Inflammatory Bowel Disease and the Risk of Anal Squamous Intraepithelial Lesions and Anal Cancer in Men Who Have Sex With Men.

BACKGROUND: The risk of anal cancer is increased in patients with human immunodeficiency virus (HIV), inflammatory bowel disease (IBD), and among men who have sex with men (MSM). High grade squamous intraepithelial lesions (HSILs) are precursor lesions to anal squamous cell carcinoma (SCC), and treatment of these lesions can decrease progression to anal SCC. This study aims to determine the prevalence of HSIL and anal cancer among MSM patients with and without IBD referred for anal cancer screening. METHODS: This is a retrospective study of all MSM patients seen at an anal squamous intraepithelial lesions (aSILs) and anal cancer screening specialty clinic. Data were manually and electronically collected from clinical documentation and pathology results for the primary outcomes of HSIL and anal cancer. Demographics, HIV status, IBD disease status, disease phenotype, and immunosuppressive medication use were collected through the electronic health record. Descriptive statistics were used. RESULTS: In all, 4623 patients were included for analysis. Among 57 MSM patients with IBD, 25 (43.9%) had a history of HSIL, and 2 (3.5%) had a history of anal cancer. Among 4618 MSM patients without IBD, 2417 (52.3%) had a history of HSIL, and 139 (3.0%) had a history of anal cancer (P = .744). Rates of HIV were 49.1% among MSM patients with IBD and 69.8% among MSM patients without IBD (P = .001). There remained no difference in prevalence of HSIL and anal cancer between groups when adjusting for HIV status. Among IBD patients, only 21.6% were referred for screening by their gastroenterologist. CONCLUSIONS: Among MSM with and without IBD, both groups had an equally high prevalence of HSIL and anal SCC. Awareness of appropriate surveillance to identify aSIL in MSM patients with IBD is needed among gastroenterologists.

This retrospective study of MSM patients with IBD referred for anal screening compared with those without IBD found equally high prevalence of anal squamous cell cancer and its precursor, HSIL, with a low rate of referral from gastroenterologists.

Prophylactic Colchicine After Radiofrequency Ablation of Atrial Fibrillation: The PAPERS Study.

BACKGROUND: Pericarditis is common after radiofrequency ablation for atrial fibrillation (AF). OBJECTIVES: Study investigators hypothesized an empirical post-AF ablation treatment protocol with colchicine may reduce the incidence and severity of pericarditis. PAPERS (Post-Ablation PEricarditis Reduction Study) aimed to quantify the risks and benefits associated with prophylactic use of colchicine to prevent pericarditis following AF ablation. METHODS: PAPERS is a multicenter, prospective, randomized controlled study. Patients were randomized on the day of the procedure to receive no postprocedure prophylaxis (group A; standard of care arm) or colchicine 0.6 mg orally twice daily for 7 days starting immediately post-procedure (group B; study arm). All participants underwent a follow-up survey at 14 days postoperatively. The primary endpoint was the development of clinical pericarditis within 2 weeks following ablation. Secondary outcomes included the incidence of pericarditis by ablation type and medical therapy. RESULTS: Among 139 patients enrolled, 66 were randomized to standard of care (group A), and 73 patients were randomized to the colchicine arm (group B). The primary outcome of clinical pericarditis was reached in 7 of 66 (10.6%) patients in group A and in 7 of 73 (9.6%) patients in group B (P = 0.84). The rate of gastrointestinal discomfort was 10 of 66 (15%) in group A and 34 of 73 (47%) in group B (P < 0.001). There was an increased incidence of pericarditis in patients who underwent cavotricuspid isthmus ablation (17 of 50; 34%) in addition to pulmonary vein isolation (6 of 69; 8.7%; P = 0.001). CONCLUSIONS: Prophylactic colchicine therapy initiated after the ablation procedure in patients with AF did not affect the incidence of post-ablation pericarditis and was associated with an increased incidence of gastrointestinal side effects.

Comparative Screening of DalPhos/Ni Catalysts in C-N Cross-couplings of (Hetero)aryl Chlorides Enables Development of Aminopyrazole Cross-couplings with Amine Base.

A systematic competitive evaluation of the DalPhos ligand family in nickel-catalyzed N-arylation chemistry is reported, involving primary (linear and branched) and secondary alkylamines, as well as a primary five-membered heteroarylamine (aminopyrazole), in combination with a diverse set of test electrophiles and bases (NaOtBu, K2 CO3 , DBU/NaTFA). In addition to providing optimal ligand/catalyst identification, and bringing to light methodology limitations (e. g., unwanted C-O cross-coupling with NaOtBu), our survey enabled the development of the first efficient catalyst system for heteroatom-dense C-N cross-coupling of aminopyrazoles and related nucleophiles with (hetero)aryl chlorides by use of an amine 'dual-base' system.

Diagnostic utility of early premature ventricular complexes in differentiating atrioventricular reentrant and atrioventricular nodal reentrant tachycardias.

BACKGROUND: His-refractory premature ventricular complexes perturbing a supraventricular tachycardia (SVT) establish the presence of an accessory pathway (AP). Earlier premature ventricular complexes (ErPVCs) may perturb SVTs but are considered nondiagnostic. OBJECTIVE: The purpose of this study was to test the hypothesis that an ErPVC will always show a difference >35 ms in its advancement of the next atrial activation during atrioventricular nodal reentrant tachycardia (AVNRT). During atrioventricular reentrant tachycardia (AVRT), a PVC delivered close to the circuit can result in greater advancement of atrial activation due to retrograde conduction via an AP. Thus, an AP response, defined as ErPVC (H1S2) advancing the subsequent atrial activation (A1-A2) more than this minimum difference (A1A2 ≤ H1S2+35 ms), establishes the presence of an AP. METHODS: Sixty-five consecutive patients with SVT were retrospectively evaluated. ErPVCs were defined when the ventricular pacing stimulus was >35 ms ahead of the His during tachycardia. RESULTS: Among the 65 cases, 43 were AVNRT and 22 AVRT. Fourteen AVRT cases had an AP response with a mean H1S2+35 ms of 336 ± 58 ms and A1A2 of 309 ± 51ms. No AVNRT cases had an AP response. The specificity of an AP response to ErPVC in predicting AVRT was 100%. CONCLUSION: An AP response to PVCs (A1A2 ≤ H1S2+35 ms) is 100% specific for the presence of an AP.

Effect of Chronic Domperidone Use on QT Interval: A Large Single Center Study.

GOALS: The goal of this study was to determine the effect and safety of domperidone on QTc interval at the commonly prescribed doses of 30 to 80 mg daily. BACKGROUND: Domperidone is a dopamine receptor antagonist used for the treatment of gastroparesis. However, it has been associated with QT prolongation, ventricular arrhythmias, and sudden cardiac death. STUDY: This study analyzed patients prescribed domperidone for treatment of gastroparesis between January 2012 and September 2017 at a single center. This study reviewed EKGs, primarily the QTc interval, taken at baseline, 2 to 6 months after initiation of domperidone, 6 to 12 months after initiation, and ≥12 months after initiation. Concurrent QTc prolonging medications were recorded for each patient. The primary endpoint was QTc prolongation >500 ms. Secondary endpoints were QTc >450 ms for males, a QTc>470 ms for females, QTc prolongation ≥20 ms above baseline, and QTc prolongation >60 ms above baseline. RESULTS: In total, 246 patients were included for analysis (age, 46.3±17.4 y; F 209). EKGs were available for all 246 patients before treatment, 170 patients at 2 to 6 months, 135 at 6 to 12 months, and 152 patients at least 1 year after domperidone initiation.Of 246 subjects, 15 patients (6.1%, 9 female) had clinically important QTc prolongation; 11 had QTc >450 ms for males or >470 ms for females; none had QTc prolongation >500 ms; 5 (2.0%) had >60 ms over baseline and 61 (24.7%) patients had QTc increase of ≥20 ms but <60 ms from baseline. CONCLUSIONS: Domperidone at the conventionally used doses to treat gastroparesis (30 to 80 mg/d) was associated with QTc prolongation in only 6% of patients with no QT interval reaching the point considered to be clinically significant. These data suggest that domperidone can be safely prescribed at doses of 30 to 80 mg daily for the treatment of gastroparesis.

Contemporary Knowledge Workers and the Boundaryless Work-Life Interface: Implications for the Human Resource Management of the Knowledge Workforce.

In the last decade, knowledge workers have seen tremendous change in ways of working and living, driven by proliferating mobile communication technologies, the rise of dual-income couples, shifting expectations of ideal motherhood and involved fatherhood, and the rise of flexible working arrangements. Drawing on 54 interviews with Australian knowledge workers in the information technology sector, we argue that the interface between work and life is now blurred and boundaryless for knowledge workers. By this, we mean that knowledge workers are empowered and enslaved by mobile devices that bring work into the home, and family into the workplace. Knowledge workers take advantage of flexible working to craft unique, personal arrangements to suit their work, family, personal and community pursuits. They choose where and when to work, often interweaving the work domain and the home-family domain multiple times per day. Teleworkers, for example, attain rapid boundary transitions rending the work-home boundary, thus making their experience of the work-life interface boundaryless.

Armour® Thyroid Rage - A Dangerous Mixture.

Armour® Thyroid (Forest Pharmaceuticals, LLC; affiliate of Allergan, Dublin, Ireland) is a natural porcine derivative thyroid supplement that is frequently used without physician monitoring by health enthusiasts as a weight loss supplement. Although there are no publications associating Armour Thyroid and major coronary events, significant drug interactions may exist. A 32-year-old male with a history of hypothyroidism, cystic acne, and solitary congenital kidney presented to the emergency room after experiencing crushing substernal chest pain radiating to his left shoulder, accompanied by diaphoresis and shortness of breath. The patient denied any tobacco use or family history of heart disease. He was self-administering 120 mg of Armour Thyroid daily.   On examination, the patient was well-developed with cystic acne and a flushed appearance. His vital signs on admission were a blood pressure of 171/106 mmHg, heart rate of 88 beats per minute (bpm), and respiratory rate of 16 breaths/min. The electrocardiogram revealed marked ST-segment elevation in the anterior chest leads. Laboratory studies revealed elevated troponins. Urine drug screen was negative. The patient underwent an emergent coronary angiogram, which confirmed an occluded left anterior descending artery. He was treated successfully by thrombectomy and stenting of his left anterior descending artery. Evaluation for other causes of thrombosis was negative: glycosylated hemoglobin (HbA1C) 5.5%, low-density lipoprotein (LDL) 127 mg/dL, high-density lipoprotein (HDL) 33 mg/dL, hypercoagulable evaluation negative, and hemoglobin (Hgb) 17.1 gm/dL. Luteinizing hormone (LH) and follicle stimulating hormone (FSH) were < 0.20 miu/mL. Thyroid profile results were thyroid-stimulating hormone (TSH) 0.20 miu/mL (low), T3 free 4.08 pg/mL (high), and T4 total 1.2 mcg/dL (low), which were consistent with exogenous thyroid hormone administration. Focused questioning triggered by his cystic acne led to the discovery that the patient was self-administering exogenous testosterone replacement therapy. The patient declined to share specifics with the healthcare team. This was confirmed by a high testosterone level of 1,311 ng/dL. Hyperthyroidism increases the risk of cardiovascular events two to three times through the propagation of a hypercoagulable, hypofibrinolytic state possibly via an increase in clotting factors, a decrease in fibrinolytic enzymes, and an increased inhibition of the protein C pathway. The effect of androgens on cardiovascular mortality is uncertain. Androgens stimulate the hemostatic system, increase adverse lipid profile, and erythropoiesis. The combined therapy likely resulted in a synergistic potentiation of hypercoagulable, hypofibrinolytic effects of both agents. Given the absence of other cardiovascular risk factors, the cause of the myocardial infarction in our patient was likely due to drug interaction between Armour Thyroid and exogenous testosterone therapy. Due to the potential drug interaction between both natural and prescribed thyroid hormone and testosterone supplements, patients should be discouraged from self-administration of thyroid or anabolic steroids. Due to the lack of standardization in the T3 content, the use of Armour Thyroid should be avoided.

Distraction Laminoplasty With Interlaminar Lumbar Instrumented Fusion (ILIF) for Lumbar Stenosis With or Without Grade 1 Spondylolisthesis: Technique and 2-Year Outcomes.

STUDY DESIGN: Prospective, nonrandomized cohort. OBJECTIVE: Describe the surgical technique and clinical outcome of distraction lumbar laminoplasty with allograft bone block augmentation and interlaminar lumbar instrumented fusion (ILIF) SUMMARY OF BACKGROUND DATA.: ILIF is a recently described technique that may offer a less invasive alternative to traditional posterior pedicle screw fixation for stabilization during posterior or posterolateral lumbar fusion after decompression for lumbar spinal stenosis. METHODS: Data from two sites of a prospective, multicenter clinical study is described in this report and includes 37 patients over age 40 with single-level degenerative disc disease between L1-2 and L4-5 with neurogenic claudication. Subjects were treated with lumbar decompression using a distraction laminoplasty procedure followed by insertion of a preshaped allograft bone block and interspinous stabilization with a fixation device. BMP-2 was not used. Follow-up clinical evaluation was performed at baseline and at 6 weeks, 3, 6, 12, and 24 months, including perioperative complications, visual analog pain score, Oswestry Disability Index, Zurich Claudication Questionnaire scores and return to activity and work. Radiographic evaluation of fusion and segmental and regional lumbar lordosis were performed to 2 years. RESULTS: Thirty-three patients (89%) of mean age 71 years (17% woman) met all follow-up criteria at 2 years. Levels treated were L4-5 (78.4%), L3-4 (16.2%), or L2-3 (5.4%). Thirty-two of 37 (86%) of patients had a grade-1 spondylolisthesis. Mean hospital length of stay (LOS) was 2 days. Complications included one dural tear, one new neuro deficit that resolved by 6 weeks, one implant failure, one seroma, and one case of cancer diagnosis. At 2 years, 67% had >2 cm improvement on visual analog pain score and 73% had >12.4% Oswestry Disability Index improvement. Symptom severity and physical function subset scores of Zurich Claudication Questionnaire improved by >0.5 cm in 76 and 73% of patients, respectively. At 2 years 94% of patients were off all narcotics and NSAIDS and 94% reported satisfaction with the procedure. Mean lumbar lordosis at baseline and 2 years was 53 ±â€Š14° and 53 ±â€Š13°, respectively. Seventy-two percent of subjects met strict fusion criterion of <3° motion on flexion/extension XRAY and bridging bone; 97% met criteria for stability by independent surgeon evaluation. CONCLUSION: Distraction laminoplasty with allograft bone block augmentation and ILIF may provide a less-invasive alternative to traditional pedicle screw fixation after decompression and posterolateral fusion. The present study describes this technique, and demonstrates excellent clinical outcomes and an acceptable rate of radiographic fusion success. LEVEL OF EVIDENCE: NA.

Allogeneic morphogenetic protein vs. recombinant human bone morphogenetic protein-2 in lumbar interbody fusion procedures: a radiographic and economic analysis.

BACKGROUND: Since the introduction of rhBMP-2 (Infuse) in 2002, surgeons have had an alternative substitute to autograft and its related donor site morbidity. Recently, the prevalence of reported adverse events and complications related to the use of rhBMP-2 has raised many ethical and legal concerns for surgeons. Additionally, the cost and decreasing reimbursement landscape of rhBMP-2 use have required identification of a viable alternative. Osteo allogeneic morphogenetic protein (OsteoAMP) is a commercially available allograft-derived growth factor rich in osteoinductive, angiogenic, and mitogenic proteins. This study compares the radiographic fusion outcomes between rhBMP-2 and OsteoAMP allogeneic morphogenetic protein in lumbar interbody fusion spine procedures. METHODS: Three hundred twenty-one (321) patients from three centers underwent a transforaminal lumbar interbody fusion (TLIF) or lateral lumbar interbody fusion (LLIF) procedure and were assessed by an independent radiologist for fusion and radiographically evident complications. The independent radiologist was blinded to the intervention, product, and surgeon information. Two hundred and twenty-six (226) patients received OsteoAMP with autologous local bone, while ninety-five (95) patients received Infuse with autologous local bone. Patients underwent radiographs (x-ray and/or CT) at standard postoperative follow-up intervals of approximately 1, 3, 6, 12, and 18 months. Fusion was defined as radiographic evidence of bridging across endplates, or bridging from endplates to interspace disc plugs. Osteobiologic surgical supply costs were also analyzed to ascertain cost differences between OsteoAMP and rhBMP-2. RESULTS: OsteoAMP produced higher rates of fusion at 6, 12, and 18 months (p ≤ 0.01). The time required for OsteoAMP to achieve fusion was approximately 40% less than rhBMP-2 with approximately 70% fewer complications. Osteobiologic supply costs were 80.5% lower for OsteoAMP patients (73.7% lower per level) than for rhBMP-2. CONCLUSIONS: Results of this study indicate that OsteoAMP is a viable alternative to rhBMP-2 both clinically and economically when used in TLIF and LLIF spine procedures.