Risk of carpal tunnel syndrome among patients with osteoarthritis: a US population-based study.

BACKGROUND: Carpal tunnel syndrome (CTS), an entrapment neuropathy caused by pressure of the median nerve, is a progressive condition that can lead to a decreased quality of life. Studies suggest an association between CTS and arthritis; however, previous studies examining osteoarthritis (OA) and CTS are limited in number, scope and study design. This study estimated the incidence and risk of CTS among patients with OA, both overall and by specific joints, in a large population-based cohort in the United States. METHODS: Patients from the Optum claims database aged ≥ 45 years and diagnosed with OA between January 1, 2018, and December 31, 2022, were eligible for the OA cohort. The non-OA cohort included those without a diagnosis of OA at the index date and no history of OA for 12 months pre-index. Baseline characteristics were balanced using propensity score matching. The risk of CTS in the OA and non-OA cohort were evaluated using incidence rates and adjusted hazard ratios that were estimated using Cox regression. RESULTS: After applying the inclusion/exclusion criteria, 3,610,240 of the 6,023,384 adults with a diagnosis of OA remained in the OA cohort. After propensity-score matching, each cohort included 1,033,439 individuals. The incidence rates for CTS per 1000 person-years were 7.35 (95% confidence interval [CI] 7.21-7.49) in the OA cohort and 1.44 (95% CI 1.38-1.50) in the non-OA cohort. The risk of developing CTS in patients with OA was ~ 4 times that of patients without (hazard ratio = 3.80; 95% CI 3.54-4.07). This increased risk was found across all OA joint types, with OA of the hand/wrist having the highest risk for CTS. Additionally, multiple OA joints presented a higher risk compared with a single affected joint. CONCLUSIONS: OA increases the risk of CTS, but this is not limited to patients with hand/wrist OA, suggesting a systemic impact of OA on CTS. While the risk appears highest for patients with hand/wrist OA, patients with more distant affected joints like knee or hip also have an increased risk of CTS.

A Pilot Nonrandomized Controlled Trial Examining the Use of Artificial Tears on the Radioactivity of Tears After Radioactive Iodine Treatment for Thyroid Cancer.

Background: Nasolacrimal duct obstruction (NLDO) is an adverse effect of high dose radioactive iodine (RAI) therapy for thyroid carcinoma. There are currently no established preventive measures. This study assesses whether preservative free artificial tears (PFATs) can decrease the 131I sodium iodide (131I) activity in the tears of patients following RAI therapy for thyroid carcinoma, and potentially serve as a preventive measure for RAI-associated NLDO. Methods: This non-randomized prospective pilot clinical trial recruited contact-lens wearing patients undergoing RAI therapy for thyroid cancer to self-administer PFATs into the right eye for four days starting on the day of RAI ingestion. Left eyes were the controls. While wearing contacts, patients self-administered PFATs per the following-Day 1: every 15 minutes for 2 hours, then every 30 minutes until bedtime, day 2: every hour for at least 12 hours, day 3: four times a day, and day 4: two times a day. Contact lenses were changed daily, and all lenses were collected one week later. Levels of 131I activity were measured by a well counter, decay-corrected, and converted to units of becquerel. Statistical analyses were performed to compare the 131I activities of the experimental and control eyes. Results: Sixteen eyes of eight patients treated with an average of 145.7 mCi (range 108-159) of 131I for papillary thyroid cancer were included. On day 1, artificial tears decreased the geometric mean 131I activity by 26% in the experimental eyes (p = 0.008). Artificial tears also decreased the geometric mean area under the curve over four days by 23% (p = 0.002). Conclusions: 131I is present in the tears following RAI therapy for thyroid carcinoma. Frequent PFATs starting on the day of RAI ingestion may decrease the level of 131I in the tears. This finding could have implications for lowering the risk of NLDO. Future multi-center clinical trials are needed to determine whether the use of artificial tears after RAI therapy may decrease the risk of NLDO. Clinical Trial Registration: NCT04327999.

A long-term, prospective, observational cohort study of the safety and effectiveness of etanercept for the treatment of patients with paediatric psoriasis in a naturalistic setting.

BACKGROUND: Psoriasis is a chronic inflammatory skin disorder that affects 125 million people worldwide, with one-third having childhood onset. OBJECTIVES: The PURPOSE study evaluated long-term safety and effectiveness of etanercept in paediatric psoriasis. MATERIALS & METHODS: This observational study enrolled patients with paediatric psoriasis who were prescribed etanercept per routine care in eight EU countries. Patients were followed retrospectively (first dose prior to 30 days before enrolment) or prospectively (first dose within 30 days prior to or any time after enrolment) for five years. Safety endpoints included serious infections, opportunistic infections, malignancies, other serious adverse events (SAEs) and adverse events. Effectiveness endpoints (prospective patients) included treatment patterns, dose change/discontinuation, and physicians' global subjective assessment of change in disease severity from baseline to follow-up. RESULTS: In total, 72 patients were enrolled (32 prospectively, 40 retrospectively), with mean age of 14.5 years and mean disease duration of 7.1 years. No serious or opportunistic infections/malignancies were reported. Psoriasis (n=8) and subcutaneous tissue disorders (system organ class) (erythema nodosum, erythrodermic psoriasis; n=1 for each) were the most frequently reported SAEs, which occurred in six (8.3%) patients with current/recent treatment and four (7.4%) with previous treatment. Of 25 treatment-emergent SAEs, seven (28.0%) were possibly related to etanercept. Assessments of prospective patients revealed that 28 (87.5%) completed 24 weeks, five (15.6%) required at least one subsequent course, and 93.8% experienced decreased disease severity. It is possible that some rare adverse events were not noted in this relatively small sample. CONCLUSION: These real-world data are consistent with the known safety and efficacy profile of etanercept in paediatric patients with moderate to severe plaque psoriasis.

Sebaceous carcinoma masquerading as ocular mucous membrane pemphigoid.

Sebaceous carcinoma is a known mimicker of benign conditions, leading to frequent delays in diagnosis and proper treatment. We present two patients with chronic cicatrizing conjunctivitis initially diagnosed as ocular mucous membrane pemphigoid (MMP) and later found to have sebaceous carcinoma. Both patients presented with unilateral conjunctivitis that failed to improve with topical and systemic therapy, eventually developing fornix foreshortening and extensive symblepharon. Case 1 was diagnosed with ocular MMP based on clinical features alone, while Case 2 was diagnosed with biopsy-negative disease. Months to years later, both patients developed lid lesions found to be sebaceous carcinoma and underwent exenteration. As diagnosis and treatment of ocular MMP without positive direct immunofluorescence testing becomes increasingly accepted, clinicians should consider sebaceous carcinoma as the initial diagnosis or as a developing phenomenon during immunosuppression in the setting of chronic inflammation. A low threshold for repeat biopsy should be maintained.

Regulatory and HTA Considerations for Development of Real-World Data Derived External Controls.

Regulators and Health Technology Assessment (HTA) bodies are increasingly familiar with, and publishing guidance on, external controls derived from real-world data (RWD) to generate real-world evidence (RWE). We recently conducted a systematic literature review (SLR) evaluating publicly available information on the use of RWD-derived external controls to contextualize outcomes from uncontrolled trials submitted to the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), and/or select HTA bodies. The review identified several key operational and methodological aspects for which more detailed guidance and alignment within and between regulatory agencies and HTA bodies is necessary. This paper builds on the SLR findings by delineating a set of key takeaways for the responsible generation of fit-for-purpose RWE. Practical methodological and operational guidelines for designing, conducting, and reporting RWD-derived external control studies are explored and discussed. These considerations include: (i) early engagement with regulators and HTA bodies during the study planning phase; (ii) consideration of the appropriateness and comparability of external controls across multiple dimensions, including eligibility criteria, temporality, population representation, and clinical evaluation; (iii) ensuring adequate sample sizes, including hypothesis testing considerations; (iv) implementation of a clear and transparent strategy for assessing and addressing data quality, including data missingness across trials and RWD; (v) selection of comparable and meaningful endpoints that are operationalized and analyzed using appropriate analytic methods; and (vi) conduct of sensitivity analyses to assess the robustness of findings in the context of uncertainty and sources of potential bias.

Factors Associated With Radioactive Iodine Therapy-Acquired Nasolacrimal Duct Obstruction.

OBJECTIVE: To identify factors associated with radioactive iodine (RAI)-acquired nasolacrimal duct obstruction (NLDO). METHODS: Retrospective chart review and telephone surveys of patients who received RAI therapy for thyroid carcinoma at an academic institution were conducted. Telephone surveys were used to screen for post-RAI NLDO diagnoses. Databases were reviewed for documented NLDO, demographics, RAI dose, total number of RAI treatments, and sialadenitis. Routine post-RAI whole-body scintigraphy (WBS) images were analyzed for the presence or absence of 131I sodium iodide (I-131) in the nasolacrimal duct. Intranasal I-131 activity was graded as none, low, moderate, and high; those with moderate or high activity were considered to have "increased" activity. Logistic and ordinal logistic regression models were used to evaluate the associations with NLDO while adjusting for I-131 dose. RESULTS: Of the 209 patients who completed the survey, 15 (7%) had NLDO diagnoses. Increased intranasal I-131 activity on WBS, presence of nasolacrimal I-131 WBS activity, presence of documented post-RAI sialadenitis, and history of >1 RAI treatment were associated with the development of NLDO from univariate analyses (P ≤ .013). After adjusting for the administered dose of I-131, the presence of sialadenitis and nasolacrimal I-131 activity on WBS were the remaining 2 factors significantly associated with NLDO development (P < .001 and P = .01, respectively). CONCLUSIONS: The presence of sialadenitis and nasolacrimal I-131 activity on WBS are I-131 dose-independent correlative factors for RAI-associated NLDO. Patients with these characteristics should be counseled on their increased risk of NLDO after RAI therapy for thyroid carcinoma.

Using EHR data to identify coronavirus infections in hospitalized patients: Impact of case definitions on disease surveillance.

PURPOSE: To evaluate the number, characteristics, and outcomes of patients identified hospitalized with coronavirus disease 2019 (COVID-19) using two different case definitions. PROCEDURES: Electronic Health Record data were evaluated from patients hospitalized with COVID-19 through May 2020 at 52 health systems across the United States. Characteristics of inpatients with positive laboratory tests for SARS-CoV-2 were compared with those with clinical diagnosis of COVID-19 but without a confirmatory lab result. FINDINGS: Of 14,371 inpatients with COVID-19, 6623 (46.1 %) had a positive laboratory result, and n = 7748 (52.9 %) had only a clinical diagnosis of COVID-19. Compared with clinically diagnosed cases, those with laboratory-confirmed COVID were similar in age and sex, but differed by race, ethnicity, and insurance status. Laboratory-confirmed cases were more likely to receive certain COVID-19 therapies including hydroxychloroquine, anti-IL6 agents and antivirals (p < 0.001). Those with laboratory-confirmed COVID-19 had lower rates of most complications such as myocardial infarction, but higher overall mortality (p < 0.001). CONCLUSION: We observed a two-fold difference in the number of patients hospitalized with COVID-19 depending on whether the case definition required laboratory confirmation. Variations in case definitions also led to differences in cohort characteristics, treatments, and outcomes.

A web-based survey of UK pharmacists to assess the effectiveness of Viagra Connect® additional risk minimisation measures.

Background To support reclassification in the UK of sildenafil citrate (50 mg) from prescription-only medicine to a pharmacy medicine (P status) under the brand name "Viagra Connect®", additional risk minimisation measures were implemented that included training materials and an optional checklist to assist community pharmacists in the safe supply of Viagra Connect® to suitable patients. Objective To evaluate the effectiveness of Viagra Connect® additional risk minimisation measures by assessing community pharmacists' participation in training, their knowledge of key risk messages, and utilisation of the checklist. Setting A post-authorisation safety study implemented as a web-based survey, conducted in a representative population of UK community pharmacists. Method A random sample of community pharmacists who received at least 1 request to supply Viagra Connect® within the past 6 months completed an online questionnaire of 33 closed-ended questions/statements with multiple-choice responses. Data were summarised using descriptive statistics. Main outcome measure Knowledge of key risk messages and dispensing practices communicated in the additional risk minimisation measures. Results The survey was completed by 345 community pharmacists. Respondents displayed a high level of knowledge of key risk messages, with ≥80 % selecting correct answers for 43/51 items. Nearly all respondents (90.1 %) reported that the training materials were useful/very useful, and reported using the checklist at the point of supply (91.9 %). Counselling of patients who requested Viagra Connect® was generally considered a positive exercise. Conclusions The Viagra Connect® additional risk minimisation measures were effective for education of community pharmacists and to ensure safe supply of Viagra Connect® behind-the-counter to patients.

Persistent mass after treatment for orbital rhabdomyosarcoma.

PURPOSE: To report a case of orbital rhabdomyosarcoma and highlight the treatment approach to the dilemma of a residual mass. OBSERVATIONS: An eleven-year-old boy was diagnosed with Stage 1, Group III embryonal rhabdomyosarcoma in the orbit. After completing a 24-week treatment regimen of chemotherapy and radiation, imaging showed a large persistent mass with erosion through the medial wall. It was uncertain whether the erosion was due to radiation osteonecrosis or to advancing tumor, creating a treatment dilemma for the providers. A repeat biopsy was planned. During the procedure, the mass was completely excised due to ease of removal, and the biopsy showed completely treated tumor. MRI surveillance at four years follow up showed that the patient remains tumor-free. CONCLUSIONS AND IMPORTANCE: Rhabdomyosarcoma was once a disease with a very poor outcome, but advances in imaging, chemotherapy, and radiation therapy have improved the prognosis of these patients. What was once a surgical disease treated with morbid resection is now predominantly a medical disease diagnosed with biopsy and treated with chemotherapy and radiation. However, such patients may have a residual mass after completing treatment. This situation presents a challenge, as it may not be clear whether the persistent mass is active tumor or treated tumor. This report describes the presentation and management of such a case in the orbit and demonstrates that a residual orbital mass may remain and represent completely treated tumor.

Parvimonas micra Necrotizing Panophthalmitis Involving the Sclera, Cornea, Uvea, Retina, and Orbit.

We present an unusual case of a patient who acquired a pansinusitis and orbital cellulitis with necrotizing features, subsequently developing scleritis, keratitis, and anterior uveitis. To date, there are no reported cases of the simultaneous involvement of these ocular structures from a pansinusitis. Our patient was urgently taken to the operating room for drainage of the abscesses within his sinuses and the orbit. Intraoperative cultures were positive for Parvimonas micra, an odontogenic anaerobic bacteria. He was additionally found to have a central retinal artery occlusion. He was treated with systemic and topical antibiotics as well as topical dilute hypochlorous acid. The mechanisms of virulence of P. micra, including its synergistic relationship with other bacteria, ability to bind plasminogen, and its expression of proteases, contributed to this diffuse infection.

Frequency and Clinical Course of Residual Orbital Masses After Treatment of Orbital Rhabdomyosarcoma.

PURPOSE: To evaluate the frequency and clinical course of residual orbital masses on imaging studies after multimodality treatment for orbital rhabdomyosarcoma. DESIGN: Retrospective case series. METHODS: We reviewed records of patients with primary orbital rhabdomyosarcoma who underwent chemotherapy and radiotherapy after surgical biopsy or debulking at 4 US centers during 1998-2019. Demographics, histologic subtype, tumor response 12 weeks after chemotherapy initiation and after completion of all treatment, and imaging findings were analyzed. RESULTS: Thirty-two patients met inclusion criteria. Twenty-two were male, and 30 were younger than 18 years. Histologic subtype was embryonal in 22 patients, alveolar in 8, and mixed embryonal/alveolar in 2. Median follow-up time was 46 months (range, 4.9-199 months). Two patients died. Twenty-seven patients had reliable end-of-treatment imaging findings, of whom 9 had a residual mass. Three residual masses disappeared spontaneously (by 4, 32, and 53 months), 2 remained at last contact, at 2 and 7 years of follow-up, and 3 were excised; 1 progressed and underwent an exenteration. Complete response at 12 weeks was associated with complete response at the end of treatment (P < .001). Patients with T1 or T2 tumor at presentation were more likely to have complete response at last contact than were those with T3 or T4 tumor (P < .05). Biopsy type (incisional or excisional) was not associated with response to treatment at any time point. CONCLUSION: A residual orbital mass on imaging may be present after multimodality treatment in approximately one-third of patients. Resolution without biopsy or excision varied from months to years.

Homeopathic Agents or Vitamins in Reducing Ecchymosis after Oculofacial Surgery: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature to determine the efficacy and safety of homeopathic agents or vitamins in reducing ecchymosis after oculofacial surgery or laser surgery. METHODS: A literature search was conducted in the PubMed database initially in December 2019 and updated in March 2020 to identify all studies in the English language literature on the use of homeopathic agents or vitamins in oculofacial procedures, including laser surgery. The search yielded 124 citations, and 11 articles met all inclusion criteria for this assessment. A panel methodologist then assigned a level of evidence rating for each study. Eleven studies met inclusion criteria; 9 were rated level I, and 2 were rated level III. RESULTS: The agents studied in the articles identified included oral or topical Arnica montana (AM), oral Melilotus extract, topical vitamin K oxide, and topical AM combined with Rhododendron tomentosum. Metrics to describe ecchymosis varied. In 7 controlled studies, perioperative AM provided no or negligible benefit versus placebo. In 2 studies, vitamin K cream was equivalent to placebo. One study of oral Melilotus extract had less ecchymosis compared with controls in paranasal and eyelid ecchymosis at postoperative day (POD) 7, but not at PODs 1 and 4. A lone cohort study of combined topical AM and R. tomentosum lacked objective metrics and adequate controls. No serious side effects from administration of homeopathic agents or vitamins were identified. CONCLUSIONS: The current literature does not support the use of AM, vitamin K oxide, R. tomentosum, or Melilotus extract for reducing ecchymosis after oculofacial surgery or pulsed dye laser surgery.

Orbital Radiation for Thyroid Eye Disease: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the current literature on the safety and efficacy of orbital radiation for the management of thyroid eye disease (TED). METHODS: A literature search was conducted last in February 2021 of the PubMed database to identify all articles published in the English language on original research that assessed the effect of orbital radiation on TED. The search identified 55 articles, and 18 met the inclusion criteria for this assessment. A panel methodologist then assigned a level of evidence rating for each study, and all of them were rated level III. RESULTS: Two large retrospective studies demonstrated the efficacy of radiation treatment, with or without corticosteroid use, in preventing or treating compressive optic neuropathy (CON). Three studies highlighted the role of orbital radiation therapy (RT) to facilitate the tapering of corticosteroids. Several other studies showed a possible role for RT to improve diplopia and soft tissue signs. CONCLUSIONS: Although no level I or level II evidence exists, the best available evidence suggests that orbital radiation, used with or without corticosteroids, is efficacious in preventing CON, improving motility restriction, and decreasing clinical activity in TED. Orbital radiation also may facilitate a corticosteroid taper. Together, these studies show that RT seems to modify the active phase of TED. Short-term risks of orbital radiation are minor, but long-term outcome data are lacking.

Presentation and outcomes of orbital cellulitis caused by Group F Streptococcus.

PURPOSE: To compare the presentation and outcomes of patients with orbital cellulitis requiring surgical intervention caused by the Group F Streptococcus (GFS) versus other bacteria. We hypothesize that patients with GFS infections have a more severe presentation and worse clinical outcomes compared to infections by other bacteria. METHODS: After Institutional Review Board approval at a large academic institutional center, 70 patients with culture-positive orbital cellulitis who required surgical intervention were identified. Clinical examinations before and after surgery as well as preoperative imaging with computed tomography and/or magnetic resonance imaging were reviewed. The study measures were preoperative and postoperative vision, motility, involved sinus disease, complications, and total hospital length of stay. Multiple imputation was used for missing data. Characteristics of patients were compared using Chi-square and Wilcoxon rank-sum. RESULTS: Nineteen patients (27%) had positive cultures for GFS and 51 patients (73%) had positive cultures for other bacterial species. There was no significant difference in visual acuity, motility, or inflammatory markers in patients with GFS compared to other patients. Patients with GFS were noted to have more sinus involvement on presentation compared to patients with other bacterial infections (P = 0.007). CONCLUSION: GFS associated orbital cellulitis is associated with significantly more sinus involvement, but has similar outcomes as orbital cellulitis from other bacterial species.