Adverse events in deceased hospitalised cancer patients as a measure of quality and safety in end-of-life cancer care.

BACKGROUND: Anticancer treatment exposes patients to negative consequences such as increased toxicity and decreased quality of life, and there are clear guidelines recommending limiting use of aggressive anticancer treatments for patients near end of life. The aim of this study is to investigate the association between anticancer treatment given during the last 30 days of life and adverse events contributing to death and elucidate how adverse events can be used as a measure of quality and safety in end-of-life cancer care. METHODS: Retrospective cohort study of 247 deceased hospitalised cancer patients at three hospitals in Norway in 2012 and 2013. The Global Trigger Tool method were used to identify adverse events. We used Poisson regression and binary logistic regression to compare adverse events and association with use of anticancer treatment given during the last 30 days of life. RESULTS: 30% of deceased hospitalised cancer patients received some kind of anticancer treatment during the last 30 days of life, mainly systemic anticancer treatment. These patients had 62% more adverse events compared to patients not being treated last 30 days, 39 vs. 24 adverse events per 1000 patient days (p < 0.001, OR 1.62 (1.23-2.15). They also had twice the odds of an adverse event contributing to death compared to patients without such treatment, 33 vs. 18% (p = 0.045, OR 1.85 (1.01-3.36)). Receiving follow up by specialist palliative care reduced the rate of AEs per 1000 patient days in both groups by 29% (p = 0.02, IRR 0.71, CI 95% 0.53-0.96). CONCLUSIONS: Anticancer treatment given during the last 30 days of life is associated with a significantly increased rate of adverse events and related mortality. Patients receiving specialist palliative care had significantly fewer adverse events, supporting recommendations of early integration of palliative care in a patient safety perspective.

Is a modified Global Trigger Tool method using automatic trigger identification valid when measuring adverse events?

OBJECTIVES: To evaluate a modified Global Trigger Tool (GTT) method with manual review of automatic triggered records to measure adverse events. DESIGN: A cross-sectional study was performed using the original GTT method as gold standard compared to a modified GTT method. SETTING: Medium size hospital trust in Northern Norway. PARTICIPANTS: One thousand two hundred thirty-three records selected between March and December 2013. MAIN OUTCOME MEASURE: Records with triggers, adverse events and number of adverse events identified. Recall (sensitivity), precision (positive predictive value), specificity and Cohen's kappa with 95 % confidence interval were calculated. RESULTS: Both methods identified 35 adverse events per 1000 patient days. The modified GTT method with manual review of 658 automatic triggered records identified adverse events (n = 214) in 189 records and the original GTT method identified adverse events (n = 216) in 186 records. One hundred and ten identical records were identified with adverse events by both methods. Recall, precision, specificity and reliability for records identified with adverse events were respectively 0.59, 0.58, 0.92 and 0.51 for the modified GTT method. The total manual review time in the modified GTT method was 23 h while the manual review time using the original GTT method was 411 h. CONCLUSIONS: The modified GTT method is as good as the original GTT method that complies with the GTTs aim monitoring the rate of adverse events. Resources saved by using the modified GTT method enable for increasing the sample size. The automatic trigger identification system may be developed to assess triggers in real-time to mitigate risk of adverse events.

Adverse events in hospitalised cancer patients: a comparison to a general hospital population.

BACKGROUND: Patients with cancer are often treated by many healthcare providers, receive complex and potentially toxic treatments that can increase the risk for iatrogenic harm. The aim of this study is to investigate whether hospitalised cancer patients are at higher risk of adverse events (AEs) compared to a general hospital population. MATERIAL AND METHODS: A total of 6720 patient records were retrospectively reviewed comparing AEs in hospitalised cancer patients to a general hospital population in Norway, using the IHI Global Trigger Tool method. RESULTS: 24.2 percent of admissions for cancer patients had an AE compared to 17.4% of admissions of other patients (p < .001, rr 1.39, 95% CI 1.19-1.62). However, cancer patients did not have a higher rate of AEs per 1000 patient days compared to other patients, 37.1 vs. 36.0 (p = .65, rr 0.94, 95% CI 0.90-1.18). No particular cancer category is at higher risk. The rate of AEs increases by 1.05 times for each day spent in hospital. For every year increase in age, the risk for AEs increases by 1.3%. Cancer patients more often have hospital-acquired infections, other surgical complications and AEs related to medications. CONCLUSIONS: Because of higher age, longer length of stay and surgical treatment, hospitalised cancer patients experience AEs more often than other patients.

Is inter-rater reliability of Global Trigger Tool results altered when members of the review team are replaced?

OBJECTIVE: To evaluate the inter-rater reliability of results from Global Trigger Tool (GTT) reviews when one of the three reviewers remains consistent, while one or two reviewers rotate. DESIGN: Comparison of results from retrospective record review performed as a cross-sectional study with three review teams each consisting of two non-physicians and one physician; Team I (three consistent reviewers), Team II (one of the two non-physician reviewers or/and the physician from Team I are replaced for different review periods) and Team III (three consistent reviewers different from reviewers in Team I and Team II). SETTING: Medium-sized hospital trust in Northern Norway. PARTICIPANTS: A total of 120 records were selected as biweekly samples of 10 from discharge lists between 1 July and 31 December 2010 for a 3-fold review. INTERVENTION: Replacement of review team members was tested to assess impact on inter-rater reliability and adverse events measurment. MAIN OUTCOME MEASURES: Inter-rater reliability assessed with the Cohen kappa coefficient between different teams regarding the presence and severity level of adverse events. RESULTS: Substantial inter-rater reliability regarding the presence and severity level of adverse events was obtained between Teams I and II, while moderate inter-rater reliability was obtained between Teams I and III. CONCLUSIONS: Replacement of reviewers did not influence the results provided that one of the non-physician reviewers remains consistent. The experience of the consistent reviewer can result in continued consistency in interpretation with the new reviewer through discussion of events. These findings could encourage more hospital to rotate reviewers in order to optimize resources when using the GTT.

Effect of the World Health Organization checklist on patient outcomes: a stepped wedge cluster randomized controlled trial.

OBJECTIVES: We hypothesized reduction of 30 days' in-hospital morbidity, mortality, and length of stay postimplementation of the World Health Organization's Surgical Safety Checklist (SSC). BACKGROUND: Reductions of morbidity and mortality have been reported after SSC implementation in pre-/postdesigned studies without controls. Here, we report a randomized controlled trial of the SSC. METHODS: A stepped wedge cluster randomized controlled trial was conducted in 2 hospitals. We examined effects on in-hospital complications registered by International Classification of Diseases, Tenth Revision codes, length of stay, and mortality. The SSC intervention was sequentially rolled out in a random order until all 5 clusters-cardiothoracic, neurosurgery, orthopedic, general, and urologic surgery had received the Checklist. Data were prospectively recorded in control and intervention stages during a 10-month period in 2009-2010. RESULTS: A total of 2212 control procedures were compared with 2263 SCC procedures. The complication rates decreased from 19.9% to 11.5% (P < 0.001), with absolute risk reduction 8.4 (95% confidence interval, 6.3-10.5) from the control to the SSC stages. Adjusted for possible confounding factors, the SSC effect on complications remained significant with odds ratio 1.95 (95% confidence interval, 1.59-2.40). Mean length of stay decreased by 0.8 days with SCC utilization (95% confidence interval, 0.11-1.43). In-hospital mortality decreased significantly from 1.9% to 0.2% in 1 of the 2 hospitals post-SSC implementation, but the overall reduction (1.6%-1.0%) across hospitals was not significant. CONCLUSIONS: Implementation of the WHO SSC was associated with robust reduction in morbidity and length of in-hospital stay and some reduction in mortality.

Nationwide improvement of rectal cancer treatment outcomes in Norway, 1993-2010.

BACKGROUND: The Norwegian Rectal Cancer Project was initated in 1993 with the aims of improving surgery, decreasing local recurrence rates, improving survival, and establishing a national rectal cancer registry. Here we present results from the Norwegian Colorectal Cancer Registry (NCCR) from 1993 to 2010. MATERIAL AND METHODS: A total of 15 193 patients were diagnosed with rectal cancer in Norway 1993-2010, and were registered with clinical data regarding diagnosis, treatment, locoregional recurrences and distant metastases. Of these, 10 796 with non-metastatic disease underwent tumour resection. The results were stratified into five time periods, and the treatment outcomes were compared. Recurrence rates are presented for the 9785 patients who underwent curative major resection (R0/R1). RESULTS: Among all 15 193 patients, relative five-year survival increased from 54.1% in 1993-1997 to 63.4% in 2007-2010 (p < 0.001). Among the 10 796 patients with stage I-III disease who underwent tumour resection, from 1993-1997 to 2007-2010, relative five-year survival improved from 71.2% to 80.6% (p < 0.001). An increasing proportion of these patients underwent surgery at large-volume hospitals; and 30- and 100-day mortality rates, respectively, decreased from 3.0% to 1.4% (p < 0.001) and from 5.1% to 3.0% (p < 0.011). Use of preoperative chemoradiotherapy increased from 6.5% in 1993 to 39.0% in 2010 (p < 0.001). Estimated local recurrence rate after major resection (R0/R1) decreased from 14.5% in 1993-1997 to 5.0% in 2007-2009 (p < 0.001), and distant recurrence rate decreased from 26.0% to 20.2% (p < 0.001). CONCLUSION: Long-term outcomes from a national population-based rectal cancer registry are presented. Improvements in rectal cancer treatment have led to decreased recurrence rates of 5% and increased survival on a national level.

Anal incontinence, urinary incontinence and sexual problems in primiparous women - a comparison between women with episiotomy only and women with episiotomy and obstetric anal sphincter injury.

BACKGROUND: Obstetric anal sphincter injuries (OASIS) might cause anal incontinence (AI) and sexual dysfunction, and might be associated with urinary incontinence (UI). Episiotomy has been identified both as a risk and a protective factor of OASIS. Lately, episiotomies with specific characteristics have shown to be protective against the risk of OASIS. However, little is known about episiotomy characteristics and pelvic floor dysfunction. This study investigates AI, UI, and sexual problems in primiparous women with episiotomy, comparing women with and without OASIS. Associations between episiotomy characteristics and AI, UI, and sexual problems were assessed. METHODS: This is a matched case-control study investigating 74 women with one vaginal birth, all with an episiotomy. Among these, 37 women sustained OASIS and were compared to 37 women without OASIS. The two groups were matched for vacuum/forceps. AI, UI and sexual problem symptoms were obtained from St. Mark's scoring-tool and self-administered questionnaires. The episiotomy characteristics were investigated and results assessed for the whole group. RESULTS: The mean time from birth was 34.5 months (range1.3-78.2) for those with OASIS and 25.9 months (range 7.0-57.4) for those without OASIS, respectively. More women with OASIS reported AI: 14 (38%) vs. 3 (8%) p = 0.05 (OR 4.66, 95% CI 1.34-16.33) as well as more problem with sexual desire p = 0.02 (OR 7.62, 95% CI 1.30-44.64) compared to women without OASIS. We found no association between episiotomy with protective characteristics and dysfunctions. CONCLUSION: Women with OASIS had more AI and sexual problems than those without OASIS. Episiotomy characteristics varied greatly between the women. Episiotomy with protective characteristics was not associated with increased dysfunctions. OASIS should be avoided, and correct episiotomy used if indicated.

Exploring variation in timely reperfusion treatment in ST-segment elevation myocardial infarction in Norway: a national register-based cohort study.

OBJECTIVES: This study aimed to investigate determinants of reperfusion within recommended time limits (timely reperfusion) for ST-segment elevation myocardial infarction patients, exploring the impact of geography, patient characteristics and socio-economy. DESIGN: National register-based cohort study. SETTING: Multilevel logistic regression models were applied to examine the associations between timely reperfusion and residency in hospital referral areas and municipalities, patient characteristics, and socio-economy. PARTICIPANTS: 7607 Norwegian ST-segment elevation myocardial infarction patients registered in the Norwegian Registry of Myocardial Infarction during 2015-2018. MAIN OUTCOME MEASURES: The odds of timely reperfusion by primary percutaneous coronary intervention (PCI) or fibrinolysis. RESULTS: Among 7607 ST-segment elevation myocardial infarction patients in Norway, 56% received timely reperfusion. The Norwegian goal is 85%. While 81% of the patients living in the Oslo hospital referral area received timely reperfusion, only 13% of the patients living in Finnmark did so.Patients aged 75-84 years had lower odds of timely reperfusion than patients below 55 years of age (OR 0.73, 95% CI 0.61 to 0.87). Patients with moderate or high comorbidity had lower odds than patients without (OR 0.81, 95% CI 0.68 to 0.95 and OR 0.61, 95% CI 0.44 to 0.84). More than 2 hours from symptom onset to first medical contact gave lower odds than less than 30 min (OR 0.63, 95% CI 0.54 to 0.72). 1-2 hours of travel time to a PCI centre (OR 0.39, 95% CI 0.31 to 0.49) and more than 2 hours (OR 0.22, 95% CI 0.16 to 0.30) gave substantially lower odds than less than 1 hour of travel time. CONCLUSIONS: The varying proportion of patients receiving timely reperfusion across hospital referral areas implies inequity in fundamental healthcare services, not compatible with established Norwegian health policy. The importance of travel time to PCI centre points at the expanded use of prehospital pharmacoinvasive strategy to obtain the goals of timely reperfusion in Norway.

Sphincter training or anal injections of dextranomer for treatment of anal incontinence: a randomized trial.

OBJECTIVE: The objective is to test if the injection of a bulking agent in the anal canal is superior to sphincter training with biofeedback in the treatment of anal incontinence. BACKGROUND: Anal incontinence is traditionally treated with conservative measures, such as pads and constipating medicine. If this fails, sphincter training with biofeedback is often offered before more advanced surgical procedures are considered. The injection of a bulking agent in the anal canal is a relatively new and promising treatment option. METHODS: In a randomized, controlled, evaluator-blinded trial, 126 adult patients with anal incontinence were randomly assigned to a transanal, submucosal injection of 4 x 1 mL of dextranomer in hyaluronic acid or to sphincter training with biofeedback. The primary outcome was severity of incontinence, evaluated by St Mark's score for incontinence (0 = continence to 24 = complete incontinence) assessed at 2 years after the start of treatment. A mixed models analysis was applied. RESULTS: Of the 126 participants, 64 patients were randomly assigned to anal injections, and among them the mean St Mark's score improved from 12.9 (95% CI: 11.8-14.0) at baseline to 8.3 (95% CI: 6.7-9.8) at the end of follow up. Among the 62 patients who were assigned to sphincter training with biofeedback, there was a corresponding improvement in St Mark's score from 12.6 (95% CI: 11.4-13.8) to 7.2 (95% CI: 7.2-8.8). Comparisons of St Mark's scores between the groups showed no differences in effect between treatments. CONCLUSION: The efficacy of anal injections and biofeedback in treating anal incontinence did not differ in this randomized, single-blinded, controlled trial.

Quality of obstetric care in the sparsely populated sub-arctic area of Norway 2009-2011.

BACKGROUND: It is challenging to obtain high quality obstetric care in a sparsely populated area. In the subarctic region of Norway, significant distances, weather conditions and seasonable darkness have called for a decentralized care model. We aimed to explore the quality of this care. METHODS: A retrospective study employing data (2009-11) from the Medical Birth Registry of Norway was initiated. Northern Norwegian and Norwegian figures were compared. Midwife administered maternity units, departments at local and regional specialist hospitals were compared. National registry data on post-caesarean wound infection (2009-2010) was added. Quality of care was measured as rate of multiple pregnancies, caesarean section, post-caesarean wound infection, Apgar score <7, birth weight <2.5 kilos, perineal rupture, stillbirth, eclampsia, pregnancy induced diabetes and vacuum or forceps assisted delivery. There were 15,586 births in 15 delivery units. RESULTS: Multiple pregnancies were less common in northern Norway (1.3 vs. 1.7%) (P = 0.02). Less use of vacuum (6.6% vs. 8.3%) (P = 0.01) and forceps (0.9% vs 1.7%) (P < 0.01) assisted delivery was observed. There was no difference with regard to pregnancy induced diabetes, caesarean section, stillbirth, Apgar score < 7 and eclampsia. A significant difference in birth weight < 2.5 kilos (4.7% vs. 5.0%) (P < 0.04) and perineal rupture grade 3 and 4 (1.5% vs. 2.3%) (P < 0.02) were revealed. The post-caesarean wound infection rate was higher (10.5% vs. 7.4%) (P < 0.01). CONCLUSION: Northern Norway had an obstetric care of good quality. Birth weight, multiple pregnancies and post-caesarean wound infection rates should be further elucidated.

Risk of anastomotic leakage with use of NSAIDs after gastrointestinal surgery.

PURPOSE: Analgesic regimes to avoid opioid-related adverse effects have been recommended in gastrointestinal surgery. Non-steroidal anti-inflammatory drugs (NSAIDs) are an important component of opioid sparing regimes in that these drugs indirectly reduce pain by inhibiting inflammation. Although beneficial for most surgical patients, animal studies and recent clinical studies suggest a harmful effect on new intestinal anastomoses by increasing the rate of leakage. NSAIDs may indirectly disturb anastomotic healing by inhibiting inflammation as an integrated part of the wound healing process in an early, critical phase after surgery. METHODS: A literature review based on a structured search in PubMed of clinical and experimental studies investigating the effects of NSAIDs on anastomotic healing and leakage rates after intestinal surgery, as well as proposed mechanisms and effects studied in animal models. RESULTS: Three recent observational cohort studies (accumulated n = 882) indicate an increased rate of anastomotic leakages (15-21%) associated with cyclooxygenase-2 (COX-2) selective NSAIDs after intestinal surgery compared to the leakage rates in controls or historical cohorts (1-4%). Three prospective studies on related topics contain relevant data on NSAIDs and are compared to these studies. Several experimental animal studies support an increased risk for anastomotic leakage with the use of NSAIDs. CONCLUSION: The reported effects of NSAIDs on anastomotic healing suggest an increased risk for leakage. A better understanding of the complex interactions of NSAID-induced inhibition on anastomotic healing is a prerequisite for the safe use of NSAIDs. Until more data are available, a careful use of NSAIDs may be warranted in gastrointestinal anastomotic surgery.

Sacral nerve stimulation.

BACKGROUND: Sacral nerve stimulation implies electrical stimulation of a sacral nerve root by an electrode and a pacemaker. Within the past few years, sacral nerve stimulation has become a possible treatment option for selected patients with urinary retention, urinary incontinence, anal incontinence and constipation. The method is furthermore being tested for several other conditions. MATERIAL AND METHODS: The article presents the method and treatment results following various indications based on the authors' own experience and non-systematic PubMed search. RESULTS: During a test period an external pacemaker is used for 3-30 days, with length of test differing according to the indication. A positive test (improvement of symptoms by 50 % or more) is achieved by 70-90 % of patients with anal incontinence, 70 % with urinary non-obstructive retention, 52-77 % with urinary urge incontinence and 43-72 % with constipation. Sacral nerve stimulation may also be effective in patients with chronic pelvic pain. Following implantation of a pacemaker a sustainable effect is seen in 50-90 % of patients with a positive test. Up to 75 % of patients will need repeated follow-up including pacemaker reprogramming or reoperations due to diminished effect. The longevity of the pacemaker is 3-10 years, and it must be replaced operatively when the battery has depleted. INTERPRETATION: Treatment with sacral nerve stimulation may be efficient over time in patients with various pelvic floor dysfunctions, especially anal incontinence and non-obstructive urinary retention. Most of the patients will need close follow-up in order to maintain an optimal result.

Dynamic changes of interleukin-8 network along the colorectal adenoma-carcinoma sequence.

The interleukin-8 (IL-8) network is involved in the colorectal cancer (CRC) progression. However, its role during the adenoma-carcinoma transition to date has not been fully investigated. To evaluate the dynamic changes of IL-8 network along the colorectal adenoma-carcinoma sequence, we examined the tissue IL-8 mRNA level in colorectal biopsies from 53 colorectal adenomas, 44 CRCs and 18 controls by quantitative real-time PCR (Q-PCR), and the expressions of IL-8 and its receptors (IL-8RA and IL-8RB) in the tumor microenvironment by immunohistochemistry (IHC) and double IHCs. The results showed that the tissue IL-8 mRNA level began to increase in the precancerous lesions (adenomas) as compared with the controls and became even higher in the CRCs. Significantly, the increase of IL-8 mRNA levels was associated with the increase of dysplastic grades in the adenomas, and also paralleled to the increase of Duke's stages in the CRCs. IHC results revealed that IL-8 and its receptors, IL-8RA and IL-8RB, were observed both in the stroma and in the adenomatous/cancerous cells. By double IHCs, the IL-8 expression was characterized in macrophages, lymphocytes and myofibroblasts in the tumor stroma. Further double IHC identified the co-expression of IL-8 receptors (IL-8RA and IL-8RB) with CD34 positive tumor-associated microvessels in both the adenomas and CRCs. We, therefore, conclude that activated IL-8 network in the tumor microenvironment may function as a significant regulatory factor for the adenoma progression and the adenoma-carcinoma transition.

Progressive cellular response in the lamina propria of the colorectal adenoma-carcinoma sequence.

AIMS: The lamina propria is inevitably involved in epithelial transformation. The aim was to evaluate the dynamic cellular changes in the tumour lamina propria throughout the colorectal adenoma-carcinoma sequence. METHODS AND RESULTS: Using immunohistochemistry and double immunohistochemistry, we examined lamina propria cellular changes in 41 colorectal adenomas, 25 colorectal cancers and 15 control tissues. The results showed that the proliferation labelling index in lamina propria cells began to increase in the precancerous lesions (adenomas) and became even higher in the colorectal cancers; these proliferative cells were primarily identified as myofibroblasts and lymphocytes. Phenotypic analysis revealed gradually increasing lymphocytic infiltration in both the lamina propria and adenomatous epithelium, as well as myofibroblasts in the lamina propria. However, the intraepithelial macrophage density also showed a tendency to increase gradually. Furthermore, cyclooxygenase-2-expressing cell density and microvessel density gradually increased in the tumour lamina propria throughout the adenoma-carcinoma sequence. CONCLUSIONS: Progressive cellular responses in the lamina propria could be involved in the adenoma-carcinoma transition.

Final results of a randomised phase III study on adjuvant chemotherapy with 5 FU and levamisol in colon and rectum cancer stage II and III by the Norwegian Gastrointestinal Cancer Group.

BACKGROUND: The recommendation of adjuvant chemotherapy for colon cancer with lymph node metastases, based on two studies from USA, was reluctantly accepted by Norwegian medical doctors. It was therefore decided to assess the role of adjuvant therapy with 5fluorouracil (5-FU) combined with levamisole (Lev) in a confirmatory randomised study. MATERIAL AND METHODS: Four hundred and twenty five patients with operable colon and rectum cancer, Stage II and III (Dukes' stage B and C), were from January 1993 to October 1996, included in a randomised multicentre trial in Norway. The age limits were 18-75 years. Therapy started with a loading course of bolus i.v. 5-FU (450 mg/m(2)) daily for 5 days and p.o. doses of Lev (50 mg x 3) for 3 days. From day 28 a weekly i.v. 5-FU dose (450 mg/m(2)) were administered for 48 weeks. From day 28 also p.o. doses of Lev (50 mg x 3) for 3 days were given every 14 days. In total 214 patients were randomised to 5FU/Lev and 211 were included in the control group with surgery alone. Some did not comply with the inclusion and exclusion criteria, thus leaving 206 evaluable patients in each group. RESULTS: There was no significant survival difference between the two groups at 5 years: Disease-free survival (DFS) was 73% after chemotherapy, 68% (p=0.24) in the control group, and corresponding cancer specific survival (CSS) 75% and 71%, respectively (p=0.69). There was no difference between the two groups when analysed for colon and rectum separately. However, the subgroup of colon cancer with stage III exhibited a statistically significant difference both for DFS, 58% vs. 37% (p=0.012) and CSS, 65% vs. 47% (p=0.032) in favour of adjuvant chemotherapy. The benefit was further statistically significant for women but not for men. Toxicity was generally mild and acceptable with no drug related fatalities. CONCLUSIONS: Colon cancer patients with lymph node metastases benefit from adjuvant chemotherapy with 5-FU/Lev with acceptable toxicity. In a subgroup analysis females did better than males. Rectal cancer does not benefit from this regimen.

Contribution of adverse events to death of hospitalised patients.

Background: There is no standardised method to investigate death as a patient safety indicator and we need valid and reliable measurements to use adverse events contributing to death as a quality measure. Objective: To investigate the contribution of severe adverse events to death in hospitalised patients and clarify methodological differences using the Global Trigger Tool method on all inpatient deaths compared with a sample of general hospitalised patients. Method: Retrospective records reviewing using the Global Trigger Tool method. Results: In 0.3% of hospital admissions, adverse events contribute to inpatient death. Patients who die in hospital have twice the rate of adverse events per 1000 patient days compared with general patients, 76.7 vs 36.5 (p<0.001, RR 2.10, 95% CI 1.79 to 2.47). Patients dying in hospital experience seven times the rate of severe adverse events, 38.4% vs 5.2% (p<0.001, RR 2.10, 95% CI 1.79 to 2.47). For 86 out of 377 inpatient deaths, the adverse event is so severe that it contributes to death. 27.9% of severe adverse events contributing to death originate in primary care. Lower respiratory infections (p<0.001, RR 2.81, 95% CI 1.76 to 4.51), medication harm (p<0.001, RR 5.21, 95% CI 3.04 to 8.94) and pressure ulcers (p=0.04, RR 2.23, 95% CI 1.03 to 4.85) are significantly more frequent for inpatient deaths than in the general sample of hospital patients. Conclusions: Patients dying in hospitals experience seven times the rate of severe adverse events. Reviewing all inpatient death by the Global Trigger Tool method discloses new valid and reliable data of severe adverse events contributing to death which otherwise would be undetected.

Dendritic cell infiltration pattern along the colorectal adenoma-carcinoma sequence.

We have previously reported that the dendritic cell (DC) functional index cytokine interleukin-12 was significantly decreased in colorectal carcinoma (CRC) tissues. In this study, the DC infiltration pattern and the density of mature DCs (mDCs; labeled by anti-CD83 and anti-CD208) and immature DCs (iDCs; labeled by anti-CD1alpha) were characterized using immunohistochemistry (IHC) in tissue samples from 23 patients with CRC, 33 patients with colorectal adenoma (CRA), and 19 healthy controls. In addition, the DC function inhibitor cyclooxygenase-2 (COX-2) and the downstream signal molecule prostaglandin E2 (PGE2) and related receptors EP2/EP4 were measured by quantitative real-time PCR and double immunofluorescence staining. The IHC analyses revealed changed densities of mDCs and iDCs in the tumor microenvironment; in CRA and CRC, the density of mDCs was decreased, but the density of iDCs was gradually increased. Furthermore, the distribution patterns of DCs were also altered. In CRA, mDCs were abundantly distributed in the subepithelial stroma of the adenomatous mass. In CRC, the distribution of mDCs in the tumor stroma was not homogeneous, and mDCs residing in the stroma at invading edges were more frequently found compared with in the intratumoral stroma (P<0.05). Increased iDCs were found in the intratumoral mass in CRC, and some infiltrated into the malignant epithelium. By quantitative real-time PCR, a gradually increased level of COX-2 mRNA was demonstrated in the local tissues along the adenoma-carcinoma sequence, and double immunofluorescence staining showed a colocalization of PGE2 receptors EP2/EP4 with mDCs in the stroma of CRC. In conclusion, our current findings revealed an altered DC infiltration pattern along the adenoma-carcinoma sequence; gradually increased COX-2 expression might contribute to the DC functional defect.

Should the surgeon or the general practitioner (GP) follow up patients after surgery for colon cancer? A randomized controlled trial protocol focusing on quality of life, cost-effectiveness and serious clinical events.

BACKGROUND: All patients who undergo surgery for colon cancer are followed up according to the guidelines of the Norwegian Gastrointestinal Cancer Group (NGICG). These guidelines state that the aims of follow-up after surgery are to perform quality assessment, provide support and improve survival. In Norway, most of these patients are followed up in a hospital setting. We describe a multi-centre randomized controlled trial to test whether these patients can be followed up by their general practitioner (GP) without altering quality of life, cost effectiveness and/or the incidence of serious clinical events. METHODS AND DESIGN: Patients undergoing surgery for colon cancer with histological grade Dukes's Stage A, B or C and below 75 years of age are eligible for inclusion. They will be randomized after surgery to follow-up at the surgical outpatient clinic (control group) or follow-up by the district GP (intervention group). Both study arms comply with the national NGICG guidelines. The primary endpoints will be quality of life (QoL) (measured by the EORTC QLQ C-30 and the EQ-5D instruments), serious clinical events (SCEs), and costs. The follow-up period will be two years after surgery, and quality of life will be measured every three months. SCEs and costs will be estimated prospectively. The sample size was 170 patients. DISCUSSION: There is an ongoing debate on the best method of follow-up for patients with CRC. Due to a wide range of follow-up programmes and paucity of randomized trials, it is impossible to draw conclusions about the best combination and frequency of clinic (or family practice) visits, blood tests, endoscopic procedures and radiological examinations that maximize the clinical outcome, quality of life and costs. Most studies on follow-up of CRC patients have been performed in a hospital outpatient setting. We hypothesize that postoperative follow-up of colon cancer patients (according to national guidelines) by GPs will not have any impact on patients' quality of life. Furthermore, we hypothesize that there will be no increase in SCEs and that the incremental cost-effectiveness ratio will improve. TRIAL REGISTRATION: This trial has been registered at ClinicalTrials.gov. The trial registration number is: NCT00572143.

The one-stop trial: does electronic referral and booking by the general practitioner (GPs) to outpatient day case surgery reduce waiting time and costs? A randomized controlled trial protocol.

BACKGROUND: Waiting time and costs from referral to day case outpatient surgery are at an unacceptably high level. The waiting time in Norway averages 240 days for common surgical conditions. Furthermore, in North Norway the population is scattered throughout a large geographic area, making the cost of travel to a specialist examination before surgery considerable. Electronic standardised referrals and booking of day case outpatient surgery by GPs are possible through the National Health Network, which links all health care providers in an electronic network. New ways of using this network might reduce the waiting time and cost of outpatient day case surgery. MATERIALS AND METHODS: In a randomised controlled trial, selected patients (inguinal hernia, gallstone disease and pilonidal sinus) referred to the university hospital are either randomised to direct electronic referral and booking for outpatient surgery (one stop), or to the traditional patient pathway where all patients are seen at the outpatient clinic several weeks ahead of surgery. Consultants in gastrointestinal surgery designed standardised referral forms and guidelines. New software has been designed making it possible to implement referral forms, guidelines and patient information in the GP's electronic health record. For "one-stop" referral, GPs must provide mandatory information about the specific condition. Referrals were linked to a booking system, enabling the GPs to book the hospital, day and time for outpatient surgery. The primary endpoints are waiting time and costs. The sample size calculation was based on waiting time. A reduction in waiting time of 60 days (effect size), 25%, is significant, resulting in a sample size of 120 patients in total. DISCUSSION: Poor communication between primary and secondary care often results in inefficiencies and unsatisfactory outcomes. We hypothesised that standardised referrals would improve the quality of information, making it feasible to use a one-stop approach for all patients undergoing surgery on an outpatient basis for inguinal hernia, pilonidal sinus and gallstones. In this study we wanted to investigate the waiting time and cost-effectiveness of direct electronic referral and booking of outpatient surgery compared to the traditional patient pathway, where the patient is seen at the outpatient clinic prior to surgery. TRIAL REGISTRATION: This trial has been registered at ClinicalTrials.gov. The trial registration number is: NCT00692497.