Scheduling practices for pregnant emergency medicine residents.

Background: Night shift work is associated with adverse pathophysiologic effects on maternal and fetal well-being. Although emergency medicine (EM) residents work frequent night shifts, there is no existing guidance for residency program directors (PDs) regarding scheduling pregnant residents. Our study assessed scheduling practices for pregnant EM residents, differences based on program and PD characteristics, barriers and attitudes toward implementing a formal scheduling policy, and PDs' awareness of literature describing adverse effects of night shifts on maternal-fetal outcomes. Methods: We conducted an anonymous, web-based survey of U.S. EM residencies (N = 276). Quantitative data were summarized; chi-square analysis and logistic regression were used to assess relationships between program and PD characteristics and schedule accommodations. Qualitative description was used to analyze an open-ended question, organizing findings into major and minor themes. Results: Of the 167 completed surveys (response rate 61%), 67% of programs reported no formal policy for scheduling pregnant residents but made adjustments on an individual basis including block changes (85%), decreased (46%) or no night shifts (34%), and working shifts earlier in pregnancy to cover later shifts (20%). Barriers to adjustments included staffing constraints (60%), equity concerns (45%), or impact on wellness (41%) among all residents and privacy (28%). PDs endorsed scheduling adjustments as important (mean 8.1, 0-10 scale) and reported guidance from graduate medical education governance would be useful (60%). Larger program size, but not PD gender or proportion of female residents, was associated with an increased likelihood of scheduling modifications. Twenty-five percent of PDs reported little knowledge of literature regarding night shift work and pregnancy. Qualitative themes supported quantitative findings. Conclusions: Most EM residency programs do not have formal scheduling policies for pregnant residents, but most PDs support making adjustments and do so informally. More education and guidance for PDs are needed to promote the development of formal policies.

Euglycemic Diabetic Ketoacidosis in Concurrent Very Low-carbohydrate Diet and Sodium-glucose Transporter-2 Inhibitor Use: A Case Report.

INTRODUCTION: With the incredibly high incidence of Type 2 Diabetes in the current population of emergency department patients, it is critical for clinicians to understand the possible complications of the treatment of this disease. Medication like canagliflozin are more common to encounter on patient's home medication lists and clinicians should be aware of how these medications, alone or combined with dietary modifications, can result in significant pathology and even mortality if not appropriately treated. CASE REPORT: We report a case of a patient with type II diabetes mellitus who presented with euglycemic diabetic ketoacidosis in the setting of concurrent use of canagliflozin, a sodium-glucose transporter-2 (SGLT-2) inhibitor, and strict adherence to a low-carbohydrate ketogenic diet for weight control. DISCUSSION: Euglycemic ketoacidosis has previously been observed in both diabetic and non-diabetic patients following strict ketogenic diets, as well as in diabetic patients being treated with SGLT-2 inhibitors. CONCLUSION: As more patients choose ketogenic diets for weight control and diabetes management, clinicians should be aware of this potentially life-threatening complication in patients concurrently taking SGLT-2 inhibitors.

Toxicity From Unintentional Pediatric Ingestion of a Performance-Enhancing Drug: A Case Report With Review of Clenbuterol Toxicity and Treatment.

BACKGROUND: Clenbuterol is a long-acting ß-adrenergic agonist that is not Food and Drug Administration-approved for use in the United States, but may be obtained without a prescription from various unregulated sellers. It has seen increasing use as a performance-enhancing drug for sports. Literature on pediatric toxicity and treatment is limited. CASE REPORT: We report a case of a 2-year-old female presenting after an exploratory ingestion of clenbuterol. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Use of performance-enhancing agents is increasing and physicians should be aware of the potential toxicity of intentional and unintentional ingestions of ß-adrenergic agonists. Patients may exhibit nausea, vomiting, tremor, tachycardia, and hypotension, along with laboratory abnormalities, including hyperglycemia, hypophosphatemia, hypokalemia, and hyperglycemia. Hypotension might not respond to adrenergic agents and may require administration of ß-adrenergic antagonists to maintain adequate perfusion.

First reported case of thrombocytopenia from a Heterodon nasicus envenomation.

CONTEXT: The vast majority of the 2.5 million annual worldwide venomous snakebites are attributed to Viperidae or Elapidae envenomations. Of the nearly 2000 Colubridae species described, only a handful are known to cause medically significant envenomations. Considered medically insignificant, Heterodon nasicus (Western Hognose Snake) is a North American rear-fanged colubrid common in the legal pet trading industry. Previously reported cases of envenomations describe local pain, swelling, edema, and blistering. However, there are no reported cases of systemic or hematologic toxicity. CASE DETAILS: A 20-year-old female sustained a bite while feeding a captive H. nasicus causing local symptoms and thrombocytopenia. On day three after envenomation, the patient was seen in the emergency department for persistent pain, swelling, and blistering. At that time, she was found to have a platelet count of 90 × 109/L. Previous routine platelet counts ranged from 315 to 373 × 109/L during the prior two years. Local symptoms peaked on day seven post envenomation. Her local symptoms and thrombocytopenia improved on evaluation four months after envenomation. DISCUSSION: We report the first Heterodon nasicus envenomation causing both local toxicity and thrombocytopenia. Potential mechanisms based on H. nasicus venom composition are discussed in detail. Treatment is largely supportive. Bites by H. nascius should be evaluated by a toxicologist familiar with Colubridae species. This represents the first reported case of hematologic toxicity from envenomation by a North American colubrid snake.

Canagliflozin-associated diabetic ketoacidosis: a case report.

Canagliflozin is a novel sodium-glucose cotransporter-2 (SGLT-2) inhibitor approved for the management of diabetes. We report the presentation and management of two cases of canagliflozin associated diabetic ketoacidosis (DKA) and discuss the mechanism of canagliflozin associated DKA. Patient 1, a 55 year old woman maintained on canagliflozin for diabetes mellitus II presented to the emergency department (ED) with 24 hours of nausea and vomiting. She was diagnosed with DKA featuring hypotension, hyperglycemia, ketosis and acidosis. A second 54 year old man also maintained on canagliflozin for diabetes mellitus I presented to the ED with 24 hours of nausea and vomiting. He was diagnosed with DKA with similar manifestations as patient 1. Both patients underwent massive volume resuscitation and intravenous insulin therapy with resolution of ketosis and acidosis. By inhibiting SGLT-2, canagliflozin promotes glucosuria, which in turn can produce up to a 10% decrease in total plasma volume rendering patients maintained on canagliflozin susceptible to dehydration. Inhibition of SGLT-2 also leads to glucagon secretion, which in the volume deplete individual, can exacerbate DKA. Physicians should be aware of the rapid onset of DKA in patients maintained on canagliflozin after just minor additional fluid losses.

Skin perfusion and oxygenation changes in radiation fibrosis.

BACKGROUND: Ionizing radiation is known to have deleterious chronic effects on skin, including fibrosis and poor wound healing, hypothesized as mediated by ischemia and hypoxia. Past studies have been unable to simultaneously investigate changes in perfusion and oxygenation as separate parameters. Hyperspectral imaging has emerged as a tool with which to concurrently measure skin perfusion and oxygenation. The authors investigated the use of hyperspectral imaging in a novel murine model of chronic radiation injury. METHODS: Areas of flank skin (n = 20) on hairless mice were exposed to a 50-Gy dose of beta-radiation. Hyperspectral imaging acquisition was performed at select points through 8 weeks. Immunohistochemical staining and gene expression analysis were performed to evaluate cutaneous vascular density, epidermal cell hypoxia, and angiogenic factors. RESULTS: All irradiated areas developed a chronic-phase wound by day 28. Hyperspectral imaging demonstrated a 21 percent decline in perfusion on day 56 (p < 0.001), whereas oxygenation levels were unchanged. A 1.7-fold reduction in blood vessel density was measured in irradiated skin compared with control tissue (p < 0.001), but no difference in epidermal cell hypoxia was observed. Vascular endothelial growth factor and related receptor expression were significantly lower in irradiated tissue. CONCLUSIONS: The authors' analysis does not support the presence of hypoxia in chronic-phase irradiated skin but suggests that hypoperfusion may be a predominant characteristic. The concurrent states of hypoperfusion and normoxia may be explained by the lower metabolic demands of fibrosed tissue.

Timing constraints of in vivo gag mutations during primary HIV-1 subtype C infection.

BACKGROUND: Aiming to answer the broad question "When does mutation occur?" this study examined the time of appearance, dominance, and completeness of in vivo Gag mutations in primary HIV-1 subtype C infection. METHODS: A primary HIV-1C infection cohort comprised of 8 acutely and 34 recently infected subjects were followed frequently up to 500 days post-seroconversion (p/s). Gag mutations were analyzed by employing single-genome amplification and direct sequencing. Gag mutations were determined in relation to the estimated time of seroconversion. Time of appearance, dominance, and completeness was compared for different types of in vivo Gag mutations. RESULTS: Reverse mutations to the wild type appeared at a median (IQR) of 62 (44;139) days p/s, while escape mutations from the wild type appeared at 234 (169;326) days p/s (p<0.001). Within the subset of mutations that became dominant, reverse and escape mutations appeared at 54 (30;78) days p/s and 104 (47;198) days p/s, respectively (p<0.001). Among the mutations that reached completeness, reverse and escape mutations appeared at 54 (30;78) days p/s and 90 (44;196) days p/s, respectively (p=0.006). Time of dominance for reverse mutations to and escape mutations from the wild type was 58 (44;105) days p/s and 219 (90;326) days p/s, respectively (p<0.001). Time of completeness for reverse and escape mutations was 152 (100;176) days p/s and 243 (101;370) days p/s, respectively (p=0.001). Fitting a Cox proportional hazards model with frailties confirmed a significantly earlier time of appearance (hazard ratio (HR): 2.6; 95% CI: 2.3-3.0), dominance (4.8 (3.4-6.8)), and completeness (3.6 (2.3-5.5)) of reverse mutations to the wild type Gag than escape mutations from the wild type. Some complex mutational pathways in Gag included sequential series of reversions and escapes. CONCLUSIONS: The study identified the timing of different types of in vivo Gag mutations in primary HIV-1 subtype C infection in relation to the estimated time of seroconversion. Overall, the in vivo reverse mutations to the wild type occurred significantly earlier than escape mutations from the wild type. This shorter time to incidence of reverse mutations remained in the subsets of in vivo Gag mutations that reached dominance or completeness.

Viral load and CD4+ T-cell dynamics in primary HIV-1 subtype C infection.

BACKGROUND: Most knowledge of primary HIV-1 infection is based on subtype B studies, whereas the evolution of viral parameters in the early phase of HIV-1 subtype C infection is not well characterized. METHODS: The kinetics of viral RNA, proviral DNA, CD4+ T-cell count, and subsets of CD4+ T cells expressing CCR5 or CXCR4 were characterized in 8 acute and 62 recent subtype C infections over the first year postseroconversion. RESULTS: The viral RNA peak was 6.25 +/- 0.92 log10 copies per milliliter. After seroconversion, heterogeneity among acute cases was evident by patterns of change in viral load and CD4+ T-cell count over time. The patterns were supported by the rate of viral RNA decline from peak (P = 0.022), viral RNA means (P = 0.005), CD4 levels (P < 0.001), and CD4 decline to 350 (P = 0.011) or 200 (P = 0.046). Proviral DNA had no apparent peak and its mean was 2.59 +/- 0.69 log10 per 106 peripheral blood mononuclear cell. In recent infections, viral RNA set point was 4.00 +/- 0.97 log10 and viral RNA correlated inversely with CD4+ T cells (P < 0.001) and directly with proviral DNA (P < 0.001). CONCLUSIONS: Distinct patterns of viral RNA evolution may exist shortly after seroconversion in HIV-1 subtype C infection. The study provides better understanding of the early phase of subtype C infection.

Evolution of proviral gp120 over the first year of HIV-1 subtype C infection.

The evolution of proviral gp120 during the first year after seroconversion in HIV-1 subtype C infection was addressed in a case series of eight subjects. Multiple viral variants were found in two out of eight cases. Slow rate of viral RNA decline and high early viral RNA set point were associated with a higher level of proviral diversity from 0 to 200 days after seroconversion. Proviral divergence from MRCA over the same period also differed between subjects with slow and fast decline of viral RNA, suggesting that evolution of proviral gp120 early in infection may be linked to the level of viral RNA replication. Changes in the length of variable loops were minimal, and length reduction was more common than length increase. Potential N-linked glycosylation sites ranged +/-one site, showing common fluctuations in the V4 and V5 loops. These results highlight the role of proviral gp120 diversity and diversification in the pathogenesis of acute HIV-1 subtype C infection.

Human centromeric chromatin is a dynamic chromosomal domain that can spread over noncentromeric DNA.

Human centromeres are specialized chromatin domains containing the centromeric histone H3 variant CENP-A. CENP-A nucleosomes are interspersed with nucleosomes containing histone H3 dimethylated at lysine 4, distinguishing centromeric chromatin (CEN chromatin) from flanking heterochromatin that is defined by H3 lysine 9 methylation. To understand the relationship between chromatin organization and the genomic structure of human centromeres, we compared molecular profiles of three endogenous human centromeres, defined by uninterrupted higher-order alpha-satellite DNA, with human artificial chromosomes that contain discontinuous blocks of higher-order alpha-satellite DNA and noncentromeric DNA. The underlying sequence did not correlate with chromatin states, because both higher-order alpha-satellite DNA and noncentromeric DNA were enriched for modifications that define CEN chromatin, euchromatin, and heterochromatin. Human artificial chromosomes were also organized into distinct domains. CENP-A and heterochromatin were assembled over noncentromeric DNA, including the gene blasticidin, into nonoverlapping domains. Blasticidin transcripts were enriched at sites of CENP-A binding but not at H3 methylated at lysine 9, indicating that formation of CEN chromatin within a repetitive DNA environment does not preclude gene expression. Finally, we tested the role of centric heterochromatin as a centromeric boundary by increasing CENP-A dosage to expand the CEN domain. In response, H3 lysine 9 dimethylation, but not trimethylation, was markedly decreased at all centromeres examined. We propose that human centromere regions normally exist in a dynamic state in which a regional boundary, defined by H3 lysine 9 dimethylation, separates CEN chromatin from constitutive heterochromatin.