Predictors of Nonadherence to Screening Colonoscopy Denberg, Thomas D.; Melhado, Trisha V.; Coombes, John M. ...
Journal of general internal medicine,
November 2005, Letnik:
20, Številka:
11
Journal Article
Recenzirano
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Background: Colonoscopy has become a preferred colorectal cancer (CRC) screening modality. Little is known about why patients who are referred for colonoscopy do not complete the recommended ...procedures. Prior adherence studies have evaluated colonoscopy only in combination with flexible sigmoidoscopy, failed to differentiate between screening and diagnostic procedures, and have examined cancellations/no‐shows, but not nonscheduling, as mechanisms of nonadherence.
Methods: Sociodemographic predictors of screening completion were assessed in a retrospective cohort of 647 patients referred for colonoscopy at a major university hospital. Then, using a qualitative study design, a convenience sample of patients who never completed screening after referral (n=52) was interviewed by telephone, and comparisons in reported reasons for nonadherence were made by gender.
Results: Half of all patients referred for colonoscopy failed to complete the procedure, overwhelmingly because of nonscheduling. In multivariable analysis, female sex, younger age, and insurance type predicted poorer adherence. Patient‐reported barriers to screening completion included cognitive‐emotional factors (e.g., lack of perceived risk for CRC, fear of pain, and concerns about modesty and the bowel preparation), logistic obstacles (e.g., cost, other health problems, and competing demands), and health system barriers (e.g., scheduling challenges, long waiting times). Women reported more concerns about modesty and other aspects of the procedure than men. Only 40% of patients were aware of alternative screening options.
Conclusions: Adherence to screening colonoscopy referrals is sub‐optimal and may be improved by better communication with patients, counseling to help resolve logistic barriers, and improvements in colonoscopy referral and scheduling mechanisms.
The low molecular weight plasma proteome and its biological relevance are not well defined; therefore, experiments were conducted to directly sequence and identify peptides observed in plasma and ...serum protein profiles. Protein fractionation, matrix-assisted laser desorption ionization mass spectrometry (MALDI−MS) profiling, and liquid-chromatography coupled to MALDI tandem mass spectrometry (MS/MS) sequencing were used to analyze the low molecular weight proteome of heparinized plasma. Four fractionation techniques using functionally derivatized 96-well plates were used to extract peptides from plasma. Tandem TOF was successful for identifying peptides up to m/z 5500 with no prior knowledge of the sequence and was also used to verify the sequence assignments for larger ion signals. The peptides (n > 250) sequenced in these profiles came from a surprisingly small number of proteins (n ≈ 20), which were all common to plasma, including fibrinogen, complement components, antiproteases, and carrier proteins. The cleavage patterns were consistent with those of known plasma proteases, including initial cleavages by thrombin, plasmin and complement proteins, followed by aminopeptidase and carboxypeptidase activity. On the basis of these data, we discuss limitations in biomarker discovery in the low molecular weight plasma or serum proteome using crude fractionation coupled to MALDI−MS profiling. Keywords: MALDI TOF/TOF mass spectrometry • low molecular weight plasma proteome
Plasma protein profiling using separations coupled to matrix-assisted laser desorption ionization mass spectrometry (MALDI
MS) has great potential in translational research; it can be used for ...biomarker discovery and contribute to disease diagnosis
and therapy. Previously reported biomarker searches have been done solely by MS protein profiling followed by bioinformatics
analysis of the data. To add to current methods, we tested an alternative strategy for plasma protein profiling using pancreatic
cancer as the model. First, offline solid-phase extraction is done with 96-well plates to fractionate and partially purify
the proteins. Then, multiple profiling and identification experiments can be conducted on the same protein fractions because
only 5% of the fractions are used for MALDI MS profiling. After MALDI MS analysis, the mass spectra are normalized and subjected
to a peak detection algorithm. Over three sets of mass spectra acquired using different instrument variables, ∼400 unique
ion signals were detected. Classification schemes employing as many as eight individual peaks were developed using a training
set with 123 members (82 cancer patients) and a blinded validation set with 125 members (57 cancer patients). The sensitivity
of the study was 88%, but the specificity was significantly lower, 75%. The reason for the low specificity becomes apparent
upon protein identification of the ion signals used for the classification. The identifications reveal only common serum proteins
and components of the acute phase response, including serum amyloid A, α-1-antitrypsin, α-1-antichymotrypsin, and inter-α-trypsin
inhibitor.
Purpose
Tumour-infiltrating lymphocytes (TILs) have been shown to be prognostic for disease-free survival and predictive for the benefit of chemotherapy in patients with early breast cancer, but have ...not been studied for endocrine therapy.
Experimental design
The number of CD8-positive TILs was assessed in a subcohort of 236 patients in the Intergroup Exemestane Study. AQ After 2–3 years of adjuvant tamoxifen, AQpatients were randomized between the schemes of continuation for 5 years on tamoxifen and switching to exemestane. The numbers of CD8-positive TILs were analysed for correlations with disease-free survival (DFS) and overall survival (OS). A similar analysis was performed on 2596 patients in the TEAM trial who were randomized between the sequential scheme and the exemestane monotherapy.
Results
In the first cohort, patients with low (below median) numbers of CD8-positive TILs had a univariate hazard ratio (HR) for DFS of 0.27 (95% CI 0.13–0.55) in favour of treatment with exemestane, whereas this benefit was not observed in patients with high numbers of CD8-positive TILs (HR 1.34, 95% CI 0.71–2.50, HR for interaction 5.02,
p
= 0.001). In the second cohort, patients with low numbers of CD8-positive TILs showed a benefit of exemestane treatment on recurrence-free survival (RFS HR 0.67, 95% CI 0.45–0.99), and not with above-median numbers of CD8-positive TILs (HR 0.86, 95% CI 0.59–1.26, HR for interaction 1.29,
p
= 0.36).
Conclusions
This study is the first to propose the number of CD8-positive TILs as potential predictive markers for endocrine therapy, with the low presence of CD8-positive TILs associated to benefit for exemestane-inclusive therapy. However, treatment-by-marker interactions were only significant in one cohort, indicating the need for further validation.
As the number of pre- and post-transplant solid organ recipients continues to grow, it becomes important for all physicians to have an understanding of the process of organ procurement and ...allocation. In the United States, the current system for allocation and transplantation of human solid organs has been heavily influenced by the experience in deceased donor liver transplantation (DDLT). This review highlights the significant changes that have occurred over the past 10 years in DDLT, with specific attention to the impact of the Model for Endstage Liver Disease (MELD) score on organ allocation and pre- and post-transplant survival. DDLT is managed by the United Network for Organ Sharing (UNOS) which oversees organ procurement and allocation across geographically defined Organ Procurement Organizations (OPOs). For many years, deceased donor livers were allocated to waiting list patients based on subjective parameters of disease severity and accrued waiting time. In addition, organs have traditionally been retained within the OPO where they are procured contributing to geographic disparities in disease severity at the time of transplantation among deceased donor recipients. In response to a perceived unfairness in organ allocation, Congress issued its "Final Rule" in 1998. The Rule called for a more objective ranking of waiting list patients and more parity in disease severity among transplant recipients across OPOs. To date, little progress has been made in eliminating geographic inequities. Patients in the smallest OPOs continue to receive liver transplants at a lower level of disease severity. However, strides have been made to standardize assessments of disease severity and better prioritize waiting list patients. The MELD score has emerged as an excellent predictor of short-term mortality in patients with advanced liver disease, and patients listed for liver transplantation are now ranked based on their respective MELD scores. This has improved organ access to the most severely ill patients without compromising waiting list mortality or post-transplant survival. The current system for DDLT remains imperfect but has improved significantly in the past decade. As the number of patients in need of DDLT grows, the system will continue to evolve to meet this increasing demand.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary Background Tamoxifen preserves bone in postmenopausal women, but non-steroidal aromatase inhibitors accelerate bone loss and increase fracture risk. We aimed to study the effect on bone ...health in a subgroup of women included in the Intergroup Exemestane Study (IES), a large randomised trial that compared the switch to the steroidal aromatase inhibitor exemestane with continuation of tamoxifen in the adjuvant treatment of postmenopausal breast cancer. Methods Results were analysed from 206 evaluable patients from the IES, in which postmenopausal women with histologically confirmed and completely resected unilateral breast cancer (that was oestrogen-receptor positive or of unknown status), who were disease-free after 2–3 years of treatment with tamoxifen were randomised to continue oral tamoxifen 20 mg/day or switch to oral exemestane 25 mg/day to complete a total of 5 years of adjuvant endocrine therapy. The primary endpoint was change in bone-mineral density (BMD) assessed by dual energy X-ray absorptiometry. Changes in biochemical markers of bone turnover were also analysed in this substudy, and the incidence of fractures in the entire study reported. The IES is registered on the Current Controlled Trials website http://www.controlled-trials.com/ISRCTN11883920. Findings Within 6 months of switching to exemestane, BMD was lowered by 0·051 g/cm3 (2·7%; 95% CI 2·0–3·4; p<0·0001) at the lumbar spine and 0·025 g/cm3 (1·4%; 0·8–1·9; p<0·0001) at the hip compared with baseline. BMD decreases were only 1·0% (0·4–1·7; p=0·002) and 0·8% (0·3–1·4; p=0·003) in year 2 at the lumbar spine and hip, respectively. No patient with BMD in the normal range at trial entry developed osteoporosis. Bone resorption and formation markers increased at all time points in women receiving exemestane (p<0·001). With a median follow-up in all IES participants (n=4274) of 58 months, 162 (7%) and 115 (5%) patients in the exemestane and tamoxifen groups, respectively, had fractures (odds ratio 1·45 1·13–1·87; p=0·003). Interpretation These results indicate that the increase in survival shown previously with the IES switch strategy is achieved at the expense of some detriment to skeletal health, so the risk-benefit ratio to women needs to be individually assessed.
Even when primary care physicians have face-to-face discussions with patients before referring them for screening colonoscopy, patient nonadherence can be substantial. Often, primary care physicians ...lack sufficient time to educate patients and address their potential misconceptions and fears about this procedure.
To test whether an informational brochure sent to patients' home addresses after referral for screening colonoscopy would increase patient completion of the procedure.
Randomized, controlled trial.
2 general internal medicine practices affiliated with the University of Colorado Health Sciences Center.
781 consecutive patients 50 years of age or older referred by their primary care physicians for screening colonoscopy.
Patients were randomly assigned to receive usual care (control group) versus usual care plus an informational brochure (intervention group). The brochure was mailed within 10 days of referral for screening colonoscopy; it mentioned the name of the patient's primary care physician and encouraged patients to schedule a procedure. It also described colorectal cancer and polyps and the similar lifetime risks for colorectal cancer for men and women, colonoscopy and risk for perforation, the nature of bowel preparation for the procedure, and alternative screening tests.
Rates of adherence to screening colonoscopy in the 2 study groups.
The overall adherence rate was 11.7 percentage points (95% CI, 5.1 to 18.4 percentage points) greater in the intervention group than in the control group (70.7% vs. 59.0%). Older patients were more adherent than younger patients. Patients with low-income insurance plans, such as Medicaid, were less adherent despite being sent a brochure.
The small number of clinical practices and minority patients may limit generalizability. In addition, it was not possible to determine the degree to which adherence was influenced by a reminder to schedule a procedure versus detailed information about colonoscopy.
An inexpensive mailed brochure is an effective way to increase patient adherence to primary care physician referral for screening colonoscopy.
Uncontrolled proliferation is a hallmark of cancer. In breast cancer, immunohistochemical assessment of the proportion of cells staining for the nuclear antigen Ki67 has become the most widely used ...method for comparing proliferation between tumor samples. Potential uses include prognosis, prediction of relative responsiveness or resistance to chemotherapy or endocrine therapy, estimation of residual risk in patients on standard therapy and as a dynamic biomarker of treatment efficacy in samples taken before, during, and after neoadjuvant therapy, particularly neoadjuvant endocrine therapy. Increasingly, Ki67 is measured in these scenarios for clinical research, including as a primary efficacy endpoint for clinical trials, and sometimes for clinical management. At present, the enormous variation in analytical practice markedly limits the value of Ki67 in each of these contexts. On March 12, 2010, an international panel of investigators with substantial expertise in the assessment of Ki67 and in the development of biomarker guidelines was convened in London by the cochairs of the Breast International Group and North American Breast Cancer Group Biomarker Working Party to consider evidence for potential applications. Comprehensive recommendations on preanalytical and analytical assessment, and interpretation and scoring of Ki67 were formulated based on current evidence. These recommendations are geared toward achieving a harmonized methodology, create greater between-laboratory and between-study comparability, and allow earlier valid applications of this marker in clinical practice.
Background
Mass spectrometry is actively being used to discover disease-related proteomic patterns in complex mixtures of proteins derived from tissue samples or from easily obtained biological ...fluids. The potential importance of these clinical applications has made the development of better methods for processing and analyzing the data an active area of research. It is, however, difficult to determine which methods are better without knowing the true biochemical composition of the samples used in the experiments.
Methods
We developed a mathematical model based on the physics of a simple MALDI-TOF mass spectrometer with time-lag focusing. Using this model, we implemented a statistical simulation of mass spectra. We used the simulation to explore some of the basic operating characteristics of MALDI or SELDI instruments.
Results
The simulation reproduced several characteristics of actual instruments. We found that the relative mass error is affected by the time discretization of the detector (about 0.01%) and the spread of initial velocities (about 0.1%). The accuracy of calibration based on external standards decays rapidly outside the range spanned by the calibrants. Natural isotope distributions play a major role in broadening peaks associated with individual proteins. The area of a peak is a more accurate measure of its size than the height.
Conclusions
The model described here is capable of simulating realistic mass spectra. The simulation should become a useful tool for generating spectra where the true inputs are known, allowing researchers to evaluate the performance of new methods for processing and analyzing mass spectra.
Availability
http://bioinformatics.mdanderson.org/cromwell.html
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