Enhancing the Delivery of an Empirically-Supported Trauma-Focused Treatment for Adolescents: Providers’ Views of the Role of Technology and Web-Based Resources

Abstract

This mixed-methods study assessed providers' views of the use of technology in the delivery of an empirically supported mental health treatment for adolescents (Trauma-Focused Cognitive Behavioral Therapy; TF-CBT). Thematic qualitative interviews were conducted with nine experienced providers. Emerging themes served as the basis for the creation of a quantitative web-based survey, completed by 56 TF-CBT experts, to assess the perceived helpfulness of the recommendations. Technology was perceived as a useful, appealing, and familiar tool that could greatly enhance the delivery of this treatment modality with adolescents. Main recommendations included the creation of a mobile application targeting all of the treatment components and a website with developmentally appropriate resources for providers, caregivers, and teens. Technology may be a useful tool for enhancing service delivery and promoting engagement among youth receiving trauma-focused mental health treatment.

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Thoron exposure in Dutch dwellings – An overview

Publication date: March 2018
Source:Journal of Environmental Radioactivity, Volume 183
Author(s): G. de With, R.C.G.M. Smetsers, H. Slaper, P. de Jong
In the Netherlands considerable attention has been given to the exposure from thoron progeny in dwellings. For this purpose a nationwide survey on the thoron exhalation and thoron progeny concentration has been completed in 2015. Furthermore, extensive laboratory studies have been performed to measure activity concentrations and thoron exhalation rates from regular Dutch building materials. The purpose of this study is to demonstrate if the findings from both field experiments and laboratory results are consistent. For this reason measured properties of building materials and surface barriers, in-situ measurements on air ventilation and thoron(progeny) in dwellings as well as advanced computational modelling on indoor air and aerosol behaviour have been used. The results demonstrate that median and mean thoron progeny concentrations of 0.53 and 0.64 Bq·m⁻³ found in the survey are comparable with the mean concentration of 0.57 Bq·m⁻³ obtained from laboratory testing and calculation. Furthermore, upper thoron progeny concentrations from the survey and the calculations are with respectively 13 and 14 Bq·m⁻³ also in good agreement. Such elevated concentrations lead to an effective doses of around 4 mSv per year. The study also includes worst-case scenarios on the application of surface materials high on ²³²Th, and the expected reduction in thoron progeny when using mainstream mitigation measures.



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Inventory and vertical distribution of 137Cs, 239+240Pu and 238Pu in soil from Raivavae and Hiva Oa, two French Polynesian islands in the southern hemisphere

Publication date: March 2018
Source:Journal of Environmental Radioactivity, Volume 183
Author(s): P. Bouisset, M. Nohl, A. Bouville, G. Leclerc
Atmospheric nuclear weapons tests carried out by the United States, the former Soviet Union, the United Kingdom, France and China between 1945 and 1980 resulted in radioactive fallout over the earth's surface of long-lived radionuclides, such as ¹³⁷Cs, ^239+240Pu and ²³⁸Pu that could be detected more than 50 years after their production. In addition, the burnup in the upper atmosphere of a thermoelectric generator fueled by ²³⁸Pu, SNAP-9A, contributed to the inventory of ²³⁸Pu deposited on the ground. In order to estimate the deposition densities of ¹³⁷Cs, ^239+240Pu and ²³⁸Pu in French Polynesia, we collected undisturbed soil samples up to 30 cm deep at eight sites in two islands (Hiva Oa, 139°W - 10°S and Raivavae, 148°W - 24°S) in 2015–2016. The top 0–10 cm of the soil cores were sliced into five 2-cm layers and the bottom 10–30 cm into four 5-cm layers for gamma spectrometry and alpha spectrometry measurements. We found that more than 50% of the radioactive inventories are still contained within the first 10 cm and that the average vertical migration velocities of ¹³⁷Cs and Pu are less than 0.2 cm y⁻¹. The average accumulated depositions, deduced from the profile measurements, are 236 ± 11 Bq.m⁻² and 313 ± 39 Bq.m⁻² for ¹³⁷Cs, 12.1 ± 1.5 Bq.m⁻² and 22.1 ± 1.7 Bq.m⁻² for ^239+240Pu, and 1.23 ± 0.46 Bq.m⁻² and 1.58 ± 0.60 Bq.m⁻² for ²³⁸Pu, in Hiva Oa and Raivavae, respectively. The ²³⁸Pu/^239+240Pu ratios are 0.102 ± 0.050 at Hiva Oa and 0.072 ± 0.033 at Raivavae. Both values are higher than the ratio in nuclear weapons tests fallout estimated to be 0.016 in 2016 (Hardy et al., 1973), because of the contribution of ²³⁸Pu fallout from SNAP-9A, which is latitude dependent. The ¹³⁷Cs/^239+240Pu ratios, 19.5 ± 3.2 at Hiva Oa and 14.2 ± 2.8 at Raivavae are in the lower part of the range of values observed in other regions of the world.



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Multiple Origin but Single Domestication Led to Oryza sativa

The domestication scenario that led to Asian rice (Oryza sativa) is a contentious topic. Here, we have reanalyzed a previously published large-scale wild and domesticated rice dataset, which were also analyzed by two studies but resulted in two contrasting domestication models. We suggest the analysis of false positive selective sweep regions and phylogenetic analysis of concatenated genomic regions may have been the sources that contributed to the different results. In the end, our result indicates Asian rice originated from multiple wild progenitor subpopulations; however, de novo domestication appears to have occurred only once and the domestication alleles were transferred between rice subpopulation through introgression.

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Laparoscopic appendectomy during the third trimester: Case presentation and literature review

Abstract

Acute appendicitis is the most common general surgical problem encountered during pregnancy. Laparoscopic appendectomy (LA) is widely accepted as a minimally invasive procedure for acute appendicitis. However, LA during the third trimester is associated with problems, including technical difficulty, risk of preterm delivery, and fetal loss. We successfully managed three cases of LA during the third trimester between 2011 and 2016. None of the cases required conversion to an open procedure, and none of the patients had postoperative complications and/or fetal loss. We reviewed the literature using the PubMED database from 2007 to 2016 to acquire further evidence and identified 6 reports and 17 cases. The conversion rate was 11.8% (2 cases), the complication rate was 6.67% (1 case), and the preterm delivery rate was 20% (3 cases); no fetal loss was observed. Our study and literature review highlights the role of LA as a potentially feasible treatment approach for appendicitis during the third trimester.

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Laparoscopic repair of bowel herniation into the space between the obturator nerve and the umbilical artery after pelvic lymphadenectomy for cervical cancer

Abstract

Bowel herniation through the space between the exposed structures after pelvic lymphadenectomy is a very rare cause of postoperative bowel obstruction. Here, a case of laparoscopic release of bowel migration into the space after pelvic lymphadenectomy is described. This is the seventh such reported case in the world. A 38-year-old woman who had a history of undergoing laparoscopic radical hysterectomy and bilateral pelvic lymphadenectomy for cervical cancer was diagnosed with strangulated bowel obstruction. Emergency laparoscopic surgery was performed, and bowel migration into the space between the right umbilical artery and the obturator nerve was detected. The loop of strangulated bowel was released laparoscopically, and bowel blood flow was improved. To prevent recurrence of bowel migration, the umbilical artery was resected. It is very important to consider the possibility of bowel herniation into the space between exposed structures in patients with bowel obstruction after minimally invasive pelvic lymphadenectomy.

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Predicting postoperative language outcome using presurgical fMRI, MEG, TMS, and high gamma ECoG

Publication date: Available online 4 January 2018
Source:Clinical Neurophysiology
Author(s): Abbas Babajani-Feremi, Christen M. Holder, Shalini Narayana, Stephen P. Fulton, Asim F. Choudhri, Frederick A. Boop, James W. Wheless
ObjectiveTo predict the postoperative language outcome using the support vector regression (SVR) and results of multimodal presurgical language mapping.MethodsEleven patients with epilepsy received presurgical language mapping using functional MRI (fMRI), magnetoencephalography (MEG), transcranial magnetic stimulation (TMS), and high-gamma electrocorticography (hgECoG), as well as pre- and postoperative neuropsychological evaluation of language. We constructed 15 (2⁴-1) SVR models by considering the extent of resected language areas identified by all subsets of four modalities as input feature vector and the postoperative language outcome as output. We trained and cross-validated SVR models, and compared the cross-validation (CV) errors of all models for prediction of language outcome.ResultsSeven patients had some level of postoperative language decline and two of them had significant postoperative decline in naming. Some parts of language areas identified by four modalities were resected in these patients. We found that an SVR model consisting of fMRI, MEG, and hgECoG provided minimum CV error, although an SVR model consisting of fMRI and MEG was the optimal model that facilitated the best trade-off between model complexity and prediction accuracy.ConclusionsA multimodal SVR can be used to predict the language outcome.SignificanceThe developed multimodal SVR models in this study can be utilized to calculate the language outcomes of different resection plans prior to surgery and select the optimal surgical plan.



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Neurophysiologic characterization of periodic paralysis episode in a patient with Andersen-Tawil syndrome

Publication date: Available online 4 January 2018
Source:Clinical Neurophysiology
Author(s): Catarina Falcão de Campos, Mamede de Carvalho




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The critical warning sign of real-time brainstem auditory evoked potentials during microvascular decompression for hemifacial spasm

Publication date: Available online 4 January 2018
Source:Clinical Neurophysiology
Author(s): Sang-Ku Park, Byung-Euk Joo, Seunghoon Lee, Jeong-A Lee, Jeong-Ho Hwang, Doo-Sik Kong, Dae-Won Seo, Kwan Park, Hoon-Taek Lee
ObjectiveThe aim of this study was to define the critical warning sign of real-time brainstem auditory evoked potential (BAEP) for predicting hearing loss (HL) after microvascular decompression (MVD) for hemifacial spasm (HFS).MethodsNine hundred and thirty-two patients with HFS who underwent MVD with intraoperative monitoring (IOM) of BAEP were analyzed. We used a 43.9 Hz/s stimulation rate and 400 averaging trials to obtain BAEP. To evaluate HL, pure-tone audiometry and speech discrimination scoring were performed before and one week after surgery. We analyzed the incidence for postoperative HL according to BAEP changes and calculated the diagnostic accuracy of significant warning criteria.ResultsOnly 11 (1.2 %) patients experienced postoperative HL. The group showing permanent loss of wave V showed the largest percentage of postoperative HL (p <0.001). No patient who experienced only latency prolongation (≥ 1 ms) had postoperative HL. Loss of wave V and latency prolongation (≥1 ms) with amplitude decrement (≥ 50%) were highly associated with postoperative HL.ConclusionsLoss of wave V and latency prolongation of 1 ms with amplitude decrement ≥ 50% were the critical warning signs of BAEP for predicting postoperative HL.SignificanceThese findings elucidate the critical warning sign of real-time BAEP.



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Inside EMS Podcast: How to make 2018 the year you achieve your EMS goals

Download this podcast on iTunes, SoundCloud or via RSS feed In this Inside EMS Podcast episode, co-hosts Chris Cebollero and Kelly Grayson kick off the new year with a discussion on vision, goal setting and developing a plan to make 2018 a great year for achieving the best outcome for your personal and professional success. Learn more about the EMS1 Academy and schedule a free demo.

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The critical warning sign of real-time brainstem auditory evoked potentials during microvascular decompression for hemifacial spasm

Hemifacial spasm (HFS) presents as involuntary, intermittent spasm and is caused by facial nerve compression, secondary to arterial or venous compression at the root exit zone (REZ) (Barker et al., 1995; McLaughlin et al., 1999). Microvascular decompression (MVD) surgery, which involves relieving neurovascular compression, is a widely popular treatment for HFS (Jannetta, 1975; Barker et al., 1995). Since the vestibulocochlear nerve is directly adjacent to the facial nerve, the vestibulocochlear nerve can be damaged during MVD surgery, which could lead to hearing loss (HL) (Barker et al., 1995; Park et al., 2009).

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Neurophysiologic characterization of periodic paralysis episode in a patient with Andersen-Tawil syndrome

Primary period paralysis (PP) are rare disorders of skeletal muscle characterized by episodic attacks of muscle weakness. These episodes can be triggered by exercise and result from abnormal muscle membrane excitability. The diagnosis is based on clinical features, positive family history, serum potassium level during episodes and response to treatment. However the diagnosis is not always straightforward since some of these features may be absent (Venance et al., 2006). Post-exercise electrophysiological testing can be useful in guiding the diagnosis, as changes in compound motor action potential (CMAP) after exercise correlate with exercise induced weakness and ion channel mutation (Fournier et al., 2004).

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Predicting postoperative language outcome using presurgical fMRI, MEG, TMS, and high gamma ECoG

About 1% of people in the United States suffer from epilepsy, and one-fifth of epilepsy cases are pharmacologically intractable (Begley et al., 2000). Resection of the seizure onset zone is an effective treatment for intractable epilepsy but it carries the risk of postoperative impairment of essential brain functions, especially language. Presurgical language mapping is usually performed to minimize this risk. Cortical stimulation mapping (CSM) serves as the clinical gold standard for presurgical language mapping (Ojemann et al., 1989), though it has several limitations (Lesser et al., 1984; Blume et al., 2004; Brunner et al., 2009; Borchers et al., 2012; Wray et al., 2012; Desmurget et al., 2013; Papanicolaou et al., 2014).

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Comparison of ENDO CUT mode and FORCED COAG mode for the formation of stricture after esophageal endoscopic submucosal dissection in an in vivo porcine model

Abstract

Background and study aim

Stricture is a major complication of esophageal endoscopic submucosal dissection (ESD) for superficial esophageal carcinoma. To date, various methods have been developed to prevent stricture. However, the mechanism by which different electrosurgical unit (ESU) modes affect the formation of post-ESD stricture has not been evaluated. This study aimed to compare the degree of stricture caused by two major ESU modes (ENDO CUT mode and FORCED COAG mode) in a porcine model.

Methods

Twelve ESD procedures covering half of the circumference were performed in six pigs. Mucosal incision was performed with a ball-tip flush knife and submucosal dissection was performed with a hook knife; the two modes used were ENDO CUT I (Effect 2, Duration 2, Interval 3) and FORCED COAG mode (Effect 3, 40 W) (VIO300D, ERBE Germany). The pigs were killed humanely 30 days after ESD, and the severity of stricture and fibrosis was assessed.

Results

The resected site of the esophagus showed complete mucosal regrowth and scar formation in all pigs. There was no significant difference between the two modes in procedure time and size of resected specimen (14.4 ± 2.4 and 15.9 ± 6.1 min, P = 0.589; 626 ± 148, 661 ± 186 mm², P = 0.74, respectively). Stricture rate and severity of fibrosis in the submucosal layer were significantly lower in ENDO CUT mode than in FORCED COAG mode (31.5 ± 16.0% vs 44.3 ± 11.6%, P = 0.046; 36.2 ± 17.1% vs 60.4 ± 26.8%, P = 0.024, respectively).

Conclusions

ENDO CUT mode showed promising ability to attenuate fibrosis and stricture after esophageal ESD.

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Editorial Board

Publication date: January 2018
Source:International Journal of Psychophysiology, Volume 123





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Musculoskeletal Ultrasound Liberating PRM: A Reinforcement for “Runners”, a Reminder for “Walkers” and the Last Call for “Couch Potatoes”

No abstract available

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Inability to Perform the Repeated Chair Stand Task Predicts Fall-related Injury in Older Primary Care Patients

AbstractObjectiveTo examine whether the chair stand component of the Short Physical Performance Battery (SPPB) predicts fall-related injury among older adult primary care patients.Design2-year longitudinal cohort study of 430 Boston-area primary care patients aged ≥65 years screened to be at risk for mobility decline. The three components of the SPPB (balance time, gait speed, and chair stand time) were measured at baseline. Participants reported incidence of fall-related injuries quarterly for two years. Complementary log-log discrete time hazard models were constructed to examine the hazard of fall-related injury across SPPB scores, adjusting for age, gender, race, Digit Symbol Substitution Test score, and fall history.ResultsParticipants were 68% female and 83% white, with a mean age of 76.6 (SD=7.0). A total of 137 (32%) reported a fall-related injury during the follow-up period. Overall, inability to perform the chair stand task was a significant predictor of fall-related injury (HR [hazard ratio]=2.11, 95% CI=1.23-3.62, p=0.01). Total SPPB score, gait component score, and balance component score were not predictive of fall-related injury.ConclusionInability to perform the repeated chair stand task was associated with increased hazard of an injurious fall over 2 years among a cohort of older adult primary care patients. Objective To examine whether the chair stand component of the Short Physical Performance Battery (SPPB) predicts fall-related injury among older adult primary care patients. Design 2-year longitudinal cohort study of 430 Boston-area primary care patients aged ≥65 years screened to be at risk for mobility decline. The three components of the SPPB (balance time, gait speed, and chair stand time) were measured at baseline. Participants reported incidence of fall-related injuries quarterly for two years. Complementary log-log discrete time hazard models were constructed to examine the hazard of fall-related injury across SPPB scores, adjusting for age, gender, race, Digit Symbol Substitution Test score, and fall history. Results Participants were 68% female and 83% white, with a mean age of 76.6 (SD=7.0). A total of 137 (32%) reported a fall-related injury during the follow-up period. Overall, inability to perform the chair stand task was a significant predictor of fall-related injury (HR [hazard ratio]=2.11, 95% CI=1.23-3.62, p=0.01). Total SPPB score, gait component score, and balance component score were not predictive of fall-related injury. Conclusion Inability to perform the repeated chair stand task was associated with increased hazard of an injurious fall over 2 years among a cohort of older adult primary care patients. Corresponding Author: Cristina Shea, Spaulding Hospital Cambridge, 1575 Cambridge St., Cambridge, MA 02138, Phone: 617-952-6956, Fax: 617-952-6965, sheacristina@gmail.com. Author Disclosures: There are no competing interests or financial benefits to the authors to disclose. This work was supported by the National Institute on Aging (R01 AG032052-03), Eunice Kennedy Shriver National Institute of Child Health and Human Development (1K24HD070966-01), and the National Center for Research Resources in a grant to the Harvard Clinical and Translational Science Center (1 UL1 RR025758-01). The main results of this study have been presented as a poster presentation at the 2017 American Congress of Rehabilitation Medicine conference. This study has not been previously submitted to any journal. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Sonographically Detected Transligamentous Median Nerve Branch

No abstract available

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Copeptin reflects physiological strain during thermal stress

Abstract

Purpose

To prevent heat-related illnesses, guidelines recommend limiting core body temperature (T _c) ≤ 38 °C during thermal stress. Copeptin, a surrogate for arginine vasopressin secretion, could provide useful information about fluid balance, thermal strain and health risks. It was hypothesised that plasma copeptin would rise with dehydration from occupational heat stress, concurrent with sympathoadrenal activation and reduced glomerular filtration, and that these changes would reflect T _c responses.

Methods

Volunteers (n = 15) were recruited from a British Army unit deployed to East Africa. During a simulated combat assault (3.5 h, final ambient temperature 27 °C), T _c was recorded by radiotelemetry to differentiate volunteers with maximum T _c > 38 °C versus ≤ 38 °C. Blood was sampled beforehand and afterwards, for measurement of copeptin, cortisol, free normetanephrine, osmolality and creatinine.

Results

There was a significant (P < 0.05) rise in copeptin from pre- to post-assault (10.0 ± 6.3 vs. 16.7 ± 9.6 pmol L⁻¹, P < 0.001). Although osmolality did not increase, copeptin correlated strongly with osmolality after the exposure (r = 0.70, P = 0.004). In volunteers with maximum T _c > 38 °C (n = 8) vs ≤ 38 °C (n = 7) there were significantly greater elevations in copeptin (10.4 vs. 2.4 pmol L⁻¹) and creatinine (10 vs. 2 μmol L⁻¹), but no differences in cortisol, free normetanephrine or osmolality.

Conclusions

Changes in copeptin reflected T _c response more closely than sympathoadrenal markers or osmolality. Dynamic relationships with tonicity and kidney function may help to explain this finding. As a surrogate for integrated physiological strain during work in a field environment, copeptin assay could inform future measures to prevent heat-related illnesses.

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Thyroid hormones and commonly cited symptoms of overtraining in collegiate female endurance runners

Abstract

Purpose

Overtraining syndrome (OTS) is reported in endurance sports. Thyroid hormones (TH) regulate metabolism, mood, and energy production, and may play a role in OTS of endurance athletes. The purpose of this study was to investigate relationships in TH and symptoms of OTS in track and field endurance runners (ER).

Methods

Sixteen female track and field middle distance (MD; n = 9; age: 20.2 ± 1.5 years; ht: 167.86 ± 5.04 cm; body-mass: 57.97 ± 5.05 kg; VO_2MAX: 53.62 ± 6.04 ml/kg/min) and long distance (LD; n = 7; age: 20.5 ± 1.5 years; ht: 162.48 ± 6.11 cm; body-mass: 56.15 ± 5.99 kg; VO_2MAX: 61.94 ± 3.29 ml/kg/min) ER participated in this descriptive study (15-weeks). Thyroid-stimulating hormone (TSH), triiodothyronine (T ₃), and thyroxine (T ₄), were collected at pre-(PRE) and post-season (POST). A fatigue scale was administered weekly, and percent change (PΔ) in race time (season best vs. championship performance) was calculated. Wilcoxon-sign ranked tests and Spearman's rho correlations were used to determine changes and relationships between TH and performance.

Results

TSH, T ₃ and T ₄ did not change from PRE to POST. The percent change (PΔ) in T ₃ from PRE to POST was correlated with running performance at the end of the season (ρ = − 0.70, p = 0.036). Fatigue at week 12 correlated with running performance at the end of the season (ρ = − 0.74, p = 0.004).

Conclusion

TH may be valuable in assessing the overall training state of ER. TH concentrations change too slowly to be a frequent marker of monitoring OTS, but are related to markers of decreased performance. Monitoring dietary intake, and fatigue may be predictive markers to assess OTS and training status of female ER.

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Effects of recreational football on women’s fitness and health: adaptations and mechanisms

Abstract

The review describes the fitness and health effects of recreational football in women aged 18–65 years. The review documents that 2 × 1 h of recreational football training for 12–16 weeks causes marked improvements in maximal oxygen uptake (5–15%) and myocardial function in women. Moreover, mean arterial blood pressure was shown to decrease by 2–5 mmHg in normotensive women and 6–8 mmHg in hypertensive women. This review also show that short-term (< 4 months) and medium-term (4–16 months) recreational football training has major beneficial impact on metabolic health profile in women, with fat losses of 1–3 kg and improvements in blood lipid profile. Lastly, 2 × 1 h per week of recreational football training for women elevates lower extremity bone mineralisation by 1–5% and whole-body bone mineralization by 1–2% within 4–12-month interventions. These training adaptations are related to the high heart rates, high number of fast runs, and multiple changes of direction and speed occurring during recreational football training for untrained women. In conclusion, regular small-sided football training for women is an intense and versatile type of training that combines elements of high-intensity interval training (HIIT), endurance training and strength training, thereby providing optimal stimuli for cardiovascular, metabolic and musculoskeletal fitness. Recreational football, therefore, seems to be an effective tool for prevention and treatment of lifestyle diseases in young and middle-aged women, including hypertension, type 2 diabetes and osteopenia. Future research should elucidate effects of football training for elderly women, and as treatment and rehabilitation of breast cancer patients and other women patient groups.

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Classical experiments in whole-body metabolism: open-circuit respirometry—diluted flow chamber, hood, or facemask systems

Abstract

For over two centuries, scientists have measured gas exchange in animals and humans and linked this to energy expenditure of the body. The aim of this review is to provide a comprehensive overview of open-circuit diluted flow indirect calorimetry and to help researchers to make the optimal choice for a certain system and its application. A historical perspective shows that 'open circuit diluted flow' is a technique first used in the 19th century and applicable today for room calorimeters, ventilated hood systems, and facemasks. Room calorimeters are a classic example of an open-circuit diluted flow system. The broadly applied ventilated hood calorimeters follow the same principle and can be classified as a derivative of these room calorimeters. The basic principle is that the subject breathes freely in a passing airflow that is fully captured and analyzed. Oxygen and CO₂ concentrations are measured in inlet ambient air and captured outlet air. The airflow, which is adapted depending on the application (e.g., rest versus exercise), is measured. For a room indirect calorimeter, the dilution in the large room volume is also taken into account, and this is the most complex application of this type of calorimeter. Validity of the systems can be tested by alcohol burns, gas infusions and by performing repeated measurements on subjects. Using the latter, the smallest CV (%) was found for repeated VO_2max tests (1.2%) with an SD of approximately 1 kJ min⁻¹. The smallest SD was found for sleeping metabolic rate (0.11 kJ min⁻¹) with a CV (%) of 2.4%.

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New pulmonary hypertension model in conscious dogs to investigate pulmonary-selectivity of acute pharmacological interventions

Abstract

Purpose

Testing of investigational drugs in animal models is a critical step in drug development. Current models of pulmonary hypertension (PH) have limitations. The most relevant outcome parameters such as pulmonary artery pressure (PAP) are measured invasively which requires anesthesia of the animal. We developed a new canine PH model in which pulmonary vasodilators can be characterized in conscious dogs and lung selectivity can be assessed non-invasively.

Methods

Telemetry devices were implanted to measure relevant hemodynamic parameters in conscious dogs. A hypoxic chamber was constructed in which the animals were placed in a conscious state. By reducing the inspired oxygen fraction (FiO₂) to 10%, a hypoxic pulmonary vasoconstriction was induced leading to PH. The PDE-5 inhibitor sildenafil, the current standard of care was compared to atrial natriuretic peptide (ANP).

Results

The new hypoxic chamber provided a stable hypoxic atmosphere during all experiments. The mean PAP under normoxic conditions was 15.8 ± 1.8 mmHg. Hypoxia caused a reliable increase in mean PAP (+ 12.2 ± 3.2 mmHg, p < 0.0001). Both, sildenafil (− 6.8 ± 4.4 mmHg) and ANP (− 6.4 ± 3.8 mmHg) significantly (p < 0.05) decreased PAP. Furthermore sildenafil and ANP showed similar effects on systemic hemodynamics. In subsequent studies, the in vitro effects and gene expression pattern of the two pathways were exemplified.

Conclusions

By combining the hypoxic environment with the telemetric approach, we could successfully establish a new acute PH model. Sildenafil and ANP demonstrated equal effects regarding pulmonary selectivity. This non-invasive model could help to rapidly screen pulmonary vasodilators with decreased animal burden.

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Causal effect of intra-abdominal pressure on maximal voluntary isometric hip extension torque

Abstract

Purpose

Intra-abdominal pressure (IAP) has been recently shown to be associated specifically with maximal voluntary isometric contraction (MVC) torque of hip extension, although the causal relationship remains unclear. The present study aimed to elucidate whether IAP has a causal effect on hip extension MVC torque.

Methods

IAP during hip extension MVC was changed by controlling the lung volume (i.e., depth of inspiration). Twelve healthy males conducted MVCs of hip extension during breath-hold at full inspiration (inspiratory condition) or expiration (expiratory condition), or during normal breath-hold (normal condition). IAP during MVCs was measured a pressure transducer placed in the rectum.

Results

The IAP during hip extension MVC was significantly higher in inspiratory condition (132.0 ± 46.1 mmHg) than in the other two conditions and also higher in normal condition (104.6 ± 35.9 mmHg) than in expiratory condition (77.0 ± 39.1 mmHg). The hip extension MVC torque was significantly higher in inspiratory condition (297.7 ± 82.7 N m) than in expiratory condition (266.4 ± 84.5 N m). In each condition, the hip extension MVC torque correlated with IAP during the MVC task.

Conclusion

The current results suggest that IAP has a positive causal effect on hip extension MVC torque and that a sufficient increase in IAP directly leads to an enhancement of hip extension MVC torque.

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Obstructive sleep apnoea in adults: peri-operative considerationsA narrative review

Obstructive sleep apnoea (OSA) is a common breathing disorder of sleep with a prevalence increasing in parallel with the worldwide rise in obesity. Alterations in sleep duration and architecture, hypersomnolence, abnormal gas exchange and also associated comorbidities may all feature in affected patients. The peri-operative period poses a special challenge for surgical patients with OSA who are often undiagnosed, and are at an increased risk for complications including pulmonary and cardiovascular, during that time. In order to ensure the best peri-operative management, anaesthetists caring for these patients should have a thorough understanding of the disorder, and be aware of the individual's peri-operative risk constellation, which depends on the severity and phenotype of OSA, the invasiveness of the surgical procedure, anaesthesia and also the requirement for postoperative opioids. The objective of this review is to educate clinicians in the epidemiology, pathogenesis and diagnosis of OSA in adults and also to highlight specific tasks in the preoperative assessment, namely to select a suitable intra-operative anaesthesia regimen, and manage the extent and duration of postoperative care to facilitate the best peri-operative outcome. Correspondence to Martin Roesslein, MD, University Medical Center, Department of Anesthesiology and Critical Care Medicine, Hugstetter Str. 55, D - 79106 Freiburg, Germany Tel: +49 761 270 23 470; fax: +49 761 270 23 930; e-mail: martin.roesslein@uniklinik-freiburg.de © 2018 European Society of Anaesthesiology

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An historical examination of nurse anaesthesia practice in the United States and other Group of 7 countries

Many factors determine whether nurses, physicians or both administer anaesthesia in any country. We examined the status of nurse-administered anaesthesia in the Group of 7 nations and explored how historical factors, mixing global and local contexts (such as professional relations, medical and nursing education, social status of nurses, demographics and World Wars in the 20th century), help explain observed differences. Nearly equal numbers of physicians and nurses are currently engaged in the delivery of anaesthesia care in the United States but, remarkably, although the introduction or re-introduction of nurse anaesthesia in the 20th century was attempted in all the other Group of 7 countries (except Japan), it has been successful only in France because of the cooperation with the United States during World War II. Correspondence to Sukumar P. Desai, MD, Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, USA; Brigham and Women's Hospital, Boston, Massachusetts, USA E-mail: sdesai@bwh.harvard.edu © 2018 European Society of Anaesthesiology

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Self-confidence and level of knowledge after cardiopulmonary resuscitation training in 14 to 18-year-old schoolchildren: A randomised-interventional controlled prospective study in secondary schools in Germany

BACKGROUND Education of schoolchildren in cardiopulmonary resuscitation (CPR) is a strategic goal for improvement of bystander CPR in society. OBJECTIVE(S) The primary objective was to analyse the impact of CPR training on the resuscitation knowledge and self-confidence of secondary schoolchildren. In addition, independent predictors of improved CPR knowledge and self-confidence were investigated. DESIGN Prospective, randomised-interventional controlled study. SETTING Four secondary schools in Germany. PARTICIPANTS Four hundred and twenty-four schoolchildren aged from 14 to 18 years were included into the study. Fifty-one percent were female, and 33% had an immigrant background. INTERVENTION The intervention group received a 90-min CPR training session, whereas controls had no intervention. Levels of knowledge and self-confidence in initiating CPR were analysed by a study questionnaire before (t0), 90 min after (t1) and 6 months after training (t2). MAIN OUTCOME MEASURES Based on the evaluation of study questionnaires, the primary endpoint was to determine the development of resuscitation knowledge and self-confidence in initiating cardiopulmonary resuscitation at survey time-points t0, t1 and t2. RESULTS Schoolchildren in the intervention group (n=207) showed a significantly higher level of knowledge (P 

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When Lightning Strikes Twice

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Exploring Gut Microbiota Composition as an Indicator of Clinical Response to Dietary FODMAP Restriction in Patients with Irritable Bowel Syndrome

Abstract

Background

A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) may relieve symptoms of irritable bowel syndrome (IBS). However, nutritional counseling is resource-demanding and not all patients will benefit.

Aims

To explore whether gut microbial composition may identify symptom response to a low-FODMAP diet in patients with IBS.

Methods

Patients were recruited consecutively to participate in a 4-week FODMAP-restricted diet. Response to diet was defined as ≥ 50% decrease in IBS symptom severity scores (IBS-SSS) compared to baseline. Fecal microbiota were analyzed by a commercially available method (the GA-map™ Dysbiosis Test), assessing 54 bacterial markers targeting more than 300 bacteria at different taxonomic levels.

Results

Sixty-one patients (54 F; 7 M) were included: 32 (29 F; 3 M) classified as responders and 29 (25 F; 4 M) as non-responders. Ten of the 54 bacterial markers differed significantly between responders and non-responders. Based on median values (used as cutoff) of responders for these 10 bacterial markers, we constructed a Response Index (RI): Each patient was given a point when the value for each selected bacterial marker differed from the cutoff. These points were summed up, giving an RI from 0 to 10. Patients with RI > 3 were 5 times more likely to respond (OR = 5.05, 95% CI [1.58; 16.10]), and the probability to respond was 83.4%, 95% CI [61.2–94%].

Conclusions

Gut microbial composition, assessed by using a new RI, may constitute a tool to identify patients that are likely to respond to dietary FODMAP restriction.

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No Effect of Muscle Stretching within a Full, Dynamic Warm-up on Athletic Performance

ABSTRACTPurposeTo examine the effects of static and dynamic stretching routines performed as part of a comprehensive warm-up on flexibility and sprint running, jumping and change of direction tests in team sport athletes.MethodsA randomized, controlled, cross-over study design with experimenter blinding was conducted. On separate days, 20 male team sport athletes completed a comprehensive warm-up routine. After a low-intensity warm-up a 5-s static stretch (5S), 30-s static stretch (30S; 3×10-s stretches), 5-repetition (per muscle group) dynamic stretch (DYN) or no stretch (NS) protocol was completed; stretches were done on 7 lower body and 2 upper body regions. This was followed by test-specific practice progressing to maximum intensity. A comprehensive test battery assessing intervention effect expectations as well as flexibility, vertical jump, sprint running and change of direction outcomes was then completed in a random order.RESULTSThere were no effects of stretch condition on test performances. Before the study, 18/20 participants nominated DYN as the most likely to improve performance and 15/20 nominated NS as least likely. Immediately before testing, NS was rated less 'effective' (4.0±2.2 on 10-point scale) than 5S, 30S and DYN (5.3-6.4). Nonetheless, these ratings were not related to test performances.CONCLUSIONParticipants felt they were more likely to perform well when stretching was performed as part of the warm-up, irrespective of stretch type. However, no effect of muscle stretching was observed on flexibility and physical function compared to no stretching. Based on the current evidence, the inclusion of short durations of either static or dynamic stretching is unlikely to affect sprint running, jumping or change of direction performance when performed as part of a comprehensive physical preparation routine. Purpose To examine the effects of static and dynamic stretching routines performed as part of a comprehensive warm-up on flexibility and sprint running, jumping and change of direction tests in team sport athletes. Methods A randomized, controlled, cross-over study design with experimenter blinding was conducted. On separate days, 20 male team sport athletes completed a comprehensive warm-up routine. After a low-intensity warm-up a 5-s static stretch (5S), 30-s static stretch (30S; 3×10-s stretches), 5-repetition (per muscle group) dynamic stretch (DYN) or no stretch (NS) protocol was completed; stretches were done on 7 lower body and 2 upper body regions. This was followed by test-specific practice progressing to maximum intensity. A comprehensive test battery assessing intervention effect expectations as well as flexibility, vertical jump, sprint running and change of direction outcomes was then completed in a random order. RESULTS There were no effects of stretch condition on test performances. Before the study, 18/20 participants nominated DYN as the most likely to improve performance and 15/20 nominated NS as least likely. Immediately before testing, NS was rated less 'effective' (4.0±2.2 on 10-point scale) than 5S, 30S and DYN (5.3-6.4). Nonetheless, these ratings were not related to test performances. CONCLUSION Participants felt they were more likely to perform well when stretching was performed as part of the warm-up, irrespective of stretch type. However, no effect of muscle stretching was observed on flexibility and physical function compared to no stretching. Based on the current evidence, the inclusion of short durations of either static or dynamic stretching is unlikely to affect sprint running, jumping or change of direction performance when performed as part of a comprehensive physical preparation routine. Corresponding author: Anthony J. Blazevich, School of Medical and Health Sciences and Centre for Exercise and Sports Science Research, Edith Cowan University, 270 Joondalup Drive, Joondalup, Australia 6027 (a.blazevich@ecu.edu.au). The authors declare no conflicts of interest. No external funding was received for this research. The results of the present study do not constitute endorsement by the American College of Sports Medicine. The authors declare that the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 19 December 2017 © 2018 American College of Sports Medicine

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Sham Feeding with Bacon Does Not Alter Transit Time or Complete Examination Rate During Small Bowel Capsule Endoscopy

Abstract

Background

During capsule endoscopy (CE) studies, the complete examination rate (CER) can be increased by prolonging capsule battery life or reducing gastric transit time (GTT) and/or small bowel transit time (SBTT). However, despite enhanced battery life, 10% of studies remain incomplete. Previously studied interventions to reduce SBTT and enhance CER have produced conflicting results. We hypothesize that this may be a consequence of an insufficiently potent stimulus of small bowel motility.

Aims

To examine whether potent stimulation of the cephalic response of digestion during small bowel CE reduces GTT and/or SBTT and thus increases the CER.

Methods

A single-blind randomized trial was performed to evaluate the effect of bacon sham feeding on GTT, SBTT and CER.

Results

Baseline characteristics were similar between 63 sham fed patients and 59 controls. The median GTT was 17 min (9–65) in the bacon group and 25 min (14–55) in the control group. The median SBTT was 199 min (119–316) and 222 min (151–287), respectively. Cox proportional hazards model demonstrated no significant difference between groups for GTT (rate ratio 1.03, 95% CI 0.71–1.51, P = 0.87) or SBTT (rate ratio 1.02, 95% CI 0.70–1.49, P = 0.93). Although the taste of bacon was considered favorably by 72% of participants, taste did not correlate with GTT (ρ = 0.03, P = 0.83) or SBTT (ρ = − 0.115, P = 0.33). The CER was 91 and 95% in the bacon and control groups, respectively (P = 0.35).

Conclusion

Bacon sham feeding has no effect on GTT, SBTT or CER and cannot be recommended in clinical practice.

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Improving the Quality of Inpatient Bowel Preparation for Colonoscopies

Abstract

Background

Hospitalized patients completing bowel preparation for colonoscopy typically have preparations of poorer quality when compared to outpatient populations.

Aims

Our study aimed to evaluate the effectiveness of a performance improvement program in improving colonoscopy preparation for an inpatient population.

Methods

We identified a cohort of adult patients (n = 641) undergoing an inpatient colonoscopy during a 12-month period at an academic medical center and compared a multifactor intervention group to a historical baseline group. During this 12-month period, a performance improvement program including use of a dedicated gastrointestinal nurse facilitator, implementation of standardized order sets, and introduction of split bowel preparations in the inpatient setting was made available to the cohort group.

Results

The primary outcome was quality of bowel preparation for colonoscopy as rated by endoscopists using the modified Aronchick scale. When comparing the baseline group to the intervention group, the rate of acceptable preparations, characterized as excellent, good, or adequate, increased from 69.9 to 78.9%, which was statistically significant (p < 0.001).

Conclusions

A comprehensive performance improvement program improved the quality of colonoscopy preparation among inpatients. The use of a dedicated gastrointestinal nurse facilitator, implementation of standardized order sets, and introduction of split bowel preparations are recommended in the inpatient setting for an effective bowel preparation.

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Bilateral balanced occlusion compared to other occlusal schemes in complete dentures: A systematic review

Summary

No consensus has been reached regarding the best occlusal scheme for making complete dentures. Thus, the purpose of this systematic review was to compare bilateral balanced occlusion (BBO) with other occlusal schemes (canine guidance, lingualized occlusion, and zero degree) in complete dentures. The schemes were compared in terms of quality of life/satisfaction and masticatory performance. Two independent reviewers performed a comprehensive search of studies published in or before October 2017 using the PubMed/MEDLINE, Scopus, and Cochrane Library databases. The search was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The focused question was: "In conventional complete denture, is bilateral balanced occlusion better than lingualized occlusion, canine guidance and zero degree in terms of quality of life, patient satisfaction and masticatory performance?". Seventeen studies were selected for analysis. In total, there were 492 patients with a mean age of 64.78 years and a mean follow-up duration of 2.96 months (range: 1–6 months). All studies compared BBO with the other occlusal schemes. Eleven studies evaluated the influence of the occlusal scheme designs on quality of life and satisfaction and eight studies evaluated masticatory performance and muscle activity between BBO and the other occlusion schemes. The present systematic review indicated that BBO does not confer better quality of life/satisfaction or masticatory performance and muscle activity. Thus, LO can be considered a predictable occlusal scheme for complete dentures in terms of quality of life/satisfaction, and masticatory performance, while CG can be used to reduce muscular activity.

This article is protected by copyright. All rights reserved.

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Isolated breast metastasis from gastric cancer in a male patient

Abstract

A 72-year-old man underwent total gastrectomy for gastric cancer (por2, T3, N2, Stage IIIA). Eleven courses of postoperative chemotherapy with TS-1 (tegafur/gimeracil/oteracil) were administered. Five months after surgery, the serum carcinoembryonic antigen value was slightly elevated. However, computed tomography did not reveal any metastatic lesions in other organs. Two years after surgery, the patient felt a mass in the left mammary. A 2-cm tumor was palpable in the central portion of the breast. Ultrasonography revealed a hypoechoic tumor, which was Class 3 on aspiration biopsy cytological examination. No mass was detected on positron emission tomography–computed tomography. The mammary gland tumor increased in size to 3 cm, and a core needle biopsy procedure was performed. Histological examination findings revealed breast metastasis of gastric cancer. No other recurrence was found, and radical mastectomy was performed 2 years and 5 months after gastrectomy. Immunohistological analysis of the resected material confirmed breast metastasis of the gastric cancer. Two courses of TS-1 + cisplatin were administered, but this treatment was subsequently terminated because the patient experienced Grade 3 diarrhea and neutropenia. Three years and 1 month after the gastrectomy, the tumor recurred in the pelvic area. Chemotherapy and radiation therapy were performed, but the patient's overall condition became progressively worse, and he died 3 years and 9 months after gastrectomy.

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In Appreciation of the Maternal and Child Health Journal’s Peer Reviewers, 2017

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Innovations in Maternal and Child Health: Pairing Undergraduate and Graduate Maternal and Child Health Students in Summer Practica in State Title V Agencies

Abstract

Objective As part of the National MCH Workforce Development Center, an innovative internship program placed MCH undergraduate and graduate students in summer practica in state Title V agencies. Graduate student mentoring of undergraduates and leadership and professional development training and support are key features of the program. The objective of this paper is to report on the results of the evaluation of the MCH Paired Practica Program in its pilot years, 2014–2016. Methods Students completed pre and post internship questionnaires which included closed as well as open-ended questions. In addition, the Title V state health agency preceptors completed a questionnaire at the end of each summer. Results Over the 3-year pilot project, a total of 17 teams participated. Students were from 6 of the 13 graduate Centers of Excellence in MCH programs in Schools of Public Health and two undergraduate MCH Pipeline Programs. There were 11 participating states. After the practicum experience, there was a significant increase in students' confidence in a number of measures related to working in complex, dynamic environments and in their ability to contribute to improvements in MCH population health. Students reported having more confidence in their ability to function effectively as an informal/formal MCH leader (p = 0.02), more confidence in their ability to contribute to improvements in MCH population health (p = 0.04), and being more prepared to enter the workforce after the practicum experience (p = 0.07), although there was no significant change in students' (n = 22) interest in seeking a job in a Title V agency or a community based organization with a MCH focus. Nearly 60% of the students did state at the posttest that they would likely seek additional education in MCH. Overall, the Title V preceptors (n = 14) were very positive about the program although in some instances there was less confidence in the knowledge and skills of the undergraduate students. Conclusion The MCH Paired Practica Program is a unique effort to go beyond the academic training of undergraduate and graduate MCH students to provide them with direct exposure to the field, as well as leadership, mentorship, and professional development training. While some challenges emerged related to differences in skills between undergraduates and graduate MCH students, participating students demonstrated clear improvements in their leadership skills including increased confidence in their ability to take initiative, provide opinions and feedback, to function informally or formally as leaders, and to contribute to improvements in MCH population health.

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Bone augmentation followed by implant surgery in the edentulous mandible: a systematic review

Abstract

Introduction

Long-standing loss of natural teeth in the mandible can lead to severe jaw atrophy and even mandibular fracture. There is no consensus on the best preprosthetic surgical treatment to reconstruct the atrophic edentulous mandible. The purpose of this review is to provide an overview of the existing literature and to give an evidence-based recommendation for bone grafting and future research.

Materials and methods

This systematic review was conducted according to the PRISMA statement. A literature search was performed in online databases Pubmed and Cochrane library for articles published between January 1980 and September 2017. The search was conducted using Medical Subject Heading (MeSH) terms: alveolar ridge augmentation; mouth, edentulous and mandible. Eligible articles were included according to in- and exclusion criteria and assessed on quality. Dental implant survival and bone stability are the primary outcomes. Secondary outcomes were complications.

Results

Twenty-four text articles matched the criteria and were included. Eleven articles were assessed to be of adequate quality for analysis. Graft stability seems to be higher in vertical distraction and tent-pole grafting but as the dental implant survival is high (91.7% or higher) regardless of the procedure used for bone augmentation, this is of no clinical relevance.

Conclusion

The survival rate of dental implants is high, regardless of the bone augmentation procedure used. High quality clinical trials are needed to support the current evidence and guidelines on pre-implant bone grafting. Reporting of future research should include proper baseline characteristics and treatment description, as well as uniform outcome rendering.

This article is protected by copyright. All rights reserved.

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Genome-wide meta-analyses identifies novel taxane-induced peripheral neuropathy-associated loci

Objective Taxane containing chemotherapy extends survival for breast cancer patients. However, taxane-induced peripheral neuropathy (TIPN) cannot be predicted, prevented or effectively treated. Using genome-wide analyses, we sought to identify common risk variants for TIPN. Patients and methods Women with high-risk breast cancer enrolled in SWOG 0221 were genotyped using the Illumina 1M chip. Genome-wide analyses were performed in relation to ≥grade 3 Common Terminology Criteria for Adverse Events (CTCAE) neuropathy in European and African Americans. Data were meta-analyzed with GW associations of CTCAE ≥grade 3 versus

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Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease

Objectives Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is particularly common in the Cavalier King Charles Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin-converting enzyme inhibitors (ACE-I). We have previously identified a canine ACE gene polymorphism associated with a decrease in angiotensin-converting enzyme (ACE) activity. The aim of this study was to evaluate for the prevalence of the ACE polymorphism in CKCS with mitral valve disease and to determine whether the presence of the polymorphism is associated with alterations in ACE activity at different stages of cardiac disease. Methods Seventy-three dogs with a diagnosis of mitral valve disease were evaluated and a blood sample was drawn for ACE polymorphism genotyping and ACE activity measurement. Results Forty-three dogs were homozygous for the ACE polymorphism; five were heterozygous and 25 were homozygous wild type. The mean age and the median severity of disease were not different for dogs with the polymorphism and dogs with the wild-type sequence. The median baseline ACE activity was significantly lower for the ACE polymorphism (27.0 U/l) than the wild-type sequence dogs (31.0 U/l) (P=0.02). Dogs with more severe disease and the ACE polymorphism had significantly lower levels of ACE activity than dogs with the wild-type sequence (P=0.03). Conclusion The CKCS appears to have a high prevalence of the ACE variant. Dogs with the ACE variant had lower levels of ACE activity even in more advanced mitral valve disease than dogs without the variant. The clinical significance of this finding and its impact on the need for ACE-I in dogs with the polymorphism and heart disease deserves further study.

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Influence of donor liver CYP3A4*20 loss-of-function genotype on tacrolimus pharmacokinetics in transplanted patients

Objective Cytochrome P450 3A4 (CYP3A4) metabolizes about half of all drugs on the market; however, the impact of CYP3A4 loss-of-function variants on drug exposures remains poorly characterized. Here, we report the effect of the CYP3A4*20 frameshift allele in two Spanish liver transplant patients treated with tacrolimus. Patients and methods A series of 90 transplanted patients (with DNA available for 89 of the recipients and 76 of the liver donors) treated with tacrolimus were included in the study. The genotypes of liver donors and of the recipients for CYP3A4*20 (rs67666821), CYP3A4*22 (rs35599367) and CYP3A5*3 (rs776746) were compared with weight-adjusted tacrolimus dose (D), tacrolimus trough concentration (C0), and dose-adjusted tacrolimus trough concentrations (C0/D) using the Mann–Whitney U-nonparametric test. Results The CYP3A4*20 allele was detected in two of the liver donors. This genotype yielded at all times higher C0/D (2.6-fold, average) than intermediate CYP3A metabolizers (CYP3A4*1/*1 and CYP3A5*3/*3) (P=0.045, 90 days after transplantation). CYP3A4*22 carriers showed a 1.9-fold average increase in C0/D (P=0.047, 0.025, and 0.053; at days 7, 14, and 30 after transplantation, respectively) compared with intermediate metabolizers. In terms of recipients' genotype, CYP3A5*1 had reduced (P=0.025) and CYP3A4*22 increased C0/D (P=0.056) 7 days after transplantation. The incidence of biopsy-proven acute rejection was 0, 12, and 20% for livers with poor, intermediate, and extensive CYP3A-metabolizing capacity, respectively (P=0.0995). Conclusion This first description of CYP3A4*20 null genotype in liver-transplanted patients, supports the relevance of CYP3A genotyping in tacrolimus therapy.

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Cost-effectiveness analysis of HLA-B*58: 01 genetic testing before initiation of allopurinol therapy to prevent allopurinol-induced Stevens–Johnson syndrome/toxic epidermal necrolysis in a Malaysian population

Objective Studies found a strong association between allopurinol-induced Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and the HLA-B*58:01 allele. HLA-B*58:01 screening-guided therapy may mitigate the risk of allopurinol-induced SJS/TEN. This study aimed to evaluate the cost-effectiveness of HLA-B*58:01 screening before allopurinol therapy initiation compared with the current practice of no screening for Malaysian patients with chronic gout in whom a hypouricemic agent is indicated. Methods This cost-effectiveness analysis adopted a societal perspective with a lifetime horizon. A decision tree model coupled with Markov models were developed to estimate the costs and outcomes, represented by quality-adjusted life years (QALYs) gained, of three treatment strategies: (a) current practice (allopurinol initiation without HLA-B*58:01 screening); (b) HLA-B*58:01 screening before allopurinol initiation; and (c) alternative treatment (probenecid) without HLA-B*58:01 screening. The model was populated with data from literature review, meta-analysis, and published government documents. Cost values were adjusted for the year 2016, with costs and health outcomes discounted at 3% per annum. A series of sensitivity analysis including probabilistic sensitivity analysis were carried out to determine the robustness of the findings. Results Both HLA-B*58:01 screening and probenecid prescribing were dominated by current practice. Compared with current practice, HLA-B*58:01 screening resulted in 0.252 QALYs loss per patient at an additional cost of USD 322, whereas probenecid prescribing resulted in 1.928 QALYs loss per patient at an additional cost of USD 2203. One SJS/TEN case would be avoided for every 556 patients screened. At the cost-effectiveness threshold of USD 8695 per QALY, the probability of current practice being the best choice is 99.9%, in contrast with 0.1 and 0% in HLA-B*58:01 screening and probenecid prescribing, respectively. This is because of the low incidence of allopurinol-induced SJS/TEN in Malaysia and the lower efficacy of probenecid compared with allopurinol in gout control. Conclusion This analysis showed that HLA-B*58:01 genetic testing before allopurinol initiation is unlikely to be a cost-effective intervention in Malaysia.

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