Setting a direction for continuing professional development in anesthesiology: A synthesis of the outcome from an Utstein style meeting.

BACKGROUND: An Utstein style meeting of key stakeholders from the existing collaboration surrounding post-graduate training was arranged to set a direction for continuing professional development (CPD) of anesthesiologists in Denmark. A 2-day meeting was planned to guide discussions about competencies in anesthesiology, facilitate the development of a blueprint for a portfolio-based CPD program and provide examples of how a portfolio can be used in practice. METHODS: The meeting agenda was based on an adaptation of Kern's six-step approach to curriculum development. Twenty-four participants from the university hospitals in Denmark were invited. Prior to the meeting participants were informed of the objectives and the Utstein style process. RESULTS: Participants acknowledged a need for a more structured approach to CPD, preferably within the current organizational set up at the departmental level, and with a portfolio-based, individualized curriculum. It was recognized that CPD should contain an array of possibilities to accommodate needs and wants of both the individual and the department. It was emphasized that, while anesthesiologists are used to give feedback to trainees, many are less familiar in providing the same to peers, and psychological safety was identified as a prerequisite to support a culture where specialists can reflect openly on each other's performance. CONCLUSION: The results provide an insight into the attitudes, opportunities, and challenges of anesthesiologists in relation to continuing professional development in Denmark. Generally, participant suggestions are in line with the shift in medical education toward workplace-based learning, feedback and lifelong learning.

European Academy of Neurology guideline on the management of medication-overuse headache.

BACKGROUND: The frequent use of medication to treat migraine attacks can lead to an increase in migraine frequency and is called medication-overuse headache (MOH). METHODS: Based on the available literature in this guideline, the first step in patient management is education and counselling. RESULTS: Patients with MOH should be managed by a multidisciplinary team of neurologists or pain specialists and behavioral psychologists. Patients in whom education is not effective should be withdrawn from overused drugs and should receive preventive treatment with drugs of proven efficacy. Patients with MOH in whom preventive treatment is not effective should undergo drug withdrawal. Drug intake can be abruptly terminated or restricted in patients overusing simple analgesics, ergots or triptan medication. In patients with long-lasting abuse of opioids, barbiturates or tranquilizers, slow tapering of these drugs is recommended. Withdrawal can be performed on an outpatient basis or in a daycare or inpatient setting.

Predicting responsiveness to fampridine in gait-impaired patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Fampridine leads to significant improvements in walking in many people with multiple sclerosis (PwMS). However, a relevant proportion of PwMS does not respond to fampridine and predictors of initial drug responsiveness are unknown. METHODS: Drug response to prolonged-release (PR)-fampridine was assessed in 55 PwMS using the timed 25-foot walk (T25FW), 6-min walk test (6MWT) and 12-item multiple sclerosis walking scale as outcome parameters. Patients were treated with PR-fampridine and placebo for 6 weeks each in a randomized, double-blind, placebo-controlled trial with crossover design (NCT01576354). Possible predictors of drug responsiveness were investigated by multiple correlation analysis and binary logistic regression models. An additional longitudinal analysis followed the drug responses of 32 patients treated with PR-fampridine over 3 years to identify potential predictors of long-term drug responsiveness. RESULTS: Severity of walking disability was positively correlated with enhanced responses to PR-fampridine. The strongest single predictor of drug responsiveness was poor 6MWT performance at baseline, which was positively correlated with enhanced drug response in the 6MWT (R = -0.541; P < 0.001). A multivariable logistic regression model including 6MWT and T25FW baseline performances predicted PR-fampridine responder status with an accuracy of 85.5% (specificity, 90.0%; sensitivity, 73.3%), with a threshold of 211 m in the 6MWT best separating responders from non-responders. Enhanced drug responsiveness after 3 years correlated with decline in walking endurance during this period (R = -0.634; P = 0.001). CONCLUSIONS: Initial walking impairment is a good predictor of therapeutic responsiveness to PR-fampridine. Valid predictors of patients' responsiveness to PR-fampridine are essential for patient stratification and optimization of multiple slcerosis treatment.

The association between pre-operative sepsis and 30-day mortality in hip fracture patients-A cohort study.

BACKGROUND: Post-operative sepsis considerably increases mortality, but the extent of pre-operative sepsis in hip fracture patients and its consequences are sparsely elucidated. The aim of this study was to assess the association between pre-operative sepsis and 30-day mortality after hip fracture surgery. METHODS: We conducted a retrospective analysis of data collected among 1894 patients who underwent hip fracture surgery in the Capital Region of Denmark in 2014 (NCT03201679). Data on vital signs, cultures and laboratory data were obtained. Sepsis was defined as a positive culture of any kind and presence of systemic inflammatory response syndrome within 24 hours and was assessed within 72 hours before surgery and 30 days post-operatively. Primary outcome was 30-day mortality. Secondary outcomes included length of hospital stay and admission to intensive care unit. RESULTS: A total of 144 (7.6%) of the hip fracture patients met the criteria for pre-operative sepsis. The 30-day mortality was 13.9% in patients with pre-operative sepsis as compared to 9.0% in those without (OR 1.69, 95% CI [1.00; 2.85], P = .08). Patients with pre-operative sepsis had longer hospital stays (median 10 days vs 9 days, mean difference 2.1 [SD 9.4] days, P = .03), and higher frequency of ICU admission (11.1% vs 2.7%, OR 4.15, 95% CI [2.19; 7.87], P < .0001). CONCLUSION: Pre-operative sepsis in hip fracture patients was associated with an increased length of hospital stay and tended to increase mortality. Pre-operative sepsis in hip fracture patients merits more intensive surveillance and increased attention to timely treatment.

An epidemiological investigation of an idiopathic myopathy in hunting dogs in New Zealand.

AIM: To conduct an epidemiological investigation of an idiopathic myopathy, known as "Go Slow" (GSM), which was initially recognised in dogs used for pig hunting. A secondary aim was to describe the hunting activities, diet and health of dogs used for pig hunting in New Zealand. METHODS: A retrospective cohort study was conducted between June 2014-June 2017. Cases of GSM in dogs were diagnosed by veterinarians using a combination of clinical history, physical examination findings, serum biochemistry and/or skeletal muscle histology. A telephone interview was conducted with the owner or primary veterinarian to provide information regarding the dog's diet and exercise over the 7 days preceding the onset of clinical signs. In August 2015, a separate online survey of owners of dogs used for pig hunting was conducted to characterise the normal hunting activities, diet and health of these dogs. RESULTS: A total of 86 cases of GSM were recruited, of which 58 (67%) were pig hunting dogs, 16 (19%) pet dogs and 12 (14%) working farm dogs. Cases were most commonly reported in the upper North Island, and 65 (76 (95% CI=67-85)%) were from the Northland region. Processed commercial dog food had been fed to 93 (95% CI=88-98)% of affected dogs. Ingestion of raw, frozen or cooked wild pig in the preceding week was reported for 76 (88 (95% CI=82-95)%) dogs with the myopathy. In the survey of owners of healthy pig hunting dogs, 203 eligible responses were received; pig hunting was reported to most commonly occur in Northland (20.2%), Waikato (22.3%) and Bay of Plenty (23.2%) regions. Commercial dog food was fed to 172 (85 (95% CI=80-90)%) of the dogs included in this survey, and 55 (27 (95% CI=20-33)%) had eaten wild pig in the preceding week. The most common reported health problem in pig hunting dogs was traumatic wounds. CONCLUSIONS: Cases of GSM were most commonly recognised in dogs used for pig hunting, but also occurred in pet and working farm dogs. The disease was most frequently reported in the upper North Island of New Zealand and ingestion of wild pig was a consistent feature in cases of this myopathy. CLINICAL RELEVANCE: To minimise the risk of dogs developing this myopathy, it would seem prudent to avoid feeding any tissues from wild pigs to dogs in areas where the disease is known to occur.

Modifications of the National Early Warning Score for patients with chronic respiratory disease.

BACKGROUND: The National Early Warning Score (NEWS) uses physiological variables to detect deterioration in hospitalized patients. However, patients with chronic respiratory disease may have abnormal variables not requiring interventions. We studied how the Capital Region of Denmark NEWS Override System (CROS), the Chronic Respiratory Early Warning Score (CREWS) and the Salford NEWS (S-NEWS) affected NEWS total scores and NEWS performance. METHODS: In an observational study, we included patients with chronic respiratory disease. The frequency of use of CROS and the NEWS total score changes caused by CROS, CREWS and S-NEWS were described. NEWS, CROS, CREWS and S-NEWS were compared using 48-h mortality and intensive care unit (ICU) admission within 48 h as outcomes. RESULTS: We studied 11,266 patients during 25,978 admissions; the use of CROS lowered NEWS total scores in 40% of included patients. CROS, CREWS and S-NEWS had lower sensitivities than NEWS for 48-h mortality and ICU admission. Specificities and PPV were higher. CROS, CREWS and S-NEWS downgraded, respectively, 51.5%, 44.9% and 32.8% of the NEWS total scores from the 'mandatory doctor presence' and 'immediate doctor presence and specialist consultation' total score intervals to lower intervals. CONCLUSION: Capital Region of Denmark NEWS Override System was frequently used in patients with chronic respiratory disease. CROS, CREWS and S-NEWS reduced sensitivity for 48-h mortality and ICU admission. Using the methodology prevalent in the NEWS literature, we cannot conclude on the safety of these systems. Future prospective studies should investigate the balance between detection rate and alarm fatigue of different systems, or use controlled designs and patient-centred outcomes.

The skin cancer prevention framework: a comprehensive tool for population-level efforts in skin cancer.

The Skin Cancer Prevention Team (SCPT) required a comprehensive approach for guiding its efforts in population-level skin cancer prevention. After identifying and reviewing several models, it concluded that an appropriate population-level model applicable to the Alberta context did not exist. Thus, the SCPT, under the Alberta Health Services - Cancer Prevention Program, developed and evaluated a model for Alberta. Three inclusion criteria for a comprehensive framework were identified: 1) use an ecological approach to population health; 2) function as a dynamic tool for planning, implementing and evaluating population-level efforts; and 3) address weaknesses in existing theory in population health and health promotion. Theoretical constructs were layered together, on the basis of the criteria, to develop an omnibus framework. The resulting Framework represents a layering of several constructs used in popular health promotion and population health theories. It merges principles of the realist approach to scientific enquiry with principles of ecological theory. The Framework outlines a three-step, dynamic process for planning, implementing and evaluating population-level efforts. It also provides insight into the larger, unifying influences for changes in health outcomes and the complex mechanisms of behaviour change processes at the population level.

A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours.

Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day(-1) of imatinib mesylate, 50 mg day(-1) of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day(-1) of imatinib had the highest MC (+/-s.d.) of treatment at $35,225.61 USD (+/-1253.65 USD); while sunitinib incurred a median MC of $17,805.87 USD (+/-694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (+/-472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients.

Infusion of hypertonic saline before elective hysterectomy: effects on cytokines and stress hormones.

BACKGROUND: Infusion of hypertonic saline provides early haemodynamic benefits and may affect the immune system. It is unknown if infusion of hypertonic saline affects plasma cytokines and stress hormones after surgery. METHODS: Sixty-two women undergoing abdominal hysterectomy were randomized in a double-blind study to infusion of NaCl 7.5% (HS), NaCl 0.9% (NS4), both 4 ml kg(-1), or NaCl 0.9% 32 ml kg(-1) (NS32) over 20 min. Blood was collected at baseline, 1, 4, and 24 h after surgery (n=34) for the determination of interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12, IL-1ra, and tumour necrosis factor-alpha. Serum cortisol and vasopressin were measured at these time points and 48 h after operation. Epinephrine and norepinephrine (n=26) were quantified at baseline, after infusion, 25 min after incision, 1, and 4 h after surgery. Finally, C-reactive protein was measured at baseline, 24, and 48 h after surgery. RESULTS: Surgery and anaesthesia induced well-reported changes in the concentrations of cytokines and hormones. The concentration of norepinephrine briefly increased after infusion of HS and NS32 but not NS4 (P<0.05). Epinephrine was increased 25 min after incision in Group NS32 compared with the other groups (P<0.05). No other differences were found between the groups. CONCLUSIONS: Infusion of a clinically relevant dose of hypertonic saline before hysterectomy appears to have limited effect on the postoperative concentration of selected plasma cytokines and the hormonal stress-response.

LGMD 2I due to the common mutation 826C>A in the FKRP gene presenting as myopathy with vacuoles and paired-helical filaments.

We report on two unrelated patients clinically presenting with late-onset progressive limb girdle weakness; cardiomyopathy was seen in one patient. Muscle biopsy revealed a necrotic myopathy with numerous rimmed vacuoles, ultrastructurally typical paired-helical filaments, and reduced immunohistochemical staining for alpha-dystroglycan. Quadriceps sparing hereditary inclusion body myopathy due to mutations in GNE gene, and OPMD due to PABPN1 mutations were excluded, genetically. We detected a homozygous mutation of the FKRP gene (826C>A) in both patients. Mutations of FKRP have been reported in congenital muscular dystrophies, LGMD2I, cardiomyopathy and hyperCKemia, but not in myopathies with vacuoles and paired-helical filaments. Therefore, our findings further extend the morphological variability of muscular dystrophies due to FKRP mutations.

Acid base and electrolyte changes after hypertonic saline (7.5%) infusion: a randomized controlled clinical trial.

Hypertonic saline solutions are effective in the treatment of haemorrhagic and septic shock, elevated intracranial pressure and perioperative fluid deficits. Infusion, however, causes electrolyte and acid-base imbalance. In a randomized double-blind study, the effects of a 10-min infusion of 4 ml/kg 7.5% NaCl or 0.9% NaCl were evaluated in 14 fasting women before hysterectomy. Venous blood from the forearm was collected at baseline, 10, 20, 30, 60 and 120 min after start of the infusion for the determination of plasma electrolytes and acid-base balance. We found that 1) a median increase in plasma sodium of 11 mmol/l (range 9-13 mmol/l) and chloride of 14 mmol/l (range 9-16 mmol/l) immediately after the infusion followed by a small decrease after 2 h, 2) a minor decrease in plasma potassium in relation to the infusion followed by a significant increase of 0.3 mmol/l (range 0.1-1.4 mmol/l) above baseline after 1 h, 3) a decrease in pH of 0.05 (range 0.02-0.07) and, finally, 4) a decrease in base excess of 1.9 mmol/l (range 0.8-2.7 mmol/l). It is concluded that infusion of 7.5% NaCl in a clinical relevant dose increases plasma potassium and causes minor changes in the acid-base balance in normovolaemic women.

Immune effect of hypertonic saline: fact or fiction?

Hypertonicity affects many parts of the immune system. Animal studies and experiments in isolated cell cultures show that hypertonicity reversibly suppresses several neutrophil functions and at the same time up-regulates T-lymphocyte function. Infusion of hypertonic saline with or without colloids may thus, besides providing efficient plasma volume expansion, ameliorate the detrimental consequences on the immune function of trauma, shock, reperfusion, and major surgery. However, the few clinical studies conducted to date, specifically addressing the immune effect of hypertonic saline infusion, have shown little, if any, effect on markers of immune function, and larger clinical trials have not demonstrated benefit in terms of morbidity or mortality. Thus, as opposed to animal and cell-culture studies, the immune-modulating properties of hypertonic saline infusion would appear to be of limited value in clinical practice. This review presents in vitro studies, animal experiments, and clinical trials which investigated the consequences of hypertonic saline on markers of immune function.

Infusion of hypertonic saline (7.5% NaCl) causes minor immunological changes in normovolaemic women.

BACKGROUND: Haemorrhagic shock is treated effectively by infusion of hypertonic saline/colloid solutions. Furthermore, previous studies found hypertonicity to affect immune responses in animals and in human blood cell cultures. It is unknown, however, whether hypertonic saline infusion affects immune responses in humans. METHODS: In a randomized double-blind study, we infused 4 ml kg-1 of 7.5% NaCl or 0.9% NaCl over 10 min in 20 fasting women before hysterectomy. We collected peripheral blood at baseline, 30, and 120 min after start of the infusion and before surgery for the determination of leucocyte and differential count; lymphocyte subtypes; neutrophil chemotaxis; elastase concentration; and the cytokine's tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-1beta, IL-6, IL-8, IL-1 receptor antagonist (IL-1ra), and IL-10. Phytohaemagglutinin (PHA)-induced lymphocyte proliferation and natural killer cell cytotoxicity were measured before and 120 min after infusion. RESULTS: Compared with normal saline, infusion of hypertonic saline temporarily increased the number of B cells in peripheral blood (P < 0.01); increased the concentration of plasma elastase, a marker of neutrophil degranulation (P < 0.05); and decreased the number of circulating neutrophils (P < 0.001). No other effects were detected in the measured immunological parameters. CONCLUSION: The immunological consequences of hypertonic saline infusion seem to be modest and are unlikely to cause any clinical effects, at least in normovolaemic women.

Remifentanil vs. alfentanil infusion in non-paralysed patients: a randomized, double-blind study.

BACKGROUND AND OBJECTIVE: Remifentanil has a short duration of action and constant elimination, which allow administration of high doses, without prolonging recovery. Remifentanil has been compared to alfentanil, as part of a total intravenous anaesthetic technique, where remifentanil provided better anaesthetic conditions than alfentanil, without adverse effect on recovery. However, these results were obtained during anaesthesia involving neuromuscular blockade, which may mask both signs of insufficient anaesthesia and side-effects such as muscle rigidity. The aim of this study was to compare remifentanil with alfentanil for anaesthesia without neuromuscular blockade. METHODS: We performed a prospective, randomized, double-blind, four-centre study to compare remifentanil infusion 15 microg kg(-1) h(-1) and alfentanil infusion 60 microg kg(-1) h(-1), using a total intravenous technique for non-paralysed patients, and the laryngeal mask airway for airway management. We enrolled 192 patients, 18-65 yr of age with ASA I-II, undergoing minor surgery. The primary endpoint was the number of patients having pre-defined responses to surgical stimulation. A number of secondary criteria was evaluated to assess undesirable properties of the procedures. RESULTS: In the alfentanil group, 85% of patients responded to surgical stimulation, vs. 35% in the remifentanil group (P < 0.0001). No difference was found in recovery data, or in any other parameter than those related to insufficient anaesthesia. CONCLUSIONS: The remifentanil-based technique provided significantly better anaesthetic conditions than the alfentanil-based technique in the setting of this study, without causing any significant adverse effects.

Luminal cross-sectional area and wall distensibility in the isolated porcine oesophagus.

Previous studies have demonstrated regional differences in pressure-cross-sectional area relations, compliance and tension-strain relations of the oesophagus in vivo. The measurements and the variation in axial direction may reflect not only intrinsic oesophageal properties but can also be influenced by the adjacent organs. Four pigs were thoracotomised and the oesophagus was isolated from adjacent organs. The isolated oesophagus was investigated in situ by means of impedance planimetric measurements of cross-sectional area during pressure-controlled balloon distension 5, 15, and 25cm proximal to the gastro-oesophageal junction. CSA increased in a nonlinear way as function of pressure at all recording sites. The CSAs at pressures above 20 cmH2O increased progressively in distal direction (p < 0.001). The CSAs at a physiological pressure level of 30 cmH2O were 197 +/- 10, 222 +/- 19, and 231 +/- 17 mm2 at 25, 15, and 5cm above the gastro-oesophageal junction, respectively. The cross-sectional area distensibility increased from the proximal to the distal recording site in the whole pressure range (p < 0.001) with the most pronounced difference in the low pressure range. In conclusion, the regional variation in passive distensibility of the porcine oesophagus is an inherent condition of the oesophageal wall. The data have significance for evaluation of oesophageal flow properties and agree with previous findings of slow bolus velocity in the distal oesophagus.

Luminal cross-sectional area and tension-strain relation of the porcine bile duct.

The bile duct is a distensible tube serving to transport bile from the liver and gallbladder to the duodenum. The purpose of this study was to characterize the luminal cross-sectional area (CSA) and tension-strain properties during distension of the normal isolated porcine common bile duct in vitro. An impedance planimetric system located inside a balloon was used. Eleven porcine bile ducts were examined in two locations, in the hepatic duct and in the common bile duct. The CSAs obtained in the common bile duct were significantly higher than those in the hepatic duct in the pressure range 0-8 kPa (P < 0.001). The circumferential wall tension (T)-strain (epsilon) relations for both locations fitted to the exponential equation T = a.eb. epsilon with determination coefficients of 0.97 +/- 0.01. The a and b constants were not statistically different between the two locations indicating that the elastic properties did not differ. In conclusion, the luminal CSAs were larger in the common bile duct when compared to the hepatic duct and the tension-strain relations did not differ between the two segments of the bile duct.