Geotemporal analysis of perinatal care changes and maternal mental health: an example from the COVID-19 pandemic

Archives of Women's Mental Health - Our primary objective was to document COVID-19 induced changes to perinatal care across the USA and examine the implication of these changes for maternal...     

A Phase I trial of high dose gefitinib for patients with leptomeningeal metastases from non-small cell lung cancer

Introduction

There are few effective treatment options for leptomeningeal metastasis (LM) in non-small-cell lung cancer (NSCLC). This study assessed the feasibility of high-dose gefitinib in patients with LM from NSCLC harboring EGFR mutations or prior systemic response to EGFR-TKI.

Methods

This phase I open-label trial of a novel gefitinib dosing schedule employed a 3+3 design. Eligible NSCLC patients with LM had known EGFR mutations and/or prior response to EGFR-TKI. Patients alternated 2 weeks of high-dose daily gefitinib (dose levels: 750 mg, 1000 mg, 1250 mg) with 2 weeks of maintenance therapy (500 mg daily). Primary endpoints were safety and toxicity. Secondary endpoints included overall survival (OS), neurological progression-free survival, radiological response, and cytological response in cerebrospinal fluid (CSF).

Results

Seven patients were treated: 3 at 750 mg dose level, 4 at 1000 mg dose level. There were no DLTs at the 750 mg dose level, and one DLT (toxic epidermal necrolysis) at the 1000 mg dose level. The study was closed due to slow accrual. Median neurological PFS was 2.3months (range 1.6–4.0 months); median OS was 3.5months (range 1.6–5.1months). Though there were no radiologically documented remissions of LM disease, four patients had improvement in neurological symptoms. One patient cleared their CSF of NSCLC cells, while 2 others had decrease in malignant cells in CSF.

Conclusion

Although the MTD was not defined due to slow accrual, this study provides important information about the tolerability and CSF penetration of high-dose gefitinib as a therapeutic option for modest palliation for NSCLC patients with LM and a known EGFR mutation.     

Treatment of peritoneal mesothelioma in pediatric patients

Peritoneal mesothelioma is a rare and often aggressive malignancy, mostly affecting asbestos exposed adults. We present four pediatric peritoneal cases treated with a cisplatin-based doublet regimen, the standard of care in the systemic therapy of adult mesothelioma. Treatment was well tolerated, and three of these patients have achieved long-term survival. The fathers of three of the patients worked in the construction industry and may have been the source of indirect asbestos exposure.     

Abdominal differential diagnosis in a patient referred to a physical therapy clinic for low back pain

STUDY DESIGN: Resident's case problem. BACKGROUND: Acute back pain most often presents as musculoskeletal in nature; however, less frequently it may be the result of an underlying, or coexisting, systemic pathology. When present, the signs and symptoms of systemic pathology can mimic, or be masked by, musculoskeletal back pain, which may pose a diagnostic challenge during the clinical evaluation. The purpose of this resident's case problem is to describe the clinical reasoning process leading to a medical referral for a patient who presented to physical therapy with debilitating low back pain. DIAGNOSIS: The patient in this resident's case problem was a 67-year-old male referred to physical therapy with a 2-week history of severe low back pain and muscle spasms. The patient history and physical examination were suggestive of musculoskeletal back pain and physical therapy treatment was initiated. Abdominal pain was elicited during an introductory therapeutic exercise, which was recognized by the therapist as a potential sign of abdominal pathology. The therapist performed an additional review of systems and an abdominal screening examination, which established the necessity of an immediate medical referral. At the emergency department, ominous abdominal pathology was safely ruled out through diagnostic imaging and the patient was treated for secondary gastrointestinal effects of opioid analgesic medications. DISCUSSION: This resident's case problem provides an opportunity to discuss the clinical reasoning process leading to the suspicion of abdominal pathology. Specifically, this case reinforces the importance of recognizing potential signs of systemic pathology, executing an appropriate physical examination, including screening of the involved anatomical region, and providing an appropriate medical referral when indicated.