Hospital volume following major surgery for gastric cancer determines in-hospital mortality rate and failure to rescue: a nation-wide study based on German billing data (2009-2017).

BACKGROUND: For many cancer resections, a hospital volume-outcome relationship exists. The data regarding gastric cancer resection-especially in the western hemisphere-are ambiguous. This study analyzes the impact of gastric cancer surgery caseload per hospital on postoperative mortality and failure to rescue in Germany. METHODS: All patients diagnosed with gastric cancer from 2009 to 2017 who underwent gastric resection were identified from nation-wide administrative data. Hospitals were grouped into five equal caseload quintiles (I-V in ascending caseload order). Postoperative deaths and failure to rescue were determined. RESULTS: Forty-six thousand one hundred eighty-seven patients were identified. There was a significant shift from partial resections in low-volume hospitals to more extended resections in high-volume centers. The overall in-house mortality rate was 6.2%. The crude in-hospital mortality rate ranged from 7.9% in quintile I to 4.4% in quintile V, with a significant trend between volume categories (p < 0.001). In the multivariable logistic regression analysis, quintile V hospitals (average of 29 interventions/year) had a risk-adjusted odds ratio of 0.50 (95% CI 0.39-0.65), compared to the baseline in-house mortality rate in quintile I (on average 1.5 interventions/year) (p < 0.001). In an analysis only evaluating hospitals with more than 30 resections per year mortality dropped below 4%. The overall postoperative complication rate was comparable between different volume quintiles, but failure to rescue (FtR) decreased significantly with increasing caseload. CONCLUSION: Patients who had gastric cancer surgery in hospitals with higher volume had better outcomes and a reduced failure to rescue rates for severe complications.

Nationwide in-hospital mortality rate following rectal resection for rectal cancer according to annual hospital volume in Germany.

BACKGROUND: The impact of hospital volume after rectal cancer surgery is seldom investigated. This study aimed to analyse the impact of annual rectal cancer surgery cases per hospital on postoperative mortality and failure to rescue. METHODS: All patients diagnosed with rectal cancer and who had a rectal resection procedure code from 2012 to 2015 were identified from nationwide administrative hospital data. Hospitals were grouped into five quintiles according to caseload. The absolute number of patients, postoperative deaths and failure to rescue (defined as in-hospital mortality after a documented postoperative complication) for severe postoperative complications were determined. RESULTS: Some 64 349 patients were identified. The overall in-house mortality rate was 3·9 per cent. The crude in-hospital mortality rate ranged from 5·3 per cent in very low-volume hospitals to 2·6 per cent in very high-volume centres, with a distinct trend between volume categories (P < 0·001). In multivariable logistic regression analysis using hospital volume as random effect, very high-volume hospitals (53 interventions/year) had a risk-adjusted odds ratio of 0·58 (95 per cent c.i. 0·47 to 0·73), compared with the baseline in-house mortality rate in very low-volume hospitals (6 interventions per year) (P < 0·001). The overall postoperative complication rate was comparable between different volume quintiles, but failure to rescue decreased significantly with increasing caseload (15·6 per cent after pulmonary embolism in the highest volume quintile versus 38 per cent in the lowest quintile; P = 0·010). CONCLUSION: Patients who had rectal cancer surgery in high-volume hospitals showed better outcomes and reduced failure to rescue rates for severe complications than those treated in low-volume hospitals.

ANTECEDENTES: El impacto del volumen hospitalario en los resultados de la cirugía del cáncer de recto ha sido poco investigado. Este estudio tuvo como objetivo analizar el impacto de los casos anuales de cirugía de cáncer de recto por hospital en la mortalidad postoperatoria (postoperative mortality, POM) y el fracaso en el rescate (failure to rescue, FtR). MÉTODOS: Todos los casos de pacientes hospitalizados con un diagnóstico de cáncer de recto y un código de procedimiento de resección rectal, tratados de 2012 a 2015, se identificaron a partir de datos hospitalarios administrativos a nivel nacional. Los hospitales se agruparon en cinco quintiles según el volumen de casos. Se determinó el número absoluto de pacientes, la POM y el FtR por complicaciones postoperatorias graves. El FtR se definió como la mortalidad hospitalaria después de una complicación postoperatoria documentada. RESULTADOS: Se identificaron 64.349 casos entre 2012 y 2015. La tasa de mortalidad hospitalaria global fue del 3,89% (n = 2.506). Las tasas brutas de mortalidad hospitalaria variaron de 5,34% (n = 687) en hospitales de muy bajo volumen a 2,63% (n = 337) en centros de muy alto volumen, con una tendencia distinta entre las categorías de centros (P < 0,001). En el análisis de regresión logística multivariante utilizando el volumen hospitalario como efecto aleatorio, los hospitales de muy alto volumen (53 intervenciones/año) tenían una razón de oportunidades (odds ratio, OR) ajustada por riesgo de 0,58 (i.c. del 95%: 0,47-0,73) en comparación con la tasa basal de mortalidad hospitalaria en hospitales de muy bajo volumen (6 intervenciones/año) (P < 0,001). La tasa global de complicaciones postoperatorias fue comparable entre los diferentes quintiles de volumen, pero el FtR disminuyó significativamente con el aumento del volumen de casos (15,63% FtR tras una embolia pulmonar en el quintil más alto versus 38,4% en el hospital del quintil más bajo, P = 0,01). CONCLUSIÓN: Los pacientes sometidos a cirugía de cáncer de recto en hospitales de gran volumen presentaron mejores resultados y una disminución de las tasas de fracaso en el rescate por complicaciones graves en comparación con los pacientes tratados en hospitales de bajo volumen.

Nationwide in-hospital mortality following colonic cancer resection according to hospital volume in Germany.

Background: Colonic cancer is the most common cancer of the gastrointestinal tract. The aim of this study was to determine mortality rates following colonic cancer resection and the effect of hospital caseload on in-hospital mortality in Germany. Methods: Patients admitted with a diagnosis of colonic cancer undergoing colonic resection from 2012 to 2015 were identified from a nationwide registry using procedure codes. The outcome measure was in-hospital mortality. Hospitals were ranked according to their caseload for colonic cancer resection, and patients were categorized into five subgroups on the basis of hospital volume. Results: Some 129 196 colonic cancer resections were reviewed. The overall in-house mortality rate was 5·8 per cent, ranging from 6·9 per cent (1775 of 25 657 patients) in very low-volume hospitals to 4·8 per cent (1239 of 25 825) in very high-volume centres (P < 0·001). In multivariable logistic regression analysis the risk-adjusted odds ratio for in-house mortality was 0·75 (95 per cent c.i. 0·66 to 0·84) in very high-volume hospitals performing a mean of 85·0 interventions per year, compared with that in very low-volume hospitals performing a mean of only 12·7 interventions annually, after adjustment for sex, age, co-morbidity, emergency procedures, prolonged mechanical ventilation and transfusion. Conclusion: In Germany, patients undergoing colonic cancer resections in high-volume hospitals had with improved outcomes compared with patients treated in low-volume hospitals.

Identification of maternal characteristics associated with the use of epidural analgesia.

The present survey aims to identify predictors associated with the use of epidural analgesia (EA). Therefore, from October 2007 to June 2008, a survey was conducted in 193 pregnant women (mean age 31.7 years (SD 4.9); 64.8% primipara) attending a German general hospital with a specialisation in integrative medicine. Questionnaires, including Antonovsky's sense of coherence (SOC) were delivered antepartum. Delivery data were recorded within the hospital quality management programme. The adjusted odds ratio (OR) for EA use was significantly greater than one for women who had previously used EA (adjusted OR =4.1; CI: 1.03-16.31) and for the desire for a delivery without pain (adjusted OR =3.05; CI: 1.36-6.83). The likelihood of EA use decreased in multipara (adjusted OR =0.05; CI: 0.01-0.22). SOC was not found to be an independent predictor for EA use. However, women with high SOC more often preferred a delivery without EA (p for trend =0.037). In conclusion, first time labour, the desire for a delivery without pain and previous use of EA are independent predictors for the use of EA in labour. Further studies should clarify the predictive role of SOC in pregnancy.

Adverse drug reactions in a complementary medicine hospital: a prospective, intensified surveillance study.

Background. Anthroposophic medicine is one of the widely used approaches of complementary and alternative medicine. However, few prospective studies have generated safety data on its use. Objectives. We aimed to assess adverse drug reactions (ADRs) caused by anthroposophical medicines (AMEDs) in the anthroposophical Community Hospital Havelhoehe, GERMANY. Study Design and Methods. Between May and November 2007, patients of six medical wards were prospectively assessed for ADRs. Suspected ADRs occurring during hospitalization were documented and classified in terms of organ manifestation (WHO SOC-code), causality (according to the Uppsala Monitoring Centre WHO criteria), and severity. Only those ADRs with a severity of grade 2 and higher according to the CTCAE classification system are described here. Results. Of the 3,813 patients hospitalized, 174 patients (4.6%) experienced 211 ADRs (CTCAE grade 2/3 n = 191, 90.5%, CTCAE grade 4/5 n = 20, 9.5%) of which 57 ADRs (27.0%) were serious. The median age of patients with ADRs (62.1% females) was 72.0 (IQR: 61.0; 80.0). Six patients (0.2%) experienced six ADRs (2.8% of ADRs) caused by eight suspected AMEDs, all of which were mild reactions (grade 2). Conclusion. Our data show that ADRs caused by AMEDs occur rarely and are limited to mild symptoms.

Does self-regulation and autonomic regulation have an influence on survival in breast and colon carcinoma patients? results of a prospective outcome study.

BACKGROUND: Cancer Related Fatigue (CRF) and circadian rhythm have a great impact on the quality of life (HRQL) of patients with breast (BC) and colon cancer (CRC). Other patient related outcomes in oncology are measured by new instruments focusing on adaptive characteristics such as sense of coherence or self-regulation, which could be more appropriate as a prognostic tool than classical HRQL. The aim of this study was to assess the association of autonomic regulation (aR) and self-regulation (SR) with survival. METHODS: 146 cancer patients and 120 healthy controls took part in an initial evaluation in 2000/2001. At a median follow up of 5.9 years later, 62 of 95 BC, 17 of 51 CRC patients, and 85 of 117 healthy controls took part in the follow-up study. 41 participants had died. For the follow-up evaluation, participants were requested to complete the standardized aR and SR questionnaires. RESULTS: On average, cancer patients had survived for 10.1 years with the disease. Using a Cox proportional hazard regression with stepwise variables such as age, diagnosis group, Charlson co-morbidity index, body mass index (BMI)) aR and SR. SR were identified as independent parameters with potential prognostic relevance on survival While aR did not significantly influence survival, SR showed a positive and independent impact on survival (OR = 0.589; 95%-CI: 0.354 - 0.979). This positive effect persisted significantly in the sensitivity analysis of the subgroup of tumour patients and in the subscale 'Achieve satisfaction and well-being' and by tendency in the UICC stages nested for the different diagnoses groups. CONCLUSIONS: Self-regulation might be an independent prognostic factor for the survival of breast and colon carcinoma patients and merits further prospective studies.

Molecular mistletoe therapy: friend or foe in established anti-tumor protocols? A multicenter, controlled, retrospective pharmaco-epidemiological study in pancreas cancer.

Mistletoe is often used as complementary therapy in oncology. The anti-tumor effects of mistletoe (Iscador) are well documented in-vitro in respect to inhibition of cell proliferation, induction of apoptosis, segmental activation of immune competent cells and trapping of chemotherapeutic drugs within cancer cells by modulating the inhibitory potential of P-glycoprotein (P-gp)-mediated transport of cell toxifying substances (cytotoxic drugs). However, the clinical activity of mistletoe treatment remains still controversial. Implementation of mistletoe therapy as supportive care into anti-cancer programs should be based on the best evidence and must continually be evaluated to ensure safety, efficacy, collection of new data, and cost-effectiveness. Useful domains that can be evaluated include symptom control, adherence to conventional treatment protocols, quality of life, individual outcome and potential advantages of a whole-system health approach. Here we report the results of a multicenter, controlled, retrospective and observational pharmaco-epidemiological study in patients suffering from a pancreatic carcinoma. After surgery the patients were treated by adjuvant chemotherapy with gemcitabine supported by Iscador, or with gemcitabine alone, or any other best of care, but not including Iscador. Using a novel methodological pharmaco-epidemiological design and statistical approach it could be shown that Iscador offers benefits--symptom control, overall survival--as supportive care within gemcitabine protocols of patients with surgically resected pancreatic carcinoma.

Validation of a questionnaire measuring the regulation of autonomic function.

BACKGROUND: To broaden the range of outcomes that we can measure for patients undergoing treatment for oncological and other chronic conditions, we aimed to validate a questionnaire measuring self-reported autonomic regulation (aR), i.e. to characterise a subject's autonomic functioning by questions on sleeping and waking, vertigo, morningness-eveningness, thermoregulation, perspiration, bowel movements and digestion. METHODS: We administered the questionnaire to 440 participants (female symbol: N = 316, male symbol: N = 124): 95 patients with breast cancer, 49 with colorectal cancer, 60 with diabetes mellitus, 39 with coronary heart disease, 28 with rheumatological conditions, 32 with Hashimoto's disease, 22 with multiple morbidities and 115 healthy people. We administered the questionnaire a second time to 50.2% of the participants. External convergence criteria included the German version of the Hospital Anxiety and Depression Scale (HADS-D), a short questionnaire on morningness-eveningness, the Herdecke Quality of Life Questionnaire (HLQ) and a short version questionnaire on self-regulation. RESULTS: A principal component analysis yielded a three dimensional 18-item inventory of aR. The subscales orthostatic-circulatory, rest/activity and digestive regulation had internal consistency (Cronbach-alpha: ralpha = 0.65 - 0.75) and test-retest reliability (rrt = 0.70 - 85). AR was negatively associated with anxiety, depression, and dysmenorrhoea but positively correlated to HLQ, self-regulation and in part to morningness (except digestive aR) (0.49 - 0.13, all p < 0.05). CONCLUSION: An internal validation of the long-version scale of aR yielded consistent relationships with health versus illness, quality of life and personality. Further studies are required to clarify the issues of external validity, clinical and physiological relevance.

Characterisation of recombinant immunoreactive antigens of the scab mite Sarcoptes scabiei.

Sarcoptic mange (or scabies) is an important skin disease which can affect a variety of species including humans, cattle, goats, sheep, horses, pigs, rabbits, and dogs. Approximately 300 million people are affected worldwide and in lifestock animals the infestation may lead to substantial economic losses caused by depression in growth and feed conversion rates. Diagnosis of Sarcoptes infestation is difficult and only a few serological tests have been developed using whole mite antigen for diagnosis of mange in animals. Here we describe the isolation and characterisation of cDNAs of several immunoreactive clones and their recombinant expression in Escherichia coli. Three of the proteins contain repetitive sequences which suggests that they might be involved in immune evasion. The application of these antigens in serodiagnosis and the suitability for diagnosis is discussed.

Measurements of heat production for estimation of maintenance energy requirements of Hereford steers.

This study aimed to test the hypothesis that maintenance energy requirement (MEm) can be estimated from continuous heat production measurements during a change from a near maintenance feeding level to far below maintenance for two consecutive days. The MEm of eight Hereford steers weighing 286 +/- 5 kg (mean +/- SE) was determined in a balance trial. In addition, during the 10-d collection period, the animals were kept in open-circuit respiration chambers to measure 24-h gas exchange continuously at 10-min intervals. During the balance trial, the animals were fed dried chopped grass twice daily at an estimated level of 1.2 x MEm. After termination of the collection period on the 11th d of the balance trial, the steers were offered 2 kg/d of wheat straw while only gas exchange was measured. Estimates of MEm were derived from heat production (HP) data. The analyses included values of 24-h HP, HP of the nocturnal period (0000 to 0630), HP of the nocturnal period (excluding HP caused by standing) during the grass-feeding period and 24-h HP, nocturnal HP, and nocturnal HP (excluding HP caused by standing) during the straw feeding period. The MEm predicted from estimates of HP measurements were 536 +/- 9, 470 +/- 8, 441 +/- 8, 435 +/- 8, 393 +/- 9, and 373 +/- 9 kJ.kg of BW(-0.75).d(-1), respectively, whereas MEm calculated from data of the balance trial were 416 +/- 9 kJ.kg of BW(-0.75).d(-1). Values predicted for nocturnal HP (excluding HP caused by standing) of grass fed animals, 24-h HP, and nocturnal HP during straw feeding did not differ significantly from MEm. The differences in MEm among animals were reflected by all estimates of HP, whereas the correlation with the 24-h HP during straw feeding reached 0.9 (P = 0.002). We conclude that the method described is adequate to determine MEm with a sufficient degree of accuracy.

Impact of complementary mistletoe extract treatment on quality of life in breast, ovarian and non-small cell lung cancer patients. A prospective randomized controlled clinical trial.

Standardized aqueous mistletoe extracts have been applied to cancer patients for several decades as complementary medicine. A multicentric, randomized, open, prospective clinical trial was conducted in three oncological centers in the People's Republic of China in Bejing, Shenyang and Tianjin. Following the guidelines of "Good Clinical Practice" (GCP) this study was performed to get information on efficacy safety and side-effects of the standardized mistletoe extract (sME). Two hundred and thirty-three patients with breast (n=68), ovarian (n=71) and non-small cell lung cancer (NSCLC; n=94) were enrolled into this study. Two hundred and twenty-four patients fulfilled the requirements for final analysis (n=115 treated with sME HELIXOR A; n=109 comprising the control group being treated with the approved immunomodulating phytopharmacon Lentinan). All patients were provided with standard tumor-destructive treatment schedules and complementarily treated with sME or Lentinan during chemotherapy according to treatment protocol. Biometrically, the patients of the control and sME treatment group were comparable regarding distribution, clinical classification (WHO) and treatment protocols. Analysis was performed according to the "Intention to treat principle". Quality of life (QoL) was significantly (p<0.05) improved for patients who were complementarily treated with sME, as determined by the questionnaires FLIC (Functional Living Index-Cancer), TCM (Traditional Chinese Medicine Index) and the KPI (Karnofsky Performance Index) in comparison to the control group. Additionally, the occurrence of adverse events (AEs) was less frequent in the sME than in the control group (total number of AEs 52 versus 90 and number of serious AEs 5 versus 10 in study and control group, most of them due to chemotherapy). Only one serious AE was allocated to complementary treatment in each group (1 angioedema in sME group). All other side-effects of the sME (7 harmless local inflammatory reactions at subcutaneous injection site, 4 cases with fever) were self-limiting and did not demand therapeutic intervention. This study showed that complementary treatment with sME can beneficially reduce the side-effects of chemotherapy in cancer patients and thus improve quality of life.

Comparison of morphine-6-glucuronide and morphine on respiratory depressant and antinociceptive responses in wild type and mu-opioid receptor deficient mice.

BACKGROUND: Morphine-6-glucuronide (M6G) is a metabolite of morphine with potent analgesic properties. The influence of M6G on respiratory and antinociceptive responses was investigated in mice lacking the micro -opioid receptor (MOR) and compared with morphine. METHODS: Experiments were performed in mice lacking exon 2 of the MOR (n=18) and their wild type (WT) littermates (n=20). The influence of M6G and morphine on respiration was measured using whole body plethysmography during three elevations of inspired carbon dioxide. Antinociception was assessed using tail flick and hotplate tests. RESULTS: In WT but not null mutant mice, a dose-dependent depression of the slope of the ventilatory carbon dioxide response was observed after M6G and morphine. Similarly, both opioids were devoid of antinociceptive effects in null mutant mice, but showed potent dose-dependent analgesia in WT animals. Potency differences between M6G and morphine in WT mice were of the same order of magnitude for analgesia and respiration. CONCLUSIONS: The data indicate that the desired (antinociceptive) and undesired (respiratory depression) effects of M6G and morphine are linked to the same gene product; that is the MOR. Other opioid- and non-opioid-receptor systems may play a minor role in the actions of M6Gs and morphine. The clinical implications of our findings are that any agent acting at the MOR will invariably cause (potent) analgesia in combination with (variable) respiratory depression.