The impact of the Covid-19 pandemic on a Greek cohort of patients with epilepsy.

BACKGROUND: The Covid-19 pandemic, the subsequent lockdown, and the measures of social distancing may have had adverse effects on patients with epilepsy (PWE). This study was designed to assess the pandemic's psychological impact on the Greek non-infected PWE and possible changes in their seizure control. METHOD: The patients were evaluated utilizing a semi-structured interview consisting of open questions regarding their demographic, social, and clinical characteristics, followed by five questions (on a scale of 0-10) related to the Covid-19 pandemic, lockdown, and social distancing measures. Anxiety and depression of PWE were screened using the Hospital Anxiety and Depression Scale (HADS), which consists of HADS-Anxiety and HADS-Depression subscales. RESULTS: We evaluated 65 PWE in the outpatient clinic (60 %) or via telephone interview (40 %). None of these patients experienced changes in seizure control. The mean scores of the Covid-19-related questions were 6.1 ± 2.7 (fear of getting infected), 4.7 ± 3.3 (fear of death), 7.1 ± 2.7 (fear of sickness for their relatives), 6.4 ± 3.1 (stress during lockdown), and 3.0 ± 2.9 (fear of antiepileptic drugs unavailability). Thirty-nine (60 %) patients screened positive for anxiety and thirty-three (50.8 %) for depression. CONCLUSION: The psychological impact of the Covid-19 pandemic, lockdown, and social distancing measures on non-infected PWE was moderate without changes in their seizure control. HIPPOKRATIA 2021, 25 (4):145-150.

Results of combined modality therapy for patients with anal cancer (E7283). An Eastern Cooperative Oncology Group study.

BACKGROUND: This prospective study assessed combined modality therapy of patients with International Union Against Cancer classification T1-4 N0 M0 anal cancer. METHODS: Protocol therapy consisted of a dose of 4000 cGy to the pelvis, anus, and perineum, followed by a 1000-1300 cGy boost. Infusions of 5-fluorouracil and mitomycin-C were administered when radiation therapy began. A second infusion of 5-fluorouracil was administered 28 days later. Biopsy was performed 6-8 weeks after completion of treatment. Positive biopsy findings resulted in abdominal-perineal resection. RESULTS: Survival at 7 years for 50 eligible patients was 58%. White patients and those with favorable performance status had significantly better survival. Of the 46 patients evaluable for response, 34 had a complete response, 11 had a partial response, and 1 had no response. Seven-year survival for partial responders was 53%. Freedom from locoregional progression was 80% at 7 years. CONCLUSION: Treatment with a combination of chemotherapy and radiation therapy is effective for patients with anal cancer. The investigation of methods of improving therapy is warranted.

Intermediate clinical events, surrogate markers and survival.

This paper investigates one- and two-sample problems comparing survival times when an individual may experience an intermediate event prior to death or reaching some well defined endpoint. The intermediate event may be polychotomous. Patients experiencing the intermediate event may have an altered survival distribution after the intermediate event. Score tests are derived for testing if the occurrence of the intermediate event actually alters survival. These models have implications for evaluating therapies without randomization as well as strengthening the log rank test for comparing two survival distributions. The exact distribution of the score tests can be found by conditioning on both the waiting time and occurrence of the intermediate event.

Global tests for multiple binary outcomes.

The applied statistician often encounters the need to compare two or more groups with respect to more than one outcome or response. Several options are generally available, including reducing the dimension of the problem by averaging or summarizing the outcomes, using Bonferroni or other adjustments for multiple comparisons, or applying a global test based on a suitable multivariate model. For normally distributed data, it is well established that global tests tend to be significantly more sensitive than other procedures. While global tests have also been proposed for multiple binary outcomes, their properties have not been well studied nor have they been widely discussed in the context of clustered data. In this paper, we derive a class of quasi-likelihood score tests for multiple binary outcomes, and show that special cases of this class correspond to other tests that have been proposed. We discuss extensions to allow for clustered data, and compare the results to the simple approach of collapsing the data to a single binary outcome, indicating the presence or absence of at least one response. The asymptotic relative efficiencies of the tests are shown to depend not only on the correlation between the outcomes, but also on the response probabilities. Although global tests based on a multivariate model are generally recommended, our findings suggest that a test based on the collapsed data can maintain surprisingly high efficiency, especially when the outcomes of interest are rare. Data from several developmental toxicity studies illustrate our results.

Methods for inference on transmission in seroprevalence data for multiple infections.

When risk factors for an infectious disease are unknown, a method commonly employed is to investigate parallels with known infections (covariate infections). Data sets of value here are those for specified populations in which the seroprevalence of antibodies for multiple infections has been ascertained. The use of markers of covariate infections in multivariable analyses is problematic when the covariate infection is not itself an independent risk factor for the outcome of interest. In the performance of these analyses, the authors recommend the following strategy: 1) For estimates of the effects of measured risk factors on the outcome, adjustment for the covariate infection should not be done; this will avoid problems of overadjustment. 2) After control for the measured risk factors, an estimate of the "effect" of the covariate infection may be used as an indicator of the presence of unmeasured shared risk factors. 3) When shared, measured risk factors exist, the authors propose the use of methods developed for analysis of repeated measures of categorical variables to assist in inference about shared mechanisms of action of these risk factors. This analytic strategy takes advantage of the method of analogy for building understanding of transmission of new agents through their parallels with better known ones and is useful in the development of hypotheses.

Commuter exposures to VOCs in Boston, Massachusetts.

This study examines the commuter's exposure to six gasoline-related volatile organic compounds (VOCs): benzene, toluene, ethylbenzene, m-/p-xylene, o-xylene, and formaldehyde. The VOC concentrations to which commuters were exposed in four different commuting modes (driving, subway, walking, and biking) in Boston, Massachusetts, are compared. The VOC concentrations in participants' homes and offices were also measured. Factors that could influence in-vehicle VOC concentrations, such as different traffic patterns, car model and vehicle ventilation conditions, were also evaluated. Driving a private car was associated with higher VOC concentrations and commuting on urban roadways resulted in the highest VOC concentrations. The use of car heaters resulted in higher in-vehicle VOC concentrations. The longer the subway commuters stayed underground, the higher their VOC exposures. The home-to-work car or subway commute represented about 10 to 20 percent of an individual's total VOC exposure for these compounds.

Quitting smoking in the United States in 1986.

In an analysis of recent behavior with regard to quitting smoking, detailed histories were obtained on a representative sample of 5,623 Americans who had smoked in the year preceding the 1986 Adult Use of Tobacco Survey. An estimated 55.8 million Americans smoked regularly for some period during the year prior to the survey. Approximately one third (34.8%) quit for at least a day during the year prior to the survey, 28.3% quit for at least 7 days during the year prior to the survey, and 16.2% were still not smoking at the time of the survey. Of those who quit for a day, 54% had relapsed by the time of the survey. Demographic characteristics, such as age, sex, race, marital status, and education, were evaluated as predictors of making a major attempt to quit for 7 days or more. Among those who had made a major attempt, a similar analysis was done predicting success in maintaining cessation for 3 months or more. Ordinal logistic regression analyses showed that younger age and higher education predicted a major attempt to quit. There was only one group who differed markedly from all others: those who were younger and were more highly educated. Older age and being white predicted those who abstained for 3 months or longer.

Issues in the design of drug trials for AIDS.

Although the fundamental principles that drive the design, conduct, and analysis of clinical trials are as applicable to AIDS as to other diseases, there is no question that we have been confronted with unusually difficult challenges in studying therapeutic approaches in this disease area. Treatments are being developed that show great promise, but when investigated further some may be seen to offer no clinical benefit and others may do active harm through toxicity. A group of biostatisticians, meeting in association with the AIDS Clinical Trials Group (ACTG), has discussed and written a report on a number of issues, primarily related to principles of study design, with the goal of stimulating thought on new study designs and the timely implementation of well-designed trials to identify effective treatment strategies for HIV-infected populations. These issues include (1) progression of clinical trials through phases, (2) choices of outcomes, (3) breadth and complexity of clinical trials (eligibility criteria and "low-tech" trials, (4) alternative designs to be used in randomized trials, and (5) the concept of randomized clinical trials as a desirable option, both for patients and for science. The current HIV epidemic makes the requirements of obtaining valid scientific comparisons more important, not less so, but the challenge is to expedite this process.

ECOG phase II trials of MGBG, chlorozotocin, COM multidrug therapy in advanced measurable colorectal cancer.

The Eastern Cooperative Oncology Group (ECOG) entered 326 patients with advanced measurable colorectal cancer into four phase II drug or drug combination trials. Previously treated and chemotherapy-naive patients were eligible. Chlorozotocin was administered to 83 patients (51 previously treated), methyl-glyoxal-bis-guanylhydrozone (MGBG) to 90 patients (58 previously treated), and two regimens of the three-drug combination of cyclophosphamide, vincristine, and methotrexate (COM) to 153 patients (120 previously treated). The multidrug regimen had been developed specifically for previously treated patients. In this trial, chemotherapy-naive patients were no more likely to respond than were members of the previously-treated group. Even among previously untreated patients, response rates did not exceed 10% in any of these phase II programs. They are not recommended for further trials in patients with colorectal cancers.