Prevalence of chronic non-cancer pain among military veterans: a systematic review and meta-analysis of observational studies.

INTRODUCTION: Chronic non-cancer pain is common among military veterans; however, the prevalence is uncertain. This information gap complicates policy decisions and resource planning to ensure veterans have access to healthcare services that align with their needs. METHODS: Following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, we searched MEDLINE, EMBASE, PsycINFO, CINAHL and Web of Science from inception to 9 February 2023 for observational studies reporting the prevalence of chronic non-cancer pain among military veterans. We performed random-effects meta-analysis to pool pain prevalence data across studies and used the Grading of Recommendations, Assessment, Development and Evaluation approach to evaluate the certainty of evidence. RESULTS: Forty-two studies that included 14 305 129 veterans were eligible for review, of which 28 studies (n=5 011 634) contributed to our meta-analysis. Most studies (90%; 38 of 42) enrolled US veterans, the median of the mean age among study participants was 55 years (IQR 45-62) and 85% were male. The pooled prevalence of chronic non-cancer pain was 45%; however, we found evidence of a credible subgroup effect based on representativeness of the study population. Moderate certainty evidence found the prevalence of chronic pain among studies enrolling military veterans from the general population was 30% (95% CI 23% to 37%) compared with 51% (95% CI 38% to 64%) among military veterans sampled from populations with high rates of conditions associated with chronic pain (p=0.005). CONCLUSION: We found moderate certainty evidence that 3 in every 10 military veterans from the general population live with chronic non-cancer pain. These findings underscore the importance of ensuring access to evidence-based care for chronic pain for veterans, and the need for prevention and early management to reduce transition from acute to chronic pain. Further research, employing a standardised assessment of chronic pain, is needed to disaggregate meaningful subgroups; for example, the proportion of veterans living with moderate to severe pain compared with mild pain.

Health measurement instruments and their applicability to military veterans: a systematic review.

INTRODUCTION: Accurate measurement of health status is essential to assess veterans' needs and the effects of interventions directed at improving veterans' well-being. We conducted a systematic review to identify instruments that measure subjective health status, considering four components (ie, physical, mental, social or spiritual well-being). METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we searched CINAHL, MEDLINE, Embase, PsycINFO, Web of Science, JSTOR, ERIC, Social Sciences Abstracts and ProQuest in June 2021 for studies reporting on the development or evaluation of instruments measuring subjective health among outpatient populations. We assessed risk of bias with the Consensus-based Standards for the Selection of Health Measurement Instruments tool and engaged three veteran partners to independently assess the clarity and applicability of identified instruments. RESULTS: Of 5863 abstracts screened, we identified 45 eligible articles that reported health-related instruments in the following categories: general health (n=19), mental health (n=7), physical health (n=8), social health (n=3) and spiritual health (n=8). We found evidence for adequate internal consistency for 39 instruments (87%) and good test-retest reliability for 24 (53%) instruments. Of these, our veteran partners identified five instruments for the measurement of subjective health (Military to Civilian Questionnaire (M2C-Q), Veterans RAND 36-Item Health Survey (VR-36), Short Form 36, Abbreviated World Health Organization Quality of Life questionnaire (WHOQOL-BREF) and Sleep Health Scale) as clear and very applicable to veterans. Of the two instruments developed and validated among veterans, the 16-item M2C-Q considered most components of health (mental, social and spiritual). Of the three instruments not validated among veterans, only the 26-item WHOQOL-BREF considered all four components of health. CONCLUSION: We identified 45 health measurement instruments of which, among those reporting adequate psychometric properties and endorsed by our veteran partners, 2 instruments showed the most promise for measurement of subjective health. The M2C-Q, which requires augmentation to capture physical health (eg, the physical component score of the VR-36), and the WHOQOL-BREF, which requires validation among veterans.

Patient coping and expectations predict recovery after major orthopaedic trauma.

BACKGROUND: Persistent post-surgical pain and associated disability are common after a traumatic fracture repair. Preliminary evidence suggests that patients' beliefs and perceptions may influence their prognosis. METHODS: We used data from the Fluid Lavage of Open Wounds trial to determine, in 1560 open fracture patients undergoing surgical repair, the association between Somatic PreOccupation and Coping (captured by the SPOC questionnaire) and recovery at 1 yr. RESULTS: Of the 1218 open fracture patients with complete data available for analysis, 813 (66.7%) reported moderate to extreme pain at 1 yr. The addition of SPOC scores to an adjusted regression model to predict persistent pain improved the concordance statistic from 0.66 to 0.74, and found the greatest risk was associated with high (≥74) SPOC scores [odds ratio: 5.63; 99% confidence interval (CI): 3.59-8.84; absolute risk increase 40.6%; 99% CI: 30.8%, 48.6%]. Thirty-eight per cent (484 of 1277) reported moderate to extreme pain interference at 1 yr. The addition of SPOC scores to an adjusted regression model to predict pain interference improved the concordance statistic from 0.66 to 0.75, and the greatest risk was associated with high SPOC scores (odds ratio: 6.06; 99% CI: 3.97-9.25; absolute risk increase: 18.3%; 95% CI: 11.7%, 26.7%). In our adjusted multivariable regression models, SPOC scores at 6 weeks post-surgery accounted for 10% of the variation in short form-12 physical component summary scores and 14% of short form-12 mental component summary scores at 1 yr. CONCLUSIONS: Amongst patients undergoing surgical repair of open extremity fractures, high SPOC questionnaire scores at 6 weeks post-surgery were predictive of persistent pain, reduced quality of life, and pain interference at 1 yr. CLINICAL TRIAL REGISTRATION: NCT00788398.

Perioperative psychotherapy for persistent post-surgical pain and physical impairment: a meta-analysis of randomised trials.

BACKGROUND: Persistent post-surgical pain affects 10-80% of individuals after common operations, and is more common among patients with psychological factors such as depression, anxiety, or catastrophising. METHODS: We conducted a systematic review and meta-analysis of randomised, controlled trials to evaluate the efficacy of perioperative psychotherapy for persistent post-surgical pain and physical impairment. Paired independent reviewers identified studies, extracted data, and assessed risk of bias. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of evidence. RESULTS: Our search of five electronic databases, up to September 1, 2016, found 15 trials (2220 patients) that were eligible for review. For both persistent post-surgical pain and physical impairment, perioperative education was ineffective, while active psychotherapy suggested a benefit (test of interaction P=0.01 for both outcomes). Moderate quality evidence showed that active perioperative psychotherapy (cognitive-behaviour therapy, relaxation therapy, or both) significantly reduced persistent post-surgical pain [weighted mean difference (WMD) -1.06 cm on a 10 cm visual analogue scale for pain, 95% confidence interval (CI) -1.56 to -0.55 cm; risk difference (RD) for achieving no more than mild pain (≤3 cm) 14%, 95% CI 8-21%] and physical impairment [WMD -9.87% on the 0-100% Oswestry Disability Index, 95% CI -13.42 to -6.32%, RD for achieving no more than mild disability (≤20%) 21%, 95% CI 13-29%]. CONCLUSIONS: Perioperative cognitive behavioural therapy and relaxation therapy are effective for reducing persistent pain and physical impairment after surgery. Future studies should explore targeted psychotherapy for surgical patients at higher risk for poor outcome. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42016047335.

Low-intensity pulsed ultrasound for treatment of tibial fractures: an economic evaluation of the TRUST study.

AIMS: This 501-patient, multi-centre, randomised controlled trial sought to establish the effect of low-intensity, pulsed, ultrasound (LIPUS) on tibial shaft fractures managed with intramedullary nailing. We conducted an economic evaluation as part of this trial. PATIENTS AND METHODS: Data for patients' use of post-operative healthcare resources and time taken to return to work were collected and costed using publicly available sources. Health-related quality of life, assessed using the Health Utilities Index Mark-3 (HUI-3), was used to derive quality-adjusted life years (QALYs). Costs and QALYs were compared between LIPUS and control (a placebo device) from a payer and societal perspective using non-parametric bootstrapping. All costs are reported in 2015 Canadian dollars unless otherwise stated. RESULTS: With a cost per device of $3,995, the mean cost was significantly higher for patients treated with LIPUS versus placebo from a payer (mean increase = $3647, 95% confidence interval (CI) $3244 to $4070; p < 0.001) or a societal perspective (mean increase = $3425, 95% CI $1568 to $5283; p < 0.001). LIPUS did not provide a significant benefit in terms of QALYs gained (mean difference = 0.023 QALYs, 95% CI -0.035 to 0.069; p = 0.474). Incremental cost-effectiveness ratios of LIPUS compared with placebo were $155 433/QALY from a payer perspective and $146 006/QALY from a societal perspective. CONCLUSION: At the current price, LIPUS is not cost-effective for fresh tibial fractures managed with intramedullary nailing. Cite this article: Bone Joint J 2017;99-B:1526-32.

Guideline for opioid therapy and chronic noncancer pain

Guideline for opioid therapy and chronic noncancer pain: the objective is to inform the prescribing of opioids for adults with chronic noncancer pain.

Patient coping and expectations about recovery predict the development of chronic post-surgical pain after traumatic tibial fracture repair.

BACKGROUND: The association of patient expectations about recovery with the development of chronic post-surgical pain (CPSP) is uncertain. METHODS: Three hundred and fifty-nine patients enrolled in the SPRINT trial completed the Somatic Preoccupation and Coping (SPOC) questionnaire six weeks after a traumatic tibial fracture repair. The SPOC questionnaire measures patients' somatic complaints, coping, and optimism for recovery. Using adjusted models, we explored the association of SPOC scores with ≥ mild CPSP and ≥ moderate pain interference with activity at one yr after surgery. RESULTS: Of 267 tibial fracture patients with data available for analysis, 147 (55.1%) reported CPSP at one yr. The incidence of CPSP was 37.6% among those with low (≤40) SPOC scores, 54.1% among those with intermediate (41-80) scores, and 81.7% among those with high (>80) scores. Addition of SPOC scores to an adjusted regression model to predict CPSP improved the c-statistic from 0.61 (95% CI 0.55-0.68) to 0.70 (95% CI 0.64-0.76, P=0.005 for the difference) and found the greatest risk was associated with high SPOC scores (OR 6.56, 95% CI 2.90-14.81). Similarly, an adjusted regression model to predict pain interference with function at one yr (c-statistic 0.77, 95% CI 0.71-0.83) found the greatest risk for those with high SPOC scores (OR 10.10, 95% CI 4.26-23.96). CONCLUSIONS: Patient's coping and expectations of recovery, as measured by the SPOC questionnaire, is an independent predictor of CPSP and pain interference one yr after traumatic tibial fracture. Future studies should explore whether these beliefs can be modified, and if doing so improves prognosis. CLINICAL TRIAL REGISTRATION: NCT 00038129.

Mass concentration in a nonlocal model of clonal selection.

Self-renewal is a constitutive property of stem cells. Testing the cancer stem cell hypothesis requires investigation of the impact of self-renewal on cancer expansion. To better understand this impact, we propose a mathematical model describing the dynamics of a continuum of cell clones structured by the self-renewal potential. The model is an extension of the finite multi-compartment models of interactions between normal and cancer cells in acute leukemias. It takes a form of a system of integro-differential equations with a nonlinear and nonlocal coupling which describes regulatory feedback loops of cell proliferation and differentiation. We show that this coupling leads to mass concentration in points corresponding to the maxima of the self-renewal potential and the solutions of the model tend asymptotically to Dirac measures multiplied by positive constants. Furthermore, using a Lyapunov function constructed for the finite dimensional counterpart of the model, we prove that the total mass of the solution converges to a globally stable equilibrium. Additionally, we show stability of the model in the space of positive Radon measures equipped with the flat metric (bounded Lipschitz distance). Analytical results are illustrated by numerical simulations.

The effect of surgical synovectomy and radiotherapy on the rate of recurrence of pigmented villonodular synovitis of the knee: an individual patient meta-analysis.

Pigmented villonodular synovitis (PVNS) is a rare proliferative process of the synovium which most commonly affects the knee and occurs in either a localised (LPVNS) or a diffuse form (DPVNS). The effect of different methods of surgical synovectomy and adjuvant radiotherapy on the rate of recurrence is unclear. We conducted a systematic review and identified 35 observational studies in English which reported the use of surgical synovectomy to treat PVNS of the knee. A meta-analysis included 630 patients, 137 (21.8%) of whom had a recurrence after synovectomy. For patients with DPVNS, low-quality evidence found that the rate of recurrence was reduced by both open synovectomy (odds ration (OR) = 0.47; 95% CI 0.25 to 0.90; p = 0.024) and combined open and arthroscopic synovectomy (OR = 0.19, 95% CI = 0.06 to 0.58; p = 0.003) compared with arthroscopic surgery. Very low-quality evidence found that the rate of recurrence of DPVNS was reduced by peri-operative radiotherapy (OR = 0.31, 95% CI 0.14 to 0.70; p = 0.01). Very low-quality evidence suggested that the rate of recurrence of LPVNS was not related to the surgical approach. This meta-analysis suggests that open synovectomy or synovectomy combined with peri-operative radiotherapy for DPVNS is associated with a reduced rate of recurrence. Large long-term prospective multicentre observational studies, with a focus on both rate of recurrence and function, are required to confirm these findings.

Targeting the actin cytoskeleton: selective antitumor action via trapping PKCɛ.

Targeting the actin cytoskeleton (CSK) of cancer cells offers a valuable strategy in cancer therapy. There are a number of natural compounds that interfere with the actin CSK, but the mode of their cytotoxic action and, moreover, their tumor-specific mechanisms are quite elusive. We used the myxobacterial compound Chondramide as a tool to first elucidate the mechanisms of cytotoxicity of actin targeting in breast cancer cells (MCF7, MDA-MB-231). Chondramide inhibits cellular actin filament dynamics shown by a fluorescence-based analysis (fluorescence recovery after photobleaching (FRAP)) and leads to apoptosis characterized by phosphatidylserine exposure, release of cytochrome C from mitochondria and finally activation of caspases. Chondramide enhances the occurrence of mitochondrial permeability transition (MPT) by affecting known MPT modulators: Hexokinase II bound to the voltage-dependent anion channel (VDAC) translocated from the outer mitochondrial membrane to the cytosol and the proapoptotic protein Bad were recruited to the mitochondria. Importantly, protein kinase C-ɛ (PKCɛ), a prosurvival kinase possessing an actin-binding site and known to regulate the hexokinase/VDAC interaction as well as Bad phosphorylation was identified as the link between actin CSK and apoptosis induction. PKCɛ, which was found overexpressed in breast cancer cells, accumulated in actin bundles induced by Chondramide and lost its activity. Our second goal was to characterize the potential tumor-specific action of actin-binding agents. As the nontumor breast epithelial cell line MCF-10A in fact shows resistance to Chondramide-induced apoptosis and notably express low level of PKCɛ, we suggest that trapping PKCɛ via Chondramide-induced actin hyperpolymerization displays tumor cell specificity. Our work provides a link between targeting the ubiquitously occurring actin CSK and selective inhibition of pro-tumorigenic PKCɛ, thus setting the stage for actin-stabilizing agents as innovative cancer drugs. This is moreover supported by the in vivo efficacy of Chondramide triggered by abrogation of PKCɛ signaling shown in a xenograft breast cancer model.

Silicon based tandem cells: novel photocathodes for hydrogen production.

A photovoltaic tandem cell made of amorphous silicon (a-Si) and microcrystalline silicon (µc-Si) was investigated as a photocathode for hydrogen evolution in a photoelectrochemical device. The electronic and electrochemical properties of the samples were characterized using X-ray photoemission spectroscopy (XPS) and cyclic voltammetry (CV), whereas the morphology of the surface in contact with the electrolyte was investigated by scanning electron microscopy (SEM). The electric efficiency of the tandem cell was determined to be 5.2% in a photoelectrochemical (PEC) setup in acidic solution which is only about half of the photovoltaic efficiency of the tandem cell. A significant improvement in efficiency was achieved with platinum as a catalyst which was deposited by physical vapour deposition (PVD) under ultra-high vacuum (UHV) conditions.

Comparing current definitions of return to work: a measurement approach.

INTRODUCTION: Return-to-work (RTW) status is an often used outcome in work and health research. In low back pain, work is regarded as a normal activity a worker should return to in order to fully recover. Comparing outcomes across studies and even jurisdictions using different definitions of RTW can be challenging for readers in general and when performing a systematic review in particular. In this study, the measurement properties of previously defined RTW outcomes were examined with data from two studies from two countries. METHODS: Data on RTW in low back pain (LBP) from the Canadian Early Claimant Cohort (ECC); a workers' compensation based study, and the Dutch Amsterdam Sherbrooke Evaluation (ASE) study were analyzed. Correlations between outcomes, differences in predictive validity when using different outcomes and construct validity when comparing outcomes to a functional status outcome were analyzed. RESULTS: In the ECC all definitions were highly correlated and performed similarly in predictive validity. When compared to functional status, RTW definitions in the ECC study performed fair to good on all time points. In the ASE study all definitions were highly correlated and performed similarly in predictive validity. The RTW definitions, however, failed to compare or compared poorly with functional status. Only one definition compared fairly on one time point. CONCLUSIONS: Differently defined outcomes are highly correlated, give similar results in prediction, but seem to differ in construct validity when compared to functional status depending on societal context or possibly birth cohort. Comparison of studies using different RTW definitions appears valid as long as RTW status is not considered as a measure of functional status.

Evaluating the evidence for assessing BNP and NT-proBNP levels.

OBJECTIVES: To provide an overview of 5 systematic reviews in this issue of Clinical Biochemistry addressing the diagnostic and prognostic power of natriuretic peptides. DESIGN AND METHODS: Editorial. RESULTS: Limited quality of the primary studies and the large variability in their results limit the inferences that can be drawn from reviews in this series. CONCLUSIONS: The current data justify neither enthusiastic use, nor confident rejection, of BNP and NT-proBNP levels to inform the prognosis or diagnosis of heart failure.

Factors associated with poor outcomes in patients with lupus nephritis.

The objective of this study was to identify the factors associated with important clinical outcomes in a case-control study of 213 patients with lupus nephritis. Included were 47% Hispanics, 44% African Americans and 9% Caucasians with a mean age of 28 years. Fifty-four (25%) patients reached the primary composite outcome of doubling serum creatinine, end-stage renal disease or death during a mean follow-up of 37 months. Thirty-four percent African Americans, 20% Hispanics and 10% Caucasians reached the primary composite outcome (P < 0.05). Patients reaching the composite outcome had predominantly proliferative lupus nephritis (WHO classes: 30% III, 32% IV, 18% V and 5% II, P < 0.025) with higher activity index score (7 +/- 6 versus 5 +/- 5, P < 0.05), chronicity index (CI) score (4 +/- 3 versus 2 +/- 2 unit, P < 0.025), higher baseline mean arterial pressure (MAP) (111 +/- 21 versus 102 +/- 14 mmHg, P < 0.025) and serum creatinine (1.9 +/- 1.3 versus 1.3 +/- 1.0 mg/dL, P < 0.025), but lower baseline hematocrit (29 +/- 6 versus 31 + 5%, P < 0.025) and complement C3 (54 +/- 26 versus 65 + 33 mg/dL, P < 0.025) compared to controls. More patients reaching the composite outcome had nephrotic range proteinuria compared to controls (74% versus 56%, P < 0.025). By multivariate analysis, CI (hazard ratio [95% CI] 1.18 [1.07-1.30] per point), MAP (HR 1.02 [1.00-1.03] per mmHg), and baseline serum creatinine (HR 1.26 [1.04-1.54] per mg/dL) were independently associated with the composite outcome. We concluded that hypertension and elevated serum creatinine at the time of the kidney biopsy as well as a high CI are associated with an increased the risk for chronic renal failure or death in patients with lupus nephritis.

Life-threatening postoperative blood loss in a Jehovah's Witness, treated with high-dose erythropoietin.

Six hours after an uncomplicated extended resection of ovarian cancer, postoperative arterial bleeding led to life-threatening blood loss in a 44-yr-old Jehovah's Witness who refused blood transfusion. Haemoglobin (Hb) decreased from 2.5 g dl(-1) directly after the emergency laparotomy, followed by a 10 h immeasurable period (below detectable minimum value of the analyser), to a measurable minimum of 1.5 g dl(-1) after 20 h. Haematopoiesis was induced by high-dose i.v. erythropoietin therapy (600 IU kg(-1)) and continued on days 3, 6, 8, 10 and 13. Iron, folic acid and vitamins were given as supplements. The patient needed ventilatory assistance for 18 days and some inotropic support. Complications included increases in pancreatic enzymes and liver enzymes, jaundice and skin necrosis at the fingertips and toes. Myopathy led to transient tetraparesis. Haemoglobin rose from 1.5 to 3.4 g dl(-1) (day 10) and the patient was discharged from the intensive care unit with haemoglobin 6.5 g dl(-1) on day 24. She made a full recovery and is still free of cancer in remission.

Rapid progression of acute sciatica to cauda equina syndrome.

OBJECTIVE: To demonstrate the importance of clinical examination and continued vigilance for neurologic deterioration in patients with sciatica. Cauda equina syndrome, a rare sequela of sciatica, is considered a medical emergency requiring surgical decompression. CLINICAL FEATURES: A 32-year-old woman had sciatica that rapidly progressed to cauda equina syndrome. Magnetic resonance imaging revealed the presence of a large nonsequestered disk fragment in the lower lumbar spine. INTERVENTION AND OUTCOME: The disk fragment was surgically excised. The patient experienced immediate pain relief after surgery but retained neurologic deficits. After 6 months of rehabilitation, neurologic integrity was restored, aside from patchy sensory loss of the left foot and buttocks. At the 6-month follow-up, the patient's sciatica had not returned. CONCLUSIONS: Most cases of sciatica, regardless of cause, will self-resolve; as a result, there might be a tendency to maintain a low index of suspicion for serious, progressive disorders such as cauda equina syndrome. Patients need to be educated as to signs of this emergency condition and informed as to the possible consequences of delaying treatment. By maintaining a high index of suspicion for any case that fails to respond as expected to a course of conservative therapy or that demonstrates signs of cauda equina syndrome, chiropractors can assume a pivotal role by investigating and referring appropriately and by aiding in active rehabilitation postoperatively.

The arabidopsis cell plate-associated dynamin-like protein, ADL1Ap, is required for multiple stages of plant growth and development.

Dynamin and dynamin-like proteins are GTP-binding proteins involved in vesicle trafficking. In soybean, a 68-kD dynamin-like protein called phragmoplastin has been shown to be associated with the cell plate in dividing cells (Gu and Verma, 1996). Five ADL1 genes encoding dynamin-like proteins related to phragmoplastin have been identified in the completed Arabidopsis genome. Here we report that ADL1Ap is associated with punctate subcellular structures and with the cell plate in dividing cells. To assess the function of ADL1Ap we utilized a reverse genetic approach to isolate three separate Arabidopsis mutant lines containing T-DNA insertions in ADL1A. Homozygous adl1A seeds were shriveled and mutant seedlings arrested soon after germination, producing only two leaf primordia and severely stunted roots. Immunoblotting revealed that ADL1Ap expression was not detectable in the mutants. Despite the loss of ADL1Ap, the mutants did not display any defects in cytokinesis, and growth of the mutant seedlings could be rescued in tissue culture by the addition of sucrose. Although these sucrose-rescued plants displayed normal vegetative growth and flowered, they set very few seeds. Thus, ADL1Ap is critical for several stages of plant development, including embryogenesis, seedling development, and reproduction. We discuss the putative role of ADL1Ap in vesicular trafficking, cytokinesis, and other aspects of plant growth.