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Circulating tumor DNA (ctDNA) is a promising intermediate end point for oncology drug development, potentially accelerating regulatory approvals by providing early insights into treatment response. However, challenges remain in standardizing ctDNA assessment, including optimal blood collection timing and defining molecular response (MR) cutoffs. The ctDNA for Monitoring Treatment Response (ctMoniTR) project, led by Friends of Cancer Research, aggregates patient-level data from clinical trials to evaluate associations between ctDNA changes and overall survival (OS). This analysis included four randomized clinical trials of patients with advanced non-small cell lung cancer (aNSCLC) treated with either anti-programmed death (ligand) 1 (anti-PD(L)1) therapy (with or without chemotherapy) or chemotherapy alone. MR was assessed using three predefined per cent-change thresholds in ctDNA levels (≥50% decrease, ≥90% decrease, and 100% clearance). ctDNA samples were analyzed at two timepoints: an early window (T1, up to 7 weeks post-treatment initiation) and a later window (T2, 7-13 weeks post-treatment initiation). Multivariable Cox proportional hazards models and time-dependent analyses were used to evaluate associations between ctDNA changes and OS. A total of 918 patients were included. In the anti-PD(L)1 group, ctDNA reductions at both T1 and T2 were significantly associated with improved OS across all MR thresholds. In the chemotherapy group, associations were weaker at T1 but became more pronounced at T2. Patients with MR at both T1 and T2 had the strongest OS associations. Overall, the results suggest that T2 had marginally stronger association with OS than T1. This study supports the potential of ctDNA as an intermediate end point in aNSCLC, with MR at both early (T1) and later (T2) timepoints showing significant associations with OS. Differences in ctDNA dynamics between treatment modalities highlight the importance of considering the timing of blood collection. Further research is needed to determine the optimal time window for assessing ctDNA response. Prospective trials and trial-level meta-analyses will be critical to validating ctDNA as a regulatory-grade intermediate end point for oncology drug development.

Rapid and robust strategies to evaluate the efficacy and effectiveness of novel and existing pharmacotherapeutic interventions (repurposed treatments) in future pandemics are required. Observational “real‐world studies” (RWS) can report more quickly than randomized controlled trials (RCTs) and would have value were they to yield reliable results. Both RCTs and RWS were deployed during the coronavirus disease 2019 (COVID‐19) pandemic. Comparing results between them offers a unique opportunity to determine the potential value and contribution of each. A learning review of these parallel evidence channels in COVID‐19, based on quantitative modeling, can help improve speed and reliability in the evaluation of repurposed therapeutics in a future pandemic. Analysis of all‐cause mortality data from 249 observational RWS and RCTs across eight treatment regimens for COVID‐19 showed that RWS yield more heterogeneous results, and generally overestimate the effect size subsequently seen in RCTs. This is explained in part by a few study factors: the presence of RWS that are imbalanced for age, gender, and disease severity, and those reporting mortality at 2 weeks or less. Smaller studies of either type contributed negligibly. Analysis of evidence generated sequentially during the pandemic indicated that larger RCTs drive our ability to make conclusive decisions regarding clinical benefit of each treatment, with limited inference drawn from RWS. These results suggest that when evaluating therapies in future pandemics, (1) large RCTs, especially platform studies, be deployed early; (2) any RWS should be large and should have adequate matching of known confounders and long follow‐up; (3) reporting standards and data standards for primary endpoints, explanatory factors, and key subgroups should be improved; in addition, (4) appropriate incentives should be in place to enable access to patient‐level data; and (5) an overall aggregate view of all available results should be available at any given time.

All organizations are social systems. The family is the first social system to which each person belongs. A business organization is also such a system. Family theorists describe family relationships and use this understanding to help families to improve their functioning. These insights can also be applied to business organizations and their governance. The present paper uses Bowen’s family systems theory to understand financial governance and governance relationships. Bowen’s eight concepts of family systems are triangles, differentiation of self, nuclear family emotional process, family projection process, multigenerational transmission process, emotional cutoff, sibling position, and societal-emotional process. These concepts are discussed in light of how financial information is shared in a business, how board composition affects the oversight of financial operations, how leadership balances financial and operational demands, and how the social interactions within the business interplay with the macro social-industrial environment. For example, a well-functioning family helps a family member develop into an independent adult. Likewise, the effective business leader enables the financial department to develop autonomy, allowing that department to provide meaningful, objective information for business decisions. When this does not occur, problems can arise which affects family stability and business efficiency. Suggestions for further research are offered. In particular, the connection between family theories and agency and social models of governance is explored. The models also are relevant to notions of who are the business’s stakeholders. The overlap between business systems and family systems which has become more evident during the COVID-19 pandemic speaks to the relevance of the concepts in this paper to future research and business planning.

Background: Multiple adverse environmental factors, among them home environments with limited resources, are associated with detrimental effects on developmental outcome of low SES children. Enhanced understanding of differences between home environments of low and higher SES infants can provide opportunities to improve child outcome. Objective: To examine differences between home environment of toddlers of Low and Higher SES. Study Design: Healthy African American female infants enrolled at …

This article highlights the need for clinicians who work with eating disorders and body image problems to address the deeper family issues underlying these symptoms. The authors propose an eclectic approach including family systems, structural and experiential family therapy theory as a guide. The paper begins with an overview of family therapy theories currently used in the treatment of eating disorders, and goes into greater detail about the three theories highlighted in the eclectic model proposed. The authors present two cases with actual case dialogue, demonstrating how they used this composite model. This article has both theoretical and practical implications for clinicians working in the field.

A 75-year-old man presented to us with a 6-month weight loss of 85 lbs. He was unable to get out of a chair and was brought in in a wheelchair by his wife. His past medical history was significant for Type II diabetes mellitus, diagnosed 20 years ago, and he hadn't seen a physician for the past 10 years. He reported that he had not taken his diabetic medications for the past 5 years and was controlling his diabetes by diet. His wife reported that for the past 6 months he had experienced progressive weight loss even though he continued to eat normally. He has also developed muscle wasting of his lower extremities and was unable to climb stairs or get out of a chair without assistance. On physical examination, the patient was found to be cachectic, with severe symmetrical muscle wasting and motor deficit of the proximal leg muscles. There was no apparent sensory impairment of the lower extremities. On laboratory evaluation the patient had a normal complete blood count, electrolytes, liver enzymes, and sedimentation rate. He had an elevated hemoglobin A1c and fasting blood glucose. The patient was initiated on a regiment of insulin and a sulfonurea, with subsequent good control of his glucose. The patient continued to loose weight, however, and had now developed diffuse deep aching pain in both thighs. An evaluation for a possible occult malignancy was initiated, with full body CT, prostate specific antigen, colonoscopy, and endoscopy results unremarkable. The patient was then sent for evaluation by endocrinology and infectious diseases; both recommended continued evaluation for occult malignancies with negative tests for HIV, tuberculosis, adrenal insufficiency, and thyroid disease. Nerve conduction studies done by neurology showed a predominant proximal lower limb axonopathy. MRI of the lumbar spine was unremarkable. Muscle biopsy was not done. The patient was treated with gabapentin 300 mg TID resulting in slow improvement of his pain syndrome. With continued diabetic control, the patient slowly gained back 65 lbs. over 10 months, with partial improvement of the proximal lower limb muscle weakness and wasting. Diabetic Amyotrophy (Bruns-Garland syndrome) is characterized by weakness followed by wasting of pelvifemoral muscles, either bilaterally or unilaterally, with associated pain.1 The pathogenesis is unknown, but it is theorized to be either metabolic or ischemic in nature. It is prevalent in .08% of diabetic patients (1.1% of type II diabetics, and .03% of type I diabetics).2 It typically affects men with type II diabetes in their fifth or sixth decade and is associated with a 10- to 30-lb. weight loss.2,3 The syndrome usually improves with glycemic control. This particular patient was much older than the typical patients, and his weight loss was much more pronounced. This unusual manifestation of diabetes must be taken into consideration when geriatric patients present with a history of type II diabetes in conjunction with weight loss and proximal limb muscle wasting and motor deficit. We as clinicians should strive to detect and characterize this syndrome further in geriatric patients, thus avoiding unnecessary, prolonged, and costly work-ups for these patients.

Letters4 April 2000Clinically Useful Problem Statement SystemsKenneth J. Gorelick, MDKenneth J. Gorelick, MDBala Cynwyd, PA 19004 (Gorelick)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-7-200004040-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Brown and colleagues (1) propose an interesting and useful system to reduce the number of terms needed to enumerate a patient's medical problems. They achieved a 60-fold reduction, from 891 770 problem statements for 74 696 patients to 15 534 “canonical” terms. They suggest that this will simplify physicians' ability to readily lump diseases together, especially when compared with the unwieldy International Classification of Diseases, 9th Revision, Clinical Modification.From this elegantly derived research and billing tool, Dr. Voytovich (2) takes us into the brave new world of the “handoff” of patients from hospitalists to ambulatory care ...

(1998). D. W. Winnicott. A Biographical Portrait. The Psychoanalytic Quarterly: Vol. 67, No. 4, pp. 726-727.

This article examines applications of complexity theory within the behavioral and social sciences. Specific attention is given to the fundamental characteristics of complex adaptive systems (CAS)—such as individuals, groups, and societies—including the underlying structure of CAS, the internal dynamics of evolving CAS, and how CAS respond to their environment. Examples drawn from psychology, sociology, economics, and political science include attitude formation, majority–minority relations, social networks, family systems, psychotherapy, norm formation, organizational development, coalition formation, economic instabilities, urban development, the electoral process, political transitions, international relations, social movements, drug policy, and criminal behavior. The discussion also addresses the obstacles to implementing the CAS perspective in the behavioral and social sciences and implications for research methodology.