Clinical Characteristics, Risk Factors, and Outcomes Among a Large Midwestern U.S. Cohort of Patients Hospitalized With COVID-19 Prior to Vaccine Availability.

Purpose: The COVID-19 pandemic posed unprecedented demands on health care. This study aimed to characterize COVID-19 inpatients and examine trends and risk factors associated with hospitalization duration, intensive care unit (ICU) admission, and in-hospital mortality. Methods: This retrospective study analyzed patients with SARS-CoV-2 infection hospitalized at an integrated health system between February 2, 2020, and December 12, 2020. Patient characteristics and clinical outcomes were obtained from medical records. Backward stepwise logistic regression analyses were used to identify independent risk factors of ICU admission and in-hospital mortality. Cox proportional hazards models were used to evaluate relationships between ICU admission and in-hospital mortality. Results: Overall, 9647 patients were analyzed. Mean age was 64.6 ± 18 years. A linear decrease was observed for hospitalization duration (0.13 days/week, R2=0.71; P<0.0001), ICU admissions (0.35%/week, R2=0.44; P<0.001), and hospital mortality (0.16%/week, R2=0.31; P<0.01). Bacterial co-infections, male sex, history of chronic lung and heart disease, diabetes, and Hispanic ethnicity were identified as independent predictors of ICU admission (P<0.001). ICU admission and age of ≥65 years were the strongest independent risk factors associated with in-hospital mortality (P<0.001). The in-hospital mortality rate was 8.3% (27.4% in ICU patients, 2.6% in non-ICU patients; P<0.001). Conclusions: Results indicate that, over the pandemic's first 10 months, COVID-19 carried a heavy burden of morbidity and mortality in older patients (>65 years), males, Hispanics, and those with bacterial co-infections and chronic comorbidities. Although disease severity has steadily declined following administration of COVID-19 vaccines along with improved understanding of effective COVID-19 interventions, these study findings reflect a "natural history" for this novel infectious disease in the U.S. Midwest.

Dose-Dependent Retention of Omega-3 Fatty Acids by Black Soldier Fly Larvae (Diptera: Stratiomyidae).

Black soldier fly larvae, Hermetia illucens (L.), are used to convert organic waste streams into insect-based animal feeds. We tested their ability to retain alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) from feeding substrates, which has important implications for their use in aquaculture. When supplementing a chicken feed diet with increasing concentrations of salmon oil (0-42%) over an increasing number of days (0-8), the concentrations of the three omega-3 acids in larvae increased significantly. Larval survival and biomass accumulation were not affected. Supplementing a chicken feed diet with increasing concentrations (0-14%) of Tetraselmis chui Butcher (Chlorodendrales: Chlorodendraceae) microalgae paste also significantly increased ALA and EPA contents of the harvested larvae. However, microalgae also decreased survival, harvested biomass, and individual growth of larvae feeding on the diet with the highest supplement concentration (14%). DHA was not detected in any microalgae diet or subsequent larval tissue samples. All three omega-3 polyunsaturated fatty acids tested in this study were accumulated in dose-dependent manner, with quadratic, and occasionally linear, equations providing the best description of the observed relationships. There were significant negative correlations between several fatty acids, indicating that they may replace one another in living larvae. Our findings confirm that black soldier fly larvae can retain ingested fatty acids and change fatty acid profiles in their tissues accordingly. However, optimizing nutrient content of harvestable larvae is likely to be more complicated than simply enriching their diets with omega-3 fatty acids.

Evaluation of genotoxicity and coumarin production in conventional and organic cultivation systems of Mikania glomerata Spreng.

Mikania glomerata Sprengel, popularly known as "guaco," is used in Brazilian folk medicine for several inflammatory and allergic conditions. Besides, the popular use "guaco" is indicated by the Brazilian Ministry of Health as a safe and effective herbal medicine. The biological activity of M. glomerata extracts is due to the presence of the coumarins, a large family of phenolic substances found in plants and is made of fused benzene and α-pyrone rings. Considering that there are few data on the biological effects of the extracts of M. glomerata, mainly in genetic level, this work aims to evaluate, in vitro, the genotoxicity and coumarin production in M. glomerata in conventional and organic growing. The data showed that the organic culture system showed double the concentration of coumarin being significantly more productive than the conventional system. Besides, the results of comet assay suggest that extracts of M. glomerata cultivated in a conventional system was genotoxic, increased DNA damage levels while the organic extracts seem to have antigenotoxic effect possibly due to the concentration of coumarins. Additional biochemical investigations are necessary to elucidate the mechanisms of action of M. glomerata extracts, which were found to have a role in protection against DNA damage.

How to implant a phrenic nerve stimulator for treatment of central sleep apnea?

BACKGROUND: Central sleep apnea (CSA) is a breathing disorder caused by the intermittent absence of central respiratory drive. Transvenous phrenic nerve stimulation is a new therapeutic option, recently approved by the FDA , for the treatment of CSA. OBJECTIVE: To describe the technique used to implant the transvenous phrenic nerve stimulation system (the remede System, Respicardia, Inc). METHODS: The remede System is placed in the pectoral region, typically on the right side. A single stimulation lead is placed in either the left pericardiophrenic vein (PPV) or the right brachiocephalic vein (RBC). A sensing lead is placed into the azygous vein to detect respiration. RESULTS: In the remede System Pivotal trial, 147 of 151 (97%) patients were successfully implanted with the system. Sixty-two percent of stimulation leads were placed in the PPV and 35% in the RBC. Mean procedure time was 2.7 ± 0.8 hours and 94% of patients were free from implant-related serious adverse events through 6 months. CONCLUSION: In patients with CSA, transvenous phrenic nerve stimulation is an effective and safe therapy with an implant procedure similar to that of cardiac implantable electronic devices.

Iodine supplementation and drinking-water perchlorate mitigation.

Ensuring adequate iodine intake is important, particularly among women of reproductive age, because iodine is necessary for early life development. Biologically based dose-response modeling of the relationships among iodide status, perchlorate dose, and thyroid hormone production in pregnant women has indicated that iodide intake has a profound effect on the likelihood that exposure to goitrogens will produce hypothyroxinemia. We evaluated the possibility of increasing iodine intake to offset potential risks from perchlorate exposure. We also explored the effect of dietary exposures to nitrate and thiocyanate on iodine uptake and thyroid hormone production. Our modeling indicates that the level of thyroid hormone perturbation associated with perchlorate exposures in the range of current regulatory limits is extremely small and would be overwhelmed by other goitrogen exposures. Our analysis also shows that microgram levels of iodine supplementation would be sufficient to prevent the goitrogenic effects of perchlorate exposure at current regulatory limits among at risk individuals. The human health risks from supplementing drinking water with iodine are negligible; therefore, this approach is worthy of regulatory consideration.

Impact of an integrated disease management program in reducing exacerbations in patients with severe asthma and COPD.

BACKGROUND: Conflicting data exists on the effectiveness of integrated programs in reducing recurrent exacerbations and hospitalizations in patients with Asthma and chronic obstructive lung disease (COPD). We developed a Pulmonologist-led Chronic Lung Disease Program (CLDP) for patients with severe asthma and COPD and analyzed its impact on healthcare utilization and predictors of its effectiveness. METHODS: CLDP elements included clinical evaluation, onsite pulmonary function testing, health education, and self-management action plan along with close scheduled and on-demand follow-up. Patients with ≥2 asthma or COPD exacerbations requiring emergency room visit or hospitalization within the prior year were enrolled, and followed for respiratory related ER visits (RER) and hospitalizations (RHA) over the year (357 ± 43 days) after CLDP interventions. RESULTS: A total of 106 patients were enrolled, and 104 patients were subject to analyses. During the year of follow-up after CLDP enrollment, there was a significant decrease in mean RER (0.56 ± 1.48 versus 2.62 ± 2.81, p < 0.0001), mean RHA (0.39 ± 0.08 versus 1.1 ± 1.62, p < 0.0001), and 30 day rehospitalizations (0.05 ± 0.02 versus 0.28 ± 0.07, p < 0.0001). Reduction of healthcare utilization was strongly associated with GERD and sinusitis therapy, and was independent of pulmonary rehabilitation. Direct variable cost analyses estimated annual savings at $1.17 million. Multivariate logistic regression analysis revealed lack of spirometry utilization as an independent risk factor for severe exacerbations. CONCLUSIONS: A Pulmonologist-led disease management program integrating key elements of care is cost effective and significantly decreases severe exacerbations. Integrated programs should be encouraged for care of frequent exacerbators of asthma and COPD.

Reduced natural oscillatory frequency of frontal thalamocortical circuits in schizophrenia.

CONTEXT: Converging evidence from electrophysiological studies suggests that in individuals with schizophrenia, electroencephalographic frontal fast oscillations are reduced. It is still unclear whether this reduction reflects an intrinsic deficit of underlying cortical/thalamocortical circuits and whether this deficit is specific for frontal regions. Recent electrophysiological studies in healthy individuals have established that, when perturbed, different brain regions oscillate at a specific, intrinsically generated dominant frequency, the natural frequency. OBJECTIVE: To assess the natural frequency of the posterior parietal, motor, premotor, and prefrontal cortices in patients with schizophrenia and healthy control subjects. DESIGN: High-density electroencephalographic recordings during transcranial magnetic stimulation of 4 cortical areas were performed. Several transcranial magnetic stimulation­evoked electroencephalographic oscillation parameters, including synchronization, amplitude, and natural frequency, were compared across the schizophrenia and healthy control groups. SETTING: Wisconsin Psychiatric Institute and Clinic, University of Wisconsin­Madison. PARTICIPANTS: Twenty patients with schizophrenia and 20 age-matched healthy control subjects. MAIN OUTCOME MEASURES: High-density electroencephalographic measurements of transcranial magnetic stimulation­evoked activity in 4 cortical areas, scores on the Positive and Negative Syndrome Scale, and performance scores (reaction time, accuracy) on 2 computerized tasks (word memory [Penn Word Recognition Test] and facial memory [Penn Facial Memory Test]). RESULTS: Patients with schizophrenia showed a slowing in the natural frequency of the frontal/prefrontal regions compared with healthy control subjects (from an average of a 2-Hz decrease for the motor area to an almost 10-Hz decrease for the prefrontal cortex). The prefrontal natural frequency of individuals with schizophrenia was slower than in any healthy comparison subject and correlated with both positive Positive and Negative Syndrome Scale scores and reaction time on the Penn Word Recognition Test. CONCLUSIONS: These findings suggest that patients with schizophrenia have an intrinsic slowing in the natural frequency of frontal cortical/thalamocortical circuits, that this slowing is not present in parietal areas, and that the prefrontal natural frequency can predict some of the symptoms as well as the cognitive dysfunctions of schizophrenia.

Probing thalamic integrity in schizophrenia using concurrent transcranial magnetic stimulation and functional magnetic resonance imaging.

CONTEXT: Schizophrenia is a devastating illness with an indeterminate pathophysiology. Several lines of evidence implicate dysfunction in the thalamus, a key node in the distributed neural networks underlying perception, emotion, and cognition. Existing evidence of aberrant thalamic function is based on indirect measures of thalamic activity, but dysfunction has not yet been demonstrated with a causal method. OBJECTIVE: To test the hypothesis that direct physiological stimulation of the cortex will produce an abnormal thalamic response in individuals with schizophrenia. DESIGN: We stimulated the precentral gyrus with single-pulse transcranial magnetic stimulation (spTMS) and measured the response to this pulse in synaptically connected regions (thalamus, medial superior frontal cortex, insula) using concurrent functional magnetic resonance imaging. The mean hemodynamic response from these regions was fit with the sum of 2 gamma functions, and response parameters were compared across groups. SETTING: Academic research laboratory. PARTICIPANTS: Patients with schizophrenia and sex- and age-matched psychiatrically healthy subjects were recruited from the community. MAIN OUTCOME MEASURE: Peak amplitude of the thalamic hemodynamic response to spTMS of the precentral gyrus. RESULTS: The spTMS-evoked responses did not differ between groups at the cortical stimulation site. Compared with healthy subjects, patients with schizophrenia showed a reduced response to spTMS in the thalamus (P=1.86 × 10(-9)) and medial superior frontal cortex (P=.02). Similar results were observed in the insula. Sham TMS indicated that these results could not be attributed to indirect effects of TMS coil discharge. Functional connectivity analyses revealed weaker thalamus-medial superior frontal cortex and thalamus-insula connectivity in patients with schizophrenia compared with control subjects. CONCLUSIONS: Individuals with schizophrenia showed reduced thalamic activation in response to direct perturbation delivered to the cortex. These results extend prior work implicating the thalamus in the pathophysiology of schizophrenia and suggest that the thalamus contributes to the patterns of aberrant connectivity characteristic of this disease.

Thalamic dysfunction in schizophrenia suggested by whole-night deficits in slow and fast spindles.

OBJECTIVE: Slow waves and sleep spindles are the two main oscillations occurring during non-REM sleep. While slow oscillations are primarily generated and modulated by the cortex, sleep spindles are initiated by the thalamic reticular nucleus and regulated by thalamo-reticular and thalamo-cortical circuits. In a recent high-density EEG study, the authors found that 18 medicated schizophrenia patients had reduced sleep spindles, compared with healthy and depressed subjects, during the first non-REM episode. In the present study, the authors investigated whether spindle deficits were present in a larger sample of schizophrenia patients, were consistent across the night, were related to antipsychotic medications, and were suggestive of impairments in specific neuronal circuits. METHOD: Whole-night high-density EEG recordings were performed in 49 schizophrenia patients, 20 nonschizophrenia patients receiving antipsychotic medication, and 44 healthy subjects. In addition to sleep spindles, several parameters of slow waves were assessed. RESULTS: Schizophrenia patients had whole-night deficits in spindle power (12-16 Hz) and in slow (12-14 Hz) and fast (14-16 Hz) spindle amplitude, duration, number, and integrated activity in the prefrontal, centroparietal, and temporal regions. Integrated spindle activity and spindle number had the largest effect sizes (effect size: ≥ 2.21). In contrast, no slow wave deficits were found in schizophrenia patients. CONCLUSIONS: These results indicate that spindle deficits can be reliably established in schizophrenia, are stable across the night, are unlikely to be due to antipsychotic medications, and point to deficits in the thalamic reticular nucleus and thalamo-reticular circuits.

Sleep-dependent improvement in visuomotor learning: a causal role for slow waves.

STUDY OBJECTIVES: Sleep after learning often benefits memory consolidation, but the underlying mechanisms remain unclear. In previous studies, we found that learning a visuomotor task is followed by an increase in sleep slow wave activity (SWA, the electroencephalographic [EEG] power density between 0.5 and 4.5 Hz during non-rapid eye movement sleep) over the right parietal cortex. The SWA increase correlates with the postsleep improvement in visuomotor performance, suggesting that SWA may be causally responsible for the consolidation of visuomotor learning. Here, we tested this hypothesis by studying the effects of slow wave deprivation (SWD). DESIGN: After learning the task, subjects went to sleep, and acoustic stimuli were timed either to suppress slow waves (SWD) or to interfere as little as possible with spontaneous slow waves (control acoustic stimulation, CAS). SETTING: Sound-attenuated research room. PARTICIPANTS: Healthy subjects (mean age 24.6 +/- 1.0 years; n = 9 for EEG analysis, n = 12 for behavior analysis; 3 women). MEASUREMENTS AND RESULTS: Sleep time and efficiency were not affected, whereas SWA and the number of slow waves decreased in SWD relative to CAS. Relative to the night before, visuomotor performance significantly improved in the CAS condition (+5.93% +/- 0.88%) but not in the SWD condition (-0.77% +/- 1.16%), and the direct CAS vs SWD comparison showed a significant difference (P = 0.0007, n = 12, paired t test). Changes in visuomotor performance after SWD were correlated with SWA changes over right parietal cortex but not with the number of arousals identified using clinically established criteria, nor with any sign of "EEG lightening" identified using a novel automatic method based on event-related spectral perturbation analysis. CONCLUSION: These results support a causal role for sleep slow waves in sleep-dependent improvement of visuomotor performance.

Reduced sleep spindle activity in schizophrenia patients.

OBJECTIVE: High-density EEG during sleep represents a powerful new tool to reveal potential abnormalities in rhythm-generating mechanisms while avoiding confounding factors associated with waking activities. As a first step in this direction, the authors employed high-density EEG to explore whether sleep rhythms differ between schizophrenia subjects, healthy individuals, and a psychiatric control group with a history of depression. METHOD: Healthy comparison subjects (N=17), medicated schizophrenia patients (N=18), and subjects with a history of depression (N=15) were recruited. Subjects were recorded during the first sleep episode of the night with a 256-electrode high-density EEG. Recordings were analyzed for changes in EEG power spectra, power topography, and sleep-specific cortical oscillations. RESULTS: The authors found that the schizophrenia group had a significant reduction in centroparietal EEG power, from 13.75 to 15.00 Hz, in relation to both the comparison and depression groups. No significant difference in EEG power between the comparison and depression groups was identified. The authors also found a decrease in sleep spindle number, amplitude, duration, and integrated spindle activity in schizophrenia patients. Furthermore, integrated spindle activity had an effect size corresponding to 93.0% or 90.2% separation of the schizophrenia from the comparison or depression group. CONCLUSIONS: Sleep spindles are generated by the thalamic reticular nucleus in conjunction with specific thalamic nuclei and are modulated by corticothalamic and thalamocortical connections. The deficit in sleep spindles in schizophrenia subjects may reflect dysfunction in thalamic-reticular and thalamocortical mechanisms and could represent a biological marker of illness.

Tanning bed exposure increases the risk of malignant melanoma.

BACKGROUND: Epidemiologic studies have associated tanning bed exposure and cutaneous melanoma. The relationship between the extent of tanning bed exposure and the risk of melanoma has not been elucidated in detail. METHODS: Surveys assessing the extent of tanning bed exposure and the history of skin cancer, including malignant melanoma, were collected from academic dermatology clinic patients (n = 1518). Of these, 551 (36.3%) completed all components of the survey. The available medical records, including pathology reports (n = 501; 33%), were reviewed to confirm cases of skin cancer. Data on potential confounding factors, including indoor vs. outdoor occupation and leisure activities, Fitzpatrick skin type, history of blistering sunburn, use of sunscreen and sun protective clothing, history of phototherapy, and level of education, were assessed and compared. RESULTS: Of the patients surveyed, 487 (32.1%) reported tanning bed exposure. Women aged 45 years or younger accounted for about 60% of all tanning bed users. Seventy-nine cases of malignant melanoma were reported, 22 in women aged 45 years or younger. In the entire cohort, the "ever-use" of tanning beds was found to be a significant risk factor for the development of melanoma [P < 0.05; odds ratio (OR), 1.64; 95% confidence interval (95% CI), 1.01-2.67]. The risk was greater in women aged 45 years or younger (P < 0.05; OR, 3.22; 95% CI, 1.01-11.46). Patients with a history of melanoma were significantly more likely to report tanning bed sessions exceeding 20 min (P < 0.01; OR, 3.18; 95% CI, 1.48-6.82); this association was even stronger for women aged 45 years or younger (OR, 4.12; 95% CI, 1.41-12.02). LIMITATIONS: The study was subject to recall bias, included only patients at a midwestern academic practice, and had a relatively low response rate. CONCLUSION: Exposure to tanning beds increases the risk of malignant melanoma, especially in women aged 45 years or younger. These findings reinforce the hazards of tanning bed exposure.

Black widow spider envenomation.

Black widow spiders are found throughout the continental United States and north into the southern Canadian provinces. Male black widow spiders are of little medical importance. Female black widow spiders can be 20 times larger than males. The female can be identified by the hourglass pattern, red or orange in color, on the ventral aspect of her shiny, globose black abdomen. Black widow spiders control the amount of venom they inject; an estimated 15% of bites to humans are non-envenomating. Cats are very sensitive to the venom and deaths are common. Dogs have severe clinical signs but are considered more resistant than cats. A single bite is capable of delivering a lethal dose of venom to companion animals. There are several toxic components consisting of five or six biologically active proteins. These include a potent mammalian neurotoxin called alpha-latrotoxin, which induces neurotransmitter release from nerve terminals. Acetylcholine, noradrenalin, dopamine, glutamate, and enkephalin systems are all susceptible to the toxin. Onset of clinical signs usually occurs during the first 8 hours post envenomation. The condition is extremely painful in moderate to severe envenomations. Abdominal rigidity without tenderness is a hallmark sign of Latrodectus envenomation. In cats, paralytic signs may occur early and are particularly marked. Hypertension is a significant threat. First aid is of no value in the treatment. The primary treatment for black widow spider envenomation is the administration of specific antivenin, which provides the most permanent and quickest relief of the envenomation syndrome, usually within 30 minutes of infusion. The prognosis of Latrodectus envenomation is uncertain of several days, and complete recovery may take weeks.