Time to Surgery Following Short-Course Radiotherapy in Rectal Cancer and its Impact on Postoperative Outcomes. A Population-Based Study Across the English National Health Service, 2009-2014.

AIMS: Preoperative short-course radiotherapy (SCRT) is an important treatment option for rectal cancer. The length of time between completing SCRT and surgery may influence postoperative outcomes, but the evidence available to determine the optimal interval is limited and often conflicting. MATERIALS AND METHODS: Information was extracted from a colorectal cancer data repository (CORECT-R) on all surgically treated rectal cancer patients who received SCRT in the English National Health Service between April 2009 and December 2014. The time from radiotherapy to surgery was described across the population. Thirty-day postoperative mortality, returns to theatre, length of stay and 1-year survival were investigated in relation to the interval between radiotherapy and surgery. RESULTS: Within the cohort of 3469 patients, the time to surgery was 0-7 days for 76% of patients, 8-14 days for 19% of patients and 15-27 days for 5% of patients. There was a clear variation in relation to different patient characteristics. There was, however, no evidence of differences in postoperative outcomes in relation to interval length. CONCLUSIONS: This study suggests that the time interval between SCRT and surgery does not influence postoperative outcomes up to a year after surgery. The study provides population-level, real-world evidence to complement that from clinical trials.

Wide Variation in the Use of Radiotherapy in the Management of Surgically Treated Rectal Cancer Across the English National Health Service.

AIMS: Radiotherapy is an important treatment modality in the multidisciplinary management of rectal cancer. It is delivered both in the neoadjuvant setting and postoperatively, but, although it reduces local recurrence, it does not influence overall survival and increases the risk of long-term complications. This has led to a variety of international practice patterns. These variations can have a significant effect on commissioning, but also future clinical research. This study explores its use within the large English National Health Service (NHS). MATERIALS AND METHODS: Information on all individuals diagnosed with a surgically treated rectal cancer between April 2009 and December 2010 were extracted from the Radiotherapy Dataset linked to the National Cancer Data Repository. Individuals were grouped into those receiving no radiotherapy, short-course radiotherapy with immediate surgery (SCRT-I), short-course radiotherapy with delayed surgery (SCRT-D), long-course chemoradiotherapy (LCCRT), other radiotherapy (ORT) and postoperative radiotherapy (PORT). Patterns of use were then investigated. RESULTS: The study consisted of 9201 individuals; 4585 (49.3%) received some form of radiotherapy. SCRT-I was used in 12.1%, SCRT-D in 1.2%, LCCRT in 29.5%, ORT in 4.7% and PORT in 2.3%. Radiotherapy was used more commonly in men and in those receiving an abdominoperineal excision and less commonly in the elderly and those with comorbidity. Significant and substantial variations were also seen in its use across all the multidisciplinary teams managing this disease. CONCLUSION: Despite the same evidence base, wide variation exists in both the use of and type of radiotherapy delivered in the management of rectal cancer across the English NHS. Prospective population-based collection of local recurrence and patient-reported early and late toxicity information is required to further improve patient selection for preoperative radiotherapy.

The Effect of the UK Coordinating Centre for Cancer Research Anal Cancer Trial (ACT1) on Population-based Treatment and Survival for Squamous Cell Cancer of the Anus.

Between 1987 and 1994, three randomised phase III trials showed that chemoradiotherapy with mitomycin C and 5-fluorouracil was superior to radiotherapy alone (ACT1, European Organization for Research and Treatment of Cancer) or radiotherapy with 5-fluorouracil (Radiation Therapy Oncology Group 87-04, Eastern Cooperative Oncology Group 1289) for squamous cell carcinoma of the anus. We explored the population-based changes in England before, during and after the UK-based ACT1 trial. Information was extracted from the National Cancer Data Repository on patients diagnosed with squamous cell anal cancer in England between 1981 and 2010 (n = 11 743). Robust treatment information was available for the Yorkshire region (n = 1065). Changes in treatment patterns and 3 year survival were investigated in 7 year cohorts before, during and after the ACT1 trial. In Yorkshire, the proportion of patients receiving surgery alone fell from 61.6% before, 29.8% during and 12.5% after ACT1; the proportion of patients receiving primary chemoradiotherapy rose from 6.5% before, 17.7% during and 58.8% after ACT1 and continued to rise to 70.3% in the subsequent period. Three year survival improved during the study period from 59.5% (95% confidence interval 56.6-62.2) before ACT1 to 73.6% (95% confidence interval 71.9-75.2) after the trial. Survival in Yorkshire was comparable with that in England. The treatment for squamous cell carcinoma of the anus changed dramatically during the study period. The predominant use of surgery before ACT1, a transition phase during the trial and a dramatic increase in the use of chemoradiotherapy after ACT1 provide strong evidence of the effect of the trial on population-based practice. Survival continued to increase during this period.

Model for risk adjustment of postoperative mortality in patients with colorectal cancer.

BACKGROUND: A model was developed for risk adjustment of postoperative mortality in patients with colorectal cancer in order to make fair comparisons between healthcare providers. Previous models were derived in relatively small studies with the use of suboptimal modelling techniques. METHODS: Data from adults included in a national study of major surgery for colorectal cancer were used to develop and validate a logistic regression model for 90-day mortality. The main risk factors were identified from a review of the literature. The association with age was modelled as a curved continuous relationship. Bootstrap resampling was used to select interactions between risk factors. RESULTS: A model based on data from 62 314 adults was developed that was well calibrated (absolute differences between observed and predicted mortality always smaller than 0·75 per cent in deciles of predicted risk). It discriminated well between low- and high-risk patients (C-index 0·800, 95 per cent c.i. 0·793 to 0·807). An interaction between age and metastatic disease was included as metastatic disease was found to increase postoperative risk in young patients aged 50 years (odds ratio 3·53, 95 per cent c.i. 2·66 to 4·67) far more than in elderly patients aged 80 years (odds ratio 1·48, 1·32 to 1·66). CONCLUSION: Use of this model, estimated in the largest number of patients with colorectal cancer to date, is recommended when comparing postoperative mortality of major colorectal cancer surgery between hospitals, clinical teams or individual surgeons.

Identifying patients at risk of emergency admission for colorectal cancer.

BACKGROUND: Patients whose colorectal cancer is treated after an emergency admission tend to have late-stage cancer and a poor prognosis. We identified risk factors for an emergency admission by linking data from the National Bowel Cancer Audit (NBCA) and the English Hospital Episode Statistics (HES), an administrative database of all admissions to English National Health Service hospitals, which includes data on mode of admission. METHODS: We identified all adults included in the NBCA with a primary diagnosis of bowel cancer, excluding cancer of the appendix, between August 2007 and July 2011 whose record could be linked to HES. Multivariable logistic regression was used to estimate adjusted odds ratios (OR) for an emergency admission for colorectal cancer. All risk factors were adjusted for cancer site and calendar year. RESULTS: 97,909 adults were identified with a primary diagnosis of bowel cancer and 82,777 patients could be linked to HES. Patients who were older, female, of a non-white ethnic background, and more socioeconomically deprived, and those with dementia or cardiac, neurologic and liver disease had an increased risk of presenting as an emergency admission. The strongest risk factors were age (90 compared with 70 years: OR 2.99, 95% CI 2.84 to 3.15), dementia (OR 2.46, 2.18 to 2.79), and liver disease (OR 1.87, 1.69 to 2.08). CONCLUSIONS: Our study identifies risk factors that may impair health-seeking behaviour and access to healthcare. An earlier recognition of symptoms in patients with these risk factors may contribute to better outcomes.

The rising incidence of anal cancer in England 1990-2010: a population-based study.

AIM: Although anal cancer is rare, its incidence has been reported to be rising in several countries. This study aimed to determine whether there have been any changes in incidence over time in England. METHOD: In the cancer registry component of the English National Cancer Data Repository, 13 940 patients were identified with a primary diagnosis of anal cancer made between 1990 and 2010. Tumours were grouped according to the ICD-O morphology codes into squamous cell carcinoma, basaloid and cloacogenic carcinoma, adenocarcinoma and other cancer types. The incidence over this period was investigated in relation to type of tumour, age and sex. RESULTS: In men there was a 69% increase in squamous cell anal carcinoma from 0.43 per 100 000 population in 1990-94 to 0.73 in 2006-10. For women these rates were 0.50 in 1990-94 and 1.13 in 2006-10, a rise of 126%. CONCLUSION: The study showed that between 1990 and 2010 there was a substantial rise in the incidence of anal cancer in England. This effect was more marked in women than men.

Gastrointestinal ostomies and sexual outcomes: a comparison of colorectal cancer patients by ostomy status.

PURPOSE: Research examining effects of ostomy use on sexual outcomes is limited. Patients with colorectal cancer were compared on sexual outcomes and body image based on ostomy status (never, past, and current ostomy). Differences in depression were also examined. METHODS: Patients were prospectively recruited during clinic visits and by tumor registry mailings. Patients with colorectal cancer (N = 141; 18 past ostomy; 25 current ostomy; and 98 no ostomy history) completed surveys assessing sexual outcomes (medical impact on sexual function, Female Sexual Function Index, International Index of Erectile Function), body image distress (Body Image Scale), and depressive symptoms (Center for Epidemiologic Studies Depression Scale-Short Form). Clinical information was obtained through patient validated self-report measures and medical records. RESULTS: Most participants reported sexual function in the dysfunctional range using established cut-off scores. In analyses adjusting for demographic and medical covariates and depression, significant group differences were found for ostomy status on impact on sexual function (p < .001), female sexual function (p = .01), and body image (p < .001). The current and past ostomy groups reported worse impact on sexual function than those who never had an ostomy (p < .001); similar differences were found for female sexual function. The current ostomy group reported worse body image distress than those who never had an ostomy (p < .001). No differences were found across the groups for depressive symptoms (p = .33) or male sexual or erectile function (p values ≥ .59). CONCLUSIONS: Colorectal cancer treatment puts patients at risk for sexual difficulties and some difficulties may be more pronounced for patients with ostomies as part of their treatment. Clinical information and support should be offered.

Nonresectional management of colorectal cancer: multidisciplinary factors that influence treatment strategy.

AIM: Surgical resection of a primary colorectal tumour remains the treatment of choice and offers the best chance of cure. However, in some patients, resection is not achieved. There are few published data on this group of patients. The aim of this study was to evaluate this group to determine the frequency and reasons for nonresection, and to analyse the subsequent management. METHOD: A retrospective review was performed using a Trust colorectal cancer database and individual electronic patient records. Patients who presented to our unit with a diagnosis of primary colorectal cancer managed by nonresectional intervention over a 2-year period were identified. Data analysed included: patient demographics, radiological staging, histological data, nonsurgical therapy, tumour-specific complications and requirement for palliative surgical procedures. RESULTS: A total of 671 patients were identified with primary colorectal cancer. One hundred and fifty-six (23%) were managed without resection, following discussion at a multidisciplinary team meeting. Of 156 patients, histological confirmation was obtained in 131 (84%), with the remainder of the diagnoses being based on unequivocal radiological imaging and/or operative findings. Complete radiological staging was achieved in 150 (96%) patients. The predominant reasons for nonresectional management were: advanced metastatic disease (66%), significant medical comorbidity (19%) and patient refusal (6%). Fifty-nine of 156 patients (38%) subsequently received palliative chemotherapy, 9 (6%) radiotherapy and or 9 (6%) combination chemo-radiotherapy. Seventy-nine (51%) of 156 patients received no therapy other than best supportive palliative care, for reasons including significant medical comorbidity (62%) and patient refusal (19%). Following the initial decision not to resect, 68 (44%) patients did at some point undergo some form of palliative intervention (stenting, stoma or bypass) for obstruction - 44 (28%) electively and 24 (15%) as an emergency. CONCLUSION: Nonresectional management of patients with primary colorectal cancer is not an uncommon outcome following discussion at a multidisciplinary meeting. In these patients, nonsurgical palliation should be employed when necessary, though is frequently limited by comorbidity. However, subsequent surgical palliation is still required in a substantial proportion of cases.

Fecal lactoferrin: a noninvasive fecal biomarker for the diagnosis and surveillance of pouchitis.

BACKGROUND: Fecal lactoferrin is a marker of intestinal inflammation and can be assessed with a simple qualitative immunochromatographic rapid test. OBJECTIVE: We aimed to assess the sensitivity and specificity of the test in the diagnosis of pouchitis and evaluate its clinical utility in the surveillance of inflammation of the pouch after antibiotic therapy. DESIGN: Between October 2005 and September 2009, we recruited a consecutive series of patients who had their ileal pouch examined under a general anesthetic. Distinctions between healthy and inflamed pouches were made by the use of the Pouch Disease Activity Index. Fecal samples were taken before biopsy of the pouch, and a clinician blinded to the examination findings performed the lactoferrin test. After antimicrobial treatment, a number of patients with pouchitis had a repeat examination and lactoferrin test. RESULTS: There were 85 (41 male) patients. Median age was 42 (interquartile range, 36-49) years. Twenty-four patients had pouchitis. The test was positive in all 24 patients with pouchitis and 5 patients with a healthy pouch. The sensitivity and specificity of the test for pouchitis was 100% and 92%. The positive predictive value was 82%. In 7 patients who received antibiotic treatment for their pouchitis, the test was able to accurately predict the resolution and/or persistence of pouchitis. CONCLUSION: The qualitative fecal lactoferrin rapid test is a sensitive method for the diagnosis and confirmation of resolution of pouchitis. The test provides clinicians with greater confidence in the prescription of antibiotics for suspected pouchitis and its surveillance.

A retrospective observational study of the relationship between family history and survival from colorectal cancer.

BACKGROUND: Although family history is well established to be a risk factor for developing colorectal cancer (CRC), much less is known about its impact on patient survival. This study aimed to link CRC patient data from the National Study of Colorectal Cancer Genetics (NSCCG) to the National Cancer Data Repository (NCDR) to examine the relationship between family history and the characteristics and outcomes of CRC. METHODS: All eligible NSCCG patients underwent a matching process to the NCDR using combinations of their personal identifiers. The characteristics and survival of CRC patients with and without a family history of CRC were compared. RESULTS: Of the 10 937 NSCCG patients eligible to be matched into the NCDR, 10 782 (98.6%) could be fully linked. There were no significant differences between those with and without a family history of CRC (defined as having at least one affected first-degree relative) in terms of age, sex, tumour stage at diagnosis, presence of multiple cancers, mode of presentation to hospital and surgical management, although patients with familial CRC were more likely to have right-sided tumours (P<0.01). The survival of patients with familial CRC was significantly better than those with sporadic CRC (HR 0.89, 95%CI: 0.81-0.98, P=0.02). CONCLUSION: We have demonstrated that it is possible to robustly match patients recruited into the NSCCG into the NCDR and, by using this record linkage, enable genetic data to be related to CRC phenotype, clinical management and outcome. This study provides evidence that a family history of CRC is associated with better survival after a diagnosis of CRC.

Population-based study of laparoscopic colorectal cancer surgery 2006-2008.

BACKGROUND: Clinical guidelines recommend that, where clinically appropriate, laparoscopic tumour resections should be available for patients with colorectal cancer. This study aimed to examine the introduction of laparoscopic surgery in the English National Health Service. METHODS: Data were extracted from the National Cancer Data Repository on all patients who underwent major resection for a primary colorectal cancer diagnosed between 2006 and 2008. Laparoscopic procedures were identified from codes in the Hospital Episode Statistics and National Bowel Cancer Audit Project data in the resource. Trends in the use of laparoscopic surgery and its influence on outcomes were examined. RESULTS: Of 58 135 resections undertaken over the study period, 10 955 (18·8 per cent) were attempted laparoscopically. This increased from 10·0 (95 per cent confidence interval (c.i.) 8·1 to 12·0) per cent in 2006 to 28·4 (25·4 to 31·4) per cent in 2008. Laparoscopic surgery was used less in patients with advanced disease (modified Dukes' stage 'D' versus A: odds ratio (OR) 0·45, 95 per cent c.i. 0·40 to 0·50), rectal tumours (OR 0·71, 0·67 to 0·75), those with more co-morbidity (Charlson score 3 or more versus 0: OR 0·69, 0·58 to 0·82) or presenting as an emergency (OR 0·15, 0·13 to 0·17). A total of 1652 laparoscopic procedures (15·1 per cent) were converted to open surgery. Conversion was more likely in advanced disease (modified Dukes' stage 'D' versus A: OR 1·56, 1·20 to 2·03), rectal tumours (OR 1·29, 1·14 to 1·46) and emergencies (OR 2·06, 1·54 to 2·76). Length of hospital stay (OR 0·65, 0·64 to 0·66), 30-day postoperative mortality (OR 0·55, 0·48 to 0·64) and risk of death within 1 year (hazard ratio 0·60, 0·55 to 0·65) were reduced in the laparoscopic group. CONCLUSION: Laparoscopic surgery was used more frequently in low-risk patients.

Early mortality from colorectal cancer in England: a retrospective observational study of the factors associated with death in the first year after diagnosis.

BACKGROUND: The United Kingdom performs poorly in international comparisons of colorectal cancer survival with much of the deficit owing to high numbers of deaths close to the time of diagnosis. This retrospective cohort study investigates the patient, tumour and treatment characteristics of those who die in the first year after diagnosis of their disease. METHODS: Patients diagnosed with colon (n=65,733) or rectal (n=26,123) cancer in England between 2006 and 2008 were identified in the National Cancer Data Repository. Multivariable logistic regression was used to investigate the odds of death within 1 month, 1-3 months and 3-12 months after diagnosis. RESULTS: In all, 11.5% of colon and 5.4% of rectal cancer patients died within a month of diagnosis: this proportion decreased significantly over the study period. For both cancer sites, older age, stage at diagnosis, deprivation and emergency presentation were associated with early death. Individuals who died shortly after diagnosis were also more likely to have missing data about important prognostic factors such as disease stage and treatment. CONCLUSION: Using routinely collected data, at no inconvenience to patients, we have identified some important areas relating to early deaths from colorectal cancer, which merit further research.

A retrospective observational study examining the characteristics and outcomes of tumours diagnosed within and without of the English NHS Bowel Cancer Screening Programme.

BACKGROUND: Colorectal cancer is common in England and, with long-term survival relatively poor, improving outcomes is a priority. A major initiative to reduce mortality from the disease has been the introduction of the National Health Service (NHS) Bowel Cancer Screening Programme (BCSP). Combining data from the BCSP with that in the National Cancer Data Repository (NCDR) allows all tumours diagnosed in England to be categorised according to their involvement with the BCSP. This study sought to quantify the characteristics of the tumours diagnosed within and outside the BCSP and investigate its impact on outcomes. METHODS: Linkage of the NCDR and BCSP data allowed all tumours diagnosed between July 2006 and December 2008 to be categorised into four groups; screen-detected tumours, screening-interval tumours, tumours diagnosed in non-participating invitees and tumours diagnosed in those never invited to participate. The characteristics, management and outcome of tumours in each category were compared. RESULTS: In all, 76 943 individuals were diagnosed with their first primary colorectal cancer during the study period. Of these 2213 (2.9%) were screen-detected, 623 (0.8%) were screening-interval cancers, 1760 (2.3%) were diagnosed in individuals in non-participating invitees and 72 437 (94.1%) were diagnosed in individuals not invited to participate in the programme due to its ongoing roll-out over the time period studied. Screen-detected tumours were identified at earlier Dukes' stages, were more likely to be managed with curative intent and had significantly better outcomes than tumours in other categories. CONCLUSION: Screen-detected cancers had a significantly better prognosis than other tumours and this would suggest that the BCSP should reduce mortality from colorectal cancer in England.

Defunctioning stomas prior to chemoradiation for anal cancer are usually permanent.

AIM: A few patients with anal cancer will require a defunctioning stoma prior to chemoradiotherapy (CRT). The purpose of this retrospective review was to determine the frequency with which a pretreatment stoma was subsequently reversed. METHOD: Between 1997 and 2007, 46/344 patients who were treated for anal cancer underwent a defunctioning stoma prior to CRT. Thirty-five of these were treated with curative intent. RESULTS: Of the 35 patients, 16 patients had T4, 17 T3 and 2 T2 disease. Sixteen were node positive. The average tumour size was 7 cm. The median interval between stoma formation and CRT was 6 (4-20) weeks. The median follow up was 26 (2-80) months. A defunctioning stoma was performed for rectovaginal fistula or risk of fistula in 18 and severe local symptoms in 17. Seven (20%) patients had the stoma reversed subsequently. The reasons for nonreversal were progressive disease (n = 9), persistent fistula (n = 3), predicted poor function (n = 4), cavity formation (n = 1), fibrosis (n = 3), death from another cause (n = 2), patient choice (n = 3) and salvage surgery (n = 2). The overall 3-year survival was only 48%, explained by the advanced stage of disease at presentation. CONCLUSION: Most patients who undergo a defunctioning stoma before CRT will not undergo subsequent reversal. The patient should therefore be informed that the stoma is likely to be permanent and this should be taken into account when considering the type and site of stoma to be formed.

Low abdominoperineal excision rates are associated with high-workload surgeons and lower tumour height. Is further specialization needed?

AIM: Wide variation, independent of disease extent and case mix, has been observed in the rate of use of abdominoperineal excision (APE) for rectal cancer. Previous analyses have, however, been confounded by failure to adjust for the location of the tumour within the rectum. This population-based study sought to examine whether variations in tumour height explained differences in APE use. METHOD: Information was obtained on all individuals who underwent a major resection for a rectal tumour diagnosed between 1998 and 2005 across the Northern and Yorkshire regions of the UK. Median distances from the dentate line were calculated for all tumours excised by APE and compared with rates of use of APE between specialists and nonspecialist surgeons and across hospital trusts. RESULTS: The completeness of pathological reporting of height of tumour within the rectum was variable. A low rate of APE use was associated with a lower median distance of tumours from the dentate line. Specialist colorectal cancer surgeons performed fewer APEs on patients with a tumour located lower in the rectum than nonspecialist surgeons. CONCLUSION: Variations in the height of tumour did not explain the variation in APE use. Specialist high-volume surgeons undertook fewer APEs and those they performed were closer to the dentate line than low-volume nonspecialist surgeons.

Measurement of anal cushions in continent women.

AIM: Anal cushions are connective tissue complexes thought to be involved in anal continence. This study aimed to assess them in continent subjects. METHOD: Continent women undergoing a transvaginal ultrasound scan for gynaecological reasons were included. The anal cushions were visualized at the mid-canal level. The cross-sectional area within the internal anal sphincter (Area 1) and the area enclosed within the anal cushions (Area 2) were measured and a Cushion:Canal (C:C) ratio was derived for each patient. The measurements were repeated in the semi-erect position. RESULTS: One hundred and two patients with a median age of 41 (IQR 32-49) years were included. The median C:C ratio was 0.68 (IQR 0.61-0.73). Inter-observer error was 0.98 and intra-observer error was 0.99. There was no significant correlation between age and C:C ratio. The C:C ratio was significantly higher in parous than in nulliparous women (P = 0.04). A history of obstetric trauma or minimal haemorrhoidal symptoms did not influence C:C ratio. There was a significant increase in C:C ratio in the erect position. (P = 0.04). CONCLUSION: There was a wide range of variability in the measurement of anal cushions in normal continent women. These were not influenced by age.

Prognostic factors for survival after curative resection of Dukes' B colonic cancer.

AIM: Data on the prognostic factors for survival in patients with locally advanced, node-negative colon cancer are limited. This study aimed to determine which factors might predict survival in patients with Dukes' B (T3 or T4, N0) colon cancer. METHOD: One hundred and eighty (93 male; median age 75 [range, 38-96] years) consecutive patients who had resection of a primary Dukes' B (on final histopathological analysis) colonic cancer between 1998 and 2003 were studied. No patient received neoadjuvant chemotherapy. Multivariate Cox regression modelling was used to assess the prognostic value of variables. Median follow up was 85 (60-125) months. RESULTS: Thirteen (7%) patients had a perforation at presentation. The median distance from tumour to the nearest longitudinal resection margin was 6 (0.3-27) cm. One hundred and twenty-four (69%) patients had a lymph node yield of 12 or more nodes. Actual 5-year survival was 59%. On multivariate regression analysis, tumour perforation (perforation vs no perforation, 5-year survival, 23%vs 61%; hazard ratio (HR), 3.7; 95% confidence interval (CI), 1.6-8.4; P = 0.002), tumour-to-margin distance (< 5 cm vs ≥ 5 cm, 48%vs 65%; HR, 1.7; 95% CI, 1.1-2.7; P = 0.039) and older age (≥ 75 years vs < 75 years, 45%vs 72%; HR, 3; 95% CI, 1.8-5; P < 0.001) were independent significant variables. CONCLUSION: A lymph node yield of 12 or more nodes is not a significant prognostic factor for survival after resection of Dukes' B colonic cancer. Patients with tumour perforation or limited resection have worse prognosis.

Interplay of concurrent positive and negative interpersonal events in the prediction of daily negative affect and fatigue for rheumatoid arthritis patients.

OBJECTIVE: The purpose of this study was to examine the interaction of daily concurrent positive interpersonal events (PIE) and negative interpersonal events (NIE) on the daily experience of negative affect and fatigue in a sample of men and women with rheumatoid arthritis. Two hypotheses were made. The blunting hypothesis predicted that NIE would nullify the beneficial influence of PIE on outcome measures, and the buffering hypothesis predicted that PIE would offset the adverse influence of NIE. DESIGN: Participants completed up to 30 consecutive daily diaries. Multilevel modeling was used to examine the day-to-day dependencies among study variables. MAIN OUTCOME MEASURES: The primary outcomes were daily negative affect and fatigue. RESULTS: In support of the blunting hypothesis, on days when NIE were diminished, PIE were associated with a greater reduction in fatigue. In contrast, consistent with the buffering hypothesis, on days when PIE were elevated, NIE were associated with a lesser increase in negative affect. CONCLUSION: The examination of concurrent PIE and NIE provides a unique perspective on the role of interpersonal events in affective and physiological outcomes, beyond that which can be gained from the examination of either type of event in isolation.