Accuracy of co-morbidity data in patients undergoing abdominal wall hernia repair: a retrospective study.

OBJECTIVES: To determine the baseline accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of routinely collected co-morbidity data in patients undergoing abdominal wall hernia repair. METHODS: All patients aged > 18 who underwent umbilical, para-umbilical, inguinal or incisional hernia repair between 1 January 2015 and 1 November 2016 were identified. All parts of the clinical notes were searched for co-morbidities by two authors independently. The following co-morbidities were considered: hypertension, ischaemic heart disease (IHD), diabetes, asthma, chronic obstructive pulmonary disease (COPD), cerebrovascular disease (CVD), chronic kidney disease (CKD), hypercholesterolemia, obesity and smoking. The co-morbidities data from clinical notes were compared with corresponding data in hospital episode statistics (HES) database to calculate accuracy, sensitivity, specificity, PPV and NPV of HES codes for co-morbidities. To assess the agreement between clinical notes and HES data, we also calculated Cohen's Kappa index value as a more robust measure of agreement. RESULTS: Overall, 346 patients comprising 3460 co-morbidity codes were included in the study. The overall accuracy of HES codes for all co-morbidities was 77% (Kappa: 0.13). When calculated separately for each co-morbidity, the accuracy was 72% (Kappa: 0.113) for hypertension, 82% (Kappa: 0.232) for IHD, 85% (Kappa: 0.203) for diabetes, 86% (Kappa: 0.287) for asthma, 91% (Kappa: 0.339) for COPD, 92% (Kappa: 0.374) for CVD, 94% (Kappa: 0.424) for CKD, 74% (Kappa: 0.074) for hypercholesterolemia, 71% (Kappa: 0.66) for obesity and 24% (Kappa: 0.005) for smoking. The overall sensitivity, specificity, PPV and NPV of HES codes were 9, 100, 100, and 77%, respectively. The results were consistent when individual co-morbidities were analyzed separately. CONCLUSIONS: Our results demonstrated that HES co-morbidity codes in patients undergoing abdominal wall hernia repair are specific with good positive predictive value; however, they have substandard accuracy, sensitivity, and negative predictive value. The presence of a relatively large number of false negative or missed cases in HES database explains our findings. Better documentation of co-morbidities in admission clerking proforma may help to improve the quality of source documents for coders, which in turn may improve the accuracy of coding.

Disruption of egg formation by Fasciola hepatica following treatment in vivo with triclabendazole in the sheep host.

Eight indoor-reared cross-bred sheep with no prior exposure to Fasciola hepatica were infected by oral gavage with 200 metacercarial cysts of the triclabendazole (TCBZ)-susceptible Cullompton isolate of F. hepatica. Twelve weeks after infection, sheep were treated with 10mg/kg triclabendazole. Two sheep were euthanised per time period; at 48 h, 72 h and 96 h post-treatment (pt). Two untreated control sheep were euthanised at 96 h pt. Flukes were recovered from the liver and, if present, from the gall bladder of the sheep. They were processed for whole mount analysis, histology and transmission electron microscopy of the female reproductive system; specifically, the uterus, vitelline follicles, Mehlis' gland and ovary. Over the 4-day post-treatment period, there was a progressive reduction in the number of oogonia and oocytes in the ovary and evidence of apoptosis. Vacuolation and a decrease in the number of Mehlis' gland cells were observed from 48 h pt onwards and disruption of the normal role of the gland in egg formation was evident. The vitelline follicles showed a gradual decrease in size and became vacuolated; the population structure in each follicle changed to be one consisting mainly of mature cells and the production of shell protein material declined. The follicle became disorganised as the cells broke down and released their contents into the lumen of the follicle. While the uterus appeared to contain eggs at 48 h pt in whole-mount specimens, no properly-formed eggs were observed in histological sections. By 96 h pt, the uterus was completely devoid of eggs. Overall, egg production was seen to be severely affected by TCBZ treatment and flukes were incapable of producing normal eggs within 2 days of treatment. The implications of this in terms of the epidemiology of the disease are discussed.

Time-dependent changes to the tegumental system and gastrodermis of adult Fasciola hepatica following treatment in vivo with triclabendazole in the sheep host.

Eight indoor-reared cross-bred sheep with no pre-exposure to Fasciola hepatica were infected by oral gavage with 200 metacercarial cysts of the triclabendazole (TCBZ)-susceptible Cullompton isolate of F. hepatica. At 12 weeks post-infection, sheep were dosed with 10mg/kg triclabendazole. Two sheep per time period were euthanized at 48 h, 72 h and 96 h post-treatment (pt). Two control sheep were euthanized alongside the 96 h triclabendazole-treated sheep. Flukes were recovered from each of the sheeps liver and, if present, from the gall bladder and they were processed for transmission electron microscopy (TEM). Disruption to the ultrastructure of the tegument became increasingly severe over time pt. Flukes recovered at 48 h pt showed widespread blebbing of the apical plasma membrane and swelling of the mucopolysaccharide masses surrounding the basal infolds. There was evidence of reduced secretory activity in the tegumental cells and spacing between the cells. Sloughing of the tegumental syncytium was observed at 72 h pt. The subtegumental musculature, parenchyma and tegumental cells were severely disrupted. At 96 h pt, all of the flukes were totally devoid of tegument. Disruption to the subtegumental tissue and somatic musculature was severe, and was so extreme in some specimens that the tegumental cells were barely discernible. Disruption to the gastrodermis was also progressive, though not as severe as disruption to the tegument. There was a general decline of secretory activity with time pt. Autophagic activity was apparent from 48 h pt and became more widespread with increasing time, culminating in breakdown of the gastrodermal cell cytoplasm. The mitochondria were swollen and electron-lucent and the cisternae of the granular endoplasmic reticulum were dilated and fragmented from 72 h pt.

Tegumental surface changes in adult Fasciola hepatica in response to treatment in vivo with triclabendazole in the sheep host.

Eight indoor-reared crossbred sheep with no pre-exposure to Fasciola hepatica were infected by oral gavage with 200 metacercarial cysts of the triclabendazole (TCBZ)-susceptible Cullompton isolate of F. hepatica. At 12 weeks post-infection, sheep were dosed with 10mg/kg triclabendazole. Two sheep per time period were euthanized at 48h, 72h and 96h post-treatment. Two control sheep were euthanized alongside the 96h triclabendazole-treated sheep. Flukes were recovered from each of the sheeps' liver and, if present, from the gall bladder, and they were processed for scanning electron microscopy (SEM). Flukes recovered 48h post-treatment were active. Disruption to the tegument took the form of swelling, widespread blebbing and some loss of the tegument covering the spines. By 72h post-treatment, all flukes recovered were dead and a number were recovered from the gall bladder. Typically, the posterior end of the flukes was elongated and in this region the tegumental syncytium had sloughed away. Tegumental loss was more widespread on flukes recovered from the gall bladder. At 96h post-treatment, only one fluke was recovered from the liver and three from the gall bladder. All the flukes were dead and they were totally devoid of tegumental syncytium.

Fasciola hepatica: histological changes in the reproductive structures of triclabendazole (TCBZ)-sensitive and TCBZ-resistant flukes after treatment in vivo with TCBZ and the related benzimidazole derivative, Compound Alpha.

Twenty-four shed-reared lambs were each infected orally with 250 metacercariae of Fasciola hepatica, using either the triclabendazole (TCBZ)-sensitive Cullompton isolate or the TCBZ-resistant Sligo isolate. Twelve weeks after infection the lambs were treated with TCBZ (10mg/kg) or with the experimental fasciolicide, Compound Alpha (Cpd alpha), a benzimidazole derivative of TCBZ (15mg/kg). The lambs were euthanised 48, 72 and 96h after TCBZ treatment, or 24, 48 and 72h after Cpd alpha treatment, and flukes were collected from the liver and/or gall bladder of each animal. Untreated animals harbouring 12-week infections were euthanized 24h after administration of anthelmintic to the treatment groups, and the untreated flukes provided control material. A semi-quantitative assessment of the degree of histological change induced by the two drugs after different times of exposure was achieved by scoring the intensity of three well-defined lesions that developed in the testes and uteri of a representative sample of flukes from each lamb. In general, it was found that in those tissues where active meiosis and/or mitosis occurred (testis, ovary, and vitelline follicles), there was progressive loss of cell content due to apparent failure of cell division to keep pace with expulsion of the mature or effete products. Further, actively dividing cell types tended to become individualised, rounded and condensed, characteristic of apoptotic cell death. Protein synthetic activity was apparently inhibited in the Mehlis' secretory cells. In the uterus, where successful formation of shelled eggs represents the culmination of a complex sequence of cytokinetic, cytological and synthetic activity involving the vitelline follicles, the ovary and the Mehlis' gland, histological evidence indicating failure of ovigenesis was evident from 24h post-treatment onwards. The development of these lesions may be related to the known anti-tubulin activity of the benzimidazole class of anthelmintics, to the induction of apoptosis in cells where mitosis or meiosis has aborted due to failure of spindle formation, and to drug-induced inhibition of protein synthesis. The semi-quantitative findings indicated that Cpd alpha is slightly less efficacious than TCBZ itself in causing histological damage to the reproductive structures of TCBZ-sensitive flukes, and that, like TCBZ, it caused no histological damage in flukes of the TCBZ-resistant isolate. This study illustrates the potential utility of histological techniques for conveniently screening representative samples of flukes in field trials designed to validate instances of drug resistance or to test the efficacy of new products against known drug-resistant and drug-susceptible fluke isolates. It also provides reference criteria for drug-induced histopathological changes in fluke reproductive structures which may aid interpretation of TEM findings.

A transmission electron microscope study on the route of entry of triclabendazole into the liver fluke, Fasciola hepatica.

Uptake of triclabendazole by the liver fluke, Fasciola hepatica has been studied by experiments designed to block either oral uptake of drug, by use of ligatures, or trans-tegumental diffusion, by allowing the drug to bind to an excess of bovine serum albumin (BSA) in the medium. Changes to the tegumental system, musculature and gut were assessed using transmission electron microscopy. Flukes were incubated in vitro for 24 h in TCBZ.SO (15 microg/ml). Disruption to the tegument and muscle was similar in ligatured and non-ligatured flukes, suggesting that closing the oral route did not affect drug uptake. The ultrastructure of the gastrodermal cells remained unchanged. Non-ligatured flukes were also incubated for 24 h in vitro in TCBZ.SO (15 microg/ml) in the presence of red blood cells (RBCs). Oral uptake of blood was demonstrated, but gut ultrastructure remained normal, whereas the tegument was severely disrupted. In separate experiments, ligatured and non-ligatured flukes were incubated in TCBZ.SO (15 microg/ml) in the presence of BSA (30 mg/ml) for 24 h in vitro. There was a marked decrease in the degree of tegumental disruption observed compared with TCBZ.SO action alone; again, the gut remained normal. The findings support previous morphological and pharmacological studies indicating that trans-tegumental uptake of triclabendazole predominates in the liver fluke.

A scanning electron microscope study on the route of entry of triclabendazole into the liver fluke, Fasciola hepatica.

SUMMARY: Studies have been carried out to establish the relative importance of oral and trans-tegumental uptake of triclabendazole by the liver fluke, Fasciola hepatica. Experiments were designed to block either oral uptake of drug, by use of ligatures, or trans-tegumental diffusion, by allowing the drug to bind to bovine serum albumin (BSA) in the medium. Changes to the surface morphology of the tegument and gut were assessed by scanning electron microscopy. Flukes were incubated in vitro for 24 h in TCBZ.SO at a concentration of 15 microg/ml. Tegumental disruption in ligatured and non-ligatured flukes was similar, suggesting that closing the oral route did not affect drug uptake. The gut remained unaffected by drug treatment. When BSA (30 mg/ml) was present in the medium, there was a marked decline in the level of tegumental disruption. Again, the gut retained a normal morphology. Non-ligatured flukes were also incubated for 24 h in vitro in TCBZ.SO (15 microg/ml) in the presence of red blood cells. Oral ingestion of blood was demonstrated, although the gut surface retained a normal morphology. In contrast, the tegumental surface was severely affected by the drug. The findings support previous pharmacological studies which suggest that trans-tegumental uptake of triclabendazole predominates in the liver fluke.

Physiological and morphological effects of genistein against the liver fluke, Fasciola hepatica.

A study has been carried out to determine the activity of genistein against adult liver fluke, Fasciola hepatica. Flukes were incubated in vitro in genistein at a concentration of 0.27 mg/ml (=1 mM). They ceased to move after 3 h, at which point the experiment was terminated and the specimens prepared for examination by scanning and transmission electron microscopy. Surface changes to the flukes comprised swelling and blebbing, especially in the posterior region of the flukes, and there was particular disruption to the spines, accompanied by some spine loss. Fine structural changes to the tegumental syncytium indicated an accelerated release of secretory bodies at the surface, but a reduction in their production within the cell bodies. Autophagic activity was evident in the tegumental cells, a phenomenon that was also observed in the gastrodermal cells. Disruption to the testis and vitelline follicles was severe, with an apparent block in the normal developmental sequence of the spermatogenic and vitelline cells, respectively. Shell protein production by the vitelline cells was also disrupted. In separate experiments, somatic muscle strips were exposed to concentrations of genistein ranging from 1 microm to 1 mm. There were statistically significant increases in the frequency and/or amplitude of muscle contractions at concentrations of 10 microm, 100 microm and 1 mm. The results suggest that genistein is capable of causing severe morphological and neuromuscular disruption to adult flukes in vitro over a short time-span.

Saint Joseph Medical Center emergency department chest pain center.

Saint Joseph Medical Center has had two years experience with operating a chest pain center (CPC) in its emergency department. The CPC has resulted in improved treatment for patients with myocardial infarction. The CPC has led to the utilization of primary angioplasty as a preferred strategy for acute myocardial infarction. The CPC has allowed rapid rule-out of acute coronary syndromes in the emergency department thereby avoiding hospital admission in 31% of patients with chest pain of possible cardiac origin.