Clozapine-induced pulmonary embolism in a patient with minimal pre-existing risk factors

ObjectivesAlthough the risk of antipsychotic-induced venous thromboembolism (VTE) has been definitively established, guidelines recommending prophylactic anticoagulation do not yet exist. Several algorithms have been proposed that suggest possible prophylaxis with an anticoagulant medication on the basis of pre-existing VTE risk factors. We present a case of antipsychotic-induced VTE despite the patient’s low-risk status so that practitioners may better understand which factors may or may not constitute a major risk in this population when making a determination about prophylactic anticoagulation.Case summaryWe present a patient case of a 56-year-old man with schizoaffective disorder who was treated with clozapine at an inpatient psychiatric unit. Although he would be classified as low risk for VTE on the basis of the proposed algorithms, he experienced a pulmonary embolism by day 17 of treatment and required transfer to a medical unit. This patient displayed sensitivity to other adverse effects associated with clozapine during his treatment course, including tachycardia, sialorrhea, enuresis, and bowel obstruction.Practice implicationsMany of the known risk factors for antipsychotic-induced VTE were not present in this patient, including immobility, hyperprolactinemia, and coagulation abnormalities. The recent initiation of clozapine and obesity seem to be the only identified risk factors, although malignancy and abnormal antiphospholipid antibody levels were not able to be ruled out. It is difficult to determine if this patient experienced a VTE owing to a relatively high degree of sensitivity to clozapine, as evidenced by the myriad of other adverse effects that he experienced. This case highlights the need to determine true antipsychotic-induced VTE risk factors, including evaluation of comorbid adverse effects that occur in addition to the VTE. This information will help to guide future decision-making regarding the risk versus benefit of providing prophylactic anticoagulation for patients during initiation of antipsychotic treatment.     

Exploring the Factors that Influence Workforce Participation for People with Multiple Sclerosis: A Discrete Choice Experiment

Journal of Occupational Rehabilitation - Purpose Research indicates that employment is beneficial for people with multiple sclerosis (MS). However, people with MS typically face reduced workforce...     

Factors Associated with Colorectal Cancer Among Jordanians: a Case- Control Study

Objective: In recent years, the incidence of colorectal cancer (CRC) in Jordan has been on the rise. We aimed todetermine associations with lifestyle factors, demographic and clinical variables. Methods: This case-control studyincluded 102 patients diagnosed with CRC and 198 age and gender matched healthy subjects as controls. Cases werepurposefully sampled; however, the control group were selected by simple random sampling of a cross-section of thepopulation in Northern Jordan. Participating cases and controls completed an anonymous questionnaire inquiring abouttheir demographic characteristics, lifestyle factors, and clinical variables. Data about the medical history and diagnosisof participating cases were obtained from the cases themselves and confirmed by reviewing their medical records.Results: In the cross tabulation analysis, the Chi square test showed that diabetes and hypertension were significantlyassociated with CRC (P <0.05). Additionally, regression modeling revealed that age ≥ 45 years (OR=10.93), positivefamily history for CRC (OR=5.53), physical inactivity (OR=7.4), cigarette smoking (OR=3.71), and having other typesof cancer (OR=13.61) were all associated with increased risk of CRC. Conclusions: Physical inactivity and cigarettesmoking are among the top modifiable risk factors for CRC among Jordanians. Moreover, diabetes and hypertensionwere found to be statistically significant risk factors in univariate, but not multivariate analysis. More effective strategiesfor elevating awareness and prevention are required at both national and international levels. Improving screeningstrategies is needed for early detection of CRC in Jordan.     

Safety of Combined PD-1 Pathway Inhibition and Intracranial Radiation Therapy in Non–Small Cell Lung Cancer

Introduction

Intracranial metastases are a common cause of morbidity and mortality in patients with advanced NSCLC, and are frequently managed with radiation therapy (RT). The safety of cranial RT in the setting of treatment with immune checkpoint inhibitors (ICIs) has not been established.

Sexual health in long-term breast cancer survivors

Purpose

Next-generation sequencing (NGS) has identified recurrent genomic alterations in metastatic breast cancer (MBC); however, the clinical utility of incorporating routine sequencing to guide treatment decisions in this setting is unclear. We examine the frequency of genomic alterations in MBC patients from academic and community hospitals and correlate with clinical outcomes.

Methods

MBC patients with good performance status were prospectively recruited at the Princess Margaret Cancer Centre (PM) in Canada. Molecular profiling on DNA extracted from FFPE archival tissues was performed on the Sequenom MassArray platform or the TruSeq Amplicon Cancer Panel (TSACP) on the MiSeq platform. Clinical trial outcomes by RECIST 1.1 and time on treatment were reviewed retrospectively.

Results

From January 2012 to November 2015, 483 MBC patients were enrolled and 440 were genotyped. At least one somatic mutation was identified in 46% of patients, most commonly in PIK3CA (28%) or TP53 (13%). Of 203 patients with ≥ 1 mutation(s), 15% were treated on genotype-matched and 9% on non-matched trials. There was no significant difference for median time on treatment for patients treated on matched vs. non-matched therapies (3.6 vs. 3.8 months; p = 0.89).

Conclusions

This study provides real-world outcomes on hotspot genotyping and small targeted panel sequencing of MBC patients from academic and community settings. Few patients were matched to clinical trials with targeted therapies. More comprehensive profiling and improved access to clinical trials may increase therapeutic options for patients with actionable mutations. Further studies are needed to evaluate if this approach leads to improved clinical outcomes.

     

Obstetric maneuvers for shoulder dystocia and associated fetal morbidity

OBJECTIVE: We sought to determine the fetal injury rate associated with shoulder dystocia and to determine whether there is a higher rate of brachial plexus injury or bone fracture when fetal manipulation techniques are required for delivery. STUDY DESIGN: A retrospective review of 285 cases of shoulder dystocia that occurred between January 1991 and December 1995 was performed. The type, sequence, and combination of obstetric maneuvers used to relieve the shoulder dystocia were noted. These cases were divided into two groups, as follows: (1) those resolved with McRoberts' maneuver, suprapubic pressure, or proctoepisiotomy or a combination of these and (2) those that required the addition of direct fetal manipulative maneuvers (Woods, posterior arm, or Zavanelli). Fetal injury was defined as the occurrence of brachial plexus palsy, clavicular fracture, humeral fracture, or fetal death caused by asphyxial complications. RESULTS: The fetal injury rate was 24.9% (71/285), including 48 (16.8%) brachial plexus palsies, 27 (9.5%) clavicular fractures, and 12 (4.2%) humeral fractures. Sixteen infants had both nerve injury and bone fracture. Four (8.9%) brachial plexus palsies had documented persistence at 1 year of follow-up. One neonatal death occurred at age 3 months after an episode of hypoxic ischemic encephalopathy. The incidence of bone fracture was not higher when direct fetal manipulation was required: 21 of 127 (16.5%) versus 18 of 158 (11.4%), p = 0.21. The incidence of brachial plexus palsy was also similar in both groups (27/127 vs 21/158, p = 0.1). CONCLUSIONS: Direct fetal manipulation techniques used to alleviate shoulder dystocia are not associated with an increased rate of bone fracture or brachial plexus injury. (Am J Obstet Gynecol 1998;178:1126-30.)     

Stillbirth evaluation: What tests are needed?

OBJECTIVE: We sought to investigate what aspects of the stillbirth evaluation are considered to be essential and what tests can potentially be eliminated. STUDY DESIGN: A retrospective analysis of 745 stillbirths occurring from January 1990 to December 1994 was conducted. A stillbirth was defined by an estimated gestational age >20 weeks' gestational age or fetal weight >500 gm. We attempted to arrive at an apparent cause for each stillbirth after evaluation of genetic or chromosomal abnormalities, obstetric history, maternal medical illnesses, laboratory tests, autopsy findings, and placental pathologic conditions. RESULTS: We found that the most important aspects of stillbirth evaluation were placental pathologic conditions and autopsy. When the placenta was examined, a significant abnormality was detected in 30% (160 of 529) of the cases. When autopsy was performed, only 31% of fetal deaths (142 of 462) were unexplained; however, when no autopsy was performed, 44% (125 of 283) were unexplained (p = 0.0002). The following laboratory evaluations that were routinely performed were found to yield little definitive information: antinuclear antibody testing, Kleihauer-Betke test, and screening for congenital infections (toxoplasmosis, other viruses, rubella, cytomegalovirus, and herpes simplex virus). Overall, 36% (267 of 745) of stillbirths still remained unexplained despite a thorough evaluation in most cases. CONCLUSION: The causes of stillbirth are many and varied, with a large proportion having no obvious cause. As this study demonstrates, certain laboratory tests can be eliminated in the workup of fetal death. In the evaluation of stillbirth a complete systematic method that incorporates placental pathologic conditions, as well as autopsy findings, should prove to be beneficial. (Am J Obstet Gynecol 1998;178:1121-5.)     

Direction of DNA sequences within chromatids determined using strand-specific FISH

The 5 to 3 direction of DNA strands within chromatids of metaphase chromosomes can be determined by using simultaneous hybridization of a single strand of the telomere probe and a single strand of a repetitive sequence to slides pretreated for strand-specific hybridization. The telomere probe identifies the direction of the DNA helical strand remaining in each chromatid of the metaphase chromosomes. The direction of the repetitive sequence is then determined from the direction of the strand to which it hybridizes. This method was used to determine the 5 to 3 direction of three repetitive DNA sequences, each for a different human repeat family.     

Caregiving arrangement and nutrition: good news with some reservations

The objective of this study was to assess the impact of caregiving arrangement on the iron and folate status of infants and toddlers reared at home or enrolled in centre-based, independent home, or licensed home care. One hundred and eighty-nine children aged 2 to 29 months were assessed 1 month prior to child care entry and at 6 months after entry into child care. Dietary (24-hour records), anthropometric (height, weight, head circumference) and biochemical (red blood cell folate, hematocrit, transferrin, and serum ferritin concentrations) methods were used to assess nutritional status. Frequency of illness was determined by a series of telephone interviews. Median intake of nutrients exceeded Canadian recommendations, regardless of care arrangement. Fifteen of 65 children had hematocrit values below age-specific cutoffs at the 6-month post-entry to child care visit. Children were frequently taken to obtain medical advice (average of 4 to 6 times during the study period) and 75% of subjects were prescribed at least one course of antibiotics. In conclusion, infants and toddlers in this study were generally well nourished, regardless of child care arrangement; however, iron status may remain an issue in this sample of infants and toddlers.