Nontreatment Studies Research Articles

Computational identification of biomarker genes for lung cancer considering treatment and non-treatment studies

BackgroundLung cancer is the number one cancer killer in the world with more than 142,670 deaths estimated in the United States alone in the year 2019. Consequently, there is an overreaching need to identify the key biomarkers for lung cancer. The aim of this study is to computationally identify biomarker genes for lung cancer that can aid in its diagnosis and treatment. The gene expression profiles of two different types of studies, namely non-treatment and treatment, are considered for discovering biomarker genes. In non-treatment studies healthy samples are control and cancer samples are cases. Whereas, in treatment studies, controls are cancer cell lines without treatment and cases are cancer cell lines with treatment.ResultsThe Differentially Expressed Genes (DEGs) for lung cancer were isolated from Gene Expression Omnibus (GEO) database using R software tool GEO2R. A total of 407 DEGs (254 upregulated and 153 downregulated) from non-treatment studies and 547 DEGs (133 upregulated and 414 downregulated) from treatment studies were isolated. Two Cytoscape apps, namely, CytoHubba and MCODE, were used for identifying biomarker genes from functional networks developed using DEG genes. This study discovered two distinct sets of biomarker genes – one from non-treatment studies and the other from treatment studies, each set containing 16 genes. Survival analysis results show that most non-treatment biomarker genes have prognostic capability by indicating low-expression groups have higher chance of survival compare to high-expression groups. Whereas, most treatment biomarkers have prognostic capability by indicating high-expression groups have higher chance of survival compare to low-expression groups.ConclusionA computational framework is developed to identify biomarker genes for lung cancer using gene expression profiles. Two different types of studies – non-treatment and treatment – are considered for experiment. Most of the biomarker genes from non-treatment studies are part of mitosis and play vital role in DNA repair and cell-cycle regulation. Whereas, most of the biomarker genes from treatment studies are associated to ubiquitination and cellular response to stress. This study discovered a list of biomarkers, which would help experimental scientists to design a lab experiment for further exploration of detail dynamics of lung cancer development.

Preferences for research participation among individuals with Lynch syndrome: Findings from the HEROIC Registry.

e19317 Background: AliveAndKickn, whose mission is to improve the lives of individuals and families affected by Lynch Syndrome (LS) through research and education, maintains the HEROIC Registry. It is the first-of-its-kind, patient-centric, genetic database that enables individuals to take an active role in furthering LS research. Methods: The HEROIC Registry allows patients to contribute medical information and their experiences living with LS and its associated cancers to help researchers develop new treatments, understand the various genetic mutations, and conduct further studies. It also asks individuals about their preferences for participating in different types of research studies. Results: The HEROIC Registry was launched in February of 2016. Potential participants were notified about the availability of the Registry in multiple ways, including social media and patient conferences. As of January 2020, 269 individuals have added their data to the Registry. Of those, 217 have a known LS mutation and were on average 42.5 years old at the time of diagnosis. 38% report having had a diagnosis of colorectal cancer with an average diagnosis age of 43; 23% of female respondents report having had endometrial cancer with an average diagnosis age of 48. 37% are cancer-unaffected. For interest in participating in future research, 69% are somewhat or very likely or definitely want to participate in research that involves a LS treatment, with rates ranging from 62-80% based on the delivery method of the treatment. For non-treatment studies, the percentage of individuals that are somewhat or very likely or definitely want to participate in research that involves community meetings, hospital stays, a medical procedure, wearing a device, or providing information by phone are text are 76%, 46%, 52%, 83%, and 78%, respectively. The percentage of individuals willing to donate a blood sample used to study their DNA is 95%. Conclusions: The HEROIC Registry provides a unique opportunity for health care providers and researchers to partner directly with a patient-advocacy organization for the purpose of improving LS care. It also has the benefit of including a diverse set of patients who are being seen in a variety of health care settings, which can aid in exploring research questions outside of a single institution. However, individuals show clear preferences for the types of research they are likely to participate in, a fact that should be taken into consideration when researchers are planning new studies in this population.

EDiary and Female Sexual Distress Scale© in Evaluating Distress in Hypoactive Sexual Desire Disorder (HSDD)

Sex-related distress is integral to the diagnosis of hypoactive sexual desire disorder (HSDD). This article describes the results of three prospective, non-treatment validation studies (two North American and one European), each testing over 200 participants with HSDD, other types of female sexual dysfunction (FSD), or no FSD in which the 12-item Female Sexual Distress Scale© (FSDS©), the 13-item FSDS–Revised©(FSDS–R©), and a single question asked using a daily electronic diary (the eDiary For HSDD Trials©; eDiary) were used to measure sex-related distress. FSDS results with 30- and seven-day recall were equivalent. The results observed with FSDS–R Item 13 (a single question assessing concern due to low sexual desire) were comparable to the FSDS. Mean eDiary monthly distress scores were closer to the minimum possible score (equivalent to “a little bit” of distress) and were about twice as variable as FSDS or FSDS–R Item 13 scores in participants with HSDD. All three measures confirmed that there is more distress in women with HSDD compared to women with no sexual dysfunction at all time points, demonstrating discriminant validity.

Large-scale, prospective, observational studies in patients with psoriasis and psoriatic arthritis: A systematic and critical review

BackgroundObservational studies, if conducted appropriately, play an important role in the decision-making process providing invaluable information on effectiveness, patient-reported outcomes and costs in a real-world environment. We conducted a systematic review of large-scale, prospective, cohort studies with the aim of (a) summarising design characteristics, the interventions or aspects of the disease studied and the outcomes measured and (b) investigating methodological quality.MethodsWe included prospective, cohort studies which included at least 100 adults with psoriasis or psoriatic arthritis. Studies were identified through searches in electronic databases (Pubmed, Medline, Cochrane library, Centre for Reviews and Dissemination). Information on study characteristics were extracted and tabulated and quality assessment, using a checklist of 18 questions, was conducted.ResultsThirty five papers covering 16 cohorts met the inclusion criteria. There were ten treatment-related studies, only two of which provided a comparison between treatments, and six non-treatment studies which examined a number of characteristics of the disease including mortality, morbidity, cost of illness and health-related quality of life. All studies included a clinical outcome measure and 11 included patient-reported outcomes, however only two studies reported information on patient utilities and two on costs. The quality of the assessed studies varied widely. Studies did well on a number of quality assessment questions including having clear objectives, documenting selection criteria, providing a representative sample, defining interventions/characteristics under study, defining and using appropriate outcomes, describing results clearly and using appropriate statistical tests. The quality assessment criteria least adhered to involved questions regarding sample size calculations, describing potential selection bias, defining and adjusting for confounders and losses to follow-up, and defining and describing a comparison group.ConclusionThe review highlights the need for well designed prospective observational studies on the effectiveness, patient-reported outcomes and economic impact of treatment regimes for patients with psoriasis and psoriatic arthritis in a real-world environment.

Should Sexual Desire and Arousal Disorders in Women Be Merged? A Response to DeRogatis, Clayton, Rosen, Sand, and Pyke (2010)

We are grateful for the opportunity to reply to the Letter to the Editor entitled‘‘Should Sexual Desire and Arousal Disorders in Women Be Merged?’’by DeRogatis, Clayton, Rosen, Sand, and Pyke (2010). Considerable debate has emerged since the publication of our proposed revisions for Hypoactive Sexual Desire Disorder (HSDD) and Female Sexual Arousal Disorder (FSAD) for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (Brotto, 2010; Graham, 2010).Published commentariesand our response (Binik, Brotto, Graham, & Segraves, 2010) appeared in a recent issue of the Journal of Sexual Medicine. At the outset, we wish to respond to a statement made by DeRogatis et al. regarding the basis for our proposed revisions. DeRogatis et al. argued that fundamental changes to psychiatric nomenclature ‘‘...should be based on confirmed data— preferably from multiple clinical trials or observational studies—rather than on theoretical speculations or expert opinion, as in the current proposal.’’The published guidelines for making changes to DSM-5 (Kendler, Kupfer, Narrow, Phillips, & Fawcett, 2009) clearly state that recommendations should be guided by research evidence but that, unlike DSM-IV,‘‘there will be no a priori constraints on the degree of change between DSM-IV and DSM-V.’’ There is simply no justification for asserting that the proposal for Sexual Interest/Arousal Disorder was based on‘‘theoretical speculations or expert opinion.’’ Comprehensive and critical reviews of the empirical literature wereundertaken(Brotto,2010;Graham,2010)and these formed the basis for the proposals. It should also be noted that the DSMIV-TR diagnoses of HSDD and FSAD were not based on any systematically collected body of data. The diagnosis of HSDD was the result of the expert opinion of Helen Singer Kaplan and Harold Lief: FSAD appears to have initially resulted from the early theorizing concerning the human sexual response cycle by Masters and Johnson and was probably saved from extinction by the hope that PDE-5 inhibitors would be effective for women. In their letter, DeRogatis et al. reported on data from two nontreatment studies funded by Boehringer Ingelheim (BI). In one study, women with primary HSDD and primary FSAD (n = 143) differed significantly from each other in terms of symptom profile. The women with HSDD had better sexual functioning, as measured by the Female Sexual Function Index (FSFI), compared to women with FSAD (total mean FSFI scores of 23.7 and 20.2, respectively). On the basis of these two groups showing ‘‘different symptom profiles,’’ DeRogatis et al. argued that the diagnostic categories ofHSDDand FSAD should not be merged in DSM-5. We believe that DeRogatis et al.’s findings of distinct symptom patterns among women with HSDD and those with FSAD are due to how the samples were recruited. As women were diagnosed using DSM-IV criteria (which separate deficient or absent desire for sex [HSDD] from impaired lubrication [FSAD], one would expect different symptom profiles in L. A. Brotto (&) Department of Obstetrics and Gynaecology, University of British Columbia, 2775 Laurel Street, 6th Floor, Vancouver, BC V5Z 1M9, Canada e-mail: lori.brotto@vch.ca

Validation of the Sexual Interest and Desire Inventory-Female in Hypoactive Sexual Desire Disorder

The Sexual Interest and Desire Inventory-Female (SIDI-F) is a 13-item scale developed as a clinician-administered assessment tool to measure hypoactive sexual desire disorder (HSDD) severity in women. To estimate the reliability and validity of the SIDI-F as a measure of HSDD severity. Women, aged 18-65 years, with primary HSDD, Female Sexual Arousal Disorder (FSAD), or no Female Sexual Dysfunction (no FSD) participated in two nontreatment studies (in North America and Europe). On days 0 and 28, subjects were assessed using the SIDI-F, Female Sexual Function Index (FSFI), Changes in Sexual Functioning Questionnaire-Female (CSFQ-F), Locke-Wallace Marital Adjustment Test (MAT) and the Female Sexual Distress Scale (FSDS). Discriminant validity, convergent validity, divergent validity, test-retest validity, and internal consistency of the SIDI-F. The North American study enrolled women with HSDD (N = 113), FSAD (N = 49) and no FSD (N = 61); the European study enrolled women with HSDD (N = 130) and no FSD (N = 124). In both studies, mean SIDI-F total score for women with HSDD was lower than for those with no FSD (P < 0.001, for all) demonstrating discriminant validity. Further, mean SIDI-F total score for women with HSDD was lower than for those with FSAD in the North American study (P < 0.001). Convergent validity with the FSFI and CSFQ-F and divergent validity with MAT were demonstrated. Test-retest reliability and internal consistency were high. The SIDI-F is a valid and reliable measure of HSDD severity in women.

Evidence-based cognitive rehabilitation: Recommendations for clinical practice

Cicerone KD, Dahlberg C, Kalmar K, Langenbahn DM, Malec JF, Bergquist TF, Felicetti T, Giacino JT, Harley JP, Harrington DE, Herzog J, Kneipp S, Laatsch L, Morse PA. Evidence-based cognitive rehabilitation: recommendations for clinical practice. Arch Phys Med Rehabil 2000;81:1596-615. Objective: To establish evidence-based recommendations for the clinical practice of cognitive rehabilitation, derived from a methodical review of the scientific literature concerning the effectiveness of cognitive rehabilitation for persons with traumatic brain injury (TBI) or stroke. Data Sources: A MEDLINE literature search using combinations of these key words as search terms: attention, awareness, cognition, communication, executive, language, memory, perception, problem solving, reasoning, rehabilitation, remediation, and training. Reference lists from identified articles also were reviewed; a total bibliography of 655 published articles was compiled. Study Selection: Studies were initially reviewed according to the following exclusion criteria: nonintervention studies; theoretical, descriptive, or review papers; papers without adequate specification of interventions; subjects other than persons with TBI or stroke; pediatric subjects; pharmacologic interventions; and non-English language papers. After screening, 232 articles were eligible for inclusion. After detailed review, 61 of these were excluded as single case reports without data, subjects other than TBI and stroke, and nontreatment studies. This screening yielded 171 articles to be evaluated. Data Extraction: Articles were assigned to 1 of 7 categories according to their primary area of intervention: attention, visual perception and constructional abilities, language and communication, memory, problem solving and executive functioning, multi-modal interventions, and comprehensive-holistic cognitive rehabilitation. All articles were independently reviewed by at least 2 committee members and abstracted according to specified criteria. The 171 studies that passed initial review were classified according to the strength of their methods. Class I studies were defined as prospective, randomized controlled trials. Class II studies were defined as prospective cohort studies, retrospective case-control studies, or clinical series with well-designed controls. Class III studies were defined as clinical series without concurrent controls, or studies with appropriate single-subject methodology. Data Synthesis: Of the 171 studies evaluated, 29 were rated as Class I, 35 as Class II, and 107 as Class III. The overall evidence within each predefined area of intervention was then synthesized and recommendations were derived based on consideration of the relative strengths of the evidence. The resulting practice parameters were organized into 3 types of recommendations: Practice Standards, Practice Guidelines, and Practice Options. Conclusions: Overall, support exists for the effectiveness of several forms of cognitive rehabilitation for persons with stroke and TBI. Specific recommendations can be made for remediation of language and perception after left and right hemisphere stroke, respectively, and for the remediation of attention, memory, functional communication, and executive functioning after TBI. These recommendations may help to establish parameters of effective treatment, which should be of assistance to practicing clinicians. © 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Role of autacoids in cardiovascular colapse in anaphylactic shock in anaesthetized dogs.

In anaphylactic shock (AS), the relative effects of the autacoids including histamine, prostaglandins (prost), and leukotrienes (leuk) on causing cardiovascular collapse and the extent to which receptor blocking agents and pathway inhibitors may prevent this collapse are not clear. In randomized design, we investigated whether blockade of histamine H1, H2, and H3 receptors or inhibition of the cyclooxygenase (cyclo) and lipoxygenase pathways (lipox) prevented AS in ragweed sensitized dogs. Seven dogs were studied under pentobarbital anesthesia in which the treatment studies were approximately 2 weeks apart. During H1 receptor blockade, the decreases in blood pressure and cardiac output otherwise observed in AS were attenuated (P < 0.05) and the release of prost, thromboxanes, and leuk were reduced as compared with nontreatment studies. Cyclo inhibition also attenuated cardiovascular collapse and mediator release in AS, but the other treatments showed no effects. H1 receptor blockade and cyclo may attenuate cardiovascular shock in AS. These agents inhibit autacoid release from mast cells in addition to any specific receptor blocking and pathway inhibition effects.

Behavioural Approaches to Headaches

Headaches are a common problem, and psychological factors are widely acknowledged as playing a critical role in the development and maintenance of a high proportion of cases. This mini series consists of six contributions to the headache literature from researchers working in Australia. The papers focus on cycles in headache activity; behavioural patterns, copying styles and personality characteristics of headache sufferers; psychophysiological pain mechanisms; and potential adverse consequences of simplistic treatment approaches. The emphasis on non-treatment studies is unusual in this field but argued to be appropriate in view of the lack of knowledge concerning basic headache processes.

Informed consent as a form of volunteer bias

Two nontreatment studies of tardive dyskinesia were examined to see if giving or refusing informed consent might bias results. Three prominent psychiatric journals were also reviewed to determine whether the outcome of informed consent procedures was sufficiently well described to permit evaluation of potential bias. The nontreatment studies suggested that the bias created by requiring informed consent may cause both false-positive and false-negative findings. The literature review showed that treatment studies have generally ignored the potential impact of these biases on results. Accurate interpretation of research reports, particularly clinical trials, demands that more attention be given to the process of obtaining and reporting informed consent.