Knowledge Of Patient Outcomes Research Articles

Outcomes and Factors Associated with Insufficient Effectiveness of Acute Treatments of Migraine in Japan: Results of the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan]) Study.

Knowledge of patient outcomes and treatment effectiveness associated with acute migraine treatments in Japan is lacking. To describe patient-reported outcomes (PROs) and treatment effectiveness in three acute treatment groups from OVERCOME (Japan): over-the-counter (OTC) only, prescription nonsteroidal anti-inflammatory drugs/acetaminophen (Rx-NSAIDs/ACE) only, and triptans. OVERCOME (Japan) was an observational, cross-sectional, population-based web survey of people with migraine (July-September 2020). PROs, including the Migraine-Specific Quality of Life Questionnaire (MSQ), Migraine Interictal Burden Scale (MIBS-4), Migraine Disability Assessment (MIDAS), and Work Productivity and Activity Impairment Questionnaire: Migraine (WPAI-M), were compared pairwise between treatment groups. Logistic regression was used to examine treatment effectiveness. The analysis included 9075 survey respondents (OTC only: n=5791; Rx-NSAIDs/ACE only: n=751; triptans: n=2533). Triptan users reported the lowest MSQ scores, most severe disability (MIDAS: 20.7% versus 6.3% and 11.6%) and severe interictal burden (MIBS-4: 50.1% versus 21.2% and 19.8%), and greatest work impairment (WPAI-M: 50.4% versus 32.2% and 30.8%) compared with the OTC and Rx-NSAIDs/ACE groups, respectively. Treatment effectiveness was very poor-to-poor for 60.9%, 43.1%, and 47.6% of the triptan, OTC, and Rx-NSAIDs/ACE groups, respectively. Severe interictal burden was significantly associated with insufficient treatment effectiveness (odds ratios, severe versus no burden: 0.47 [95% confidence interval: 0.40-0.54], 0.56 [0.35-0.89], and 0.41 [0.32-0.52], for the OTC, Rx-NSAIDs/ACE, and triptan groups, respectively). People with high migraine burden used triptans for acute treatment, but many reported poor treatment effectiveness. Education may be required to promote better treatments, including earlier introduction of migraine-specific acute and preventive medications.

The Patient Experience of Acute Lymphoblastic Leukemia and Its Treatment: Social Media Review.

Adult patients with acute lymphoblastic leukemia (ALL) report substantial disease- and treatment-related impacts on their health-related quality of life (HRQOL). Patient-reported information (PRI) shared on social media may provide a distinct opportunity to understand the patient experience outside of formal research contexts and help inform the development of novel therapies. This qualitative social media review aimed to assess PRI shared on social media websites to gain a better understanding of the symptom, HRQOL, and treatment impacts on individuals with ALL. We identified English-language posts on 3 patient advocacy websites (Patient Power, The Patient Story, and Leukaemia Care) and YouTube that included PRI about experiences with ALL or ALL treatments shared by adults (aged ≥18 years) with a self-reported ALL diagnosis. Patients' demographic and disease characteristics were extracted from posts (where available), and the posts were analyzed thematically. A network analysis was conducted to delineate possible associations among ALL symptoms, HRQOL impacts, and treatment-related symptoms and impacts. Of the 935 social media posts identified, 63 (7%) met the review criteria, including 40 (63%) videos, 5 (8%) comments posted in response to videos, and 18 (29%) blog posts. The 63 posts were contributed by 41 patients comprised of 21 (51%) males, 18 females (44%), and 2 (5%) whose gender was not reported. Among the patients, 13 (32%) contributed >1 source of data. Fatigue (n=20, 49%), shortness of breath (n=13, 32%), and bruising (n=12, 29%) were the symptoms prior to treatment most frequently discussed by patients. Patients also reported impacts on personal relationships (n=26, 63%), psychological and emotional well-being (n=25, 61%), and work (n=16, 39%). Although inpatient treatment reportedly restricted patients' independence and social functioning, it also provided a few patients with a sense of safety. Patients frequently relied on their doctors to drive their treatment decisions but were also influenced by family members. The network analysis indicated that disease-related symptoms were primarily associated with patients' physical functioning, activities of daily living, and ability to work, while treatment-related symptoms were primarily associated with emotional well-being. This social media review explored PRI through a thematic analysis of patient-contributed content on patient advocacy websites and YouTube to identify and contextualize emergent themes in patient experiences with ALL and its treatments. To our knowledge, this is the first study to leverage this novel tool to generate new insights into patients' experiences with ALL. Patients' social media posts suggest that inpatient care for ALL is associated with restricted independence and social functioning. However, inpatient care also provided a sense of safety for some patients. Studies such as this one that capture patients' experiences in their own words are valuable tools to further our knowledge of patient outcomes with ALL.

Non-small cell lung cancer (NSCLC) case study examining whether results in a randomized control arm are replicated by a synthetic control arm (SCA).

9108 Background: The FDA’s accelerated approval (AA) pathway provides conditional approval for an investigational product (IP) after positive effect on a surrogate endpoint has been provided, allowing patients earlier access to the therapy. Confirmation of a positive effect on the clinical endpoint after conditional approval is required and usually includes a randomized trial. However, such a trial is challenged by availability of the IP outside the trial. Recruitment becomes more difficult, and patients assigned to control are more likely to drop-out and use the non-assigned IP, which may bias the observed treatment effect. In AA settings we propose a SCA composed of patient level data from previous clinical trials to augment or replace the randomized control. Validity of this approach in one case study is assessed by examining if a SCA can replicate the outcomes of a target randomized control (TRC) from a recent NSCLC trial. Methods: The patients for the NSCLC SCA were required to have satisfied the key eligibility criteria of the target trial and were further selected using a propensity score-based approach to balance the baseline characteristics in the SCA and TRC. All patient selections were made without knowledge of patient outcomes. Results: The results show comparable balance in observed baseline characteristics of the SCA and TRC was achieved. Overall survival (OS) in TRC was replicated by SCA. The Kaplan Meier curves for OS in the SCA and TRC visually overlap. In addition, the log rank test (p = 0.65) and hazard ratio of 1.04 (95% CI: (0.88, 1.23)) were not statistically significant. Conclusions: If the SCA had been in place of the randomized control in this study, conclusions about the treatment effect would have been the same. While this may not hold when it is not possible to balance the groups on all confounders, this suggests that in some settings, SCA could augment or replace the randomized control in future trials easing recruitment, retention, and crossover challenges without compromising the understanding of the treatment effect. Future work should examine in what settings SCA is appropriate and consider the implications of potential unobserved confounders.

Regulating Off-Label Prescribing: The Good, the Bad and the Uncertain

Off-label prescribing is a double-edged sword that offers both benefits and risks depending on a range of different factors such as whether the off-label use is new or well-established; the strength of the evidence supporting the off-label use; the urgency of the patient’s situation; and the availability of alternative treatment options. In this memorandum, prepared for a expert witness hearing of the Canadian Standing Senate Committee on Social Affairs, Science and Technology for its study of Prescription Pharmaceuticals in Canada, we discuss the rationale for permitting off-label prescribing and the problems associated with the practice in the Canadian context. We argue that reform efforts should focus on improving the monitoring of off-label use of drug products and in promoting an expanded post-market research agenda for off-label prescribing. In particular, better and more systematic adverse event reporting is essential for a proper assessment of the risks and benefits of medication use. Improving our knowledge of patient outcomes from off-label prescribing in real-world settings may support new beneficial uses of drug products, but will also help to prevent harmful off-label use. Supporting prescribers with access to timely and accurate information on off-label use of drugs will also help to ensure that off-label prescribing decisions are not made off-the-cuff.

Medication recommendations to physicians by pharmacists for seniors: expected clinical impact in relation to implementation and expected time frame to effect

Abstract Aims and objectives To describe recommendations made by pharmacists in a trial that had found no improvements in selected clinical outcomes (the Seniors Medication Assessment Research Trial, SMART) in terms of expected impact on clinical outcomes and whether they had been implemented by the end of the 5-month period of follow-up. Setting SMART was conducted in a non-academic community practice setting. Method Recommendations made by the pharmacists during SMART, a cluster-randomised controlled trial conducted in family physician offices, were evaluated in this descriptive study. All recommendations to physicians were evaluated independently by two assessors using criteria established a priori and without knowledge of patient outcomes. Each recommendation was evaluated on likely strength and time to impact the patient's health and whether the recommendation was based on published evidence. Relationships between these criteria were analysed. Key findings Overall, the pharmacists made 1099 recommendations for 431 patients randomly assigned to the intervention group or a mean of 2.6 recommendations (standard deviation, 2.1) per patient. A moderate or marked impact on patient health within the 5-month follow-up period would have been expected for 15.5% of all recommendations. At study end, physicians fully implemented 45.8% of the recommendations. Among the recommendations that had been fully implemented, 64.5% of those expected to have a marked impact and 27.5% of those expected to have a moderate impact were anticipated to have the effect on patients' health beyond the 5-month period of follow-up reported in the study results. Conclusion It is likely that one of the contributing factors to not finding statistically significant differences in the SMART study was that only a small proportion of recommendations (15.5%) made by the SMART pharmacists would have an expected clinical effect within the study's follow-up period.

Surgical Resection Provides Excellent Outcomes for Patients With Cystic Clear Cell Renal Cell Carcinoma

Previous observations suggest that cystic clear cell renal cell carcinoma (RCC) is cured with surgical resection. However, long-term outcome data are lacking. We reviewed our experience with RCC and report on pathologic features and patient outcome associated with the cystic variant. We identified 2431 patients treated with nephrectomy for unilateral, sporadic clear cell RCC between 1970 and 2002. A single urologic pathologist (J.C.C.) reviewed all of the microscopic slides without knowledge of patient outcome. Cystic clear cell RCC was characterized by numerous confluent cysts lined by clear cells, and containing nests of clear cells within the cyst walls. There were 85 (3.5%) patients with cystic RCC. Among these patients, 22 died during follow-up, although no patient died of RCC. The median follow-up for the remaining 63 patients was 5 years. The estimated cancer-specific survival rate at 5 years after surgery for patients with noncystic clear cell RCC was 70.6% compared with 100% for patients with the cystic variant (P <0.001). This difference persisted even when comparing patients with cystic RCC to the subset with noncystic RCC who had pT1, pNx/pN0, and no clinical evidence of metastases (cM0). No patient with cystic clear cell RCC had extrarenal disease at time of nephrectomy with the exception of 1 patient who had perinephric fat invasion. Cystic RCC is a distinct pathologic entity and should be assessed routinely during pathologic evaluation. Furthermore, we present data supporting that cystic RCC patients should expect to be cured after surgical extirpation.

Measurement of the Uncomplexed Fraction of Tissue Inhibitor of Metalloproteinases-1 in the Prognostic Evaluation of Primary Breast Cancer Patients*

Several studies have demonstrated an association between high tumor tissue levels of total tissue inhibitor of metalloproteinases-1 (TIMP-1) and a poor prognosis of primary breast cancer patients. In the present study we investigated whether measurements of the uncomplexed fraction of TIMP-1 added prognostic information to that already obtained from total TIMP-1. We measured the uncomplexed fraction of TIMP-1, using a thoroughly validated ELISA specific for this fraction, in 341 tumor tissue extracts obtained from patients with primary breast cancer. These measurements were related to previously performed measurements of total TIMP-1 as well as to patient outcome. The observation time was 8.3 years (range, 7.3-11.3 years). During this period 136 patients died, and 153 patients experienced recurrence of disease. Cox regression analysis of recurrence-free survival (RFS) suggested that a score based on both uncomplexed and total TIMP-1, reflecting the tumor level of TIMP-1/MMP complexes, would be a more precise estimate of prognosis than total TIMP-1 alone. Univariate survival analysis showed a highly significant relationship between high values of the score and poor outcomes for RFS (p = 0.0002; hazard ratio = 2.7; 95% confidence interval, 1.5-4.8). Similar results were found for overall survival (p = 0.0001; hazard ratio = 3.3; 95% confidence interval, 1.8-6.3). Multivariate analysis of RFS and overall survival demonstrated that the score was significant including the classical prognostic factors used in breast cancer (p < 0.0001). The present study raises the hypothesis that it is the tumor level of TIMP-1/MMP complexes (i.e. activated matrix metalloproteinases) rather than TIMP-1 itself that determines prognosis, supporting the use of the combined score and not only total TIMP-1 in stratification of breast cancer patients.

Primary mucosal melanoma of the head and neck

The current study was conducted to identify histologic predictors of survival in patients with localized, lymph node-negative (Stage I, N0M0) primary mucosal melanomas of the head and neck (HNMM). The histology of 39 sinonasal, 20 oral, 1 pharyngeal, and 1 laryngeal Stage I HNMM was reviewed by 2 pathologists without knowledge of patient outcome. The invasion was evaluated as Level I: melanoma in situ (without invasion or with microinvasion only); Level II: invasion into the lamina propria only; and Level III: invasion into deep tissue (e.g., skeletal muscle, bone, or cartilage). The tumor architecture was defined as pseudopapillary when tumor cells clustered around blood vessels resembling papillae and sarcomatoid when they resembled high-grade pleomorphic sarcoma. Survival analysis was performed with Kaplan-Meier survival curves using disease-specific survival (DSS) as the endpoint. The 5-year DSS rate was 43% (median, 41.5 months). The median survival was found to decrease significantly with increasing level of invasion: Level I (n = 4): 138 months; Level II (n = 29): 69 months; and Level III (n = 28): 17 months (P = 0.003). The presence of pseudopapillary and sarcomatoid architecture (n = 20) and undifferentiated cells (n = 16) were found to be associated with a significantly poor DSS (P < 0.05). However, on multivariate analysis, only the level of invasion remained an independent predictor of survival (P = 0.03). Tumor thickness, vascular invasion, and necrosis were found to have no significant influence on survival. Microstaging according to invasion into three tissue compartments was found to be a significant and independent predictor of poor survival in patients with localized, lymph node-negative, Stage I HNMM. The presence of sarcomatoid and pseudopapillary architecture and undifferentiated cells also appear to be associated with significantly poor DSS.

Impact of targeting deviations on outcome in medulloblastoma: study of the French society of pediatric oncology (SFOP)

Purpose: To correlate targeting deviation in external beam radiation therapy with site of relapse in a prospective study of 174 patients treated for medulloblastoma.Methods and Materials: Between February 1992 and February 1998 the radiotherapy treatment records were reviewed by a panel of radiation oncologists for 174 children treated with radiation therapy for medulloblastoma. The review was done without knowledge of patient outcome. Patterns of relapse were correlated with the results of the quality control review.Results: Among the 174 patients five relapsed before the start of radiotherapy. One hundred sixty-nine patients were evaluable for correlation between targeting deviation and site of relapse. Number of major deviations in radiation therapy treatment is strongly correlated with the risk of tumor relapse (67% [95% CI: 28–91] of 3-year relapse rate in patient group with 2 major deviations and 78% [95% CI: 35–96] with 3 major deviations). This is particularly correlated with relapse in the frontal region of the brain: 5 relapses occurred in the frontal region in patients with major deviation in this area. An erroneous choice of electron beam energy is also linked with craniospinal fluid (CSF) relapse (3-year relapse rate of 68% [95% CI: 42–86]). Minor deviations in therapy technique are slightly associated with an increased risk of relapse in the same range as the group with only one major deviation.Conclusion: The quality of medulloblastoma radiation therapy technique is strongly correlated with outcome. Pretreatment central quality assurance review or standardized computer-designed blocks would improve survival to an extent equivalent to that attributed to adjuvant chemotherapy.

Vessel counts and vascular endothelial growth factor expression in pancreatic adenocarcinoma.

Angiogenesis is essential for growth and metastasis of solid malignancies. In several tumours, tumour vessel count and expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, have been associated with prognosis. To determine if vessel count and VEGF expression are prognostic factors in pancreatic cancer, we examined these parameters in resected tumour specimens from 22 patients who did not receive pre-operative therapy. Paraffin-embedded tumour specimens were immunohistochemically stained for factor VIII (surrogate for vessels) and VEGF. Vessel counts and VEGF expression were evaluated without knowledge of patient outcome. The median follow-up for the entire group had not been reached as of 23.1 months (range 10-69 months). The mean vessel count and VEGF expression were no different between those patients who had recurrences and those who did not. By linear regression analysis, the correlation of VEGF expression with vessel count did not reach statistical significance (P = 0.0685). Survival and time to recurrence were similar in patients with high and low vessel counts and VEGF expression of 1, 2 or 3. Tumour differentiation or lymph node positivity had no effect on either VEGF expression or vessel count. Our data suggest that, in contrast to findings in other solid malignancies, vessel count and VEGF expression are not predictors of survival or recurrence in patients with resectable adenocarcinoma of the pancreas.

An evaluation of tumour vascularity as a prognostic indicator in uveal melanoma.

Experimental and clinical evidence suggests that tumour angiogenesis plays a role in the tendency for certain neoplasms, including cutaneous melanomas, to metastasize. We evaluated whether tumour vasculature is associated with the rate of metastases in patients with melanoma of the choroid or ciliary body. The study was based on a group of 63 patients enucleated between 1976 and 1984 with paraffin-embedded tissue blocks available for sectioning and with known survival status as of December 1988. Vessel endothelial cells were highlighted with Ulex europaeus agglutinin I (UEA-I) conjugated with peroxidase. UEA-I-stained microvessels were counted at varying levels in the tumour (apex, centre and base) without knowledge of patient outcome. Patients with (n = 30) and without (n = 33) metastases had similar total vessel counts (P = 0.31). There was no evidence of greater vessel density in tumours that had metastasized, by level within the tumour. Similar results were obtained in multivariate analyses. Findings of this study suggest that tumour microvessel density is unrelated to patient survival in uveal melanoma.

Maternal serum thromboxane B2 reduction versus pregnancy outcome in a low-dose aspirin trial

Objective: Our purpose was to determine whether in a low-dose aspirin trial a longitudinal decrease in maternal serum thromboxane B2 is associated with improvement in pregnancy outcomes.Study Design: a total of 606 healthy nulliparous women with singleton gestations were randomized at 24 weeks to either 60 mg of aspirin or a placebo. Maternal serum thromboxane B2 was measured at randomization, at 29 to 31 weeks, at 34 to 36 weeks, and at delivery. After delivery, and without knowledge of patient outcome or group assignment, patients were categorized as having had either a longitudinal twofold or greater (≥50%) or less than twofold reduction (<50%) in thromboxane B2 from baseline levels at randomization.Results: Of 606 entrants, 92% had sufficient thromboxane B2 determinations to allow categorizatino. Whether patients were assigned to aspirin or placebo, birth weight was significantly greater in women who had a twofold or greater reduction in maternal serum thromboxane B2 levels. When the aspirin and placebo groups were combined, women with a twofold or greater reduction in thromboxane B2 levels had less preeclampsia, 1.9% (6314) versus 5.7% (14244) (p = 0.016), less preterm delivery (5.7% vs 10.7%, p = 0.032), fewer small-for-gestational-age newborns, 9 of 314 (2.95) versus 17 of 244 (7%) (p = 0.023). and a higher mean birth weight, 3314 gm versus 3121 gm(p = 0.0001).Conclusion: Women with a twofold or greater longitudinal reduction in maternal serum thromboxane B2 had less preeclampsia and prematurity, fewer small-for-gestational-age newborns, and higher birth weights than women with less than a twofold reduction.

Tumor angiogenesis in human lung adenocarcinoma

BACKGROUND Hematogenous metastasis requires angiogenesis within the tumor. Previous studies have shown that microvessel counts in histologic sections of the primary tumor, which reflect angiogenesis, are correlated with metastasis in breast, prostate and Stage I nonsmall cell lung carcinoma. In this study, the authors investigated the association between angiogenesis, hematogenous metastasis and lymph node metastasis in all stages of lung adenocarcinoma. METHODS Microvessels were highlighted by immunostaining endothelial cells for factor VIII. We counted microvessels within the tumors of 42 patients who had surgical resection (25 with relapse and 11 without relapse more than 5 years after surgical resection). Without knowledge of patient outcome, microvessels were counted on a 200x field (0.723 mm2) in the most active areas of neovascularization. RESULTS The microvessel counts from patients with relapse after surgical resection (mean +/- standard deviation, 75.4 +/- 64.3) were significantly higher than those without relapse more than 5 years after surgical resection (42.6 +/- 26.0) (P = 0.027). Analysis of regional lymph node metastases (factor N) revealed that the microvessel counts were 62.6 +/- 35.1 for N0 (no regional lymph node metastasis), 51.7 +/- 22.2 for N1 (metastasis in ipsilateral, peribronchial and/or ipsilateral hilar lymph nodes, including direct extension), 75.4 +/- 75.3 for N2 (metastasis in ipsilateral mediastinal and/or subcarinal lymph nodes), and 74.0 for N3 (metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph node[s]), and these values were not significantly different from each other. CONCLUSIONS Angiogenesis assessed by microvessel counts, correlated positively with relapse after surgical resection and hematogenous metastasis in all stages of lung adenocarcinoma; there was no correlation with lymph node metastasis in lung adenocarcinoma.

Tumor Angiogenesis as a Prognostic Factor in Cervical Carcinoma

Angiogenesis, the induction of new capillaries and venules, has been associated with tumor growth. Increased tumor size and new vessel growth may further the opportunity for tumor cells to enter the circulation and potentiate metastatic disease. To investigate if tumor angiogenesis could serve as a prognostic factor in cervical carcinoma, we counted microvessels (capillaries and venules) in 29 patients with squamous cell carcinoma of the cervix. Surgical specimens were stained for endothelial cells specifically with Factor VIII to identify all vessels. The microvessels were counted by light microscopy (per 200× field) in tumor sections with the highest population of microvessels. This was performed by two investigators without knowledge of patient outcome or extent of disease. Microvessel counts in patients with squamous cell carcinoma were significantly different from those of control subjects: 56 ± 28.9 and 16.3 ± 3.3 ( P = 0.013). There was no correlation between microvessel count and node status, parametrial involvement, depth of invasion, or gross disease. Microvessel count was significantly correlated with vascular space involvement ( P = 0.017). Four patients who developed recurrent disease within 1 year had high microvessel counts and yet were node negative and VSI negative at surgery. As shown by Folkman in breast cancer, angiogenesis may also be an independent predictor for recurrent disease in squamous cell carcinoma of the cervix. Microvessel counts could be of prognostic value in patients who do not have other risk factors for disease recurrence.

Tumor angiogenesis in human lung adenocarcinoma.

Hematogenous metastasis requires angiogenesis within the tumor. Previous studies have shown that microvessel counts in histologic sections of the primary tumor, which reflect angiogenesis, are correlated with metastasis in breast, prostate and Stage I nonsmall cell lung carcinoma. In this study, the authors investigated the association between angiogenesis, hematogenous metastasis and lymph node metastasis in all stages of lung adenocarcinoma. Microvessels were highlighted by immunostaining endothelial cells for factor VIII. We counted microvessels within the tumors of 42 patients who had surgical resection (25 with relapse and 11 without relapse more than 5 years after surgical resection). Without knowledge of patient outcome, microvessels were counted on a 200x field (0.723 mm2) in the most active areas of neovascularization. The microvessel counts from patients with relapse after surgical resection (mean +/- standard deviation, 75.4 +/- 64.3) were significantly higher than those without relapse more than 5 years after surgical resection (42.6 +/- 26.0) (P = 0.027). Analysis of regional lymph node metastases (factor N) revealed that the microvessel counts were 62.6 +/- 35.1 for N0 (no regional lymph node metastasis), 51.7 +/- 22.2 for N1 (metastasis in ipsilateral, peribronchial and/or ipsilateral hilar lymph nodes, including direct extension), 75.4 +/- 75.3 for N2 (metastasis in ipsilateral mediastinal and/or subcarinal lymph nodes), and 74.0 for N3 (metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph node[s]), and these values were not significantly different from each other. Angiogenesis assessed by microvessel counts, correlated positively with relapse after surgical resection and hematogenous metastasis in all stages of lung adenocarcinoma; there was no correlation with lymph node metastasis in lung adenocarcinoma.

Prediction of prognosis in untreated stage A2 prostatic carcinoma

Carcinoma is found unexpectedly in approximately 10% or more of the 400,000 prostatectomies performed annually in the United States. Patients with Stage A2 carcinoma die of their disease in only 35% of the cases. To alter the course of disease in these patients, 65% of Stage A2 patients may be treated unnecessarily by radical prostatectomy, radiation therapy, or hormonal therapy. An accurate method to predict the outcome of patients with Stage A2 carcinoma is needed. Histologic sections from 18 patients with Stage A2 prostatic carcinoma followed without further treatment until progression, or followed without progression, were evaluated by several investigators who did not have knowledge of patient outcomes and who employed standard pathologic grading systems as well as morphometric, cytophotometric, flow cytometric, and immunohistochemical techniques. Outcome was predicted correctly by random sampled absolute (17 of 18 cases) and relative (16 of 18) nuclear roundness factor (NRF), tumor volume expressed as percent of specimen (13 of 16), primary (13 of 18), secondary (14 of 18), sum (15 of 18), and worse (14 of 18) Gleason grades and prostate-specific antigen immunohistochemical findings (13 of 18) that produced statistically significant separation of the two groups. Significant separation was not obtained with Mostofi's pattern, nuclear, sum, and worse grades, Johns Hopkins' grade, absolute tumor volume, nuclear DNA content measured by image cytophotometric study of Feulgen-stained histologic sections and flow cytometric study of propidium iodide-labeled suspensions of nuclei obtained from paraffin blocks, nonrandom sampled NRF of worse and most prevalent neoplastic areas, and prostatic acid phosphatase and peanut agglutinin immunohistochemical study. NRF measured by a random technique best predicted outcome in these patients with A2 prostatic carcinoma and should be evaluated prospectively as a means for selecting patients who require therapy.

Limitations of a conventional logistic regression model based on left ventricular ejection fraction in predicting coronary events after myocardial infarction

The clinical utility of conventional logistic regression models based on left ventricular ejection fraction (LVEF) for the prediction of cardiac events (death or recurrent infarction) was assessed in 646 postinfarction patients undergoing radionuclide ventriculography at rest and during exercise. The discriminant power of 2 different models (LVEF at rest alone vs LVEF at rest plus LVEF at peak exercise) was quantified in terms of the area under receiver-operating characteristic curves based on knowledge of patient outcome in the year after testing and the logistic probability of that outcome. Although LVEF at rest provided a significant amount of prognostic information (receiver-operating characteristic curve area = 62 ±4%, p < 0.001), several limitations were observed: (1) powerful predictors of risk were uncommon (32% of patients with an LVEF at rest < 0.20 had a cardiac event, but only 3% of the population had such extreme values); (2) the accuracy of predictions for high risk patients was less than for low risk patients (28 vs 98%, p < 0.001); (3) addition of exercise LVEF to the model did not improve the accuracy of prediction (receiver-operating characteristic curve area = 68 ±4%, p = 0.11); and (4) predictions for individual patients were very imprecise (the 95% confidence interval of percent risk for an LVEF at rest of 0.20 [11 to 36%] overlapped that for an LVEF at rest of 0.60 [0 to 14%]). These limitations restrict the utility of statistical prediction models when applied to individual patient decisions, and indicate that observations should not be interpreted in isolation of other clinical findings just because they have been identified as “important” by some statistical procedure.