The colonic opportunist Streptococcus gallolyticus subspecies gallolyticus (SGG) is potentially associated with colorectal cancer (CRC). Large‐scale seroepidemiological data for SGG antibodies and ...their possible association with CRC is currently missing. Associations between CRC and antibody responses to SGG were examined in 576 CRC cases and 576 controls matched by sex, age and province from a population‐based multicase–control project (MCC‐Spain). MCC‐Spain was conducted between 2008 and 2013 in 12 Spanish provinces. Antibody responses to recombinant affinity‐purified SGG pilus proteins Gallo1569, 2039, 2178 and 2179 were analysed by multiplex serology. Polyomavirus (PyV) JC VP1 and PyV 6 VP1 proteins served as disease‐specificity controls. In the control population, antibody responses to pilus proteins were mostly weak. Antibody responses to individual pilus proteins Gallo2039 (OR: 1.58, 95% CI: 1.09–2.28), Gallo2178 (OR: 1.58, 95% CI: 1.09–2.30) and Gallo2179 (OR: 1.45, 95% CI: 1.00–2.11) were significantly associated with CRC risk. The association was stronger for positivity to two or more pilus proteins of Gallo1569, Gallo2178 and Gallo2179 (OR:1.93, 95% CI: 1.04–3.56) and for double‐positivity to Gallo2178 and Gallo2179 (OR: 3.54, 95% CI: 1.49–8.44). The association between SGG infection and CRC risk was stronger among individuals younger than 65 years. For the first time we demonstrated a statistically significant association of exposure to SGG antigens and CRC in a large seroepidemiological study. These results should stimulate further studies on the role of SGG in CRC pathogenesis.
What's new?
The colonic opportunistic Streptococcus gallolyticus subspecies gallolyticus (SGG) is potentially associated with colorectal cancer (CRC). Large‐scale seroepidemiological data for SGG antibodies and their possible association with CRC are however currently lacking. Using SGG pilus proteins Gallo1569, Gallo2039, Gallo2178 and Gallo2179 as antigens for multiplex serology in a population‐based case–control study, here the authors for the first time demonstrate a significant epidemiological association of antibodies to SGG antigens with CRC. SGG serology might thus provide a marker to identify a subgroup of patients at increased risk of CRC. Studies on the potential role of SGG infection in CRC development appear warranted.
Incorporating promising biomarkers into cancer screening practices for early‐detection is increasingly appealing because of the unsatisfactory performance of current cancer screening strategies. The ...matched case‐control design is commonly adopted in biomarker development studies to evaluate the discriminative power of biomarker candidates, with an intention to eliminate confounding effects. Data from matched case‐control studies have been routinely analyzed by the conditional logistic regression, although the assumed logit link between biomarker combinations and disease risk may not always hold. We propose a conditional concordance‐assisted learning method, which is distribution‐free, for identifying an optimal combination of biomarkers to discriminate cases and controls. We are particularly interested in combinations with a clinically and practically meaningful specificity to prevent disease‐free subjects from unnecessary and possibly intrusive diagnostic procedures, which is a top priority for cancer population screening. We establish asymptotic properties for the derived combination and confirm its favorable finite sample performance in simulations. We apply the proposed method to the prostate cancer data from the carotene and retinol efficacy trial (CARET).
Alcohol drinking and, to a lesser extent, cigarette smoking are risk factors for a first primary breast cancer. Information on these behaviours at diagnosis may contribute to risk prediction of ...contralateral breast cancer (CBC) and they are potentially modifiable. The WECARE Study is a large population‐based case‐control study of women with breast cancer where cases (N = 1,521) had asynchronous CBC and controls (N = 2,212), matched on survival time and other factors, had unilateral breast cancer (UBC). Using multivariable conditional logistic regression to estimate rate ratios (RR) and 95% confidence intervals (CI), we examined the risk of CBC in relation to drinking and smoking history at and following first diagnosis. We adjusted for treatment, disease characteristics and other factors. There was some evidence for an association between CBC risk and current drinking or current smoking at the time of first breast cancer diagnosis, but the increased risk occurred primarily among women exposed to both (RR = 1.62, 95% CI 1.24–2.11). CBC risk was also elevated in women who both smoked and drank alcohol after diagnosis (RR = 1.54, 95% CI 1.18–1.99). In the subset of women with detailed information on amount consumed, smoking an average of ≥10 cigarettes per day following diagnosis was also associated with increased CBC risk (RR = 1.50, 95% CI 1.08–2.08; p‐trend = 0.03). Among women with a diagnosis of breast cancer, information on current drinking and smoking could contribute to the prediction of CBC risk. Women who both drink and smoke may represent a group who merit targeted lifestyle intervention to modify their risk of CBC.
What's new?
Do alcohol and smoking contribute to the risk of developing breast cancer … a second time? Both are risk factors for first breast cancer, and this study set out to identify their impact on contralateral breast cancer risk. The authors set up a case‐control study, where cases had developed cancer in both breasts at different times, and controls had developed cancer in only one breast. They found that alcohol use and smoking after first diagnosis did increase the risk of developing cancer in the second breast, and recommending lifestyle changes could reduce their risk.
An autoimmune component in the cause of sarcoidosis long has been debated, but population-based data on the clustering of immune-mediated diseases (IMDs) and sarcoidosis in individuals and families ...suggestive of shared cause is limited.
Do patients with a history of IMDs have a higher risk of sarcoidosis and do IMDs cluster in families with sarcoidosis?
We conducted a case-control family study (2001-2020). Patients with sarcoidosis (N = 14,146) were identified in the Swedish National Patient Register using a previously validated definition (≥ 2 International Classification of Diseases ICD-coded inpatient or outpatient visits). At diagnosis, patients were matched to up to 10 control participants from the general population (N = 118,478) for birth year, sex, and residential location. Patients, control participants, and their first-degree relatives (FDRs; Multi-Generation Register) were ascertained for IMDs by means of ICD codes in the Patient Register (1968-2020). Conditional logistic regression was used to estimate ORs and 95% CIs of sarcoidosis associated with a history of IMDs in patients and control participants and in FDRs.
Patients with sarcoidosis exhibited a higher prevalence of IMDs compared with control participants (7.7% vs 4.7%), especially connective tissue diseases, cytopenia, and celiac disease. Familial aggregation was observed across IMDs; the strongest association was with celiac disease (OR, 2.09; 95% CI, 1.22-3.58), followed by cytopenia (OR, 1.88; 95% CI, 0.97-3.65), thyroiditis (OR, 1.72; 95% CI, 1.14-2.60), skin psoriasis (OR, 1.70; 95% CI, 1.34-2.15), inflammatory bowel disease (OR, 1.53; 95% CI, 1.14-2.03), immune-mediated arthritis (OR, 1.49; 95% CI, 1.20-1.85), and connective tissue disease (OR, 1.39; 95% CI, 1.00-1.93).
IMDs confer a higher risk of sarcoidosis and they aggregate in families with sarcoidosis, signaling a shared cause between IMDs and sarcoidosis. Our findings warrant further evaluation of shared genetic mechanisms.
Misconceptions about the impact of case—control matching remain common. We discuss several subtle problems associated with matched case-control studies that do not arise or are minor in matched ...cohort studies: (1) matching, even for non-confounders, can create selection bias; (2) matching distorts dose-response relations between matching variables and the outcome; (3) unbiased estimation requires accounting for the actual matching protocol as well as for any residual confounding effects; (4) for efficiency, identically matched groups should be collapsed; (5) matching may harm precision and power; (6) matched analyses may suffer from sparse-data bias, even when using basic sparse-data methods. These problems support advice to limit case-control matching to a few strong wellmeasured confounders, which would devolve to no matching if no such confounders are measured. On the positive side, odds ratio modification by matched variables can be assessed in matched case-control studies without further data, and when one knows either the distribution of the matching factors or their relation to the outcome in the source population, one can estimate and study patterns in absolute rates. Throughout, we emphasize distinctions from the more intuitive impacts of cohort matching.
Background
Surgical resection is currently the only treatment with the potential for long‐term survival and cure of pancreatic cancer. Surgical resection is provided as distal pancreatectomy for ...cancers of the body and tail of the pancreas. It can be performed by laparoscopic or open surgery. In operations on other organs, laparoscopic surgery has been shown to reduce complications and length of hospital stay as compared with open surgery. However, concerns remain about the safety of laparoscopic distal pancreatectomy compared with open distal pancreatectomy in terms of postoperative complications and oncological clearance.
Objectives
To assess the benefits and harms of laparoscopic distal pancreatectomy versus open distal pancreatectomy for people undergoing distal pancreatectomy for pancreatic ductal adenocarcinoma of the body or tail of the pancreas, or both.
Search methods
We used search strategies to search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded and trials registers until June 2015 to identify randomised controlled trials (RCTs) and non‐randomised studies. We also searched the reference lists of included trials to identify additional studies.
Selection criteria
We considered for inclusion in the review RCTs and non‐randomised studies comparing laparoscopic versus open distal pancreatectomy in patients with resectable pancreatic cancer, irrespective of language, blinding or publication status..
Data collection and analysis
Two review authors independently identified trials and independently extracted data. We calculated odds ratios (ORs), mean differences (MDs) or hazard ratios (HRs) along with 95% confidence intervals (CIs) using both fixed‐effect and random‐effects models with RevMan 5 on the basis of intention‐to‐treat analysis when possible.
Main results
We found no RCTs on this topic. We included in this review 12 non‐randomised studies that compared laparoscopic versus open distal pancreatectomy (1576 participants: 394 underwent laparoscopic distal pancreatectomy and 1182 underwent open distal pancreatectomy); 11 studies (1506 participants: 353 undergoing laparoscopic distal pancreatectomy and 1153 undergoing open distal pancreatectomy) provided information for one or more outcomes. All of these studies were retrospective cohort‐like studies or case‐control studies. Most were at unclear or high risk of bias, and the overall quality of evidence was very low for all reported outcomes.
Differences in short‐term mortality (laparoscopic group: 1/329 (adjusted proportion based on meta‐analysis estimate: 0.5%) vs open group: 11/1122 (1%); OR 0.48, 95% CI 0.11 to 2.17; 1451 participants; nine studies; I2 = 0%), long‐term mortality (HR 0.96, 95% CI 0.82 to 1.12; 277 participants; three studies; I2 = 0%), proportion of people with serious adverse events (laparoscopic group: 7/89 (adjusted proportion: 8.8%) vs open group: 6/117 (5.1%); OR 1.79, 95% CI 0.53 to 6.06; 206 participants; three studies; I2 = 0%), proportion of people with a clinically significant pancreatic fistula (laparoscopic group: 9/109 (adjusted proportion: 7.7%) vs open group: 9/137 (6.6%); OR 1.19, 95% CI 0.47 to 3.02; 246 participants; four studies; I2 = 61%) were imprecise. Differences in recurrence at maximal follow‐up (laparoscopic group: 37/81 (adjusted proportion based on meta‐analysis estimate: 36.3%) vs open group: 59/103 (49.5%); OR 0.58, 95% CI 0.32 to 1.05; 184 participants; two studies; I2 = 13%), adverse events of any severity (laparoscopic group: 33/109 (adjusted proportion: 31.7%) vs open group: 45/137 (32.8%); OR 0.95, 95% CI 0.54 to 1.66; 246 participants; four studies; I2 = 18%) and proportion of participants with positive resection margins (laparoscopic group: 49/333 (adjusted proportion based on meta‐analysis estimate: 14.3%) vs open group: 208/1133 (18.4%); OR 0.74, 95% CI 0.49 to 1.10; 1466 participants; 10 studies; I2 = 6%) were also imprecise. Mean length of hospital stay was shorter by 2.43 days in the laparoscopic group than in the open group (MD ‐2.43 days, 95% CI ‐3.13 to ‐1.73; 1068 participants; five studies; I2 = 0%). None of the included studies reported quality of life at any point in time, recurrence within six months, time to return to normal activity and time to return to work or blood transfusion requirements.
Authors' conclusions
Currently, no randomised controlled trials have compared laparoscopic distal pancreatectomy versus open distal pancreatectomy for patients with pancreatic cancers. In observational studies, laparoscopic distal pancreatectomy has been associated with shorter hospital stay as compared with open distal pancreatectomy. Currently, no information is available to determine a causal association in the differences between laparoscopic versus open distal pancreatectomy. Observed differences may be a result of confounding due to laparoscopic operation on less extensive cancer and open surgery on more extensive cancer. In addition, differences in length of hospital stay are relevant only if laparoscopic and open surgery procedures are equivalent oncologically. This information is not available currently. Thus, randomised controlled trials are needed to compare laparoscopic distal pancreatectomy versus open distal pancreatectomy with at least two to three years of follow‐up. Such studies should include patient‐oriented outcomes such as short‐term mortality and long‐term mortality (at least two to three years); health‐related quality of life; complications and the sequelae of complications; resection margins; measures of earlier postoperative recovery such as length of hospital stay, time to return to normal activity and time to return to work (in those who are employed); and recurrence of cancer.
Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. DTC is one of the cancers with the highest ...familial risk suggesting a major role of genetic risk factors, but only few susceptibility loci were identified so far. In order to assess the contribution of known DTC susceptibility loci and to identify new ones, we conducted a multiethnic genome‐wide association study (GWAS) in individuals of European ancestry and of Oceanian ancestry from Pacific Islands. Our study included 1554 cases/1973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from seven population‐based case‐control studies participating to the EPITHYR consortium. All participants were genotyped using the OncoArray‐500K Beadchip (Illumina). We confirmed the association with the known DTC susceptibility loci at 2q35, 8p12, 9q22.33 and 14q13.3 in the European ancestry population and suggested two novel signals at 1p31.3 and 16q23.2, which were associated with thyroid‐stimulating hormone levels in previous GWAS. We additionally replicated an association with 5p15.33 reported previously in Chinese and European populations. Except at 1p31.3, all associations were in the same direction in the population of Oceanian ancestry. We also observed that the frequencies of risk alleles at 2q35, 5p15.33 and 16q23.2 were significantly higher in Oceanians than in Europeans. However, additional GWAS and epidemiological studies in Oceanian populations are needed to fully understand the highest incidence observed in these populations.
What's new?
Differentiated thyroid carcinoma (DTC) has a strong genetic component, and Pacific Islanders have a particularly high incidence of the disease. Here, the authors conducted a genome‐wide association study (GWAS) in a mixed population including individuals of European and Pacific Islander ancestry. The study drew from the EPITHYR consortium, a collection of 2000 DTC cases and age‐matched controls. The analysis confirmed 5 previously known susceptibility loci and identified 2 new ones. Three of these loci were more prevalent among Pacific Islanders. More studies are needed to fully account for the rate of DTC in that population.
In a large case–control study in England, immunity to the omicron variant was very low and less than that to the delta variant 20 weeks after the second vaccine dose, regardless of the initial ...vaccine type. A booster dose of one of the mRNA vaccines improved efficacy to approximately 65 to 70%, but protection waned over a 10-week period.
Time‐related biases in pharmacoepidemiology Suissa, Samy; Dell'Aniello, Sophie
Pharmacoepidemiology and drug safety,
September 2020, Letnik:
29, Številka:
9
Journal Article
Recenzirano
Purpose
Observational studies using computerized healthcare databases have become popular to investigate the potential effectiveness of old drugs for new indications. Many of these studies reporting ...remarkable effectiveness were shown to be affected by different time‐related biases. We describe these biases and illustrate their effects using a cohort of patients treated for chronic obstructive pulmonary disease (COPD).
Methods
The Quebec healthcare databases were used to form a cohort of 124 030 patients with COPD, 50 years or older, treated between 2000 and 2015. Inhaled corticosteroids (ICS) and long‐acting bronchodilators were used as exposures, with diverse outcomes, including lung cancer, acute myocardial infarction and death, to illustrate protopathic, latency time, immortal time, time‐window, depletion of susceptibles, and immeasurable time biases.
Results
Protopathic bias affected bronchodilator‐defined cohort entry with an incident rate of lung cancer of 23.9 per 1000 in the first year, compared with around 12.0 in the subsequent years. When latency and immortal times were misclassified, ICS were associated with decreased incidence of lung cancer (hazard ratio HR 0.32; 95% CI: 0.30‐0.34), compared with 0.50 (95% CI: 0.48‐0.53) after correcting for immortal time bias and 0.96 (95% CI: 0.91‐1.02) after also correcting for latency time bias. Time‐window, depletion of susceptibles and immeasurable time biases also affected the findings similarly.
Conclusions
Many observational studies of new indications for older drugs reporting unrealistic effectiveness were affected by avoidable time‐related biases. The apparent effectiveness often disappears with proper design and analysis. Future studies should consider these time‐related issues to avoid severely biased results.
Background
Epidemiological data on infant feeding practices and allergic diseases are controversial. The purpose of this study was to explore the association of early weaning with the occurrence of ...atopic dermatitis (AD).
Methods
We conducted a matched case–control study on incident physician‐diagnosed AD in early childhood including 451 cases and 451 controls. Data on several factors, including feeding practices, were collected through an interviewer‐administered questionnaire. Odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were estimated through logistic regression models, conditioned on study center, age, sex, and period of interview, and adjusted for potential confounders.
Results
Early weaning, defined as the introduction of solid foods at 4 or 5 months of age, was inversely related to the risk of AD, with children weaned at 4 months having lower AD risk (OR = 0.41, 95% CI, 0.20–0.87) compared to those exclusively breastfed. Similar results were observed for weaning started at 5 months of age (OR = 0.39, 95% CI, 0.18–0.83). This association persisted when children with and without family history of allergy were considered separately. Prolonged partial breastfeeding (breastmilk plus milk formulas) was not associated with AD. Consistently, the introduction of a high number of different solid foods reduced the risk of AD (P trend = 0.02 at 4 months of age and P trend = 0.04 at 5 months).
Conclusion
Our data provide evidence against the preventing role of prolonged exclusive (but not partial) breastfeeding in AD occurrence and confirm recent results indicating a beneficial role of early weaning in AD.
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