Recent Publications by CFE Educators

Background

In this study, we use a competing risks analysis to assess factors predictive of early-salvage whole brain radiotherapy (WBRT) and early death after upfront stereotactic radiosurgery (SRS) alone for brain metastases in an attempt to identify populations that benefit less from upfront SRS.

Patients and methods

Patients from eight academic centers were treated with SRS for brain metastasis. Competing risks analysis was carried out for distant brain failure (DBF) versus death prior to DBF as well as for salvage SRS versus salvage WBRT versus death prior to salvage. Linear regression was used to determine predictors of the number of brain metastases at initial DBF (nDBF).

Results

A total of 2657 patients were treated with upfront SRS alone. Multivariate analysis (MVA) identified an increased hazard of DBF associated with increasing number of brain metastases (P  0.001), lowest SRS dose received (P  0.001), and melanoma histology (P  0.001), while there was a decreased hazard of DBF associated with increasing age (P  0.001), KPS  70 (P  0.001), and progressive systemic disease (P = 0.004). MVA for first salvage SRS versus WBRT versus death prior to salvage revealed an increased hazard of first salvage WBRT seen with increasing number of brain metastases (P  0.001) and a decreased hazard with widespread systemic disease (P = 0.002) and increasing age (P  0.001). Variables associated with nDBF included age (P = 0.02), systemic disease status (P = 0.03), melanoma histology (P = 0.05), and initial number of brain metastases (P  0.001).

Conclusions

Patients with a higher initial number of brain metastases were more likely to experience DBF, have a higher nDBF, and receive early-salvage WBRT, while patients who were older, had lower KPS, or had more systemic disease were more likely to experience death prior to DBF or salvage WBRT.

BACKGROUND

Hypoparathyroidism is a potential outcome of anterior neck surgery. Commonly it is managed by calcium and vitamin D supplementation in large doses, with attendant side effects. A recombinant human parathyroid hormone (rhPTH) is now available in the USA, offering a potentially more effective treatment. No cost-effectiveness model investigating this new medication versus standard care has yet been published.

METHODS

We constructed a decision analytic model comparing usual care versus rhPTH treatment for postsurgical hypoparathyroidism. Threshold and sensitivity analyses on key parameters were conducted to assess robustness of the model. Costs and health outcomes were represented in US dollars and quality-adjusted life-years (QALYs).

RESULTS

The rhPTH strategy was both more costly and more effective than the usual care (UC) strategy. In the base case, UC cost $37,196 and provided 7.54 QALYs. The rhPTH strategy cost $777,224 and provided 8.46 QALYs for an incremental cost-effectiveness ratio of $804,378/QALY. As this was above our willingness-to-pay of $100,000, treatment with rhPTH was not considered cost-effective. The model was robust to all other parameters.

CONCLUSIONS

To our knowledge, this is the first formal cost-effectiveness analysis of rhPTH in comparison with UC. Our model suggests that although the new treatment is slightly more effective than UC, the modest gain in quality of life for patients who are reasonably well-managed by UC does not justify the cost. However, consideration must be given to rhPTH for patients who have failed UC, as the expenditure may be justified in that context.

Importance

Frailty is a measure of decreased physiological reserve that is associated with morbidity and mortality in major elective and emergency general surgery operations, independent of chronological age. To date, the association of frailty with outcomes in ambulatory general surgery has not been established.

Objective

To determine the association between frailty and perioperative morbidity in patients undergoing ambulatory general surgery operations.

Design, Setting, and Participants

A retrospective cohort study was conducted of 140 828 patients older than 40 years of age from the 2007-2010 American College of Surgeons National Surgical Quality Improvement Program Participant Use File who underwent ambulatory and 23-hour-stay hernia, breast, thyroid, or parathyroid surgery. Data analysis was performed from August 18, 2016, to June 21, 2017.

Main Outcomes and Measures

The association between the National Surgical Quality Improvement Program modified frailty index and perioperative morbidity was determined via multivariable logistic regression with random-effects modeling to control for clustering within Current Procedural Terminology codes.

Results

A total of 140 828 patients (80 147 women and 60 681 men; mean [SD] age, 59.3 [12.0] years) underwent ambulatory hernia (n = 71 455), breast (n = 51 267), thyroid, or parathyroid surgery (n = 18 106). Of these patients, 2457 (1.7%) experienced any type of perioperative complication and 971 (0.7%) experienced serious perioperative complications. An increasing modified frailty index was associated with a stepwise increase in the incidence of complications. In multivariable analysis adjusting for age, sex, race/ethnicity, anesthesia type, tobacco use, renal failure, corticosteroid use, and clustering by Current Procedural Terminology codes, an intermediate modified frailty index score (0.18-0.35, corresponding to 2-3 frailty traits) was associated with statistically significant odds ratios of 1.70 (95% CI, 1.54-1.88; P  .001) for any complication and 2.00 (95% CI, 1.72-2.34; P  .001) for serious complications. A high modified frailty index score (≥0.36, corresponding to ≥4 frailty traits) was associated with statistically significant odds ratios of 3.35 (95% CI, 2.52-4.46; P  .001) for any complication and 3.95 (95% CI, 2.65-5.87; P  .001) for serious complications. Anesthesia with local and monitored anesthesia care was the only modifiable covariate associated with decreased odds of serious 30-day complications, with an adjusted odds ratio of 0.66 (95% CI, 0.53-0.81; P  .001).

Conclusions and Relevance

Frailty is associated with increased perioperative morbidity in common ambulatory general surgery operations, independent of age, type of anesthesia, and other comorbidities. Surgeons should consider frailty rather than chronological age when counseling and selecting patients for elective ambulatory surgery.

Faciobrachial dystonic seizures and limbic encephalitis closely associate with antibodies to leucine-rich glioma-inactivated 1 (LGI1). Here, we describe 103 consecutive patients with faciobrachial dystonic seizures and LGI1 antibodies to understand clinical, therapeutic and serological differences between those with and without cognitive impairment, and to determine whether cessation of faciobrachial dystonic seizures can prevent cognitive impairment. The 22/103 patients without cognitive impairment typically had normal brain MRI, EEGs and serum sodium levels (P 0.0001). Overall, cessation of faciobrachial dystonic seizures with antiepileptic drugs alone occurred in only 9/89 (10%) patients. By contrast, 51% showed cessation of faciobrachial dystonic seizures 30 days after addition of immunotherapy (P 0.0001), with earlier cessation in cognitively normal patients (P = 0.038). Indeed, expedited immunotherapy (P = 0.031) and normal cognition (P = 0.0014) also predicted reduced disability at 24 months. Furthermore, of 80 patients with faciobrachial dystonic seizures as their initial feature, 56% developed cognitive impairment after 90 days of active faciobrachial dystonic seizures. Whereas only one patient developed cognitive impairment after cessation of faciobrachial dystonic seizures (P 0.0001). All patients had IgG4-LGI1 antibodies, but those with cognitive impairment had higher proportions of complement-fixing IgG1 antibodies (P = 0.03). Both subclasses caused LGI1-ADAM22 complex internalization, a potential non-inflammatory epileptogenic mechanism. In summary, faciobrachial dystonic seizures show striking time-sensitive responses to immunotherapy, and their cessation can prevent the development of cognitive impairment.awx323media15681705685001.

CONTEXT

Transitions of patient care responsibility occur frequently between physicians. Resultant discontinuities make it difficult for physicians to observe clinical outcomes. Little is known about what physicians do to overcome the practical challenges to learning these discontinuities create. This study explored physicians' activities in practice as they sought follow-up information about patients.

METHODS

Using a constructivist grounded theory approach, semi-structured interviews with 18 internal medicine hospitalist and resident physicians at a single tertiary care academic medical center explored participants' strategies when deliberately conducting follow-up after they transitioned responsibility for patients to other physicians. Following open coding, the authors used activity theory (AT) to explore interactions among the social, cultural and material influences related to follow-up.

RESULTS

The authors identified three themes related to follow-up: (i) keeping lists to track patients, (ii) learning to create tracking systems and (iii) conducting follow-up. Analysis of participants' follow-up processes as an activity system highlighted key tensions in the system and participants' work adaptations. Tension within functionality of electronic health records for keeping lists (tools) to find information about patients' outcomes (object) resulted in using paper lists as workarounds. Tension between paper lists (tools) and protecting patients' health information (rules) led to rule-breaking or abandoning activities of locating information. Finding time to conduct desired follow-up produced tension between this and other activity systems.

CONCLUSION

In clinical environments characterised by discontinuity, lists of patients served as tools for guiding patient care follow-up. The authors offer four recommendations to address the tensions identified through AT: (i) optimise electronic health record tracking systems to eliminate the need for paper lists; (ii) support physicians' skill development in developing and maintaining tracking systems for follow-up; (iii) dedicate time in physicians' work schedules for conducting follow-up; and (iv) engage physicians and patients in determining guidelines for longitudinal tracking that optimise physicians' learning and respect patients' privacy.

OBJECTIVE

The Psychopharmacotherapy-Structured Clinical Observation (P-SCO) tool is designed to assess performance of a medication management visit and to enhance feedback. Prior research indicated that the P-SCO was feasible to implement in a resident clinic and generated behaviorally specific, high-quality feedback. This research also highlighted problems with some of the instrument's items. This study seeks to improve the items.

METHODS

The authors initially revised the P-SCO items based on the problems identified by a prior study. Next, these items were iteratively modified by experts in clinical pharmacotherapy and educational assessment. Forty-five items emerged. Finally, faculty attending an annual department education retreat rated each item on its relevance (4-point scale) and provided comments on how the item might be revised. For final inclusion, an item must have met a quantitative threshold (i.e., content validity index equal to or greater than 0.8 and the lower end of the asymmetric confidence interval equal to or greater than 3.0) and received comments that were supportive.

RESULTS

Forty-one of the 45 items had strong quantitative support. However, the comments endorsed lumping a number of items in order to decrease overlap between items and to shorten the instrument. This process resulted in the further elimination of 15 items.

CONCLUSIONS

The revised 26-item P-SCO builds upon prior evidence of feasibility and utility and now possesses additional evidence of content validity. The use of the tool should enhance feedback and improve the capacity of educational programs to assess performance.

OBJECTIVE

To characterize the features associated with PCDH19-related epilepsy, also known as "female-limited epilepsy."

METHODS

We analyzed data from participants enrolled in the PCDH19 Registry, focusing on the seizure-related, developmental, neurobehavioral, and sleep-related features. We evaluated variants for pathogenicity based on previous reports, population databases, and in silico predictions, and included individuals with pathogenic or potentially pathogenic variants. We performed a retrospective analysis of medical records and administered a targeted questionnaire to characterize current or past features in probands and genotype-positive family members.

RESULTS

We included 38 individuals with pathogenic or potentially pathogenic variants in PCDH19: 21 de novo, 5 maternally inherited, 7 paternally inherited, and 5 unknown. All 38 had epilepsy; seizure burden varied, but typical features of clustering of seizures and association with fever were present. Thirty individuals had intellectual disability (ID), with a wide range of severity reported; notably, 8/38 (22%) had average intellect. Behavioral and sleep dysregulation were prominent, in 29/38 (76%) and 20/38 (53%), respectively. Autistic features were present in 22/38 (58%), of whom 12 had a formal diagnosis of autism spectrum disorder. We had additional data from 5 genotype-positive mothers, all with average intellect and 3 with epilepsy, and from 1 genotype-positive father.

SIGNIFICANCE

Our series represents a robust cohort with carefully curated PCDH19 variants. We observed seizures as a core feature with a range of seizure types and severity. Whereas the majority of individuals had ID, we highlight the possibility of average intellect in the setting of PCDH19-related epilepsy. We also note the high prevalence and severity of neurobehavioral phenotypes associated with likely pathogenic variants in PCDH19. Sleep dysregulation was also a major area of concern. Our data emphasize the importance of appropriate referrals for formal neuropsychological evaluations as well as the need for formal prospective studies to characterize the PCDH19-related neurodevelopmental syndrome in children and their genotype-positive parents.