Antidepressants Are Effective in Decreasing Neuropathic Pain After SCI: A Meta-Analysis

Objective:

To systematically review and assess the effectiveness and safety of antidepressants for neuropathic pain among individuals with spinal cord injury (SCI).

Methods:

A systematic search was conducted using multiple databases for relevant articles published from 1980 to April 2014. Randomized controlled trials (RCTs) involving antidepressant treatment of neuropathic pain with ≥3 individuals and ≥50% of study population with SCI were included. Two independent reviewers selected studies based on inclusion criteria and then extracted data. Pooled analysis using Cohen’s d to calculate standardized mean difference, standard error, and 95% confidence interval for primary (pain) and other secondary outcomes was conducted.

Results:

Four RCTs met inclusion criteria. Of these, 2 studies assessed amitriptyline, 1 trazadone, and 1 duloxetine among individuals with neuropathic SCI pain. A small effect was seen in the effectiveness of antidepressants in decreasing pain among individuals with SCI (standardized mean difference = 0.34 ± 0.15; 95% CI, 0.05-0.62; P = .02). A number needed to treat of 3.4 for 30% or more pain relief was found by pooling 2 studies. Of these, significantly higher risk of experiencing constipation (risk ratio [RR] = 1.74; 95% CI, 1.09-2.78; P = .02) and dry mouth (RR = 1.39; 95% CI, 1.04-1.85; P = .02) was found amongst individuals receiving antidepressant treatment compared to those in the control group.

Conclusion:

The current meta-analysis demonstrates that antidepressants are effective in reducing neuropathic SCI pain. However, this should be interpreted with caution due to the limited number of studies. Further evaluation of long-term therapeutic options may be required.     

Fibrillary glomerulonephritis: An apparent familial form?

Fibrillary glomerulonephritis is a rare cause of glomerulonephritis characterized by non‐amyloid fibrillary deposits of unknown aetiology. It is generally considered idiopathic but may be associated with secondary causes such as monoclonal gammopathy, hepatitis B and C infections, autoimmune diseases and malignancies. We report two Australian families with apparent familial fibrillary glomerulonephritis inherited in an autosomal dominant pattern, and postulate the existence of a primary familial entity. Family 1 consists of an affected father and daughter; the daughter progressed to end‐stage renal failure within 18 months of diagnosis, despite immunosuppressive therapy. The father, however, remains stable at 10 months follow up. Family 2 comprises an affected mother and son; the mother commenced haemodialysis 5 years after diagnosis and subsequently underwent successful renal transplantation. The son is presently stable at last follow‐up after 5 years. A further review of the second family history reveals a third family member (maternal father) dying of ‘Bright's disease’. We describe their histopathology, clinical progression and treatment outcomes, and provide a review of the current understanding of this heterogeneous condition that is associated with poor renal outcomes.     

Atrial flutter ablation: efficacy and cost-effectiveness of a single decapolar electrode to demonstrate bidirectional isthmus block.

AIMS: To evaluate whether a single decapolar electrode is a reliable and cost-effective substitute for the 'Halo' catheter to map the circuit and detect bidirectional isthmus block during atrial flutter (AFL) ablation. METHODS AND RESULTS: Twenty-four patients underwent AFL ablation by using the decapolar electrode in the infero-lateral wall of right atrium (group A) while a 'Halo' catheter was used in 11 patients (group B). Both groups had similar clinical characteristics. Anti-clockwise rotation (20 patients), clockwise (3 patients) or both forms of AFL (1 patient) were detected in group A. All patients in group B had anti-clockwise AFL. Bidirectional isthmus block was completed in 22 patients of group A and in 9 of group B (P=NS) while incomplete isthmus block was detected in 2 patients in each group (P=NS). Mean fluoroscopy and procedure time was 27 +/- 47 min, 107 +/- 36 min in group A and 14 +/- 19 min, 114 +/- 65 min in group B (P=NS). AFL relapsed in 3 patients of group A (follow-up 7 +/- 4 months) and in 2 of group B (4 +/- 2 months). CONCLUSION: A single decapolar electrode is a reliable method to map the circuit and demonstrate bidirectional isthmus block during AFL ablation. The cost of the decapolar electrode is a quarter of that of the 'Halo' catheter. This represents a significant saving particularly for centres with a substantial number of AFL ablations.     

Are we getting the critical view? A prospective study of photographic documentation during laparoscopic cholecystectomy

Background

At laparoscopic cholecystectomy, most surgeons have adopted the operative approach where the ‘critical view of safety’ (CVS) is achieved prior to dividing the cystic duct and artery. This prospective study evaluated whether an adequate critical view was achieved by scoring standardized intra-operative photographic views and whether there were other factors that might impact on the ability to obtain an adequate critical view.

Methods

One hundred consecutive patients undergoing a laparoscopic cholecystectomy were studied. At each operation, two photographs were taken. Two independent experienced hepatobiliary surgeons scored the photographs on whether a critical view of safety was achieved. Inter-observer agreement was calculated using the weighted kappa coefficient. The Cochran–Mantel–Haenszel test was used to analyse the scores with potential confounding clinical factors.

Results

The kappa coefficient for adequate display of the cystic duct and artery was 0.49; 95% confidence interval (CI) 0.33 to 0.64; P = 0.001. No bias was detected in the overall scorings between the two observers (χ² 1.33; P = 0.312). Other clinical factors including surgeon seniority did not alter the outcome [odds ratio (OR) 0.902; 95% confidence interval 0.622 to 1.264].

Conclusion

Heightened awareness of the CVS through mandatory documentation may improve both trainee and surgeon technique.     

Social Support From the Athletic Trainer and Symptoms of Depression and Anxiety at Return to Play

Context:

Few empirical studies have examined social support from athletic trainers (ATs) and its buffering effect during injury recovery.

Objective:

To examine the effect of social support received from ATs during injury recovery on reported symptoms of depression and anxiety at return to play among a cohort of collegiate athletes.

Design:

Cohort study.

Setting:

Two Big 10 Conference universities.

Patients or Other Participants:

A total of 594 injuries sustained by 387 collegiate athletes (397 injuries by 256 males, 197 injuries by 131 females) on 9 sports teams.

Main Outcome Measure(s):

Data were collected during the 2007–2011 seasons. Social support was measured using the 6-item Social Support Questionnaire. Symptoms of depression were assessed using the Center for Epidemiological Studies Depression Scale. Anxiety was measured by the State-Trait Anxiety Inventory. We used generalized estimation equation regression models to examine the effect of the social support from ATs on the odds of symptoms of depression and anxiety at return to play.

Results:

In 84.3% (n = 501) of injury events, injured athletes received social support from ATs during their recovery. Of these, 264 (53.1%) athletes reported being very satisfied with this social support. Whether or not athletes received social support from ATs during recovery did not affect the symptoms of depression or anxiety experienced at return to play. However, compared with athletes who were dissatisfied with the social support received from ATs, athletes who were very satisfied or satisfied with this social support were 87% (95% confidence interval = 0.06, 0.30) and 70% (95% confidence interval = 0.13, 0.70) less likely to report symptoms of depression at return to play, respectively. Similar results were observed for anxiety.

Conclusions:

Our findings support the buffering effect of social support from ATs and have important implications for successful recovery in both the physical and psychological aspects for injured athletes.Key Words: collegiate athletes, psychological distress, coping, injury recovery

Key Points

• More than 80% of injured athletes in this study relied on social support from their athletic trainers during their recovery.
• Athletes who reported higher levels of satisfaction with the social support from their athletic trainers during recovery were less likely to experience symptoms of depression and anxiety at return to play.
• However, whether or not injured athletes received social support from athletic trainers during their injury recovery did not correlate with psychological outcomes at return to play.

Approximately 40% to 50% of collegiate athletes sustain at least 1 injury requiring medical attention or restricting participation for 1 day or more (or both) during their athletic careers.¹ In addition to negative physical consequences, these injuries often cause psychological disturbances among injured athletes, including depression and anxiety, which in turn play a role in their injury recovery.^2–4 Results from previous studies show that social support is an important coping resource for athletes dealing with psychological recovery from an injury.^5–9 Social support could “buffer” the effect of stress on injured athletes and thus indirectly influence their emotional wellbeing. In other words, social support could first help an injured athlete interpret an injury event as less stressful than he or she otherwise would, thus helping to reduce distress after an injury. Second, social support could help an injured athlete cope with the injury and improve motivation during rehabilitation.^8,9 Growing evidence also suggests that emotional social support, defined as expressions of empathy, love, trust, and caring,^10,11 may be crucial to recovery for injured collegiate athletes; other types of social support, including instrumental support (ie, provision of tangible aid and services) and informational support (ie, provision of advice, suggestions, and information), may be available to injured collegiate athletes as part of injury treatment.^10,11 However, although many universities provide psychological services to their students, including injured student–athletes, the psychologists are not always specially trained in the areas of sport and exercise and may not fulfill the injured athletes'' needs. Thus, certified athletic trainers (ATs), who are active in the day-to-day tasks of prevention, recognition, management, and rehabilitation of injuries among athletes, become an important source of emotional social support for injured athletes.¹¹Advances in sport medicine have reduced the average time required for physical healing from an athletic injury, yet a rapid physical recovery may not provide sufficient time for psychological recovery. Current practices in evaluation and management of injuries address the physical problems underlying an injury and return athletes to full participation as soon as possible, but psychological assessment or care is not usually included.^12,13 The potential discrepancy between physical healing and psychological recovery necessitates that more attention be given to the latter.¹³ We need to better understand how athletes respond to athletic injury and how external factors, such as social support, may affect athletes'' postinjury psychological status and facilitate their injury recovery. Yet relatively few empirical studies have directly examined social support from ATs and its buffering effect during injury recovery among competitive collegiate athletes.^11,12The aim of our study was 2-fold: (1) to describe the social support that injured collegiate athletes received from their ATs during their injury recovery and their satisfaction with such support and (2) to examine the effect of this social support from ATs during the recovery on reported symptoms of depression and anxiety at return to play.     

Neuromuscular disorders: a guide for the orthopaedic surgeon

Patients with neuromuscular conditions are frequently seen in final professional clinical examinations as they have good clinical signs, which often point towards the underlying diagnosis. This paper outlines some of the most common neuromuscular disorders that you are likely to come across in orthopaedic practise.     

From the Cover: JAK/STAT1 signaling promotes HMGB1 hyperacetylation and nuclear translocation

Extracellular high-mobility group box (HMGB)1 mediates inflammation during sterile and infectious injury and contributes importantly to disease pathogenesis. The first critical step in the release of HMGB1 from activated immune cells is mobilization from the nucleus to the cytoplasm, a process dependent upon hyperacetylation within two HMGB1 nuclear localization sequence (NLS) sites. The inflammasomes mediate the release of cytoplasmic HMGB1 in activated immune cells, but the mechanism of HMGB1 translocation from nucleus to cytoplasm was previously unknown. Here, we show that pharmacological inhibition of JAK/STAT1 inhibits LPS-induced HMGB1 nuclear translocation. Conversely, activation of JAK/STAT1 by type 1 interferon (IFN) stimulation induces HMGB1 translocation from nucleus to cytoplasm. Mass spectrometric analysis unequivocally revealed that pharmacological inhibition of the JAK/STAT1 pathway or genetic deletion of STAT1 abrogated LPS- or type 1 IFN-induced HMGB1 acetylation within the NLS sites. Together, these results identify a critical role of the JAK/STAT1 pathway in mediating HMGB1 cytoplasmic accumulation for subsequent release, suggesting that the JAK/STAT1 pathway is a potential drug target for inhibiting HMGB1 release.High-mobility group box 1 (HMGB1), a ubiquitous DNA-binding protein, is a promiscuous sensor driving nucleic acid-mediated immune responses and a pathogenic inflammatory mediator in sepsis, arthritis, colitis, and other disease syndromes (1–5). Immune cells actively release HMGB1 after activation by exposure to pathogen-associated molecular patterns or damage-associated molecular patterns, including lipopolysaccharide (LPS) and inflammasome agonists (1, 6, 7). High levels of extracellular HMGB1 accumulate in patients with infectious and sterile inflammatory diseases. Extracellular disulfide HMGB1 stimulates macrophages to release TNF and other inflammatory mediators by binding and signaling through Toll-like receptor (TLR)4. Reduced HMGB1 facilitates immune cell migration by interacting with the receptor for advanced glycation end products (RAGE) and CXCL12 (8–12), a process regulated by posttranslational redox-dependent mechanisms. Administration of neutralizing anti-HMGB1 mAbs or other HMGB1 antagonists significantly reduces the severity of inflammatory disease, promotes bacterial clearance during Pseudomonas aeruginosa or Salmonella typhimurium infection and attenuates memory impairment in sepsis survivors (1, 13–15). Together, these and other findings indicate the importance of a mechanistic understanding of HMGB1 release from activated immune cells and the regulatory signaling pathways controlling these processes.Most cytokines harbor a leader peptide that facilitates secretion through the endoplasmic reticulum–Golgi exocytotic route. HMGB1, which lacks a leader peptide, is released via unconventional protein secretion pathways (1, 6, 7). In quiescent cells, most HMGB1 is localized in the nucleus. Upon activation of immune cells, efficient HMGB1 release requires acetylation of HMGB1 within the two nuclear localization sequence (NLS) sites and subsequent HMGB1 accumulation in the cytoplasm (1, 6, 16–20). HMGB1 release is mediated by inflammasome activation during pyroptosis, a form of proinflammatory programmed cell death (6, 7, 22–24). Protein kinase (PK)R is a critical regulator of inflammasome-dependent HMGB1 release (6, 25). Pharmacological inhibition of PKR abrogates LPS-induced HMGB1 release by macrophages but does not prevent nuclear translocation of HMGB1 to cytoplasm. This suggests that some other, as yet unknown, inflammasome-independent pathway regulates HMGB1 translocation from nucleus to cytoplasm.We and others have previously established an important role of type 1 and type 2 interferons (IFNs) and downstream JAK/STAT1 signaling activation in mediating HMGB1 release (26–28). Pharmacological inhibition of JAK/STAT, genetic deletion of STAT1, or inhibition of extracellular IFN-β with neutralizing antibodies significantly abrogates LPS-induced HMGB1 release from macrophages (26–28). Importantly, pharmacological inhibition of the JAK/STAT1 pathway, genetic deletion of STAT1, or inhibition of IFN-β expression by genetic deletion of IRF3 significantly promotes survival in both lethal endotoxemia and experimental sepsis (28–30). Accordingly, we reasoned here that JAK/STAT1 may represent a critical signaling mechanism controlling HMGB1 translocation from nucleus to cytoplasm.