Colonoscopy performance monitoring: do we need to adjust for case mix?

INTRODUCTION: Overall caecum intubation rate(oCIR) and overall polyp detection rate(oPDR) have been proposed as performance indicators, but varying complexity in case mix among endoscopists may potentially affect validity. The study aims to explore the effect of adjusting for case mix on individual endoscopist performance by calculating case mix-adjusted performance estimates (cmCIR and cmPDR) and comparing them to overall performance estimates (oCIR and oPDR). The study also provides an R program for case mix analysis. METHODS: Logistic regression associated endoscopist, colonoscopy indication, patient age and patient gender with the binary outcomes of cecum intubation and polyp detection. Case mix-adjusted performance indicators were calculated for each endoscopist based on logistic regression and bootstraps. Endoscopists were ranked from best to worst by overall and case mix-adjusted performance estimates, and differences were evaluated using percentage points(pp) and rank changes. RESULTS: The dataset consisted of 7376 colonoscopies performed by 47 endoscopists. The maximum rank change for an endoscopist comparing oCIR and cmCIR was eight positions, interquartile range (IQR 1-3). The maximum change in CIR was 1.95 percentage point (pp) (IQR 0.27-0.86). The maximum rank change in the oPDR versus cmPDR analysis was 17 positions (IQR 1.5-8.5). The maximum change in PDR was 11.21 pp (IQR 2.05-6.70). Three endoscopists improved their performance from significantly inferior to within the 95% confidence interval (CI) range of performance targets using case mix-adjusted estimates. CONCLUSIONS: The majority of endoscopists were unaffected by adjustment for case mix, but a few unfortunate endoscopists had an unfavourable case mix that could invite incorrect suspicion of inferior performance.

Improving colonoscopy quality through individualised training programmes.

INTRODUCTION: In Denmark, quality-improvement initiatives aimed at providing a better colonoscopy service are few. The primary objective of this study was to improve colonoscopy quality at Aalborg University Hospital, Denmark, using structured training programmes. The secondary aim was to introduce a system for individual colonoscopist performance monitoring. METHODS: We conducted a colonoscopy-quality pilot study covering two major quality performance indicators: caecum intubation rate (CIR) and polyp detection rate (PDR). The pilot study was followed by colonoscopy training programmes offering experienced colonoscopists colonoscopy skills upgrading, polypectomy and train-the-trainers courses taught by English experts. Junior doctors completed a 20-day module-based colonoscopy-training programme. A regional individual colonoscopy quality-reporting system was developed as a supplementary file within the electronic health records. RESULTS: The CIR increased from 87.1% to 92.1% (p less-than 0.001) and the PDR from 33.7% to 41.7% (p less-than 0.001) in the course of the structured training programme. Multivariable analysis adjusting for patient sex, patient age and colonoscopy indication showed a significant increase in CIR (p less-than 0.001), but not in PDR (p = 0.19). The colonoscopy quality reporting system was introduced and now provides biannual feedback to all colonoscopists. CONCLUSIONS: Quality-improvement initiatives may lead to an improved CIR and possibly PDR. Nationwide training programmes and performance monitoring should be implemented to further improve and monitor colonoscopy quality. FUNDING: none. TRIAL REGISTRATION: not relevant.

Colonoscopy adverse events: are we getting the full picture?

INTRODUCTION: Colonoscopy adverse events (AEs) are commonly underreported and standardised reporting is rarely used. We aimed to investigate AEs associated with colonoscopy in a real world setting, using the American Society of Gastrointestinal Endoscopy (ASGE) lexicon. METHODS: This retrospective cohort study of AEs related to outpatient colonoscopies performed in the North Denmark Region from 2015 to 2018 identified AEs from readmission within eight days or death within 30 days of colonoscopy. AEs were investigated in electronic health records and categorised, attributed and graded according to the ASGE lexicon. RESULTS: Of 49,445 colonoscopies performed, 1141 were potentially associated with AEs (23.07‰). Electronic health record review left 489 AEs attributed to colonoscopy (9.9‰); categorised as cardiovascular (0.65‰), pulmonary (0.36‰), thromboembolic (0.10‰), instrumental incl. perforations (0.99‰), bleeding (3.07‰), infection (0.87‰), drug reactions (0.04‰), pain (2.00‰), integument (damage to skin/bones) (0.34‰) and other (1.62‰) AEs. Ten (0.20‰) AEs were fatal, but only one was procedure related (perforation). All shearing force perforations occurred in the sigmoid colon. Most polypectomy perforations occurred in the caecum (60%). CONCLUSIONS: Colonoscopy carries important procedure and non-procedure related risks. Non-procedure related AEs are likely underreported. Better attention to patients with pre-existing diseases and further colonoscopist training may lower AE rates. A standardised colonoscopy AE reporting system is warranted.

[One third of Danish doctors specializing in diagnostic radiology do not feel sufficiently equipped in terms of medical expertise]. / Hver tredje hoveduddannelseslæge i diagnostisk radiologi føler sig ikke rustet til rollen som medicinsk ekspert.

An internet-based survey among Danish doctors specializing in diagnostic radiology revealed differences with respect to the length of internships at regional and university hospitals as well as the educational environment. The university hospitals were generally evaluated to have the best educational facilities except within practical skills. Therefore, it seems necessary to optimize the educational environment at regional hospitals, especially within medical expertise and scientific skills which are key elements regarding continuous development and quality assurance within radiology.

Is current surgical training efficient? A national survey.

OBJECTIVES: Evaluation of surgical training in Denmark is competency based with no requirement for a specific number of procedures. This may affect monitoring of surgical progress adversely and cause an underestimation of the time needed to acquire surgical competencies. We investigated the number of common surgical procedures performed by trainees. Trainees' and consultants' expectations from the training program were also investigated. DESIGN AND PARTICIPANTS: A questionnaire was sent to all 115 surgical trainees in Denmark. We asked how many common surgical procedures the trainees had performed during their postgraduate training, whether self-reported procedural confidence was achieved during their training, and whether their training expectations were met. Another questionnaire dealt with the consultants' expectations of the surgical training. RESULTS: The total number of common surgical procedures (Lichtenstein hernia repair, appendectomy, laparoscopic appendectomy, and laparoscopic cholecystectomy) that were performed varied between trainees. One group performed few common procedures during training. A low number in 1 procedure correlated with a similar pattern in other procedures. Approximately one-third did not perform common elective procedures independently until their fifth year. Consultants and trainees viewed training differently. CONCLUSIONS: Our study reveals no common trend in the numbers and types of procedures performed during training. The number of procedures seems to reflect the individual trainee and a local tradition rather than the particular training program. An informal competency-based assessment system with lack of quantitative requirements evidently involves a risk of skewness in training.

Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial.

CONTEXT: Use of 80% oxygen during surgery has been suggested to reduce the risk of surgical wound infections, but this effect has not been consistently identified. The effect of 80% oxygen on pulmonary complications has not been well defined. OBJECTIVE: To assess whether use of 80% oxygen reduces the frequency of surgical site infection without increasing the frequency of pulmonary complications in patients undergoing abdominal surgery. DESIGN, SETTING, AND PATIENTS: The PROXI trial, a patient- and observer-blinded randomized clinical trial conducted in 14 Danish hospitals between October 2006 and October 2008 among 1400 patients undergoing acute or elective laparotomy. INTERVENTIONS: Patients were randomly assigned to receive either 80% or 30% oxygen during and for 2 hours after surgery. MAIN OUTCOME MEASURES: Surgical site infection within 14 days, defined according to the Centers for Disease Control and Prevention. Secondary outcomes included atelectasis, pneumonia, respiratory failure, and mortality. RESULTS: Surgical site infection occurred in 131 of 685 patients (19.1%) assigned to receive 80% oxygen vs 141 of 701 (20.1%) assigned to receive 30% oxygen (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.72-1.22; P = .64). Atelectasis occurred in 54 of 685 patients (7.9%) assigned to receive 80% oxygen vs 50 of 701 (7.1%) assigned to receive 30% oxygen (OR, 1.11; 95% CI, 0.75-1.66; P = .60), pneumonia in 41 (6.0%) vs 44 (6.3%) (OR, 0.95; 95% CI, 0.61-1.48; P = .82), respiratory failure in 38 (5.5%) vs 31 (4.4%) (OR, 1.27; 95% CI, 0.78-2.07; P = .34), and mortality within 30 days in 30 (4.4%) vs 20 (2.9%) (OR, 1.56; 95% CI, 0.88-2.77; P = .13). CONCLUSION: Administration of 80% oxygen compared with 30% oxygen did not result in a difference in risk of surgical site infection after abdominal surgery. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00364741.

Peptides as antioxidants and carbonyl quenchers in biological model systems.

Subjecting selected peptides to in vitro analyses covering their ability to interfere with the lipid oxidation chain reaction as well as to protect proteins from direct and indirect oxidation has provided the basis for a more detailed understanding of peptide-mediated protection in biological systems. The efficiency of peptides as radical scavengers and chain-breaking antioxidants in oxidizing lipid membranes was found to be low. Previous studies on antioxidative activity of peptides tend not to include comparisons with efficiencies of more well-documented antioxidants and/or use irrelevantly high dosages of peptides. The present study demonstrates that the effect of the investigated peptides towards oxidation in biological membrane systems is mainly a protection of vital proteins from being oxidatively modified. This protection is obtained through a prevention of lipid oxidation derived carbonylation (indirect protein oxidation) and through interference with aqueous radical species (direct protein oxidation), and it is only achieved if the peptides are present in high concentrations as sacrificial antioxidants.

Browning of freeze-dried probiotic bacteria cultures in relation to loss of viability during storage.

Freeze-dried cultures of Lactobacillus acidophilus (La-5) showed visible brown discoloration even after a short storage at relatively mild conditions (a(w) = 0.22 and 30 degrees C), and the browning processes were found to coincide with bacteria inactivation. It was demonstrated, by using high-pressure treatment for obtaining bacteria samples with different ratios of live/dead bacteria, that death of bacteria is not a prerequisite for the browning processes. Furthermore, it was shown that hydroxymethylfurfural (HMF) (or condensation products of HMF) introduces accelerated viability loss when HMF is added to the freeze-drying medium. Discoloration of bacteria cultures containing only sucrose/maltodextrin or lactose/maltodextrin in the freeze-drying matrices is suggested to be related to various types of nonenzymatic browning reactions, including carbonyl-protein (or carbonyl-DNA) interactions and carbohydrate condensation/polymerization (without involvement of proteins), the latter proceeding at low a(w) following hydrolysis of the peptidoglycan layer in the bacteria cell wall. More than one single type of browning reaction is accordingly concluded to be related to bacteria death, and the loss of viability in freeze-dried bacteria seems to be influenced by oxidation reactions, browning reactions, and the physical instability of the bacteria membrane/cell wall.

Investigation of oxidation in freeze-dried membranes using the fluorescent probe C11-BODIPY(581/591).

Incorporation of the fluorescent probe C11-BODIPY(581/591) in two dried membrane systems, soy bean phosphatidylcholine liposomes freeze-dried in a carbohydrate/protein matrix and Lactobacillus acidophilus (La-5) freeze-dried in a carbohydrate matrix, was successful and could be visualised by Confocal Laser Scanning Microscopy (CLSM). The C11-BODIPY(581/591) probe is a lipid oxidation reporter molecule, which is known to associate with the lipids of biological membranes and exhibit a fluorescence shift from the red range to the green range of the visible spectrum when it is oxidised together with the lipids. The present study is the first to demonstrate that the C11-BODIPY(581/591) probe can be used in dried membrane systems, and that a detection of oxidation is possible by CLSM analysis directly on the dried samples.

[Initial experiences with laparoscopic incisional hernial repair]. / Initielle erfaringer med laparoskopisk operationfor hernia incisionalis.

INTRODUCTION: Incisional hernia following laparotomy remains an important problem. Laparoscopic repair has become the method of choice in recent years. The present article presents the outcome of laparoscopic incisional hernia mesh repair at Viborg Hospital in the years 2003-2006. MATERIAL AND METHODS: We retrospectively identified 114 patients who had undergone laparoscopic hernia repair during the relevant period. The patients received a questionnaire regarding satisfaction, pain and recurrence. Patients reporting any inconvenience were offered a consultation. RESULTS: Among the 114 included patients, ten procedures were converted to open laparotomy, six of which were converted due to recognized bowel injury. One case of bowel injury was managed laparoscopically. One case of bowel injury was recognized during reoperation the following day. Another four patients experienced reoperations for other reasons, mainly bleeding. The mean hospital stay was one day. A total of 12 patients had a recurrent hernia. The mean follow-up was 14 months. CONCLUSION: We conclude that laparoscopic incisional hernia repair is a useful surgical procedure with short hospital stay and high patient satisfaction. There is, however, a certain risk of bowel injury associated with this procedure.

Water activity-temperature state diagrams of freeze-dried Lactobacillus acidophilus (La-5): influence of physical state on bacterial survival during storage.

Water activity-temperature state diagrams for Lactobacillus acidophilus freeze-dried in a sucrose or a lactose matrix were established based on determination of stabilized glass transition temperatures by differential scanning calorimetry during equilibration with respect to water activity at fixed temperatures. The bacteria in the lactose matrix had higher stabilized glass transition temperatures for all a(w) investigated. The survival of Lactobacillus acidophilus determined as colony forming units for up to 10 weeks of storage at 20 degrees C for (i) a(w) = 0.11 with both freeze-dried matrices in the glassy state, (ii) a(w) = 0.23 with the bacteria in the lactose matrix in a glassy state but with the bacteria in sucrose matrix in the nonglassy state, and (iii) a(w) = 0.43 with both freeze-dried matrices in a nonglassy state showed that the nature of the sugar was more important for storage stability than the physical state of the matrix with the nonreducing sucrose providing better stability than the reducing lactose.

Storage stability of freeze-dried Lactobacillus acidophilus (La-5) in relation to water activity and presence of oxygen and ascorbate.

Storage stability of freeze-dried Lactobacillus acidophilus was found to depend on water activity (0.11-0.43), oxygen level (atmospheric oxygen level and <4% oxygen compared) and presence of sodium ascorbate (0% and 10% (w/w)). Increasing water activities decreased bacterial survival, and a reduced oxygen level (<4% oxygen) improved the storage stability, which strongly indicates a connection between oxidative reactions and bacterial instability. The detrimental effect of atmospheric oxygen was reduced by including ascorbate in the freeze drying medium. However, when ascorbate was present a pink/red colour was observed on the surface of the dried samples increasing with the water activity and oxygen level. Increased water activity lead to increased browning also for samples without ascorbate. Free radicals were detected in the dried bacteria by ESR spectroscopy (broad single-peak ESR spectra), where the shape and the g-value was found to depend on the presence of ascorbate and the extent of browning. For increasing water activities the content of radicals increased to a certain level, after which it levelled off and/or decreased. The highest concentrations of radicals were detected in the dried bacteria with highest survival for a given water activity, i.e. low oxygen level and presence of ascorbate, pointing towards a role of semi-stable ascorbyl radicals as a "dead end" for otherwise detrimental free radical reactions.

Perioperative oxygen fraction - effect on surgical site infection and pulmonary complications after abdominal surgery: a randomized clinical trial. Rationale and design of the PROXI-Trial.

BACKGROUND: A high perioperative inspiratory oxygen fraction may reduce the risk of surgical site infections, as bacterial eradication by neutrophils depends on wound oxygen tension. Two trials have shown that a high perioperative inspiratory oxygen fraction (FiO(2) = 0.80) significantly reduced risk of surgical site infections after elective colorectal surgery, but a third trial was stopped early because the frequency of surgical site infections was more than doubled in the group receiving FiO(2) = 0.80. It has not been settled if a high inspiratory oxygen fraction increases the risk of pulmonary complications, such as atelectasis, pneumonia and respiratory failure. The aim of our trial is to assess the potential benefits and harms of a high perioperative oxygen fraction in patients undergoing abdominal surgery. METHODS AND DESIGN: The PROXI-Trial is a randomized, patient- and assessor blinded trial of perioperative supplemental oxygen in 1400 patients undergoing acute or elective laparotomy in 14 Danish hospitals. Patients are randomized to receive either 80% oxygen (FiO(2) = 0.80) or 30% oxygen (FiO(2) = 0.30) during surgery and for the first 2 postoperative hours. The primary outcome is surgical site infection within 14 days. The secondary outcomes are: atelectasis, pneumonia, respiratory failure, re-operation, mortality, duration of postoperative hospitalization, and admission to intensive care unit. The sample size allows detection of a 33% relative risk reduction in the primary outcome with 80% power. DISCUSSION: This trial assesses benefits and harms of a high inspiratory oxygen fraction, and the trial may be generalizable to a general surgical population undergoing laparotomy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00364741.

Impact of water activity, temperature, and physical state on the storage stability of Lactobacillus paracasei ssp. paracasei freeze-dried in a lactose matrix.

The aim of this study was to determine whether the combined effect of water activity and temperature on inactivation rates of freeze-dried microorganisms in a lactose matrix could be explained in terms of the glass transition theory. The stabilized glass transition temperature, Tg, of the freeze-dried products was determined by differential scanning calorimetry at two different temperatures, T (20 and 37 degrees C), and different water activities (0.07-0.48). This information served as a basis for defining conditions of T and water activity, which led to storage of the bacteria in the glassy (T < Tg) and nonglassy (T > Tg) states. The rates of inactivation of the dry microorganisms subjected to different storage conditions were determined by plate counts and could be described by first-order kinetics. Rates were analyzed as a function of water activity, storage temperature, and the difference between Tg and T. Inactivation below Tg was low; however, Tg could not be regarded as an absolute threshold of bacteria stability during storage. When the cells were stored in the nonglassy state (T > Tg), inactivation proceeded faster, however, not as rapid as suggested by the temperature dependence of the viscosity above the glass transition temperature. Furthermore, the first-order rate constant, k, was dependent on the storage temperature per se rather than on the temperature difference between the glass transition temperature and the storage temperature (T - Tg).

[Multiple bowel perforations after swallowing magnetic toys]. / Multiple tarmperforationer efter indtagelse af magnetisk legetøj.

Ingestion of small foreign bodies is common in children, and usually does not cause any harm to the gastrointestinal tract. But ingestion of multiple magnets can be hazardous because of the strong attraction of the magnets through the bowel wall, which may lead to bowel wall necrosis and perforation. We describe the case of a 6-year-old autistic boy who swallowed 4 magnets which led to bowel obstruction and 8 small perforations. It is important to be aware of this potential risk if children ingest small magnetic toys.

Evaluation of the flexion relaxation phenomenon of the trunk muscles in sitting.

STUDY DESIGN: A normative, single-group study was conducted. OBJECTIVE: To investigate the flexion relaxation phenomenon in the thoraco-lumbopelvic muscles among a pain-free population when moving from an upright to a slump sitting posture. SUMMARY OF BACKGROUND DATA: The presence of the flexion relaxation phenomenon (FRP) of the back muscles is well documented at end-range spinal flexion when standing. This phenomenon is commonly found disrupted in low back subjects. However, whether FRP occurs in sitting remains controversial. METHODS: The sample consisted of 24 healthy pain-free adults. Surface electromyography was used to measure activity in the superficial lumbar multifidus (SLM), the thoracic erector spinae (TES), and the transverse fibers of the internal oblique (IO) muscles while subjects moved from an erect to a slump sitting posture. An electromagnetic motion-tracking device simultaneously measured thoracolumbar kinematics during this task. RESULTS: There was a significant decrease in both the SLM and the IO activity when moving from an erect to a slump sitting posture (P = 0.001 and P = 0.004, respectively), indicating the presence of FRP. TES activity was highly variable. While 13 subjects exhibited an increase in activity (P = 0.001), 11 demonstrated a decrease in activity (P = 0.001), indicating the presence of FRP. FRP occurred in the mid-range of spinal flexion for the SLM, IO and TES when present. CONCLUSION: The findings show that the SLM and the IO are facilitated in neutral lordotic sitting postures and exhibit FRP at mid range flexion while moving from upright sitting to slump sitting. These findings show that FRP in sitting differs from that in standing. Variable motor patterns (activation or FRP) of the TES were observed. These findings suggest that sustaining mid to end-range flexed sitting spinal postures result in relaxation of the spinal stabilizing muscles.

Myoglobin species with enhanced prooxidative activity is formed during mild proteolysis by pepsin.

Pepsin proteolysis at pH approximately 4 resulted in a lowering of the (pseudo)peroxidase activity of metmyoglobin both at physiological pH and at meat pH, as measured by a peroxidase assay with H(2)O(2) and ABTS as substrates. In contrast, the mildly proteolyzed myoglobin had a strongly enhanced prooxidative effect on lipid oxidation in an oil in water methyl linoleate emulsion compared to native metmyoglobin, as evidenced by rates of oxygen depletion. More severe proteolysis of metmyoglobin at lower pH values near the optimum for pepsin did not result in a similar enhancement of prooxidative activity. The mildly proteolyzed metmyoglobin had spectral characteristics in agreement with a relative stabilization of the iron(II) state. On the basis of the observed effects of metal chelators, of lipophilic and hydrophilic peroxides and of radical scavengers on oxygen depletion rates, it is suggested that the increased prooxidative effect is due to radicals formed by cleavage of lipid peroxides by iron(II)/iron(III) cycling of a heme pigment with affinity for the lipid/water interface.

Pseudoperoxidase activity of myoglobin: kinetics and mechanism of the peroxidase cycle of myoglobin with H2O2 and 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonate) as substrates.

Using 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonate) (ABTS) as substrate, it has been shown that the increased peroxidase activity for decreasing pH of myoglobin activated by hydrogen peroxide is due to a protonization of ferrylmyoglobin, MbFe(IV)=O, facilitating electron transfer from the substrate and corresponding to pK(a) approximately 5.2 at 25.0 degrees C and ionic strength 0.16, rather than due to specific acid catalysis. On the basis of stopped flow absorption spectroscopy with detection of the radical cation ABTS(.+), the second-order rate constant and activation parameters for the reaction between MbFe(IV)=O and ABTS were found to have the values k = 698 +/- 32 M(-1) s(-1), DeltaH# = 66 +/- 4 kJ mol(-1), and DeltaS# = 30 +/- 15 J mol(-1) K(-1) at 25.0 degrees C and physiological pH (7.4) and ionic strength (= 0.16 M NaCl). At a lower pH (5.8) corresponding to the conditions in meat, values were found as follows: k = 3.5 +/- 0.3 x 10(4) M(-1) s(-1), DeltaH# = 31 +/- 6 kJ mol(-1), and DeltaS# = -53 +/- 19 J mol(-1) K(-1), indicative of a shift from outersphere electron transfer to an innersphere mechanism. For steady state assay conditions, this shift is paralleled by a shift from saturation kinetics at pH 7.4 to first-order kinetics for H2O2 as substrate at pH 5.8. In contrast, the activation reaction between myoglobin and hydrogen peroxide was found at 25.0 degrees C to be slow and independent of pH with values of 171 +/- 7 and 196 +/- 19 M(-1) s(-1) found at physiological and meat pH, respectively, as determined by sequential stopped flow spectroscopy, from which a lower limit of k = 6 x 10(5) M(-1) s(-1) for the reaction between perferrylmyoglobin, .MbFe(IV)=O, and ABTS could be estimated. As compared to the traditional peroxidase assay, a better characterization of pseudoperoxidase activity of heme pigments and their denatured or proteolyzed forms is thus becoming possible, and specific kinetic effects on activation, substrate oxidation, or shift in rate determining steps may be detected.

Antioxidant properties of carnosine re-evaluated in a ferrylmyoglobin model system and in cooked pork patties.

The antioxidative effect of purified carnosine (i.e., separated from the common contaminant hydrazine) has been evaluated in two systems: (i) Carnosine was found to possess poor reducing properties toward the prooxidant ferrylmyoglobin; at pH approximately 5 the presence of carnosine did not increase the rate of reduction of MbFe(IV)=O compared to autoreduction, whereas at pH 7.4 the rate constant for reduction by carnosine was 0.010 +/- 0.002 M(-1).s(-1) (I = 0.16; 25.0 degrees C). (ii) In cooked pork patties prepared from meat (longissimus dorsi and masseter) with purified or nonpurified carnosine added, the effect of purified carnosine was insignificant when compared to control patties, whereas patties with carnosine contaminated with hydrazine had a lower oxidation level than patties with purified carnosine. Carnosine is concluded not to deactivate the prooxidant ferrylmyoglobin and not to have any antioxidative effect in cooked pork.