EVALUATION OF TWO MEDETOMIDINE-AZAPERONE-ALFAXALONE COMBINATIONS IN CAPTIVE ROCKY MOUNTAIN ELK (CERVUS ELAPHUS NELSONI).

Alfaxalone has been successfully used intramuscularly (im) combined with medetomidine and azaperone for immobilization of small ungulates. An experimental 40 mg/ml alfaxalone solution (RD0387) was recently formulated for reduced injection volume. The objective of this study was to assess the efficacy and cardiopulmonary effects of high-concentration alfaxalone combined with medetomidine and azaperone for the intramuscular immobilization of captive Rocky Mountain elk (Cervus elaphus nelsoni). Seven adult female elk were used in a crossover design in which they were administered alfaxalone 1 mg/kg, medetomidine 0.05 mg/kg, and azaperone 0.1 mg/kg or alfaxalone 0.5 mg/kg, medetomidine 0.1 mg/kg, and azaperone 0.1 mg/kg im approximately 3 wk apart. Drugs were delivered to each elk in a chute by hand injection. Once recumbent, elk were placed in sternal recumbency for a period of 30 min, during which time level of sedation, response to minor procedures, heart rate, respiratory rate, rectal temperature, oxygen saturation, and direct arterial blood pressures were recorded every 5 min. Arterial blood gases were performed every 15 min. At 30 min, elk were administered atipamezole 0.25 or 0.5 mg/kg im and recovery quality and times were recorded. Statistical comparisons were made by t test, Wilcoxon signed rank test, and repeated measures analysis (significance level P < 0.05). Both drug combinations provided effective immobilization for 30 min, with induction and recovery time and quality similar to other medetomidine-based combinations used in elk. Cardiopulmonary effects included bradycardia, hypertension, and hypoxemia that resolved with oxygen supplementation. The average injection volume in the low-dose alfaxalone combination was approximately 5 ml. These combinations provided deep sedation and the ability to perform minor procedures in captive elk, with acceptable cardiopulmonary parameters as long as supplemental oxygen was provided.

The unclosing premature mortality gap in gout: a general population-based study.

OBJECTIVE: Gout, the most common inflammatory arthritis, is associated with premature mortality. Whether this mortality gap has improved over time, as observed in rheumatoid arthritis (RA), is unknown. METHODS: Using an electronic medical record database representative of the UK general population, we identified incident gout cases and controls between 1999 and 2014. The gout cohort was divided based on year of diagnosis into early (1999-2006) and late (2007-2014) cohorts. We compared the mortality rates and HRs, adjusting for potential confounders between the cohorts. We conducted sensitivity analyses among patients with gout who received at least one prescription for urate-lowering therapy, which has been found to have a validity of 90%. RESULTS: In both cohorts, patients with gout showed similar levels of excess mortality compared with their corresponding comparison cohort (ie, 29.1 vs 23.5 deaths/1000 person-years and 23.0 vs 18.8 deaths/1000 person-years in the early and late cohorts, respectively). The corresponding mortality HRs were 1.25 (95% CI 1.21 to 1.30) and 1.24 (95% CI 1.20 to 1.29), and the multivariable HRs were 1.10 (95% CI 1.06 to 1.15) and 1.09 (95% CI 1.05 to 1.13), respectively (both p values for interaction >0.72). Our sensitivity analyses showed similar findings (both p values for interaction >0.88). CONCLUSIONS: This general population-based cohort study indicates that the level of premature mortality among patients with gout remains unimproved over the past 16 years, unlike RA during the same period. This unclosing premature mortality gap calls for improved management of gout and its comorbidities.

Survival benefit of statin use in ankylosing spondylitis: a general population-based cohort study.

OBJECTIVES: Recent studies have shown an increase in both cardiovascular and all-cause mortality in ankylosing spondylitis (AS). We examined the potential survival benefit of statin use in AS within a general population context. METHODS: We performed an incident user cohort study with time-stratified propensity score matching using a UK general population database between 1 January 2000 and 31 December 2014. To account for potential confounders, we compared propensity score-matched cohorts of statin initiators and non-initiators using 1-year cohort accrual blocks. The variables used to create the propensity score model included disease duration, body mass index, lifestyle factors, comorbidities and medication use. RESULTS: Using unmatched AS cohorts, statin initiators (n=1430) showed a 43% higher risk of mortality than non-initiators (n=1430) (HR=1.43; 95% CI 1.12 to 1.84). After propensity score matching, patients with AS who initiated statins (n=1108) had 96 deaths, and matched non-initiators (n=1108) had 134 deaths over a mean follow-up of 5.3 and 5.1 years, respectively. This corresponded to mortality rates of 16.5 and 23.8 per 1000 person-years (PY), respectively, resulting in an HR of 0.63 (95% CI 0.46 to 0.85) and an absolute mortality rate difference of 7.3 deaths per 1000 PY (95% CI 2.1 to 12.5). CONCLUSION: This general population-based cohort study suggests that statin initiation is associated with a substantially lower risk of mortality among patients with AS. The magnitude of the inverse association appears to be larger than that observed in randomised trials of the general population and in population-based cohort studies of patients with rheumatoid arthritis.

Review on the influence of protocol design on clinical outcomes in rheumatoid arthritis treated with rituximab.

OBJECTIVE: To critically analyze the influence of protocol design on clinical outcome in patients with rheumatoid arthritis (RA) treated with rituximab. DATA SOURCES: A PubMed and EMBASE search (January 2000-January 2012) using the key words rheumatoid arthritis and rituximab was performed. STUDY SELECTION AND DATA EXTRACTION: A search of English-language studies from the data sources was conducted for randomized, double-blind, placebo-controlled studies with 100 patients or more assessing the efficacy and safety of rituximab in the treatment of RA. From these studies, 2 authors independently extracted, compiled, and aggregated the data. DATA SYNTHESIS: Eight studies met the inclusion criteria. In these studies, some patients had not been treated with tumor necrosis factor-alfa (TNF-α) inhibitors, while most did not respond to it. The variables compared included dose (500 vs 1000 mg), duration of study (24 vs 48 weeks), and number of cycles (1 vs 2). They were statistically analyzed using the χ(2) test. There was a statistically significant difference in the response to rituximab compared to the control (methotrexate) (p < 0.001). In patients who were studied for only 24 weeks, given 500 or 1000 mg for 1 or 2 cycles, a 90% or greater response rate was reported in those who achieved an ACR 20, but no statistically significant differences were observed (p = 0.75). In patients studied for 48 weeks who received 2 cycles of either 500 mg or 1000 mg of rituximab and achieved an ACR 20, a statistically significant difference (p < 0.001) was observed in those who received a dose of 1000 mg for 2 cycles (42.77% vs 67.49%). CONCLUSIONS: In patients who are nonresponsive to disease-modifying antirheumatic drugs and TNF-α inhibitors, rituximab may be a promising and well-tolerated biologic agent. The capacity of rituximab to produce long-term, sustained remissions could not be evaluated because the duration of the studies was limited to 24 weeks or 48 weeks. Studies with longer periods of observation are warranted.

Malignancy validation in a United States registry of rheumatoid arthritis patients.

BACKGROUND: Physician reporting is commonly used to ascertain adverse events or outcomes measured in epidemiologic studies. However, little is known on the accuracy of physician reported malignancies compared to pertinent medical record review in large cohort studies. METHODS: The Consortium of Rheumatology Researchers of North America (CORRONA) registry gathers physician-completed questionnaires for rheumatoid arthritis (RA) patients, including request for information on incident malignancies, approximately every three months. For incident malignancies reported from October 1st, 2001, through December 31st, 2007, we retrospectively requested completion of a Targeted Adverse Event (TAE) form for additional information as well as primary source documents to adjudicate the malignancy reports. CORRONA has employed a prospective request for source documentation for these events since 2008. We classified each malignancy as definite, probable, possible, or not a malignancy. RESULTS: From 20,837 RA patients enrolled in CORRONA, 461 incident malignancies were initially reported on physician questionnaires. After review of returned source documents with adjudication, 234 were deemed definite, 69 probable, 101 possible, and 57 not an incident malignancy. The positive predictive value (PPV) of initial physician report of a malignancy versus "definite or probable" malignancy based on adjudication was 0.66 (95% CI 0.61 - 0.70). The PPV was 0.68 (95% CI 0.63 - 0.72) when the subsequent TAE form also confirmed the presence of malignancy. When possible malignancies were included, the PPV of physician-reported malignancies without a subsequent TAE form increased to 0.86 (0.83 - 0.89), and with a subsequent TAE form, 0.89 (0.85-0.91). CONCLUSION: Twelve percent of initial physician reports of incident malignancy could not be confirmed with review of source documents. The most common reason for lack of confirmation was inability to obtain documents or insufficient data in source materials. These results suggest that timely collection of relevant medical records and an adjudication process are required to improve the accuracy of cancer reporting in epidemiologic studies.

A comparison of arthrocentesis teaching tools: cadavers, synthetic joint models, and the relative utility of different educational modalities in improving trainees' comfort with procedures.

BACKGROUND: Each year, rheumatology programs across the country teach incoming trainees the skill of arthrocentesis, but the relative effectiveness of various teaching techniques has not been assessed in a systematic way. OBJECTIVES: We compared approaches to teaching arthrocentesis using cadavers versus anatomic models. METHODS: In a pilot study, new rheumatology fellows (n = 7) from 2 academic institutions were surveyed at 3 points during arthrocentesis training: (1) before assuming patient care; (2) after lecture with handouts, followed by practice either on cadavers (group A) or on synthetic joint models (group B); and (3) 6 weeks into fellowship. Fellows rated their comfort levels for arthrocentesis of specific joints using 9-point Likert scales. Fellows also retrospectively rated the utility of individual teaching modalities in helping them to learn. As a follow-up study, internal medicine residents taking part in a month-long rheumatology rotation were similarly surveyed on their comfort level performing knee and shoulder arthrocentesis before a cadaver teaching laboratory and at the end of their month rotation. RESULTS: The initial mean comfort level performing arthrocentesis for all fellows was low (2.01). After the cadaver teaching session, group A fellows experienced an overall comfort level increase of 1.95, with the largest single increase reported for shoulder arthrocentesis (3.86). After the anatomic model teaching session, group B fellows reported a mean comfort increase of 1.29, with the largest increase reported for knee arthrocentesis (3.13). The subsequent study with residents confirmed significant increases in comfort after the cadaver laboratory. When surveyed, the learning experience fellows considered most effective was the opportunity to perform procedures under supervision and guidance, followed by training on cadavers. CONCLUSIONS: Although all teaching interventions for trainees learning arthrocentesis were helpful for increasing trainee's comfort with arthrocentesis, the use of cadavers seemed to be superior to synthetic anatomic models or lectures alone. The specific impact of these teaching interventions on actual competence, defined as a performance outcome, deserves additional study.

Apparent stability masks underlying change in a mule deer herd with unmanaged chronic wasting disease.

The contagious prion disease "chronic wasting disease" (CWD) infects mule deer (Odocoileus hemionus) and related species. Unchecked epidemics raise ecological, socioeconomic, and public health concerns. Prion infection shortens a deer's lifespan, and when prevalence (proportion of adults infected) becomes sufficiently high CWD can affect herd dynamics. Understanding population responses over time is key to forecasting long-term impacts. Here we describe unexpected stability in prevalence and abundance in a mule deer herd where CWD has been left unmanaged. High apparent prevalence (~30%) since at least 2005 likely drove observed changes in the proportion and age distribution of wild-type native prion protein (PRNP) gene homozygotes among deer sampled. Predation by mountain lions (Puma concolor) may be helping keep CWD in check. Despite stable appearances, prion disease nonetheless impairs adult survival and likely resilience in this deer herd, limiting its potential for growth despite refuge from hunter harvest and favorable habitat and winter conditions.

Efficacy and safety of gout flare prophylaxis and therapy use in people with chronic kidney disease: a Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN)-initiated literature review.

Gout flare prophylaxis and therapy use in people with underlying chronic kidney disease (CKD) is challenging, given limited treatment options and risk of worsening renal function with inappropriate treatment dosing. This literature review aimed to describe the current literature on the efficacy and safety of gout flare prophylaxis and therapy use in people with CKD stages 3-5. A literature search via PubMed, the Cochrane Library, and EMBASE was performed from 1 January 1959 to 31 January 2018. Inclusion criteria were studies with people with gout and renal impairment (i.e. estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) < 60 ml/min/1.73 m2), and with exposure to colchicine, interleukin-1 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids. All study designs were included. A total of 33 studies with efficacy and/or safety analysis stratified by renal function were reviewed-colchicine (n = 20), anakinra (n = 7), canakinumab (n = 1), NSAIDs (n = 3), and glucocorticoids (n = 2). A total of 58 studies reported these primary outcomes without renal function stratification-colchicine (n = 29), anakinra (n = 10), canakinumab (n = 6), rilonacept (n = 2), NSAIDs (n = 1), and glucocorticoids (n = 10). Most clinical trials excluded study participants with severe CKD (i.e. eGFR or CrCl of < 30 mL/min/1.73 m2). Information on the efficacy and safety outcomes of gout flare prophylaxis and therapy use stratified by renal function is lacking. Clinical trial results cannot be extrapolated for those with advanced CKD. Where possible, current and future gout flare studies should include patients with CKD and with study outcomes reported based on renal function and using standardised gout flare definition.

Tissue Residue Levels of the Tranquilizer Combination of Butorphanol, Azaperone, and Medetomidine, and the Antagonists, Naltrexone, Atipamezole, and Tolazoline, in Black Bears (Ursus americanus) Postimmobilization.

The tranquilizer combination of butorphanol, azaperone, and medetomidine (BAM) has shown good efficacy for immobilization of wildlife, including black bears (Ursus americanus). BAM is antagonized with a combination of naltrexone and atipamezole. We immobilized 19 adult captive wild caught black bears and, except for three bears that were euthanized immediately, bears were recovered with naltrexone and atipamezole. Tissue residues (≥0.01 ppm) for the tranquilizers butorphanol, azaperone, and medetomidine were detected in liver and muscle of all three bears euthanized on day 0 postinjection (PI). Azaperone was not detected after 1 d PI. Residue for medetomidine was detected in two bears: in the liver 3 d PI and in the kidney 6 d PI. Butorphanol was reported in three bears: in fat 5 d PI, in kidney 6 d PI, and, surprisingly, in kidney, muscle, and fat 7 d PI. No tissue residues were detected in the three bears euthanized at 8 d PI. Tissue residues for the antagonists, naltrexone and atipamezole, were detected in bears euthanized 2 and 6 d PI, but not in tissues from animals euthanized at 7 or 8 d PI.

Blocking extracellular Galectin-3 in patients with osteoarthritis.

OBJECTIVE: This pilot clinical trial examined the efficacy of blocking extracellular Galectin-3 (Gal-3) with modified citrus pectin (MCP), in patients suffering from knee osteoarthritis (OA). METHODS: 50 patients were randomized in a 1:1 ratio to receive MCP or placebo at a dose of 4 g (5 capsules) twice daily for 12 weeks. Serum Gal-3 levels and OA severity were evaluated at baseline and 12 weeks. Gal-3 levels were detected by sandwich ELISA and OA severity was determined using WOMAC-knee, SF-36, and RAPID3 surveys during these visits. MCP tolerability was assessed by a basic metabolic panel during a week 6 follow up visit. RESULTS: Patients enrolled in both the MCP treatment and placebo groups shared similar baseline characteristics in OA severity, serum Gal-3 levels, and pain management. Improvement across all surveys was noted independent of supplement or placebo treatment. No significant change in Gal-3 levels were observed in either cohort over the 12-week study. CONCLUSION: Treatment of knee OA with a 12-week course of MCP did not significantly improve disease burden compared to placebo.

Colchicine Use and Incident Coronary Artery Disease in Male Patients With Gout.

BACKGROUND: Inflammation is associated with coronary artery disease (CAD) and myocardial infarction (MI). Patients with gout are at increased risk of MI, and colchicine is associated with a reduced risk of MI. The objective of this study was to determine whether colchicine prevents incident development of CAD in patients with gout. METHODS: This retrospective study followed a cohort of male patients with gout without known CAD at the time of diagnosis of gout in the VA New York Harbor Healthcare System. The association between colchicine use and development of incident CAD, defined as evidence of ischemia or obstructive CAD on stress test or angiography, was determined using an inverse probability weighted (IPW) Cox proportional hazard model. RESULTS: Among 178,877 patients, 1638 met criteria of gout, of whom 722 without known CAD at baseline (446 colchicine users and 276 nonusers) were followed for a median of 96 months (57 to 117). A trend toward association between use of colchicine and reduced incident CAD was observed but not statistically significant (IPW hazard ratio [HR], 0.49; 0.23-1.05). In patients without chronic kidney disease, use of colchicine was associated with a lower rate of incident CAD (interaction P = 0.005, IPW HR, 0.31; 0.14-0.70). Colchicine was also associated with a lower rate of the composite of incident CAD and MI (IPW HR, 0.37; 0.16-0.83). CONCLUSIONS: In male patients with gout and no known CAD, a trend of reduced incident CAD was observed with use of colchicine that was not statistically significant. Larger, prospective studies will be required to assess the primary prevention benefit of colchicine definitively.

EVALUATION OF CHEMICAL IMMOBILIZATION IN CAPTIVE BLACK BEARS ( URSUS AMERICANUS) RECEIVING A COMBINATION OF NALBUPHINE, MEDETOMIDINE, AND AZAPERONE.

To assess potential seasonal differences in responses to immobilization, we sedated eight orphaned yearling black bears ( Ursus americanus) being held for rehabilitation at a wildlife facility in Colorado, US, using a premixed combination of nalbuphine (40 mg/mL), azaperone (10 mg/mL), and medetomidine (10 mg/mL; NalMed-A) in October (autumn) prior to hibernation and again after emergence in May (spring) prior to their release. We dosed all bears at 1 mL NalMed-A per estimated 45 kg body mass (1 mL NalMed-A/45 kg), delivered by intramuscular injection using a pole syringe, to facilitate routine examination and ear tagging. Arterial blood gases were measured to assess oxygenation and acid-base status of bears both pre and post oxygen supplementation. The mean (SE) dose calculated post hoc was 0.9 (0.04) mg nalbuphine/kg, 0.2 (0.01) mg azaperone/kg, and 0.2 (0.01) mg medetomidine/kg. The mean induction time was 8 (1) min for six of the bears in October and 6 (1) min for eight bears in May. The NalMed-A combination provided good sedation in captive yearling black bears in autumn and spring and was effectively antagonized with a combination of naltrexone and atipamezole. Mild hypoxemia (PaO2: 53.5-54.4 mmHg) was the most significant side effect and was corrected (PaO2: 68.4-150.1 mmHg) with supplemental oxygen administered at 2-5 L/min for 5 min (point of sampling).

Low-Dose Allopurinol Promotes Greater Serum Urate Lowering in Gout Patients with Chronic Kidney Disease Compared with Normal Kidney Function.

OBJECTIVES: Gout patients with chronic kidney disease (CKD) accumulate the active allopurinol metabolite oxypurinol, suggesting that allopurinol may promote greater serum urate (sU) lowering in CKD patients. METHODS: We identified all patientswith gout diagnoses on either 100 mg or 300 mg of allopurinol daily, with available pre- and on-treatment sU levels, in our system in a 1-year period. Mean sU decrement by dosing per CKD groups was determined by CKD stage. RESULTS: Of 1,288 subjects with gout, 180 met entry criteria, with 83 subjects receiving 100 mg and 97 receiving 300 mg allopurinol. Subjects with CKD stage 1 experienced less sU lowering with 100 mg than 300 mg of allopurinol. Subjects with stage 4 and 5 CKD had equivalent sU decreases across the 100 mg and 300 mg allopurinol groups. However, the 100 mg group started at a higher pre-treatment sU and ended at a higher final sU than the 300 mg group. CONCLUSIONS: The strategy of titrating allopurinol to sU in patients with kidney impairment may result in greater sU lowering at lower doses than in patients without CKD but may also pose a treatment challenge from a possible drug ceiling effect.

Gout, Hyperuricemia, and Crystal-Associated Disease Network Consensus Statement Regarding Labels and Definitions for Disease Elements in Gout.

OBJECTIVE: The language currently used to describe gout lacks standardization. The aim of this project was to develop a consensus statement on the labels and definitions used to describe the basic disease elements of gout. METHODS: Experts in gout (n = 130) were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach consensus on the labeling and definitions for the basic disease elements of gout. Disease elements and labels in current use were derived from a content analysis of the contemporary medical literature, and the results of this analysis were used for item selection in the Delphi exercise and face-to-face consensus meeting. RESULTS: There were 51 respondents to the Delphi exercise and 30 attendees at the face-to-face meeting. Consensus agreement (≥80%) was achieved for the labels of 8 disease elements through the Delphi exercise; the remaining 3 labels reached consensus agreement through the face-to-face consensus meeting. The agreed labels were monosodium urate crystals, urate, hyperuric(a)emia, tophus, subcutaneous tophus, gout flare, intercritical gout, chronic gouty arthritis, imaging evidence of monosodium urate crystal deposition, gouty bone erosion, and podagra. Participants at the face-to-face meeting achieved consensus agreement for the definitions of all 11 elements and a recommendation that the label "chronic gout" should not be used. CONCLUSION: Consensus agreement was achieved for the labels and definitions of 11 elements representing the fundamental components of gout etiology, pathophysiology, and clinical presentation. The Gout, Hyperuricemia, and Crystal-Associated Disease Network recommends the use of these labels when describing the basic disease elements of gout.

Tissue Residue Levels after Immobilization of Rocky Mountain Elk ( Cervus elaphus nelsoni) using a Combination of Nalbuphine, Medetomidine, and Azaperone Antagonized with Naltrexone, Atipamezole, and Tolazoline.

Previous studies demonstrated that nalbuphine, medetomidine, and azaperone (NalMed-A) can effectively immobilize adult elk ( Cervus elaphus nelsoni), and be antagonized using naltrexone and atipamezole, with or without tolazoline. To assess duration of tissue residues for this immobilization package, we immobilized 14 captive adult elk with NalMed-A, then euthanized animals and collected tissues 0, 3, 6, 14, 21, or 28 d later. Except for two animals euthanized immediately, all elk were recovered using naltrexone, atipamezole, and tolazoline. Tissue residues (≥0.01 parts per million) for the tranquilizers nalbuphine, medetomidine, and azaperone were detected in liver and muscle tissue samples from elk euthanized within 40 min postinjection (PI) and one animal that died 12-24 h PI, but not in tissues from any of the animals euthanized at 3, 6, 14, 21, or 28 d PI. Tissue residues for the antagonists naltrexone, atipamezole, and tolazoline were detected in liver and muscle of the animal that died 12-24 h PI. Only naltrexone was detected in liver from the two elk euthanized at day 3, and no antagonist residues were detected thereafter.

THE EFFICACY OF NALBUPHINE, MEDETOMIDINE, AND AZAPERONE IN IMMOBILIZING AMERICAN BISON (BISON BISON).

We evaluated a combination of nalbuphine, medetomidine, and azaperone (NalMed-A) in 12 American bison ( Bison bison ) during 13 sedation handling events. The mean (SE) dosage was 0.4 (0.02) mg/kg nalbuphine, 0.08 (0.003) mg/kg medetomidine, and 0.08 (0.003) mg/kg azaperone contained in an average delivery volume of 0.8 mL/100 kg. Two animals required a supplemental dose for safe handling (additive dose used in calculating means) and a third animal was not adequately sedated despite a supplemental dose. Bison immobilized with NalMed-A showed good sedation in 12 of 13 handling attempts. Advantages of this drug combination included a relatively low delivery volume, rapid antagonism, and minimal regulatory burden for component drugs. The most consistent disadvantage was hypoxemia, and oxygen supplementation is recommended when using this sedative combination in bison.

Anatomic variants associated with newborn circumcision complications.

OBJECTIVE: Circumcision is one of the commonly performed procedures on males in the United States, Canada, Australia, and the United Kingdom. The association of minor anatomic variations of the newborn genitalia in patients with minor circumcision complications has not been previously examined. In this study, we looked for an association between subtle genital anatomic variations and newborn circumcision complications. MATERIALS AND METHODS: Over an 18-month period, children presenting for circumcision revision were examined for minor variations in genital anatomy. Children referred for other urological problems during the same period comprised the control group. The same physician evaluated all of the children. RESULTS: During this period, 68 children were evaluated for possible circumcision complications. A confirmed complication was present in 57 infants. Patients with a minor circumcision complication were found to have a 9-fold higher incidence of a prominent suprapubic fat pad, penoscrotal webbing, or being a premature infant as compared to the control group. CONCLUSIONS: Subtle anatomic variations may be associated with a higher incidence of circumcision complications. Physicians performing newborn circumcisions should thoroughly examine the genitalia for these anatomic variations prior to the procedure in order to reduce potential complications.