Effectiveness of a quality improvement collaborative in reducing time to surgery for patients requiring emergency cholecystectomy.

Background: Acute gallstone disease is a high-volume emergency general surgery presentation with wide variations in the quality of care provided across the UK. This controlled cohort evaluation assessed whether participation in a quality improvement collaborative approach reduced time to surgery for patients with acute gallstone disease to fewer than 8 days from presentation, in line with national guidance. Methods: Patients admitted to hospital with acute biliary conditions in England and Wales between 1 April 2014 and 31 December 2017 were identified from Hospital Episode Statistics data. Time series of quarterly activity were produced for the Cholecystectomy Quality Improvement Collaborative (Chole-QuIC) and all other acute National Health Service hospitals (control group). A negative binomial regression model was used to compare the proportion of patients having surgery within 8 days in the baseline and intervention periods. Results: Of 13 sites invited to join Chole-QuIC, 12 participated throughout the collaborative, which ran from October 2016 to January 2018. Of 7944 admissions, 1160 patients had a cholecystectomy within 8 days of admission, a significant improvement (P < 0·050) from baseline performance. This represented a relative change of 1·56 (95 per cent c.i. 1·38 to 1·75), compared with 1·08 for the control group. At the individual site level, eight of the 12 Chole-QuIC sites showed a significant improvement (P < 0·050), with four sites increasing their 8-day surgery rate to over 20 per cent of all emergency admissions, well above the mean of 15·3 per cent for control hospitals. Conclusion: A surgeon-led quality improvement collaborative approach improved care for patients requiring emergency cholecystectomy.

Antecedentes: La patología biliar aguda litiásica es una de las urgencias con más volumen de casos en cirugía general, con amplias variaciones en la calidad de la atención prestada en todo el Reino Unido. En este estudio de cohortes controlado se valoró si la participación en un enfoque colaborativo de mejora de la calidad disminuía el tiempo hasta la cirugía en pacientes con patología biliar aguda litiásica a menos de 8 días desde la presentación, de acuerdo con la guía nacional. Métodos: Se identificó a los pacientes que precisaron un ingreso hospitalario por patología biliar aguda en Inglaterra y Gales, del 1 de abril de 2014 al 31 de diciembre de 2017, a partir de datos de las estadísticas de episodios hospitalarios. Se crearon series temporales de actividad trimestral para Chole­QuIC y para todos los demás hospitales de agudos del NHS (grupo control). Se utilizó un modelo de regresión binomial negativa para comparar la proporción de pacientes sometidos a cirugía dentro de los primeros 8 días en los periodos basal y de intervención. Resultados: De los 13 sitios invitados a unirse a Chole­QuIC, 12 participaron durante toda la colaboración, que se desarrolló entre octubre de 2016 y enero de 2018. De los 7.944 ingresos, en 1.160 pacientes se realizó la colecistectomía dentro de los 8 días posteriores a su ingreso, una mejora significativa (P < 0,05) en comparación con el periodo previo a la intervención. Esto representó un cambio relativo de 1,56 (i.c. del 95%: 1,38 a 1,75) en comparación con 1,08 para el grupo de control. A nivel de cada uno de los hospitales, ocho de los 12 centros Chole­QuIC presentaron una mejora significativa (P < 0,05), y en cuatro de ellos el porcentaje de cirugía en 8 días aumentó a más del 20% de todos los ingresos urgentes, muy por encima del promedio de 15,3% para hospitales de control. Conclusión: Un enfoque colaborativo de mejora de la calidad dirigido por el cirujano mejoró la atención a los pacientes que precisan una colecistectomía urgente.

Correction to: Improving care at scale: process evaluation of a multi-component quality improvement intervention to reduce mortality after emergency abdominal surgery (EPOCH trial).

Following the publication of this article [1], the authors reported a number of errors which are given below.

Improving care at scale: process evaluation of a multi-component quality improvement intervention to reduce mortality after emergency abdominal surgery (EPOCH trial).

BACKGROUND: Improving the quality and safety of perioperative care is a global priority. The Enhanced Peri-Operative Care for High-risk patients (EPOCH) trial was a stepped-wedge cluster randomised trial of a quality improvement (QI) programme to improve 90-day survival for patients undergoing emergency abdominal surgery in 93 hospitals in the UK National Health Service. METHODS: The aim of this process evaluation is to describe how the EPOCH intervention was planned, delivered and received, at both cluster and local hospital levels. The QI programme comprised of two interventions: a care pathway and a QI intervention to aid pathway implementation, focussed on stakeholder engagement, QI teamwork, data analysis and feedback and applying the model for improvement. Face-to-face training and online resources were provided to support senior clinicians in each hospital (QI leads) to lead improvement. For this evaluation, we collated programme activity data, administered an exit questionnaire to QI leads and collected ethnographic data in six hospitals. Qualitative data were analysed with thematic or comparative analysis; quantitative data were analysed using descriptive statistics. RESULTS: The EPOCH trial did not demonstrate any improvement in survival or length of hospital stay. Whilst the QI programme was delivered as planned at the cluster level, self-assessed intervention fidelity at the hospital level was variable. Seventy-seven of 93 hospitals responded to the exit questionnaire (60 from a single QI lead response on behalf of the team); 33 respondents described following the QI intervention closely (35%) and there were only 11 of 37 care pathway processes that > 50% of respondents reported attempting to improve. Analysis of qualitative data suggests QI leads were often attempting to deliver the intervention in challenging contexts: the social aspects of change such as engaging colleagues were identified as important but often difficult and clinicians frequently attempted to lead change with limited time or organisational resources. CONCLUSIONS: Significant organisational challenges faced by QI leads shaped their choice of pathway components to focus on and implementation approaches taken. Adaptation causing loss of intervention fidelity was therefore due to rational choices made by those implementing change within constrained contexts. Future large-scale QI programmes will need to focus on dedicating local time and resources to improvement as well as on training to develop QI capabilities. EPOCH TRIAL REGISTRATION: ISRCTN80682973 https://doi.org/10.1186/ISRCTN80682973 Registered 27 February 2014 and Lancet protocol 13PRT/7655.

Segmented interlocking nail: an in vivo evaluation of a novel humeral osteotomy fixation device in a caprine model.

OBJECTIVES: To describe a novel humeral fixation device, the insertion technique, healing of humeral osteotomies, and clinical outcomes in a caprine model over a six month period. METHODS: Fourteen mature female Boer/Nubian cross goats with a mean body weight of 50.7 kg were implanted with a proprietary segmented interlocking nail (SILN) in both humeri. Each goat had one humerus randomly selected for mid-diaphyseal osteotomy. RESULTS: Immediately after surgery all but one goat was able to stand, although none of the goats were weight bearing on the osteotomy limb. During the six month study, clinical lameness was always associated with the osteotomy limb. One month after surgery, lameness for twelve of the goats was grade 2/5 or better. At three months, 11 of the 14 did not exhibit any signs of lameness. On radiographic images, notable malalignment of the osteotomy was observed, although all osteotomies went to bone union. CLINICAL SIGNIFICANCE: The results of this study suggest that despite misalignment, the SILN maintained adequate osteotomy fixation to achieve bone union in the research model studied, with reduced morbidity and early return to function with bilateral implantation. The SILN used in this study allowed intramedullary fixation of humeral diaphyseal osteotomies with a limited and safe surgical approach.

Analysis of optical damage mechanisms in hollow-core waveguides delivering nanosecond pulses from a Q-switched Nd:YAG laser.

Hollow-core waveguides consisting of a glass capillary tube with an internal reflective coating are capable of delivering pulse energies of tens of millijoules with improved focusability compared to step index fibers of similar core diameter. We demonstrate the capability of these fibers to deliver high-power Q-switched pulses at the fundamental (1064 nm), second (532 nm), and third (355 nm) harmonics of a Nd:YAG laser, both in terms of peak power and beam quality delivered. In terms of peak power delivery, the primary limitation is the occurrence of bend-induced optical damage to the reflective coating. The damage mechanism and the influential factors are analyzed, in particular, the dependence upon the number of guided modes, core diameter, coating thicknesses, and input polarization alignment.

5'-aminoimidazole-4-carboxyamide-ribonucleoside-activated glucose transport is not prevented by nitric oxide synthase inhibition in rat isolated skeletal muscle.

1. The nucleoside intermediate 5'-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR) activates skeletal muscle AMP-activated protein kinase (AMPK) and increases glucose uptake. The AMPK phosphorylates neuronal nitric oxide synthase (nNOS)mu in skeletal muscle fibres. There is evidence that both AMPK and nNOSmu may be involved in the regulation of contraction-stimulated glucose uptake. 2. We examined whether both AICAR- and contraction-stimulated glucose uptake were mediated by NOS in rat skeletal muscle. 3. Rat isolated epitrochlearis muscles were subjected in vitro to electrically stimulated contractions for 10 min and/or incubated in the presence or absence of AICAR (2 mmol/L) or the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA; 100 micromol/L). 4. Muscle contraction significantly (P < 0.05) altered the metabolic profile of the muscle. In contrast, AICAR and L-NMMA had no effect on the metabolic profile of the muscle, except that AICAR increased muscle 5'-aminoimidazole-4-carboxyamide-ribonucleotide (ZMP) and AICAR content. Nitric oxide synthase inhibition caused a small but significant (P < 0.05) reduction in basal 3-O-methylglucose transport, which was observed in all treatments. 5'-Aminoimidazole-4-carboxyamide-ribonucleoside significantly increased (P < 0.05) glucose transport above basal, with NOS inhibition decreasing this slightly (increased by 209% above basal compared with 184% above basal with NOS inhibition). Contraction significantly increased glucose transport above basal, with NOS inhibition substantially reducing this (107% increase vs 31% increase). 5'-Aminoimidazole-4-carboxyamide-ribonucleoside plus contraction in combination were not additive on glucose transport. 5. These results suggest that NO plays a role in basal glucose uptake and may regulate contraction-stimulated glucose uptake. However, NOS/nitric oxide do not appear to be signalling intermediates in AICAR-stimulated skeletal muscle glucose uptake.

Progressive increase in human skeletal muscle AMPKalpha2 activity and ACC phosphorylation during exercise.

The effect of prolonged moderate-intensity exercise on human skeletal muscle AMP-activated protein kinase (AMPK)alpha1 and -alpha2 activity and acetyl-CoA carboxylase (ACCbeta) and neuronal nitric oxide synthase (nNOSmu) phosphorylation was investigated. Seven active healthy individuals cycled for 30 min at a workload requiring 62.8 +/- 1.3% of peak O(2) consumption (VO(2 peak)) with muscle biopsies obtained from the vastus lateralis at rest and at 5 and 30 min of exercise. AMPKalpha1 activity was not altered by exercise; however, AMPKalpha2 activity was significantly (P < 0.05) elevated after 5 min (approximately 2-fold), and further elevated (P < 0.05) after 30 min (approximately 3-fold) of exercise. ACCbeta phosphorylation was increased (P < 0.05) after 5 min (approximately 18-fold compared with rest) and increased (P < 0.05) further after 30 min of exercise (approximately 36-fold compared with rest). Increases in AMPKalpha2 activity were significantly correlated with both increases in ACCbeta phosphorylation and reductions in muscle glycogen content. Fat oxidation tended (P = 0.058) to increase progressively during exercise. Muscle creatine phosphate was lower (P < 0.05), and muscle creatine, calculated free AMP, and free AMP-to-ATP ratio were higher (P < 0.05) at both 5 and 30 min of exercise compared with those at rest. At 30 min of exercise, the values of these metabolites were not significantly different from those at 5 min of exercise. Phosphorylation of nNOSmu was variable, and despite the mean doubling with exercise, statistically significance was not achieved (P = 0.304). Western blots indicated that AMPKapproximately 2 was associated with both nNOSmu and ACCbeta consistent with them both being substrates of AMPKalpha2 in vivo. In conclusion, AMPKalpha2 activity and ACCbeta phosphorylation increase progressively during moderate exercise at approximately 60% of VO(2 peak) in humans, with these responses more closely coupled to muscle glycogen content than muscle AMP/ATP ratio.

Stimulus characteristics within directives: effects on accuracy of task completion.

Three experiments were conducted in an outpatient setting with young children who had been referred for treatment of noncompliant behavior and who had coexisting receptive language or receptive vocabulary difficulties. Experiment 1 studied differential responding of the participants to a brief hierarchical directive analysis (least-to-most complex stimulus prompts) to identify directives that functioned as discriminative stimuli for accurate responding. Experiment 1 identified distinct patterns of accurate responding relative to manipulation of directive stimulus characteristics. Experiment 2 demonstrated that directives identified as effective or ineffective in obtaining stimulus control of accurate responding during Experiment 1 continued to control accurate responding across play activities and academic tasks. Experiment 3 probed effects of the interaction between the type of directive (effective vs. ineffective) and the reinforcement contingency (differential reinforcement for attempts vs. differential reinforcement for accurate responses) on accurate task completion and disruptive behavior. Results suggested that behavioral escalation from inaccurate responding to disruptive behavior occurred only when ineffective directives were combined with differential reinforcement for accurate task completion. The overall results are discussed in terms of developing a methodology for identifying stimulus characteristics of directives that affect accurate responding.

Fluid ingestion does not influence intense 1-h exercise performance in a mild environment.

PURPOSE: It is generally recommended that fluid be ingested during exercise at a rate that prevents body mass loss and prevents dehydration. It is, however, not known whether these recommendations are valid during intense endurance exercise in a mild environment. The purpose of this study was to examine the effect of fluid ingestion volume on heart rate (HR), rectal temperature, plasma electrolytes, and performance during intense endurance exercise at 21 degrees C. METHODS: Eight well-trained men (26+/-1 yr; 79.6+/-3.5 kg; VO2peak = 5.05+/-0.17 L.min(-1) ; mean+/-SEM) cycled for 45 min at 80+/-1% VO2peak while receiving either no fluid replacement (NF), a volume of water that prevented body mass loss (FR-100 = 1.47+/-0.05 L), or 50% of this volume (FR-50 = 0.72+/-0.03 L). The 45-min exercise bout was followed immediately by a 15-min "all-out" performance ride. RESULTS: NF was associated with a 1.9+/-0.0% body mass loss, while FR-50 and FR-100 resulted in losses of 1.0 = 0.1% and 0.0+/-0.1%, respectively. Although values tended to be higher in NF, fluid ingestion had no significant effect on HR or rectal temperature during exercise. Reductions in plasma volume and increases in plasma sodium and potassium concentrations during exercise were largely unaffected by fluid ingestion. RPE increased to a similar extent during exercise in the three trials while a mild increase in the degree of stomach bloating/fullness was evident in FR-100. Work completed during the 15-min performance ride was similar in the three trials (NF: 273+/-8, FR-50: 267+/-8, FR-100: 269+/-9 kJ). CONCLUSIONS: There appears to be little benefit from ingesting water during intense 1-h cycling exercise in mild environmental conditions since such ingestion has no significant effect on HR, body temperature, plasma volume, plasma electrolytes, or performance.

Experimental delayed contact sensitization to diazolidinyl urea (Germall II) in guinea pigs.

Diazolidinyl urea (Germall II) is a new preservative recommended for use in certain consumer products. Although 2 reports document the human sensitization rates of this preservative, no publications quantify its sensitization potential in controlled animal experiments. Diazolidinyl urea induced mild sensitization (grade 2) under maximization test conditions. Further, there was evidence of cross-reactions with both imidazolidinyl urea (Germall 115) and formaldehyde in diazolidinyl-urea-sensitized animals. Rechallenge of diazolidinyl-urea-sensitized animals with diazolidinyl urea 4 weeks following the primary challenge only elicited a weak response (0.5) from 1 animal out of 8.

The prevalence, six-month persistence, and predictive values of laboratory indicators of bacterial vaginosis (nonspecific vaginitis) in asymptomatic women.

The natural course of signs and laboratory test findings indicative of bacterial vaginosis was followed in an observational noninterventive 6-month longitudinal study of 270 asymptomatic women. Only the minority of positive Gardnerella vaginalis cultures (5 of 33), wet mount clue cells (5 of 14), sniff tests (3 of 11), Papanicolaou smear clue cells (0 of 5), and discharge consistent with bacterial vaginosis (11 of 49) persisted in the absence of therapy. While these four laboratory parameters as well as chromatographic succinate/lactate ratios (performed only on the final visit) were abnormal significantly more often in patients with abnormal discharge than in those with normal discharge (p = 0.006, p less than 0.0001, p less than 0.0001, p = 0.0003, and p = 0.002, respectively), all were insensitive predictors of abnormal discharge with sensitivities ranging between 10.6% and 20.2% and abnormal test predictive values between 30.6% and 65.2%. We conclude that G. vaginalis represents indigenous flora in some normal women and that therapy is unwarranted for the incidental finding of a positive laboratory indicator of bacterial vaginosis in the patient without symptoms.

Binding of benzo [a]pyrene to epidermal DNA and RNA as detected by synchronous luminescence spectrometry at 77 K.

The fluorescence associated with benzo[a]pyrene [BP] moieties covalently attached to the nucleic acid (DNA plus RNA) isolated from the epidermis of BP-treated mice was examined at 77 K in frozen aqueous solutions by use of a photon-counting fluorimeter operating in the synchronous scanning mode. The excitation and emission wavelengths were scanned simultaneously with the monochromators set 28 nm apart. This setting coincides with the difference in wavelength between the excitation and emission maxima for the fluorescence of bound BP. Currently the level of detection is in the order of 1 BP residue per 200,000 bases in 40 microgram of nucleic acid. This amount of nucleic acid can be isolated from the skin of a single mouse. The method described here is generally useful for detecting the binding to DNA of nonradioactive carcinogenic polynuclear aromatic which might occur following the topical application to animal skin in vivo of complex hydrocarbon mixtures such as synthetic fuels and crude oils.

Skin carcinogenicity of synthetic and natural petroleums.

In a series of three separate experiments mice were exposed to various concentrations of fossil liquids obtained from coal, oil shale or natural petroleum. All materials were capable of inducing squamous cell carcinoma, but potency differed substantially. Skin carcinogenicity was markedly greater for both coal or oil shale liquids than for natural petroleums. None of the syncrudes approached the skin carcinogenicity of a pure reference carcinogen, benzo(a)pyrene (BP). It is unlikely that determination of the concentration of an active compound in material applied to the test animal will allow meaningful comparison among the diverse agents of interest to the synthetic fuels industry. To better establish the relationship between actual tissue dose and surface concentration the authors are investigating various in vitro and biochemical measures of hydrocarbon-skin interaction to determine which, if any, could serve as a more definitive measure of surface dose. Results, using BP as a marker carcinogenic hydocarbon, suggest that carcinogenic crudes inhibit both BP metabolism in skin organ culture and the interaction of BP adducts with epidermal DNA, in vivo.

Chimeric drift in allophenic mice.

The composition of the immune system of 33 allophenic mice of four different types [C57BL/6 in equilibrium DBA/1, C57BL/6 in equilibrium (CBA X CBA/H-T6), C57BL/6 in equilibrium (A X SJL), DBA/1 in equilibrium (CBA X CBA/H-T6)] was studied. It was found that the parental composition of the peripheral white blood cells changed significantly during a two-month interval in 11/33 or 33% of the mice studied. This phenomenon has been termed chimeric drift. The animals were sacrificed between 9 and 16 months of age, and the parental composition of the peripheral white blood cells, spleen white blood cells, and thymocytes was determined on the day of sacrifice. It was foound that the peripheral white blood cell and spleen white blood cell compositions showed a high degree of correlation. However 8/33 or 24% of the mice studied showed discordance of the spleen and thymocyte cell populations. Seven of the 8 mice which showed spleen-thymocyte discordance, had also shown evidence of chimeric drift earlier in their lives. We suggest that this is evidence that chimeric drift may have an immunological basis.

Chimeric drift in allophenic mice: analysis of changes in red blood cell and white blood cell populations in C57Bl/6 in equilibrium (A X SJL)F1, C57Bl/6 in equilibrium (CBA X CBA/H-T6)F1, and C57Bl/6 in equilibrium DBA/1 mice.

Forty-seven allophenic mice of three different types (C57BL/6 in equilibrium (A X SJL), C57BL/6 in equilibrium (CBA X CBA/H-T6), and C57BL/6 in equilibrium DBA/1) were analyzed for changes in their peripheral white blood cell composition and hemoglobin composition with age. It was found that 10 of the 47 mice showed significant changes termed "chimeric drift" in one or the other or both of these parameters. These 10 mice were classified as unstable chimeras, as opposed to the 37 stable chimeras, which showed no apparent chimeric drift. There was an excellent correlation of peripheral white blood cell and hemoglobin compositions of the stable chimeras. However, the unstable chimeras showed little or no correlation of these two markers. Possible mechanisms of chimeric drift are discussed.