Fredrik Mattsson

Contextual social capital as a risk factor for poor self-rated health: a multilevel analysis.

In this study, we critically examine whether contextual social capital (CSC) is associated with self-rated health, with an emphasis on the problem of confounding. We also examine different components of CSC and their association with self-rated health. Finally, we look at differences in susceptibility between different socio-demographic groups. We use the cross-sectional base line study of the Stockholm Public Health Cohort, conducted in 2002. A postal questionnaire was answered by 31,182 randomly selected citizens, 18-84 years old, in Stockholm County. We used four measures of social capital: horizontal (civic trust and participation), vertical (political trust and participation), cognitive (civic and political trust) and structural (civic and political participation). CSC was measured at parish level from aggregated individual data, and multilevel regression procedures were employed. We show a twofold greater risk of poor self-rated health in areas with very low CSC compared with areas with very high CSC. Adjustments for individual socio-demographic factors, contextual economic factors and individual social capital lowered the excess risk. Simultaneous adjustment for all three forms of confounding further weakened the association and rendered it insignificant. Cognitive and structural social capital show relatively similar associations with self-rated health, while horizontal CSC seems to be more strongly related to self-rated health than vertical CSC. In conclusion, whether there is none or a moderate association between CSC and self-rated health, depends on the extent to which individual social capital is seen as a mediator or confounder. The association with self-rated health is similar independent of the measure of CSC used. It is also similar in different socio-demographic groups.

Tumor Stage After Neoadjuvant Chemotherapy Determines Survival After Surgery for Adenocarcinoma of the Esophagus and Esophagogastric Junction

PURPOSE Neoadjuvant chemotherapy is established in the management of most resectable esophageal and esophagogastric junction adenocarcinomas. However, assessing the downstaging effects of chemotherapy and predicting response to treatment remain challenging, and the relative importance of tumor stage before and after chemotherapy is debatable. METHODS We analyzed consecutive resections for esophageal or esophagogastric junction adenocarcinomas performed at two high-volume cancer centers in London between 2000 and 2010. After standard investigations and multidisciplinary team consensus, all patients were allocated a clinical tumor stage before treatment, which was compared with pathologic stage after surgical resection. Survival analysis was conducted using Kaplan-Meier analysis and Cox regression analysis. RESULTS Among 584 included patients, 400 patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors after neoadjuvant chemotherapy experienced improved survival compared with patients without response (P < .001), and such downstaging (hazard ratio, 0.43; 95% CI, 0.31 to 0.59) was the strongest independent predictor of survival after adjusting for patient age, tumor grade, clinical tumor stage, lymphovascular invasion, resection margin status, and surgical resection type. Patients downstaged by chemotherapy, compared with patients with no response, experienced lower rates of local recurrence (6% v. 13%, respectively; P = .030) and systemic recurrence (19% v. 29%, respectively; P = .027) and improved Mandard tumor regression scores (P = .001). Survival was strongly dictated by stage after neoadjuvant chemotherapy, rather than clinical stage at presentation. CONCLUSION The stage of esophageal or esophagogastric junction adenocarcinoma after neoadjuvant chemotherapy determines prognosis rather than the clinical stage before neoadjuvant chemotherapy, indicating the importance of focusing on postchemotherapy staging to more accurately predict outcome and eligibility for surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from reduced rates of local and systemic recurrence.

Complications after percutaneous endoscopic gastrostomy in a prospective study

Abstract Background. Insertion of a percutaneous endoscopic gastrostomy (PEG) is an increasingly common procedure in patients with nutritional needs and dysphagia. Better knowledge of rates and patterns of complications after PEG might influence decision-making. Material and methods. The objective was to prospectively evaluate the rate of six pre-defined complications (leakage, diarrhea, constipation, abdominal pain, fever and peristomal infection) and mortality occurring within 2 months after PEG in an unselected sample of patients. All patients (n = 484) who had a PEG inserted at the hospital during the study period were included. Kaplan–Meier curves were used to estimate mortality over the first 60 days following PEG and Fishers exact test was used to test equality of proportions. Results. Of the 484 patients included, 85 (18%) died within 2 months after PEG insertion. The risk of early mortality was higher in the group with neurological disease than in the group with a tumor as indication (p < 0.001). After excluding mortality, the overall complication rates at 2 weeks and 2 months were 39% and 27%, respectively. The most common complications within 2 weeks were abdominal pain (13%), peristomal infection (11%), diarrhea (11%) and leakage (10%). At 2 months the most frequent complications were diarrhea (10%), leakage (8%) and peristomal infection (6%). Conclusions. In the short-term perspective, there is a substantial risk of complications, including mortality, after PEG insertion. This should be considered during clinical decision-making and when informing the patients and caregivers.

Hospital and surgeon volume in relation to long-term survival after oesophagectomy: systematic review and meta-analysis

Background Centralisation of healthcare, especially for advanced cancer surgery, has been a matter of debate. Clear short-term mortality benefits have been described for oesophageal cancer surgery conducted at high-volume hospitals and by high-volume surgeons. Objective To clarify the association between hospital volume, surgeon volume and hospital type in relation to long-term survival after oesophagectomy for cancer, by a meta-analysis. Design The systematic literature search included PubMed, Web of Science, Cochrane library, EMBASE and Science Citation Index, for the period 1990–2013. Eligible articles were those which reported survival (time to death) as HRs after oesophagectomy for cancer by hospital volume, surgeon volume or hospital type. Fully adjusted HRs for the longest follow-up were the main outcomes. Results were pooled by a meta-analysis, and reported as HRs and 95% CIs. Results Sixteen studies from seven countries met the inclusion criteria. These studies reported hospital volume (N=13), surgeon volume (N=4) or hospital type (N=4). A survival benefit was found for high-volume hospitals (HR=0.82, 95% CI 0.75 to 0.90), and possibly also, for high-volume surgeons (HR=0.87, 95% CI 0.74 to 1.02) compared with their low-volume counterparts. No association with survival remained for hospital volume after adjustment for surgeon volume (HR=1.01, 95% CI 0.97 to 1.06; N=2), while a survival benefit was found in favour of high-volume surgeons after adjustment for hospital volume (HR=0.91, 95% CI 0.85 to 0.98; N=2). Conclusions This meta-analysis demonstrated better long-term survival (even after excluding early deaths) after oesophagectomy with high-volume surgery, and surgeon volume might be more important than hospital volume. These findings support centralisation with fewer surgeons working at large centres.

Albumin and C-reactive protein levels predict short-term mortality after percutaneous endoscopic gastrostomy in a prospective cohort study

BACKGROUND Percutaneous endoscopic gastrostomy (PEG) is a procedure with many complications that sometimes can be devastating. To give better advice to patients referred for PEG regarding risk of complications, important risk factors should be known. OBJECTIVE To evaluate whether age, body mass index, albumin levels, C-reactive protein (CRP) levels, indication for PEG, and comorbidity influence the risk of mortality or peristomal infection after PEG insertion. DESIGN Prospective cohort study from 2005 to 2009. Follow-up 14 days after PEG. SETTING University hospital. PATIENTS This study involved 484 patients referred for PEG. INTERVENTION PEG. MAIN OUTCOME MEASUREMENTS Mortality within 30 days and peristomal infection within 14 days after PEG insertion. All risk estimates were calculated with 95% CIs and adjusted for confounding. RESULTS Among 484 patients, 58 (12%) died within 30 days after PEG insertion. Albumin <30 g/L (hazard ratio [HR], 3.46; 95% CI, 1.75-6.88), CRP ≥10 (HR, 3.47; 95% CI, 1.68-7.18), age ≥65 years (HR, 2.26; 95% CI, 1.20-4.25) and possibly body mass index <18.5 (HR, 2.04; 95% CI, 0.97-4.31) were associated with increased mortality. Patients with a combination of low albumin and high CRP levels had a mortality rate of 20.5% compared with 2.6% among patients with normal values, rendering an over 7-fold increased adjusted risk of mortality (HR, 7.45; 95% CI, 2.62-21.19). LIMITATIONS Missing data in some study variables. Although the sample size was large, weaker associations could not be established. CONCLUSION The combination of low albumin and high CRP levels indicates a substantially increased short-term mortality risk after PEG, which should be considered in decision making.

No further increase in the incidence of esophageal adenocarcinoma in Sweden

Since 1970, the incidence of esophageal adenocarcinoma has increased rapidly in Western populations, whereas the incidences of gastric cardia and gastric non‐cardia adenocarcinoma have increased moderately and declined, respectively. The Swedish Cancer Register and Total Population Register provided opportunities for a valid update of incidence trends of these tumors including the year 2008. Joinpoint regression was used to assess any shifts in trends with calendar time. The esophageal adenocarcinoma incidence reached a peak in 2005, and then showed a decrease. During the period 2001–2008, the joinpoint regression analysis indicates a virtually stable incidence (annual percentage increase 1.1, 95% confidence interval [CI] −2.7 to 5.1). The cardia adenocarcinoma incidence has slightly decreased after 1990 (annual percentage decrease −1.0, 95% CI −1.6 to −0.3). The decreasing incidence of gastric non‐cardia adenocarcinoma has continued steadily during recent years (annual percentage decrease −4.9 (95% CI −5.2 to −4.7). Thus, an encouraging break in the rising incidence of esophageal adenocarcinoma has been seen in Sweden since 2005, whereas the corresponding incidences of gastric cardia and non‐cardia adenocarcinoma have been stable and decreasing, respectively.

Novel approach to antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG): randomised controlled trial

Objective To evaluate a new and simpler strategy of antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG). Design Single centre, two arm, randomised, controlled, double blind clinical trial. Setting Endoscopy unit in Karolinska University Hospital, Stockholm, Sweden, between 3 June 2005 and 31 October 2009. Participants 234 patients with an indication for PEG who gave informed consent to participate. Intervention A single 20 ml dose of the oral solution of sulfamethoxazole and trimethoprim (also known as co-trimoxazole or Bactrim; F Hoffmann-La Roche Ltd, Basel, Switzerland) deposited in the PEG catheter immediately after insertion. The control group received standard prophylaxis consisting of a single intravenous dose of 1.5 g cefuroxime (Zinacef; GlaxoSmithKline, London) administered before insertion of the PEG tube. Main outcome measure Primary outcome was the occurrence of clinically evident wound infection within 14 days after insertion of the PEG catheter. Secondary outcomes were positive bacterial culture and blood tests (highly sensitive C reactive protein and white blood cell count). All randomised patients were included in an intention to treat analysis. Results Of the 234 patients included in this study, 116 were randomly assigned to co-trimoxazole and 118 to cefuroxime. At follow-up 7-14 days after insertion of the PEG catheter, wound infection was found in 10 (8.6%) patients in the co-trimoxazole group and 14 (11.9%) in the cefuroxime group, which corresponds to a percentage point difference of −3.3% (95% confidence interval −10.9% to 4.5%). The per protocol analysis, which comprised 100 patients in each group, gave similar results—10% and 13% infection in the co-trimoxazole and cefuroxime groups, respectively (percentage point difference −3.0%, 95% CI −11.8% to 5.8%). Both these analyses indicate non-inferiority of co-trimoxazole compared with cefuroxime because the upper bounds of the confidence intervals are lower than the pre-determined non-inferiority margin of 15%. Analyses of the secondary outcomes supported this finding. Conclusion 20 ml of co-trimoxazole solution deposited in a newly inserted PEG catheter is at least as effective as cefuroxime prophylaxis given intravenously before PEG at preventing wound infections in patients undergoing PEG. Trial registration Current Controlled Trials ISRCTN18677736.

Association of Oral Glucocorticoid Use With an Increased Risk of Acute Pancreatitis: A Population-Based Nested Case-Control Study

IMPORTANCE Oral glucocorticoid use has been suggested to cause acute pancreatitis in several case reports. However, no epidemiological study has investigated this association. OBJECTIVE To conduct a nationwide population-based case-control study to investigate the potential association between oral glucocorticoid use and acute pancreatitis. DESIGN In this population-based case-control study, all individuals aged 40 to 84 years who developed a first episode of acute pancreatitis between 2006 and 2008 in Sweden were identified. SETTING Population-based, nationwide, register-based study. PARTICIPANTS A total of 6161 cases with a first episode of acute pancreatitis and 61,637 controls were included in the final analyses. Cases were all patients diagnosed as having a first episode of acute pancreatitis during the study period, defined by the diagnosis code K85 in the International Statistical Classification of Diseases, 10th Revision (ICD-10). Controls were randomly selected from the source population at risk of developing acute pancreatitis. For each case, 10 controls, matched for age, sex, and calendar period, were randomly selected from the general population. Oral glucocorticoid use was assessed from the Swedish Prescribed Drug Register. Current, recent, and former users were defined as patients who collected their glucocorticoid prescription within 30, 31 to 180, and after 180 days before the index date, respectively. MAIN OUTCOME MEASURES Unconditional logistic regression was performed to calculate the odds ratios (ORs) with 95% confidence intervals for the association between oral glucocorticoid use and acute pancreatitis. Multivariable adjustment was made for potential confounders including, among others, alcohol abuse, diabetes, and concomitant drug use. RESULTS The study included 6161 cases of acute pancreatitis and 61,637 controls. The risk of acute pancreatitis was increased among current users of oral glucocorticoids compared with nonusers (OR, 1.53; 95% CI, 1.27-1.84). This risk was highest 4 to 14 days after drug dispensation (OR, 1.73; 95% CI, 1.31-2.28) and attenuated thereafter. There was no association between oral glucocorticoid use and acute pancreatitis immediately after drug dispensation. There was no increased risk of acute pancreatitis among recent or former users of glucocorticoids compared with nonusers. CONCLUSIONS AND RELEVANCE Current oral glucocorticoid use is associated with an increased risk of acute pancreatitis.

Extent of lymphadenectomy and prognosis after esophageal cancer surgery

IMPORTANCE The prognostic role of the extent of lymphadenectomy during surgery for esophageal cancer is uncertain and requires clarification. OBJECTIVE To clarify whether the number of removed lymph nodes influences mortality following surgery for esophageal cancer. DESIGN, SETTING, AND PARTICIPANTS Conducted from January 1, 2000, to January 31, 2014, this was a cohort study of patients who underwent esophagectomy for cancer in 2000-2012 at a high-volume hospital for esophageal cancer surgery, with follow-up until 2014. EXPOSURES The main exposure was the number of resected lymph nodes. Secondary exposures were the number of metastatic lymph nodes and positive to negative lymph node ratio. MAIN OUTCOMES AND MEASURES The independent role of the extent of lymphadenectomy in relation to all-cause and disease-specific 5-year mortality was analyzed using Cox proportional hazard regression models, providing hazard ratios (HRs) with 95% CIs. The HRs were adjusted for age, pathological T category, tumor differentiation, margin status, calendar period of surgery, and response to preoperative chemotherapy. RESULTS Among 606 included patients, 506 (83.5%) had adenocarcinoma of the esophagus, 323 (53%) died within 5 years of surgery, and 235 (39%) died of tumor recurrence. The extent of lymphadenectomy was not statistically significantly associated with all-cause or disease-specific mortality, independent of the categorization of lymphadenectomy or stratification for T category, calendar period, or chemotherapy. Patients in the fourth quartile of the number of removed nodes (21-52 nodes) did not demonstrate a statistically significant reduction in all-cause 5-year mortality compared with those in the lowest quartile (0-10 nodes) (HR, 0.86; 95% CI, 0.63-1.17), particularly not in the most recent calendar period (HR, 0.98; 95% CI, 0.57-1.66 for years 2007-2012). A greater number of metastatic nodes and a higher positive to negative node ratio was associated with increased mortality rates, and these associations showed dose-response associations. CONCLUSIONS AND RELEVANCE This study indicated that the extent of lymphadenectomy during surgery for esophageal cancer might not influence 5-year all-cause or disease-specific survival. These results challenge current clinical guidelines.

Gallstones and cholecystectomy in relation to risk of intra- and extrahepatic cholangiocarcinoma

Background:Cholangiocarcinomas are highly lethal tumours of the intrahepatic or extrahepatic biliary tract. The aetiology is largely unknown, and the potential roles of gallstones and gall bladder removal (cholecystectomy) need to be addressed in a large study with a long follow-up.Methods:A population-based nationwide Swedish cohort study was carried out, in which patients hospitalised for gallstone diagnosis with or without gallbladder removal (cholecystectomy) between 1965 and 2008 were identified in the Swedish Patient Registry. The cohort was followed up for cancer in the Swedish Cancer Registry. The observed numbers of intra- and extrahepatic cholangiocarcinomas that developed after one year of follow-up were compared with the expected numbers, calculated from the corresponding background population, and the relative risks were estimated by standardised incidence ratios (SIRs) and 95% confidence intervals (CIs).Results:Among the 192 960 non-cholecystectomised individuals with gallstones, there was a more than two-fold overall increased risk of both intra- and extra- hepatic cholangiocarcinomas, which remained stable over the follow-up period (SIR 2.77, 95% CI 2.17–3.49, and SIR 2.58, 95% CI 2.21–3.00, respectively). In the cholecystectomy cohort, including 345 251 people and 4 854 969 person-years, 325 incident cholangiocarcinomas were identified, of which 98 (30%) were intrahepatic and 227 (70%) were extrahepatic. Initially (1–4 years after surgery), the risk was increased for both intrahepatic cholangiocarcinoma (SIR 1.80, 95% CI 1.19–2.62) and extrahepatic cholangiocarcinoma (SIR 2.29, 95% CI 1.83–2.82), but no increase remained after 10 years of follow-up or more (SIR 1.10, 95% CI 0.79–1.48, and SIR 0.87, 95% CI 0.70–1.07, respectively).Interpretation:Gallstones seem to increase the risk of both intra- and extrahepatic cholangiocarcinoma. However, this risk seems to decline to the level of the background population with time after cholecystectomy.