Prospective Study Comparing Outcome following Complete Polypropylene Suture Ligation versus Partial Thin Film Band Attenuation of Congenital Portosystemic Shunts in Dogs.

The main objective was to conduct a prospective study reporting the outcome for dogs with an extrahepatic congenital portosystemic shunt (CPSS) treated with a 'complete ligation where possible' philosophy. The second aim was to compare the outcomes following complete (C) polypropylene suture ligation versus partial thin film band (TFB) attenuation of a CPSS in dogs. Dogs that could not tolerate acute complete shunt ligation at surgery received partial shunt attenuation with TFB. Peri-operative complications, mortality, follow-up imaging findings, pre- and post-operative bile acid stimulation test results and details of any revision surgery performed were recorded. A follow-up health-related quality of life questionnaire enabled the calculation of a postoperative clinical shunt score, a quality of life score, and determined if any dogs were still on a hepatic diet and/or other medical management at a minimum of 6 months after surgery. Of the 110 dogs enrolled, 57 received complete ligation and 53 received partial TFB attenuation. Peri-operative mortality, the occurrence of post-attenuation neurological complications, the occurrence of multiple acquired shunts, the postoperative clinical shunt score and quality of life score were not significantly different between the two groups. Dogs in the C group were older, heavier and demonstrated a greater number of shunt classifications where the entry into the systemic circulation was the phrenic vein or azygous vein. Dogs in the TFB group had a greater number of unchanged bile acid concentrations after surgery, were more likely to remain on the hepatic diet and/or medical management after surgery and underwent a greater number of revision surgeries. There was variability in the precision of both ultrasound and computed tomographic angiography follow-up imaging compared to intra-operative mesenteric portovenography findings at revision surgery. Overall, dogs with an extrahepatic portosystemic shunt receiving either complete acute shunt ligation or partial TFB shunt attenuation are expected to have an excellent long-term clinical outcome and there is no reason to suggest that a dog able to tolerate complete acute shunt closure should be denied the benefit of this.

Characterizing candidate decompression rates for hypobaric hypoxic stunning of pigs. Part 1: Reflexive behavior and physiological responses.

Alternatives to carbon dioxide (CO2) stunning for the commercial slaughter of pigs are urgently needed because there is robust evidence that exposing pigs to hypercapnic environments is associated with pain, fear, and distress. Hypobaric hypoxia (via gradual decompression, also known as Low Atmospheric Pressure Stunning or LAPS) has been validated in poultry as a humane option, but its potential to improve the welfare of pigs at slaughter is unknown. We investigated the potential of hypobaric hypoxia to reliably elicit a non-recovery state in anesthetized weaner-grower pigs within a commercially viable timeframe. We determined the effect of candidate decompression rates (40, 60, 80, 100 ms-1, at two cycle durations 480 s and 720 s) on a range of physiological and reflexive behavioral indicators of hypoxia and death. We found that the decompression rates tested caused a 100% death rate. As expected, the decompression rate had overarching effects on behavioral and physiological markers of hypoxia and death, with faster decompression rates resulting in shorter latencies to cardiac arrest and cessation of breathing. We observed a higher proportion of pigs displaying repeated and prolonged whole-body movements (likely indicative of convulsive activity) at higher frequencies when we applied the slowest decompression rate (40 ms-1) compared to all other rates. Since these responses may impact the carcass and meat quality, the slower rate of decompression (40 ms-1) should be excluded as a candidate decompression rate. Furthermore, given the marginal effects of decompression rate on physiological indicators of death and reflexive behavioral parameters, we also recommend that the fastest rate tested (100 ms-1) is excluded in further study on conscious pigs (to prevent conscious animals from being exposed to unnecessary faster decompression rates which may compromise animal welfare). This work represents a necessary proof of principle step and confirms the potential of gradual decompression for stunning purposes in pigs. Importantly, however, the data presented provide no information on the welfare outcomes associated with decompression in conscious pigs. Subsequent work should focus on the comprehensive welfare assessment of intermediate decompression rates to determine the potential of hypobaric hypoxia to provide a humane stunning method for pigs.

Characterizing candidate decompression rates for hypobaric hypoxic stunning of pigs. Part 2: Pathological consequences.

Pigs are commonly stunned pre-slaughter by exposure to carbon dioxide (CO2), but this approach is associated with significant welfare concerns. Hypobaric hypoxia, achieved with gradual decompression (also known as Low Atmospheric Pressure Stunning or LAPS) may be an alternative, allowing the retention of welfare friendly handling approaches and group stunning. Although validated in poultry, the feasibility and welfare consequences of gradual decompression for pigs are unknown. Here, we characterize pathological changes in 60 pigs resulting from exposure to a range of candidate decompression curves (ranging from 40 to 100 ms-1 ascent equivalent, with two cycle durations 480 and 720 s). To protect welfare, we worked on unconscious, terminally anesthetized pigs which were subject to detailed post-mortem examinations by a specialized porcine veterinary pathologist. All pigs were killed as a result of exposure to decompression, irrespective of cycle rate or length. Pigs showed no external injuries during ante-mortem inspections. Exposing pigs to decompression and the unavoidable subsequent recompression resulted in generalized congestion of the carcass, organs and body cavities including the ears, oral cavity, conjunctivae and sclera, mucosa of other external orifices (anus and vulva), nasal planum, nasal cavities including nasal conchae, frontal sinuses, cranium, meninges, brain, larynx, trachea, lungs, heart, parietal pleura of the thoracic cavity, peritoneum of the abdominal cavity, stomach, small intestine, caecum, colon, liver, spleen and kidneys and representative joint cavities in the limbs (stifles and elbows). Various severities of hemorrhage were observed in the conjunctivae and sclera, mucosa of other external orifices (anus and vulva), nasal cavities including nasal conchae, frontal sinuses, cranium, meninges, brain, larynx, tracheal lumen, lungs, parietal pleura of the thoracic cavity, liver, spleen and kidneys and representative joint cavities in the limbs (stifles and elbows). In general, faster decompression rates produced higher scores, but in the conjunctivae, sclera and kidneys, faster decompression rates were associated with marginally lower congestion scores. There was considerable individual variation in pathological scores across all body regions. The congestion and hemorrhage observed could translate into welfare harms in conscious pigs undergoing this type of stunning, depending when in the cycle the damage is occurring, but no welfare related conclusions can be drawn from the responses of unconscious pigs. Since recompression is always required, its effects cannot be separated from decompression, however cessation of cardiac activity several minutes before recompression should have eliminated any haemodynamic effects relating to cardiac function and blood pressure. This study represents the first systematic attempt to identify candidate rate profiles to underpin future explorations of decompression as a stunning method for pigs. These pathological findings also inform discussions about the likely carcass quality implications of this novel stunning method.

Cross-species efficacy of enzyme replacement therapy for CLN1 disease in mice and sheep.

CLN1 disease, also called infantile neuronal ceroid lipofuscinosis (NCL) or infantile Batten disease, is a fatal neurodegenerative lysosomal storage disorder resulting from mutations in the CLN1 gene encoding the soluble lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1). Therapies for CLN1 disease have proven challenging because of the aggressive disease course and the need to treat widespread areas of the brain and spinal cord. Indeed, gene therapy has proven less effective for CLN1 disease than for other similar lysosomal enzyme deficiencies. We therefore tested the efficacy of enzyme replacement therapy (ERT) by administering monthly infusions of recombinant human PPT1 (rhPPT1) to PPT1-deficient mice (Cln1-/-) and CLN1R151X sheep to assess how to potentially scale up for translation. In Cln1-/- mice, intracerebrovascular (i.c.v.) rhPPT1 delivery was the most effective route of administration, resulting in therapeutically relevant CNS levels of PPT1 activity. rhPPT1-treated mice had improved motor function, reduced disease-associated pathology, and diminished neuronal loss. In CLN1R151X sheep, i.c.v. infusions resulted in widespread rhPPT1 distribution and positive treatment effects measured by quantitative structural MRI and neuropathology. This study demonstrates the feasibility and therapeutic efficacy of i.c.v. rhPPT1 ERT. These findings represent a key step toward clinical testing of ERT in children with CLN1 disease and highlight the importance of a cross-species approach to developing a successful treatment strategy.

In vivo application of an implantable tri-anchored methylene blue-based electrochemical pH sensor.

The development of robust implantable sensors is important in the successful advancement of personalised medicine as they have the potential to provide in situ real-time data regarding the status of health and disease and the effectiveness of treatment. Tissue pH is a key physiological parameter and herein, we report the design, fabrication, functionalisation, encapsulation and protection of a miniaturised, self-contained, electrochemical pH sensor system and characterisation of sensor performance. Notably for the first time in this environment the pH sensor was based on a methylene blue redox reporter which showed remarkable robustness, accuracy and sensitivity. This was achieved by encapsulation of a self-assembled monolayer containing methylene blue entrapped within a Nafion layer. Another powerful feature was the incorporation, within the same implanted device, of a fabricated on-chip Ag/AgCl reference electrode - vital in any electrochemical sensor, but often ignored. When utilised in vivo, the sensor allowed accurate tracking of externally induced pH changes within a naturally occurring ovine lung cancer model, and correlated well with single point laboratory measurements made on extracted arterial blood, whilst enabling in vivo time-dependent measurements. The sensors functioned robustly whilst implanted, and maintained in vitro function once extracted and together, these results demonstrate proof-of-concept of the ability to sense real-time intratumoral tissue pH changes in vivo.

Feeding management before gastrointestinal studies in pigs.

Pigs are used to model humans in gastrointestinal (GI) studies because of their comparable size, physiology and behaviour: both are monogastric omnivores. A porcine surgical model for testing novel, tethered ultrasound capsule endoscopes (USCE) requires a clean, motile small intestine. Recommendations for human GI tract preparation before the mechanically similar process of video capsule endoscopy describe using oral purgatives, while high-carbohydrate drinks are recommended before colorectal surgery. Reports of the GI preparation of pigs exist but lack technical details, that is, administration, efficacy and side effects. This report details feeding a high-energy liquid diet to 11 female pigs undergoing surgery and USCE which was readily accepted and easily administered, and which produced a clean, motile small intestine and caused no detectable physiological/behavioural abnormalities.

Modest and variable efficacy of pre-exposure hydroxocobalamin and dicobalt edetate in a porcine model of acute cyanide salt poisoning.

Background: Dicobalt edetate and hydroxocobalamin are widely used to treat hydrogen cyanide poisoning. However, comparative and quantitative efficacy data are lacking. Although post-exposure treatment is typical, it may be possible to administer these antidotes before exposure to first attenders entering a known site of cyanide release, as supplementary protection to their personal protective equipment.Methods: We established an anaesthetised Gottingen minipig model of lethal bolus potassium cyanide (KCN) injection to simulate high dose hydrogen cyanide inhalation. Doses were similar to human lethal doses of KCN. Dicobalt edetate and hydroxocobalamin were administered shortly before KCN and their effect on metabolic and cardiovascular variables and survival time were measured.Results: Increases in arterial lactate were similar after 0.08 and 0.12 mmol/kg KCN. KCN 0.08 mmol/kg was survived by 4/4 animals with moderate cardiovascular effects, while the 0.12 mmol/kg dose was lethal in 4/4 animals, with a mean time to euthanasia of 28.3 (SEM: 13.9) min. Administration of dicobalt edetate (0.021 mmol/kg, 8.6 mg/kg) or hydroxocobalamin (0.054 mmol/kg, 75 mg/kg) at clinically licenced doses had modest effect on lactate concentrations but increased survival after administration of KCN 0.12 mmol/kg (survival: dicobalt edetate 4/4, hydroxocobalamin 2/4) but not 0.15 mmol/kg (0/4 and 0/4, respectively). In a subsequent larger study, doubling the dose of hydroxocobalamin (0.108 mmol/kg, 150 mg/kg) was associated with a modest but inconsistent increased survival after 0.15 mmol/kg KCN (survival: control 0/8, 75 mg/kg 1/10, 150 mg/kg 3/10) likely due to variable pharmacokinetics.Conclusions: In this porcine study of cyanide exposure, with pre-exposure antidote administration, licenced doses of dicobalt edetate and hydroxocobalamin were effective at just lethal doses but ineffective at less than twice the estimated LD50. The efficacy of a rapidly-administered double-dose of hydroxocobalamin was limited by variable pharmacokinetics. In clinical poisoning scenarios, with delayed administration, the antidotes are likely to be even less effective. New antidotes are required for treatment of cyanide exposures appreciably above the minimum lethal dose.

A Novel Translational Ovine Pulmonary Adenocarcinoma Model for Human Lung Cancer.

In vitro cell line and in vivo murine models have historically dominated pre-clinical cancer research. These models can be expensive and time consuming and lead to only a small percentage of anti-cancer drugs gaining a license for human use. Large animal models that reflect human disease have high translational value; these can be used to overcome current pre-clinical research limitations through the integration of drug development techniques with surgical procedures and anesthetic protocols, along with emerging fields such as implantable medical devices. Ovine pulmonary adenocarcinoma (OPA) is a naturally-occurring lung cancer that is caused by the jaagsiekte sheep retrovirus. The disease has similar histological classification and oncogenic pathway activation to that of human lung adenocarcinomas making it a valuable model for studying human lung cancer. Developing OPA models to include techniques used in the treatment of human lung cancer would enhance its translational potential, making it an excellent research tool in assessing cancer therapeutics. In this study we developed a novel OPA model to validate the ability of miniaturized implantable O2 and pH sensors to monitor the tumor microenvironment. Naturally-occurring pre-clinical OPA cases were obtained through an on-farm ultrasound screening programme. Sensors were implanted into OPA tumors of anesthetized sheep using a CT-guided trans-thoracic percutaneous implantation procedure. This study reports the findings from 9 sheep that received sensor implantations. Time taken from initial CT scans to the placement of a single sensor into an OPA tumor was 45 ± 5 min, with all implantations resulting in the successful delivery of sensors into tumors. Immediate post-implantation mild pneumothoraces occurred in 4 sheep, which was successfully managed in all cases. This is, to the best of our knowledge, the first description of the use of naturally-occurring OPA cases as a pre-clinical surgical model. Through the integration of techniques used in the treatment of human lung cancer patients, including ultrasound, general anesthesia, CT and surgery into the OPA model, we have demonstrated its translational potential. Although our research was tailored specifically for the implantation of sensors into lung tumors, we believe the model could also be developed for other pre-clinical applications.

Ovine Pulmonary Adenocarcinoma: A Unique Model to Improve Lung Cancer Research.

Lung cancer represents a major worldwide health concern; although advances in patient management have improved outcomes for some patients, overall 5-year survival rates are only around 15%. In vitro studies and mouse models are commonly used to study lung cancer and their use has increased the molecular understanding of the disease. Unfortunately, mouse models are poor predictors of clinical outcome and seldom mimic advanced stages of the human disease. Animal models that more accurately reflect human disease are required for progress to be made in improving treatment outcomes and prognosis. Similarities in pulmonary anatomy and physiology potentially make sheep better models for studying human lung function and disease. Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung cancer that is caused by the jaagsiekte sheep retrovirus. The disease is endemic in many countries throughout the world and has several features in common with human lung adenocarcinomas, including histological classification and activation of common cellular signaling pathways. Here we discuss the in vivo and in vitro OPA models that are currently available and describe the advantages of using pre-clinical naturally occurring OPA cases as a translational animal model for human lung adenocarcinoma. The challenges and options for obtaining these OPA cases for research purposes, along with their use in developing novel techniques for the evaluation of chemotherapeutic agents or for monitoring the tumor microenvironment in response to treatment, are also discussed.

Loss of Integrin αvß8 in Murine Hepatocytes Accelerates Liver Regeneration.

Recent fate-mapping studies in mice have provided substantial evidence that mature adult hepatocytes are a major source of new hepatocytes after liver injury. In other systems, integrin αvß8 has a major role in activating transforming growth factor (TGF)-ß, a potent inhibitor of hepatocyte proliferation. We hypothesized that depletion of hepatocyte integrin αvß8 would increase hepatocyte proliferation and accelerate liver regeneration after injury. Using Itgb8flox/flox;Alb-Cre mice to deplete hepatocyte αvß8, after partial hepatectomy, hepatocyte proliferation and liver-to-body weight ratio were significantly increased in Itgb8flox/flox;Alb-Cre mice compared with control mice. Antibody-mediated blockade of hepatocyte αvß8 in vitro, with assessment of TGF-ß signaling pathways by real-time quantitative PCR array, supported the hypothesis that integrin αvß8 inhibition alters hepatocyte TGF-ß signaling toward a pro-regenerative phenotype. A diethylnitrosamine-induced model of hepatocellular carcinoma, used to examine the possibility that this pro-proliferative phenotype might be oncogenic, revealed no difference in either tumor number or size between Itgb8flox/flox;Alb-Cre and control mice. Immunohistochemistry for integrin αvß8 in healthy and injured human liver demonstrated that human hepatocytes express integrin αvß8. Depletion of hepatocyte integrin αvß8 results in increased hepatocyte proliferation and accelerated liver regeneration after partial hepatectomy in mice. These data demonstrate that targeting integrin αvß8 may represent a promising therapeutic strategy to drive liver regeneration in patients with a broad range of liver diseases.

The effect of recumbency and hindlimb position on the lumbosacral interlaminar distance in dogs: a cadaveric computed tomography study.

OBJECTIVE: To examine the effect of sternal or lateral recumbency, with or without cranial extension of the hindlimbs, on the distance between the dorsal lumbosacral laminae in dogs. STUDY DESIGN: Blinded, randomized, crossover, experimental study. ANIMALS: A total of 19 canine cadavers. METHODS: Computed tomography of the lumbosacral junction was performed in four positions: sternal and right lateral recumbency, with hindlimbs extended cranially or not. Order of positioning was randomized. The lumbosacral interlaminar (LSI) distance, defined as the distance between the dorsal laminae of the seventh lumbar vertebra (caudal margin) and sacrum (cranial margin), was measured for each position by two independent assessors who were unaware of positioning. Mean distances in each position were compared using a paired t-test, corrected for multiple comparisons. RESULTS: For n = 19 cadavers [6 female; median (range) age 9 (0.3-16) years; weight, 20.4 (1.0-34.0) kg], cranial extension of the hindlimbs increased the LSI distance, compared with control, in both sternal (9.2 ± 2.2 mm versus 3.1 ± 1.3 mm, p < 0.001) and right lateral recumbency (8.2 ± 1.9 mm versus 4.9 ± 1.5 mm, p < 0.001). With the hindlimbs extended cranially, sternal recumbency increased LSI distance when compared with right lateral recumbency (p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Cranial extension of the hindlimbs in both sternal and lateral recumbency increases the LSI distance to an extent that is both statistically significant and of potential clinical relevance. Although ease of epidural access or injection was not assessed, the small (1 mm) difference in LSI distance between cranial hindlimb extension in sternal and right lateral recumbency is unlikely to be of clinical relevance. Conversely, cranial extension of the hindlimbs in either sternal or lateral recumbency would be expected to facilitate epidural injection.

The STAT3-IL-10-IL-6 Pathway Is a Novel Regulator of Macrophage Efferocytosis and Phenotypic Conversion in Sterile Liver Injury.

The disposal of apoptotic bodies by professional phagocytes is crucial to effective inflammation resolution. Our ability to improve the disposal of apoptotic bodies by professional phagocytes is impaired by a limited understanding of the molecular mechanisms that regulate the engulfment and digestion of the efferocytic cargo. Macrophages are professional phagocytes necessary for liver inflammation, fibrosis, and resolution, switching their phenotype from proinflammatory to restorative. Using sterile liver injury models, we show that the STAT3-IL-10-IL-6 axis is a positive regulator of macrophage efferocytosis, survival, and phenotypic conversion, directly linking debris engulfment to tissue repair.

Cre-ativity in the liver: transgenic approaches to targeting hepatic nonparenchymal cells.

Rapid evolution in transgenic (Tg) mouse technology now permits cell-specific and temporal control of fluorescent cell-labeling and gene inactivation. Here, we discuss the principal strategies that have been utilized to target, label, and manipulate hepatic nonparenchymal cells, with emphasis on the utility of constitutive and inducible Cre-lox systems. We summarize key findings of studies employing Tg technology to target hepatic stellate cells, myofibroblasts, liver sinusoidal endothelial cells, and macrophages to illustrate the power of these approaches in identifying cell-specific molecular mechanisms critical to the pathophysiology of liver disease. Increasing adoption of Tg techniques will help to answer fundamental questions regarding the pathogenesis of hepatic diseases and provide the mechanistic rationale to allow identification of novel drug targets, ultimately translating into effective therapies for patients with liver disease.

Long-term survival and quality of life in dogs with clinical signs associated with a congenital portosystemic shunt after surgical or medical treatment.

OBJECTIVE: To compare long-term survival and quality of life data in dogs with clinical signs associated with a congenital portosystemic shunt (CPSS) that underwent medical or surgical treatment. DESIGN: Prospective cohort study. ANIMALS: 124 client-owned dogs with CPSS. PROCEDURES: Dogs received medical or surgical treatment without regard to signalment, clinical signs, or clinicopathologic results. Survival data were analyzed with a Cox regression model. Quality of life information, obtained from owner questionnaires, included frequency of CPSS-associated clinical signs (from which a clinical score was derived), whether owners considered their dog normal, and (for surgically treated dogs) any ongoing medical treatment for CPSS. A Mann-Whitney U test was used to compare mean clinical score data between surgically and medically managed dogs during predetermined follow-up intervals. RESULTS: 97 dogs underwent surgical treatment; 27 were managed medically. Median follow-up time for all dogs was 1,936 days. Forty-five dogs (24 medically managed and 21 surgically managed) died or were euthanized during the follow-up period. Survival rate was significantly improved in dogs that underwent surgical treatment (hazard ratio, 8.11; 95% CI, 4.20 to 15.66) than in those treated medically for CPSS. Neither age at diagnosis nor shunt type affected survival rate. Frequency of clinical signs was lower in surgically versus medically managed dogs for all follow-up intervals, with a significant difference between groups at 4 to 7 years after study entry. CONCLUSIONS AND CLINICAL RELEVANCE: Surgical treatment of CPSS in dogs resulted in significantly improved survival rate and lower frequency of ongoing clinical signs, compared with medical management. Age at diagnosis did not affect survival rate and should not influence treatment choice.

Origins of fibrosis: pericytes take centre stage.

Pericytes are ubiquitous perivascular cells that have recently attracted interest as potential myofibroblast precursors. In turn, myofibroblasts are the major source of extracellular matrix components that accumulate during tissue fibrosis. Given the worldwide burden of fibrotic disease and paucity of therapeutic options available to halt its progression, elucidating the origins of myofibroblasts is of prime importance. The advent of genetic strategies that permit fate-mapping of specific cell populations through permanent and heritable expression of reporter proteins has begun to shed light on the source of the fibrogenic myofibroblast. Here we discuss recent studies in multiple organs that highlight the central role of pericytes in the origins of fibrosis.

Comparison of survival after surgical or medical treatment in dogs with a congenital portosystemic shunt.

OBJECTIVE: To compare survival of dogs with a congenital portosystemic shunt (CPSS) that received medical or surgical treatment. DESIGN: Prospective cohort study. ANIMALS: 126 client-owned dogs with a single CPSS. PROCEDURES: Dogs were examined at 1 of 3 referral clinics, and a single CPSS was diagnosed in each. Dogs received medical or surgical treatment without regard to signalment, clinical signs, or results of hematologic or biochemical analysis. Survival data were analyzed via a Cox regression model. RESULTS: During a median follow-up period of 579 days, 18 of 126 dogs died as a result of CPSS. Dogs treated via surgical intervention survived significantly longer than did those treated medically. Hazard ratio for medical versus surgical treatment of CPSS (for the treatment-only model) was 2.9 (95% confidence interval, 1.1 to 7.2). Age at CPSS diagnosis did not affect survival. CONCLUSIONS AND CLINICAL RELEVANCE: Both medical and surgical treatment can be used to achieve long-term survival of dogs with CPSS, although results of statistical analysis supported the widely held belief that surgery is preferable to medical treatment. However, the study population consisted of dogs at referral clinics, which suggested that efficacy of medical treatment may have been underestimated. Although surgical intervention was associated with a better chance of long-term survival, medical management provided an acceptable first-line option. Age at examination did not affect survival, which implied that early surgical intervention was not essential. Dogs with CPSS that do not achieve acceptable resolution with medical treatment can subsequently be treated surgically.

Methods for the best evidence synthesis on neck pain and its associated disorders: the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders.

STUDY DESIGN: Best evidence synthesis. OBJECTIVE: To provide a detailed description of the methods undertaken in a systematic search and perform a best evidence synthesis on the frequency, determinants, assessment, interventions, course and prognosis of neck pain, and its associated disorders. SUMMARY OF BACKGROUND DATA: Neck pain is an important cause of health burden; however, the published information is vast, and stakeholders would benefit from a summary of the best evidence. METHODS: The Bone and Joint Decade 2000-2010 Task Force on Neck Pain and its Associated Disorders conducted a systematic search and critical review of the literature published between 1980 and 2006 to assemble the best evidence on neck pain. Citations were screened for relevance to the Neck Pain Task Force mandate, using a priori criteria, and relevant studies were critically reviewed for their internal scientific validity. Findings from studies meeting criteria for scientific validity were synthesized into a best evidence synthesis. RESULTS: We found 31,878 citations, of which 1203 were relevant to the mandate of the Neck Pain Task Force. After critical review, 552 studies (46%) were judged scientifically admissible and were compiled into the best evidence synthesis. CONCLUSION: The Bone and Joint Decade 2000-2010 Task Force on Neck Pain and its Associated Disorders undertook a best evidence synthesis to establish a baseline of the current best evidence on the epidemiology, assessment and classification of neck pain, as well as interventions and prognosis for this symptom. This article reports the methods used and the outcomes from the review. We found that 46% of the research literature was of acceptable scientific quality to inform clinical practice, policy-making, and future research.

Methods for the best evidence synthesis on neck pain and its associated disorders: the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders.

STUDY DESIGN: Best evidence synthesis. OBJECTIVE: To provide a detailed description of the methods undertaken in a systematic search and perform a best evidence synthesis on the frequency, determinants, assessment, interventions, course and prognosis of neck pain, and its associated disorders. SUMMARY OF BACKGROUND DATA: Neck pain is an important cause of health burden; however, the published information is vast, and stakeholders would benefit from a summary of the best evidence. METHODS: The Bone and Joint Decade 2000-2010 Task Force on Neck Pain and its Associated Disorders conducted a systematic search and critical review of the literature published between 1980 and 2006 to assemble the best evidence on neck pain. Citations were screened for relevance to the Neck Pain Task Force mandate, using a priori criteria, and relevant studies were critically reviewed for their internal scientific validity. Findings from studies meeting criteria for scientific validity were synthesized into a best evidence synthesis. RESULTS: We found 31,878 citations, of which 1203 were relevant to the mandate of the Neck Pain Task Force. After critical review, 552 studies (46%) were judged scientifically admissible and were compiled into the best evidence synthesis. CONCLUSION: The Bone and Joint Decade 2000-2010 Task Force on Neck Pain and its Associated Disorders undertook a best evidence synthesis to establish a baseline of the current best evidence on the epidemiology, assessment and classification of neck pain, as well as interventions and prognosis for this symptom. This article reports the methods used and the outcomes from the review. We found that 46% of the research literature was of acceptable scientific quality to inform clinical practice, policy-making, and future research.