Pulmonary Aspiration of Gastric Contents: A Closed Claims Analysis.

BACKGROUND: Perioperative pulmonary aspiration of gastric contents has been associated with severe morbidity and death. The primary aim of this study was to identify outcomes and patient and process of care risk factors associated with gastric aspiration claims in the Anesthesia Closed Claims Project. The secondary aim was to assess these claims for appropriateness of care. The hypothesis was that these data could suggest opportunities to reduce either the risk or severity of perioperative pulmonary aspiration. METHODS: Inclusion criteria were anesthesia malpractice claims in the American Society of Anesthesiologists Closed Claims Project that were associated with surgical, procedural, or obstetric anesthesia care with the year of the aspiration event 2000 to 2014. Claims involving pulmonary aspiration were identified and assessed for patient and process factors that may have contributed to the aspiration event and outcome. The standard of care was assessed for each claim. RESULTS: Aspiration of gastric contents accounted for 115 of the 2,496 (5%) claims in the American Society of Anesthesiologists Closed Claims Project that met inclusion criteria. Death directly related to pulmonary aspiration occurred in 66 of the 115 (57%) aspiration claims. Another 16 of the 115 (14%) claims documented permanent severe injury. Seventy of the 115 (61%) patients who aspirated had either gastrointestinal obstruction or another acute intraabdominal process. Anesthetic management was judged to be substandard in 62 of the 115 (59%) claims. CONCLUSIONS: Death and permanent severe injury were common outcomes of perioperative pulmonary aspiration of gastric contents in this series of closed anesthesia malpractice claims. The majority of the patients who aspirated had either gastrointestinal obstruction or acute intraabdominal processes. Anesthesia care was frequently judged to be substandard. These findings suggest that clinical practice modifications to preoperative assessment and anesthetic management of patients at risk for pulmonary aspiration may lead to improvement of their perioperative outcomes.

Communication failures contributing to patient injury in anaesthesia malpractice claims☆.

BACKGROUND: Communication amongst team members is critical to providing safe, effective medical care. We investigated the role of communication failures in patient injury using the Anesthesia Closed Claims Project database. METHODS: Claims associated with surgical/procedural and obstetric anaesthesia and postoperative pain management for adverse events from 2004 or later were included. Communication was defined as transfer of information between two or more parties. Failure was defined as communication that was incomplete, inaccurate, absent, or not timely. We classified root causes of failures as content, audience, purpose, or occasion with inter-rater reliability assessed by kappa. Claims with communication failures contributing to injury (injury-related communication failures; n=389) were compared with claims without any communication failures (n=521) using Fisher's exact test, t-test, or Mann-Whitney U-tests. RESULTS: At least one communication failure contributing to patient injury occurred in 43% (n=389) out of 910 claims (κ=0.885). Patients in claims with injury-related communication failures were similar to patients in claims without failures, except that failures were more common in outpatient settings (34% vs 26%; P=0.004). Fifty-two claims had multiple communication failures for a total of 446 injury-related failures, and 47% of failures occurred during surgery, 28% preoperatively, and 23% postoperatively. Content failures (insufficient, inaccurate, or no information transmitted) accounted for 60% of the 446 communication failures. CONCLUSIONS: Communication failure contributed to patient injury in 43% of anaesthesia malpractice claims. Patient/case characteristics in claims with communication failures were similar to those without failures, except that failures were more common in outpatient settings.

Obstetric Anesthesia Liability Concerns.

Obstetric practice carries a high risk of medical liability and involves both obstetricians and anesthesiologists. Analysis of data from the Anesthesia Closed Claims Project database shows an increase in the proportion of anesthesia claims for maternal death and brain damage between the 1990s and 2000 and later, primarily due to hemorrhage. The proportion of claims for newborn brain damage remained unchanged while those for maternal nerve injury and minor injuries decreased. Use of massive transfusion protocols and clinical drills have been shown to improve outcomes from hemorrhage. Good communication and teamwork are critical for reducing obstetric liability.

What Adverse Events and Injuries Are Cited in Anesthesia Malpractice Claims for Nonspine Orthopaedic Surgery?

BACKGROUND: Malpractice claims that arise during the perioperative care of patients receiving orthopaedic procedures will frequently involve both orthopaedic surgeons and anesthesiologists. The Anesthesia Closed Claims database contains anesthesia malpractice claim data that can be used to investigate patient safety events arising during the care of orthopaedic patients and can provide insight into the medicolegal liability shared by the two specialties. QUESTIONS/PURPOSES: (1) How do orthopaedic anesthetic malpractice claims differ from other anesthesia claims with regard to patient and case characteristics, common events and injuries, and liability profile? (2) What are the characteristics of patients who had neuraxial hematomas after spinal and epidural anesthesia for orthopaedic procedures? (3) What are the characteristics of patients who had orthopaedic anesthesia malpractice claims for central ischemic neurologic injury occurring during shoulder surgery in the beach chair position? (4) What are the characteristics of patients who had malpractice claims for respiratory depression and respiratory arrests in the postoperative period? METHODS: The Anesthesia Closed Claims Project database was the source of data for this study. This national database derives data from a panel of liability companies (national and regional) and includes closed malpractice claims against anesthesiologists representing > 30% of practicing anesthesiologists in the United States from all types of practice settings (hospital, surgery centers, and offices). Claims for damage to teeth or dentures are not included in the database. Patient characteristics, type of anesthesia, damaging events, outcomes, and liability characteristics of anesthesia malpractice claims for events occurring in the years 2000 to 2013 related to nonspine orthopaedic surgery (n = 475) were compared with claims related to other procedures (n = 1592) with p < 0.05 as the criterion for statistical significance and two-tailed tests. Odds ratios and their 95% confidence intervals were calculated for all comparisons. Three types of claims involving high-impact injuries in patients undergoing nonspine orthopaedic surgery were identified through database query for in-depth descriptive review: neuraxial hematoma (n = 10), central ischemic neurologic injury in the beach chair position (n = 9), and injuries caused by postoperative respiratory depression (n = 23). RESULTS: Nonspine orthopaedic anesthesia malpractice claims were more frequently associated with nerve injuries (125 of 475 [26%], odds ratio [OR] 2.12 [1.66-2.71]) and events arising from the use of regional anesthesia (125 of 475 [26%], OR 6.18 (4.59-8.32) than in malpractice claims in other areas of anesthesia malpractice (230 of 1592 [14%] and 87 of 1592 [6%], respectively, p < 0.001 for both comparisons). Ninety percent (nine of 10) of patients with claims for neuraxial hematomas were receiving anticoagulant medication and all had severe long-term injuries, most with a history of significant delay in diagnosis and treatment after first appearance of signs and symptoms. Central ischemic injuries occurring during orthopaedic surgery in the beach chair position did not occur solely in patients who would have been considered at high risk for ischemic stroke. Patients with malpractice claims for injuries resulting from postoperative respiratory depression events had undergone lower extremity procedures (20 of 23 [87%]) and most events (22 of 23 [96%]) occurred on the day of surgery or the first postoperative day. CONCLUSIONS: Nonspine orthopaedic anesthesia malpractice claims more frequently cited nerve injury and events arising from the use of regional anesthesia than other surgical anesthesia malpractice claims. This may reflect the frequency of regional anesthesia in orthopaedic cases rather than increased risk of injury associated with regional techniques. When neuraxial procedures and anticoagulation regimens are used concurrently, care pathways should emphasize clear lines of responsibility for coordination of care and early investigation of any unusual neurologic findings that might indicate neuraxial hematoma. We do not have a good understanding of the factors that render some patients vulnerable to the rare occurrence of intraoperative central ischemic injury in the beach chair position, but providers should carefully calculate cerebral perfusion pressure relative to measured blood pressure for patients in the upright position. Postoperative use of multiple opioids by different concurrent modes of administration warrant special precautions with consideration given to the provision of care in settings with enhanced respiratory monitoring. The limitations of retrospective closed claims database review prevent conclusions regarding causation. Nonetheless, the collection of relatively rare events with substantial clinical detail provides valuable data to generate hypotheses about causation with potential for future study to improve patient safety. LEVEL OF EVIDENCE: Level III, therapeutic study.

Injury and Liability Associated with Implantable Devices for Chronic Pain.

BACKGROUND: Due to an increase in implantable device-related anesthesia pain medicine claims, the authors investigated anesthesia liability associated with these devices. METHODS: After institutional review board approval, the authors identified 148 pain medicine device claims from 1990 or later in the Anesthesia Closed Claims Project Database. Device-related damaging events included medication administration events, infections, hematomas, retained catheter fragments, cerebrospinal fluid leaks, cord or cauda equina trauma, device placed at wrong level, stimulator incorrectly programmed, delay in recognition of granuloma formation, and other issues. RESULTS: The most common devices were implantable drug delivery systems (IDDS; 64%) and spinal cord stimulators (29%). Device-related care consisted of surgical device procedures (n = 107) and IDDS maintenance (n = 41). Severity of injury was greater in IDDS maintenance claims (56% death or severe permanent injury) than in surgical device procedures (26%, P < 0.001). Death and brain damage in IDDS maintenance claims resulted from medication administration errors (n = 13; 32%); spinal cord injury resulted from delayed recognition of granuloma formation (n = 9; 22%). The most common damaging events for surgical device procedures were infections, inadequate pain relief, cord trauma, retained catheter fragments, and subcutaneous hygroma. Care was more commonly assessed as less than appropriate (78%) and payments more common (63%) in IDDS maintenance than in surgical device procedure claims (P < 0.001). CONCLUSIONS: Half of IDDS maintenance claims were associated with death or permanent severe injury, most commonly from medication errors or failure to recognize progressive neurologic deterioration. Practitioners implanting or managing devices for chronic pain should exercise caution in these areas to minimize patient harm.

Trends in Pain Medicine Liability.

BACKGROUND: The authors examined changes in the frequency of pain medicine malpractice claims and associated treatment modalities and outcomes over time. METHODS: The authors analyzed trends in pain medicine claims from 1980 to 2012 in the Anesthesia Closed Claims Project database by binary logistic regression on year of event. Pain procedures in claims from 2000 to 2012 were compared with the proportion of pain procedures reported to the National Anesthesia Clinical Outcomes Registry in 2010-2014. RESULTS: Malpractice claims for pain medicine increased from 3% of 2,966 total malpractice claims in the Anesthesia Closed Claims Project database in 1980-1989 to 18% of 2,743 anesthesia claims in 2000-2012 (odds ratio [OR], 1.088 per year; 95% CI, 1.078 to 1.098; P < 0.001). Outcomes in pain claims became more severe over time, with increases in death and permanent disabling injury (OR, 1.094 per year; P < 0.001). Nonneurolytic cervical injections increased to 27% of pain claims in 2000-2012 (OR, 1.054; P < 0.001), whereas National Anesthesia Clinical Outcomes Registry demonstrates that lumbar injections are a more common procedure. Claims associated with medication management increased to 17% of pain claims in 2000-2012 (OR, 1.116 per year; P < 0.001). CONCLUSIONS: Pain medicine claims have increased over time and have increased in severity. Claims related to cervical procedures were out of proportion to the frequency with which they are performed. These liability findings suggest that pain specialists should aggressively continue the search for safer and more effective therapies.

Postoperative opioid-induced respiratory depression: a closed claims analysis.

BACKGROUND: Postoperative opioid-induced respiratory depression (RD) is a significant cause of death and brain damage in the perioperative period. The authors examined anesthesia closed malpractice claims associated with RD to determine whether patterns of injuries could guide preventative strategies. METHODS: From the Anesthesia Closed Claims Project database of 9,799 claims, three authors reviewed 357 acute pain claims that occurred between 1990 and 2009 for the likelihood of RD using literature-based criteria. Previously cited patient risk factors for RD, clinical management, nursing assessments, and timing of events were abstracted from claim narratives to identify recurrent patterns. RESULTS: RD was judged as possible, probable, or definite in 92 claims (κ = 0.690) of which 77% resulted in severe brain damage or death. The vast majority of RD events (88%) occurred within 24 h of surgery, and 97% were judged as preventable with better monitoring and response. Contributing and potentially actionable factors included multiple prescribers (33%), concurrent administration of nonopioid sedating medications (34%), and inadequate nursing assessments or response (31%). The time between the last nursing check and the discovery of a patient with RD was within 2 h in 42% and within 15 min in 16% of claims. Somnolence was noted in 62% of patients before the event. CONCLUSIONS: This claims review supports a growing consensus that opioid-related adverse events are multifactorial and potentially preventable with improvements in assessment of sedation level, monitoring of oxygenation and ventilation, and early response and intervention, particularly within the first 24 h postoperatively.

Massive hemorrhage: a report from the anesthesia closed claims project.

BACKGROUND: Hemorrhage is a potentially preventable cause of adverse outcomes in surgical and obstetric patients. New understanding of the pathophysiology of hemorrhagic shock, including development of coagulopathy, has led to evolution of recommendations for treatment. However, no recent study has examined the legal outcomes of these claims. The authors reviewed closed anesthesia malpractice claims related to hemorrhage, seeking common factors to guide future management strategies. METHODS: The authors analyzed 3,211 closed surgical or obstetric anesthesia malpractice claims from 1995 to 2011 in the Anesthesia Closed Claims Project. Claims where patient injury was attributed to hemorrhage were compared with all other surgical and obstetric claims. Risk factors for hemorrhage and coagulopathy, clinical factors, management, and communication issues were abstracted from claim narratives to identify recurrent patterns. RESULTS: Hemorrhage occurred in 141 (4%) claims. Obstetrics accounted for 30% of hemorrhage claims compared with 13% of nonhemorrhage claims (P < 0.001); thoracic or lumbar spine surgery was similarly overrepresented (24 vs. 6%, P < 0.001). Mortality was higher in hemorrhage than nonhemorrhage claims (77 vs. 27%, P < 0.001), and anesthesia care was more often judged to be less than appropriate (55 vs. 38%, P < 0.001). Median payments were higher in hemorrhage versus nonhemorrhage claims ($607,750 vs. $276,000, P < 0.001). Risk factors for hemorrhage and coagulopathy were common, and initiation of transfusion therapy was commonly delayed. CONCLUSIONS: Hemorrhage is a rare, but serious, cause of anesthesia malpractice claims. Understanding which patients are at risk can aid in patient referral decisions, design of institutional systems for responding to hemorrhage, and education of surgeons, obstetricians, and anesthesiologists.

The quality of upper extremity orthopedic care in liability claims filed and claims paid.

PURPOSE: To review a series of closed liability claims for upper extremity conditions to guide improvements for upper extremity care and thereby reduce the frequency of paid claims. METHODS: The authors, a team of 3 orthopedic surgeons and 3 nonphysician investigators experienced in closed claims research, investigated 108 closed upper extremity liability claims from a large United States-wide insurer for events that occurred between 1996 and 2009. We sought to determine the types of conditions, treatments, and surgeon factors common to claims made and claims paid. RESULTS: Liability claims were primarily for the care of common problems, such as fractures (n = 52; 48%) or degenerative conditions (n = 24; 26%), rather than complex challenging conditions or disorders, such as deficiencies treated with replantations or tissue transfers. The most common adverse outcomes in these claims were nonunion or malunion of fractures (n = 29; 27%), nerve injury (n = 20; 19%), and infection (n = 13; 12%). Most claims (n = 57; 53%) involved a permanent injury. The surgeon's operative skills were more commonly an issue in paid claims (n = 13; 45%) than in claims without payment (n = 14; 19%). Claims for mismanagement of fractures (n = 52; 48% of all claims) were more likely to result in payment (n = 20; 38%) than nonfracture claims (n = 10; 18%). CONCLUSIONS: This analysis suggests that the incidence of upper extremity claims made and claims paid may be reduced if surgeons acquire and maintain the knowledge and skills necessary for the care of the common conditions they encounter, including fractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

The human immunodeficiency virus, (HIV-1), pandemic: cellular therapies, stem cells and biobanking.

The Human Immunodeficiency Virus, (HIV-1), has become a major global health threat with recent estimates suggesting that 68% of people living with HIV (PLWH) reside in Sub-Saharan Africa. The current strategies for containment of this disease in the absence of an effective vaccine are of concern in terms of long-term fiscal sustainability and cost effectiveness. HIV prevalence rates are set to rise, not because of increasing incidence but rather because of the effort involved in implementing the anti-retroviral (ARV) programmes, especially on the African continent. Even when sub-optimally delivered, these therapies will lead to a decrease in mortality rates and prevent early death from opportunistic infections. However, evidence is emerging for long-term systemic effects of chronic HIV infection in persons on ARV therapy, including increased incidence of Haematological abnormalities and malignancies.

Similar liability for trauma and nontrauma surgical anesthesia: a closed claims analysis.

BACKGROUND: Trauma care has many challenges, including the perception by nonanesthesia physicians of increased medical malpractice liability. We used the American Society of Anesthesiologists' Closed Claims Project database and the National Inpatient Sample (NIS) to compare the rate of claims for trauma anesthesia care to national trauma surgery data. We also used the American Society of Anesthesiologists' Closed Claims Project database to evaluate injury and liability profiles of trauma anesthesia malpractice claims compared to nontrauma surgical anesthesia claims. METHODS: Surgical anesthesia claims for injuries that occurred between 1980 and 2005 in the American Society of Anesthesiologists' Closed Claims Project database of 8954 claims were included in this analysis. Trauma was defined using cause of injury criteria in state trauma registries, including out-of-hospital falls. To estimate national trauma anesthesia rates, we used injury codes in NIS reports to define trauma discharges and NIS discharges with surgical procedure codes for the denominator. The year-adjusted odds ratio and P value comparing the national trauma anesthesia injury rates and American Society of Anesthesiologists' Closed Claims Project inpatient claim rates in the 1990 to 2001 time period were calculated by a multivariate logistic regression of the injury/trauma outcome on year and the NIS/Closed Claims Project indicator. Payments in claim resolution between trauma claims and nontraumatic surgical anesthesia claims were compared by χ(2) analysis, Fisher exact test for proportions, and Kolmogorov-Smirnov test for payment amounts. RESULTS: Trauma claims represented 6% of the total 6215 surgical anesthesia claims in the study period. The inpatient trauma claims rates were consistently lower than the NIS injury rates for 1990 to 2001. The year-adjusted odds ratio comparing the trauma claims rates to the NIS injury rates was 0.62 (95% confidence interval [CI], 0.53 to 0.72; P < 0.001, likelihood ratio test). Trauma claims and nontrauma surgical anesthesia claims did not differ in appropriateness of care, whether or not a payment was made to the plaintiff, or size of payments. CONCLUSION: Despite reported perceptions that trauma care involves a high risk of medical liability, there was no apparent increased risk of liability among inpatients presenting for trauma anesthesia care. The proportion in malpractice claims in trauma anesthesia care was not increased compared to nontraumatic surgical anesthesia care. With respect to medicolegal liability, these results support participation of anesthesia providers in multidisciplinary trauma care and organized systems.

Screening for small molecule modulators of Hsp70 chaperone activity using protein aggregation suppression assays: inhibition of the plasmodial chaperone PfHsp70-1.

Plasmodium falciparum heat shock protein 70 (PfHsp70-1) is thought to play an essential role in parasite survival and virulence in the human host, making it a potential antimalarial drug target. A malate dehydrogenase based aggregation suppression assay was adapted for the screening of small molecule modulators of Hsp70. A number of small molecules of natural (marine prenylated alkaloids and terrestrial plant naphthoquinones) and related synthetic origin were screened for their effects on the protein aggregation suppression activity of purified recombinant PfHsp70-1. Five compounds (malonganenone A-C, lapachol and bromo-ß-lapachona) were found to inhibit the chaperone activity of PfHsp70-1 in a concentration dependent manner, with lapachol preferentially inhibiting PfHsp70-1 compared to another control Hsp70. Using growth inhibition assays on P. falciparum infected erythrocytes, all of the compounds, except for malonganenone B, were found to inhibit parasite growth with IC(50) values in the low micromolar range. Overall, this study has identified two novel classes of small molecule inhibitors of PfHsp70-1, one representing a new class of antiplasmodial compounds (malonganenones). In addition to demonstrating the validity of PfHsp70-1 as a possible drug target, the compounds reported in this study will be potentially useful as molecular probes for fundamental studies on Hsp70 chaperone function.

Co-expression of the Plasmodium falciparum molecular chaperone, PfHsp70, improves the heterologous production of the antimalarial drug target GTP cyclohydrolase I, PfGCHI.

Molecular chaperones have been used for the improved expression of target proteins within heterologous systems; however, the chaperone and target protein have seldom been matched in terms of origin. We have developed a heterologous co-expression system that allows independent expression of the plasmodial chaperone, PfHsp70, and a plasmodial target protein. In this study, the target was Plasmodium falciparum GTP cyclohydrolase I (PfGCHI), the first enzyme in the plasmodial folate pathway. The sequential expression of the molecular chaperone followed by the target protein increased the expression of soluble functional PfGCHI. His-tagged PfGCHI was successfully purified using nickel affinity chromatography, and the specific activity was determined by high performance liquid chromatography with spectrofluorometeric detection to be 5.93nmol/h/mg. This is the first report of a heterologous co-expression system in which a plasmodial chaperone is harnessed for the improved production and purification of a plasmodial target protein.

Injury and liability associated with cervical procedures for chronic pain.

BACKGROUND: Prompted by an increase in interventional pain treatments performed at the level of the cervical spine, we investigated the characteristics and patterns of injury in malpractice claims collected from January 1, 2005 to December 31, 2008. METHODS: We compared claims arising from cervical pain treatments with all other chronic pain claims collected from the American Society of Anesthesiologists' closed claims database between 2005 and 2008. Claims for spinal cord injury underwent in-depth analysis for mechanisms of injury and use of sedation during the procedure. RESULTS: Claims related to cervical interventions represented 22% (64/294) of chronic pain treatment claims. Patients who underwent cervical procedures were healthier (American Society of Anesthesiologists' score, 1-2; P < 0.001) and were more often women (P = 0.011). Of the patients who underwent a cervical procedure, 59% experienced spinal cord damage compared with 11% of patients with other chronic pain (P < 0.001), with direct needle trauma as the predominant cause (31%). General anesthesia or sedation was used in 67% of cervical procedure claims associated with spinal cord injuries but in only 19% of cervical procedure claims not associated with spinal cord injuries (P < 0.001). Of the patients who underwent cervical procedures and had spinal cord injuries, 25% were nonresponsive during the procedure compared with 5% of the patients who underwent cervical procedures and did not have spinal cord injuries (P < 0.05, κ = 0.52). CONCLUSIONS: Injuries related to cervical interventional pain treatment were often severe and related to direct needle trauma to the spinal cord. Traumatic spinal cord injury was more common in patients who received sedation or general anesthesia and in those who were unresponsive during the procedure. Further studies are crucial to define the usefulness of cervical interventions and to improve their safety.

Autopsy utilization in medicolegal defense of anesthesiologists.

BACKGROUND: The rate of autopsy in hospital deaths has declined from more than 50% to 2.4% over the past 50 yr. To understand the role of autopsies in anesthesia malpractice claims, we examined 980 closed claims for deaths that occurred in 1990 or later in the American Society of Anesthesiologists Closed Claims Project Database. METHODS: Deaths with autopsy were compared with deaths without autopsy. Deaths with autopsy were evaluated to answer the following four questions: Did autopsy findings establish a cause of death? Did autopsy provide new information? Did autopsy identify a significant nonanesthetic contribution to death? Did autopsy help or hurt the defense of the anesthesiologist? Reliability was assessed by κ scores. Differences between groups were compared with chi-square analysis and Kolmogorov-Smirnov test with P < 0.05 for statistical significance. RESULTS: Autopsies were performed in 551 (56%) of 980 claims for death. Evaluable autopsy information was available in 288 (52%) of 551 claims with autopsy. Patients in these 288 claims were younger and healthier than those in claims for death without autopsy (P < 0.01). Autopsy provided pathologic diagnoses and an unequivocal cause of death in 21% of these 288 claims (κ= 0.71). An unexpected pathologic diagnosis was found in 50% of claims with evaluable autopsy information (κ = 0.59). Autopsy identified a significant nonanesthetic contribution in 61% (κ = 0.64) of these 288 claims. Autopsy helped in the defense of the anesthesiologist in 55% of claims and harmed the defense in 27% (κ = 0.58) of claims with evaluable autopsy information. CONCLUSIONS: Autopsy findings were more often helpful than harmful in the medicolegal defense of anesthesiologists. Autopsy identified a significant nonanesthetic contribution to death in two thirds of claims with evaluable autopsy information.

Malpractice claims associated with medication management for chronic pain.

BACKGROUND: Medication management is an integral part of chronic pain management. Prompted by an increase in the role of medication management in anesthesia chronic pain liability, we investigated the characteristics of malpractice claims collected from 2005 to 2008. METHODS: After Institutional Review Board approval, we compared medication management claims with other chronic pain claims from the American Society of Anesthesiologists Closed Claims Database of 8,954 claims. Claims for death underwent in-depth analysis. RESULTS: Medication management represented 17% of 295 chronic non-cancer pain claims. Compared with other chronic pain claims, medication management patients tended to be younger men (P < 0.01) with back pain. Most patients were prescribed opioids (94%) and also additional psychoactive medications (58%). Eighty percent of patients had at least one factor commonly associated with medication misuse and 24% had >or= 3 factors. Most claims (82%) involved patients who did not cooperate in their care (69%) or inappropriate medication management by physicians (59%). Death was the most common outcome in medication management claims (57% vs. 9% in other chronic pain claims, P < 0.01). Factors associated with death included long-acting opioids, additional psychoactive medications, and >or= 3 factors commonly associated with medication misuse. Alleged addiction from prescribed opioids was the complaint in 24%. Appropriateness of care and payments was similar for medication management versus other chronic pain claims. CONCLUSIONS: Most anesthesia malpractice claims for medication management problems involved patients with a history of risk behaviors commonly associated with medication misuse. Malpractice claims arising from medication management had a high proportion of deaths with both patient and physician contributions to the outcome.

The role of gaping behaviour in habitat partitioning between coexisting intertidal mussels.

BACKGROUND: Environmental heterogeneity plays a major role in invasion and coexistence dynamics. Habitat segregation between introduced species and their native competitors is usually described in terms of different physiological and behavioural abilities. However little attention has been paid to the effects of behaviour in habitat partitioning among invertebrates, partially because their behavioural repertoires, especially marine benthic taxa, are extremely limited. This study investigates the effect of gaping behaviour on habitat segregation of the two dominant mussel species living in South Africa, the invasive Mytilus galloprovincialis and the indigenous Perna perna. These two species show partial habitat segregation on the south coast of South Africa, the lower and upper areas of the mussel zone are dominated by P. perna and M. galloprovincialis respectively, with overlap in the middle zone. During emergence, intertidal mussels will either keep the valves closed, minimizing water loss and undergoing anaerobic metabolism, or will periodically open the valves maintaining a more efficient aerobic metabolism but increasing the risk of desiccation. RESULTS: Our results show that, when air exposed, the two species adopt clearly different behaviours. M. galloprovincialis keeps the shell valves closed, while P. perna periodically gapes. Gaping behaviour increased water loss in the indigenous species, and consequently the risk of desiccation. The indigenous species expressed significantly higher levels of stress protein (Hsp70) than M. galloprovincialis under field conditions and suffered significantly higher mortality rates when exposed to air in the laboratory. In general, no intra-specific differences were observed in relation to intertidal height. The absence of gaping minimises water loss but exposes the invasive species to other stresses, probably related to anoxic respiration. CONCLUSIONS: Gaping affects tolerance to desiccation, thus influencing the vertical zonation of the two species. Valve closure exposes the invasive species to higher stress and associated energy demands, but it minimizes water loss, allowing this species to dominate the upper mussel zone, where the gaping indigenous P. perna cannot survive. Thus even very simple behaviour can influence the outcome of interactions between indigenous and invasive species.

Community pharmacy: a crucial enabler in creating the effectiveness study environment in the Salford Lung Studies.

OBJECTIVE: Creating an environment that supports conditions of routine clinical practice and enables an effectiveness trial design with a pre-licensed medicine is extremely challenging. Here, we summarise our experiences and achievements with engaging and mobilising community pharmacies in and around Salford, United Kingdom, in the Phase III effectiveness Salford Lung Studies (SLS). METHODS: This article provides the authors' personal experiences and viewpoints on community pharmacy involvement in the SLS. KEY FINDINGS: More than 130 community pharmacies were enabled, and >2500 pharmacy staff trained, for involvement in the SLS. Key to community pharmacy participation in the SLS was the formation of the SLS Pharmacy Steering Group (PSG), contributing to study oversight, and the development of a pharmacy standard operating procedure document, the major principle of which was to ensure minimum disruption to the normal medicine dispensing process while ensuring compliance with regulations, guidelines, good clinical practice and requirements for pharmacovigilance. The high level of commitment and collaboration of community pharmacy in the SLS demonstrated a willingness to work together and take on additional and novel roles beyond their everyday commercial functions for the benefit of patients, despite normally competing for prescription business. CONCLUSIONS: The involvement and integration of community pharmacy as a key partner in the SLS was pivotal in securing the delivery of these world-first clinical effectiveness studies. To our knowledge, this has not been previously achieved in a study of a pre-licensed maintenance therapy for a common disease in primary care.

The TPR2B domain of the Hsp70/Hsp90 organizing protein (Hop) may contribute towards its dimerization.

The role of the TPR2B domain of Hop is as yet unknown. We have shown here by site directed mutagenesis and size exclusion chromatography for the first time that the TPR1 and TPR2B domains of Hop independently dimerized, and that the dimerization of TPR2B was not dependent on its predicted two-carboxylate clamp residues. Furthermore, our data indicated that the dimerization of Hop and its domains was not disrupted in the presence of Hsp70 and Hsp90 peptides.

The Agrobacterium tumefaciens DnaK: ATPase cycle, oligomeric state and chaperone properties.

DnaK is a molecular chaperone that promotes cell survival during stress by preventing protein misfolding. The chaperone activity is regulated by nucleotide binding and hydrolysis events in the N-terminal ATPase domain, which in turn mediate substrate binding and release in the C-terminal substrate binding domain. In this study we determined that ATP hydrolysis was the rate limiting step in the ATPase cycle of Agrobacterium tumefaciens DnaK (Agt DnaK); however the data suggested that Agt DnaK had a significantly lower affinity for ATP than Escherichia coli DnaK. We show for the first time that Agt DnaK was very effective at preventing thermal aggregation of malate dehydrogenase (MDH) in a concentration dependent manner. This is in contrast to E. coli DnaK which was ineffective at preventing thermal aggregation of MDH. A mutant Agt DnaK-V431F, with a blocked hydrophobic pocket in the substrate binding domain, was unable to suppress the thermosensitivty of an E. coli dnaK103 deletion strain. However the mutation did not inhibit Agt DnaK-V431F from preventing the thermal aggregation of MDH. The oligomeric state of Agt DnaK was studied using size exclusion chromatography. We demonstrated that dilution of the Agt DnaK protein, the addition of ATP and the removal of the 10kDa C-terminal alpha-helical subdomain reduced higher order associations but did not abrogate dimerisation. Our research implies that the C-terminal alpha-helical subdomain is involved in higher order associations, while the substrate binding domain is possibly involved in dimerisation.