Long-term follow up of systemic rituximab therapy as first-line and salvage therapy for idiopathic orbital inflammation and review of the literature.

PURPOSE: To report long-term outcomes of systemic rituximab therapy for idiopathic orbital inflammation (IOI) as both primary and salvage therapy and to review the English literature. METHODS: A retrospective review of four consecutive biopsy-proven IOI cases managed with systemic rituximab including demographics, management, and outcomes, and review of English literature, were performed. Primary outcome measures included resolution of symptoms, recurrence, and length of follow up. RESULTS: Of four cases, systemic rituximab was the first-line therapy in two cases and salvage therapy in two cases. The mean age of the patients was 62 years (range, 50-68 years). The orbit was involved in three cases and extraocular muscle in one case. Systemic rituximab (1 g weekly for 4 weeks) was given for one session in three patients and for 12 sessions in 1 patient. All four patients responded with the resolution of all symptoms without recurrence after at least 5 years of follow up. Review of the literature showed systemic rituximab had provided clinical improvement at shorter follow up in 14 of 15 cases when used as a salvage therapy. CONCLUSIONS: Systemic rituximab therapy seems to be an effective therapy for IOI as salvage or first-line therapy with long-term clinical durability.

Calculation of test-retest variability in phase I/IIa clinical trials for Inherited Retinal Degenerations.

Background: Several novel treatments of inherited retinal degenerations have undergone phase I/IIa clinical trials with limited sample size, yet investigators must still determine if toxicity or an efficacy signal occurred or if the change was due to test-retest variability (TRV) of the measurement tool.Materials and Methods: Synthetic datasets were used to compare three types of TRV estimators under different sample sizes, mean drift, skewness, and number of baseline measurements.Results: Mixed effects models underestimated the standard deviation of measurement error (SDEM); the unbiased change score estimator method (UBS) was more accurate. The fixed effect model had less bias and smaller standard deviation than UBS if >2 baseline measurements. The change score estimator had no bias; other estimators introduced bias for lower variability. With sample size <10, all estimators had high variance. With sample size ≥10, the differences between methods were often minimal. The pooled estimator model did not capture drift, whereas a fixed effect regression or mixed effects models accounted for drift while maintaining an accurate measure of variance. With small sample sizes, the bootstrap estimates of SDEM were severe underestimates, while the jackknife estimates were mildly low but much better. The jackknife was more accurate for the unbiased change score method than for the pooled estimator.Conclusions: The ideal phase I/IIa study has ≥20 subjects and uses UBS or its fixed effect model generalization if >2 baseline measurements. With non-ideal study parameters, investigators should at least quantify the error estimate present in their data analysis.

Resuscitating the Socratic Method: Student and Faculty Perspectives on Posing Probing Questions During Clinical Teaching.

PURPOSE: Teaching by way of asking questions is a time-honored practice that has taken on the negative connotation of "pimping" among medical students and has made some faculty hesitant to ask students questions during clerkship rotations. Yet, quantitative studies exploring student perspectives on this practice are limited. This study aimed to solicit student and faculty views and investigate faculty perceptions of students' preferences. METHOD: Students who completed their internal medicine clerkship during the 2017-2018 academic year (n = 165) and were from the 2020 graduating class and their supervising faculty (n = 144) at the University of Michigan Medical School were asked to complete a Likert response survey in April 2019. The survey solicited perspectives on questions probing medical knowledge posed to students by faculty. Surveys were constructed using an iterative process, and data were analyzed using t tests and linear regressions. RESULTS: A total of 140 (85%) students and 112 (78%) faculty participated. Of those, 125 (89%) students and 109 (97%) faculty agreed that probing questions are valuable for student education, but only 73 (65%) faculty perceived that students agreed with this statement (P < .001). In addition, 115 (82%) students preferred to be asked too many questions than none at all. Fifty-five (39%) students agreed that they feel humiliated when they answer a question incorrectly. However, only 7 (5%) students agreed that faculty ask questions to humiliate them, and only 20 (14%) preferred that faculty stop asking questions if they answer a question incorrectly. CONCLUSIONS: Students valued probing questions more than faculty perceived, which argues against a withdrawal from the Socratic teaching method in the clinical arena. The students' experience of humiliation when answering incorrectly requires further study and perhaps can be tempered by more explicit framing of the role of the questioning process.

Vision impairment and depression among older adults in low- and middle-income countries.

OBJECTIVES: To investigate the association between visual impairment (VI) and depression in low- and middle-income countries (LMICs) and the mediating role of disability and social participation. METHODS/DESIGN: The World Health Organization Study on global AGEing and adult health (SAGE) provided data on objective and subjective visual function, depression, disability (WHODAS-12), and social participation for nationally representative samples of adults 50 years and older in China, India, Ghana, Mexico, Russia, and South Africa. Multivariable logistic and linear models were used to test the association between VI and depression and the indirect pathways through disability and social participation. Analyses were adjusted for sociodemographics, medical comorbidities, and complex survey design features. RESULTS: Visual acuity was worse in respondents with depression compared to those without depression in China (0.32 vs 0.23 logMAR; P < .001), Ghana (0.26 vs 0.18 logMAR; P < .001), and India (0.36 vs 0.30 logMAR; P < .001); self-reported vision was also significantly worse in these three countries, but not in Mexico, Russia, or South Africa. Greater disability significantly mediated the association of both objective and self-reported VI with depression in China and India. Social participation significantly mediated the association between subjective vision and depression in Ghana. CONCLUSIONS: There is variability in the association between VI and depression across LMICs and in the mediating role of disability and social participation. Culture-specific instruments may be needed to better characterize the association between VI and depression and further research is needed to assess causality.

Haemophilus influenzae Type f Meningitis Complicated by Bilateral Subdural Empyema, Central Venous Thrombosis, and Bilateral Sensorineural Hearing Loss in an Immunocompetent 12-month-old.

Haemophilus influenzae is a gram-negative coccobacillus that colonizes the nasopharyngeal surface and upper respiratory tract of healthy individuals and includes six encapsulated serotypes as well as non-encapsulated, non-typeable strains. Since the widespread use of the Haemophilus influenzae type b (Hib) conjugate vaccine implemented in 1990, the majority of invasive illness now seen in the United States is secondary to capsular serotypes other than type b and non-typeable strains with the largest burden of disease affecting the extremes of age-infants and the elderly. We report a case of acute Haemophilus influenzae type f meningitis in a 12-month-old female who was previously healthy and had been fully immunized. She demonstrated clinical improvement on ceftriaxone, but persistent fever and ear-tugging resulted in obtaining an MRI that displayed bilateral subdural empyemas requiring burr-hole craniotomy, central venous thrombosis requiring anticoagulation, and bilateral sensorineural hearing loss requiring cochlear implants. Immunological studies confirmed immunocompetency and appropriate response to her previous Hib vaccination, suggesting a significant impact of bacterial virulence. These complications, with the exception of sensorineural hearing loss, have not been reported in the literature for Haemophilus influenzae type f and should be considered in the care of these patients despite clinical appearance given the severity of complications and potential for acute decompensation. Despite the success of vaccination in reducing invasive disease, cases of H. influenzae meningitis continue to occur via less common encapsulated serotypes with unknown complications, making the management and treatment of these infections more difficult for practitioners.

Activation of AMP-activated protein kinase in response to temperature elevation shows seasonal variation in the zebra mussel, Dreissena polymorpha.

Global climate change is affecting ectothermic species, and a variety of studies are needed on thermal tolerances, especially from cellular and physiological perspectives. This study utilized AMP-activated protein kinase (AMPK), a key regulator of cellular energy levels, to examine the effects of high water temperatures on zebra mussel (Dreissena polymorpha) physiology. During heating, AMPK activity increased as water temperature increased to a point, and maximum AMPK activity was detected at high, but sublethal, water temperatures. This pattern varied with season, suggesting that cellular mechanisms of seasonal thermal acclimatization affect basic metabolic processes during sublethal heat stress. There was a greater seasonal variation in the water temperature at which maximum AMPK activity was measured than in lethal water temperature. Furthermore, baseline AMPK activity varied significantly across seasons, most likely reflecting altered metabolic states during times of growth and reproduction. In addition, when summer-collected mussels were lab-acclimated to winter and spring water temperatures, patterns of heat stress mirrored those of field-collected animals. These data suggest that water temperature is the main driver of the seasonal variation in physiology. This study concluded that AMPK activity, which reflects changes in energy supply and demand during heat stress, can serve as a sensitive and early indicator of temperature stress in mussels.