8mo [2y 3mo]). The HIVE group had lower scores than the typically developing group for all pegboard tasks and three of the four PEDI-CAT domains (p≤0.001). However, individual outcome scores varied substantially within each GMFCS level. INTERPRETATION: Children with HIVE and BLL spasticity may have significantly poorer upper limb motor performance and lower levels of activity and participation than typically developing children. These findings suggest that an assessment of upper limb motor function should form part of optimal care for this population.

Resolved lower limb muscle tone abnormalities in children with HIV encephalopathy receiving standard antiretroviral therapy.

BACKGROUND: This short report arose from a follow-up study of children previously diagnosed with human immunodeficiency virus (HIV) encephalopathy and spastic diplegia and is among the first to describe that increased lower limb muscle tone in children with a confirmed HIV encephalopathy diagnosis may resolve over time in some cases. RESULTS: Of 19 children previously diagnosed with HIV encephalopathy and increased lower limb muscle tone, some were found to have resolved muscle tone abnormalities during a follow-up physical examination [resolved group, n = 13, median age 9 years 7 months (interquartile range 7 years 3 months-10 years 9 months)] whereas others continued to show increased lower limb muscle tone at follow-up [unresolved group, n = 6 median age 8 years 6 months (interquartile range 7 years 9 months-9 years 7 months)]. A review of clinical records showed no significant differences in age or follow-up time between the resolved and unresolved groups. However, the unresolved group appeared to have severe disease at an earlier age than the resolved group, based on the age at antiretroviral treatment initiation [median age at start of treatment 2 years 3 months (interquartile range 7 months-5 years 3 months) vs. 8 months (interquartile range 6-12 months), p = 0.08] and had more severe neurological signs at the initial assessment. CONCLUSIONS: It is anticipated that this information may be of immediate value to those involved in the treatment of children with HIV encephalopathy and increased lower limb muscle tone whilst awaiting the outcome of future controlled clinical trials.

Faster Heart Rate Recovery With Increased RPE: Paradoxical Responses After an 87-km Ultramarathon.

The aim of this study was to determine the relationship between heart rate recovery (HRR) and an acute training "overload" by comparing HRR responses before and after an ultramarathon road race. Ten runners completed a standardized laboratory protocol ∼7 days before and between 2 and 4 days after participating in the 87-km Comrades Marathon. The protocol included muscle pain ratings, a 5-bound test, and 20 minutes of treadmill exercise at 70% of maximal oxygen uptake followed by 15 minutes of recovery. Respiratory gases and heart rate measurements were used to calculate steady-state exercise responses, HRR, and excess postexercise oxygen consumption (EPOC), and participants also provided a rating of perceived exertion (RPE) during exercise. The RPE was significantly increased (13 ± 2 vs. 11 ± 1) (p < 0.01), and HRR was significantly faster (35 ± 5 beats vs. 29 ± 4 beats) (p < 0.01) following the postrace vs. prerace submaximal exercise bout, with no significant changes in respiratory or heart rate parameters during exercise or in EPOC. Although previous studies have shown that faster HRR reflected an "adapted" state with enhanced training status, the current findings suggest that this may not always be the case. It follows that changes in HRR should be considered in the context of other factors, such as recent training load and RPE during submaximal exercise.

Effect of exercise intensity on post-exercise oxygen consumption and heart rate recovery.

PURPOSE: There is some evidence that measures of acute post-exercise recovery are sensitive to the homeostatic stress of the preceding exercise and these measurements warrant further investigation as possible markers of training load. The current study investigated which of four different measures of metabolic and autonomic recovery was most sensitive to changes in exercise intensity. METHODS: Thirty-eight moderately trained runners completed 20-min bouts of treadmill exercise at 60, 70 and 80% of maximal oxygen uptake (VO2max) and four different recovery measurements were determined: the magnitude of excess post-exercise oxygen consumption (EPOCMAG), the time constant of the oxygen consumption recovery curve (EPOCτ), heart rate recovery within 1 min (HRR60s) and the time constant of the heart rate recovery curve (HRRτ) . RESULTS: Despite significant differences in exercise parameters at each exercise intensity, only EPOCMAG showed significantly slower recovery with each increase in exercise intensity at the group level and in the majority of individuals. EPOCτ was significantly slower at 70 and 80% of VO2max vs. 60% VO2max and HRRτ was only significantly slower when comparing the 80 vs. 60% VO2max exercise bouts. In contrast, HRR60s reflected faster recovery at 70 and 80% of VO2max than at 60% VO2max. CONCLUSION: Of the four recovery measurements investigated, EPOCMAG was the most sensitive to changes in exercise intensity and shows potential to reflect changes in the homeostatic stress of exercise at the group and individual level. Determining EPOCMAG may help to interpret the homeostatic stress of laboratory-based research trials or training sessions.

Culture filtrate supplementation can be used to improve Mycobacterium tuberculosis culture positivity for spinal tuberculosis diagnosis.

Culture remains the gold standard to diagnose spinal tuberculosis (STB) despite the paucibacillary nature of the disease. Current methods can take up to 42 days to yield a result, delaying the ability to rapidly detect drug resistance. Studies have demonstrated the use of supplementation with culture filtrate (CF) from an axenic culture of Mycobacterium tuberculosis (Mtb) as a source of growth factors to improve culture rates. Our objective was to test a modified culture assay, utilizing CF supplemented media (CFSM), to improve culture positivity rates for suspected STB. Twelve patients with suspected STB were assessed by conventional culture (BACTEC™ MGIT 960), GeneXpert™ and standard histopathological examination. Spinal biopsies were taken from areas of diseased vertebral tissue or abscess, predetermined from MRI. Additional biopsies were obtained to assess CFSM for improved detection and faster culture of Mtb. All cases were diagnosed as STB and treated empirically for tuberculosis based on either bacteriological evidence (GeneXpert™, MGIT and/or CFSM positive), or based on clinical presentation. 5 specimens (45.45%) were positive for Mtb DNA as detected by GeneXpert™ and 1 specimen (8.33%) was cultured using MGIT (time to detection; 18 days). CFSM was able to culture 7 specimens (58.3%), with all CFSM positive specimens yielding a culture within 14 days. Two samples were positive only using the CFSM assay pointing to additional yield for diagnostic workup. Modification of standard culture can improve detection of Mtb and reduce time to positivity in individuals with STB where culture material is a requirement.

Candidate Biomarkers to Distinguish Spinal Tuberculosis From Mechanical Back Pain in a Tuberculosis Endemic Setting.

Background: Spinal tuberculosis (TB) may have a variable, non-specific presentation including back pain with- or without- constitutional symptoms. Further tools are needed to aid early diagnosis of this potentially severe form of TB and immunological biomarkers may show potential in this regard. The aim of this study was to investigate the utility of host serum biomarkers to distinguish spinal TB from mechanical back pain. Methods: Patients with suspected spinal TB or suspected mechanical back pain were recruited from a tertiary hospital in the Western Cape, South Africa, and provided a blood sample for biomarker analysis. Diagnosis was subsequently confirmed using bacteriological testing, advanced imaging and/or clinical evaluation, as appropriate. The concentrations of 19 host biomarkers were evaluated in serum samples using the Luminex platform. Receiver Operating Characteristic (ROC) curves and General Discriminant Analysis were used to identify biomarkers with the potential to distinguish spinal TB from mechanical back pain. Results: Twenty-six patients with spinal TB and 17 with mechanical back pain were recruited. Seven out of 19 biomarkers were significantly different between groups, of which Fibrinogen, CRP, IFN-γ and NCAM were the individual markers with the highest discrimination utility (Area Under Curve ROC plot 0.88-0.99). A five-marker biosignature (CRP, NCAM, Ferritin, CXCL8 and GDF-15) correctly classified all study participants after leave-one-out cross-validation. Conclusion: This study identified host serum biomarkers with the potential to diagnose spinal TB, including a five-marker biosignature. These preliminary findings require validation in larger studies.

Biomarkers to predict FDG PET/CT activity after the standard duration of treatment for spinal tuberculosis: An exploratory study.

OBJECTIVES: 18F-Fluorodeoxyglucose (FDG) Positron Emission Tomography- Computed Tomography (PET/CT) scans can be used to assess healing following treatment for spinal tuberculosis (TB) but have limited accessibility and high cost. This study investigated the association between immune biomarkers and FDG-PET/CT activity after ≥9 months of treatment for spinal TB. METHODS: Patients who had completed ≥9 months of treatment for spinal TB were recruited from a major hospital in the Western Cape, South Africa. Participants underwent a FDG-PET/CT scan and FDG- PET/CT activity was quantified for all spinal and extra-spinal sites. Participants also provided a blood sample, which was evaluated for 19 cytokines along with erythrocyte sedimentation rate (ESR). Correlations and multiple regression analyses were used to investigate the association between biomarkers and PET/CT measures. RESULTS: Twenty-eight patients were recruited, of whom 24 (86%) had spinal and/or extra-spinal FDG-PET/CT activity. In the strongest multiple regression model, CXCL10/IP-10, VEGFA, IFN-γ, CRP and Factor D/Adipsin explained 52% of the variation in overall maximal FDG uptake. Conventional monitoring marker ESR showed no significant association with PET/CT measures. CONCLUSIONS: The current findings offered encouragement that biomarkers to predict FDG-PET/CT activity may show some promise and identified candidate biomarkers for further investigation in this regard.

High responders and low responders: factors associated with individual variation in response to standardized training.

The response to an exercise intervention is often described in general terms, with the assumption that the group average represents a typical response for most individuals. In reality, however, it is more common for individuals to show a wide range of responses to an intervention rather than a similar response. This phenomenon of 'high responders' and 'low responders' following a standardized training intervention may provide helpful insights into mechanisms of training adaptation and methods of training prescription. Therefore, the aim of this review was to discuss factors associated with inter-individual variation in response to standardized, endurance-type training. It is well-known that genetic influences make an important contribution to individual variation in certain training responses. The association between genotype and training response has often been supported using heritability estimates; however, recent studies have been able to link variation in some training responses to specific single nucleotide polymorphisms. It would appear that hereditary influences are often expressed through hereditary influences on the pre-training phenotype, with some parameters showing a hereditary influence in the pre-training phenotype but not in the subsequent training response. In most cases, the pre-training phenotype appears to predict only a small amount of variation in the subsequent training response of that phenotype. However, the relationship between pre-training autonomic activity and subsequent maximal oxygen uptake response appears to show relatively stronger predictive potential. Individual variation in response to standardized training that cannot be explained by genetic influences may be related to the characteristics of the training program or lifestyle factors. Although standardized programs usually involve training prescribed by relative intensity and duration, some methods of relative exercise intensity prescription may be more successful in creating an equivalent homeostatic stress between individuals than other methods. Individual variation in the homeostatic stress associated with each training session would result in individuals experiencing a different exercise 'stimulus' and contribute to individual variation in the adaptive responses incurred over the course of the training program. Furthermore, recovery between the sessions of a standardized training program may vary amongst individuals due to factors such as training status, sleep, psychological stress, and habitual physical activity. If there is an imbalance between overall stress and recovery, some individuals may develop fatigue and even maladaptation, contributing to variation in pre-post training responses. There is some evidence that training response can be modulated by the timing and composition of dietary intake, and hence nutritional factors could also potentially contribute to individual variation in training responses. Finally, a certain amount of individual variation in responses may also be attributed to measurement error, a factor that should be accounted for wherever possible in future studies. In conclusion, there are several factors that could contribute to individual variation in response to standardized training. However, more studies are required to help clarify and quantify the role of these factors. Future studies addressing such topics may aid in the early prediction of high or low training responses and provide further insight into the mechanisms of training adaptation.