Comparison of all completed suicides in Frankfurt am Main (Hessen) before and during the early COVID-19 pandemic.

To research the effect of the COVID-19 pandemic on mental health, the prevalence and characteristics of all completed suicides in the city of Frankfurt am Main were compared for a 10-month period before the pandemic (March 2019-December 2019) with one during the early pandemic (March 2020-December 2020). Medicolegal data collected in the context of the FraPPE suicide prevention project were evaluated using descriptive statistical methods. In total, there were 81 suicides during the early pandemic period, as opposed to 86 in the pre-pandemic period. Though statistically not significant, the proportion of male suicides (73%) was higher during the early pandemic period than before (63%). The age-at-death was comparable in the pre-pandemic and pandemic periods (average, 54.8 vs. 53.1 years). Between these two periods, there was no difference in respect to the three most commonly used suicide methods by men: fall from a height (26% vs. 22%), intoxication, and strangulation (each 24% vs. 19%). For women, there was, however, a shift in methods from strangulation (38%), intoxication (28%), and fall from a height (19%) to fall from a height (50%), strangulation (18%), intoxication, and collision with a rail vehicle (14% each). There was a trend towards more suicides among non-German nationals during the early pandemic (suicide rate/100,000 inhabitants: German, 14.3 vs. 11.5; non-German, 4.4 vs. 8.8). Before the pandemic, 54% of the suicides were known to have a mental illness in contrast to 44% during the early pandemic. Overall, no increase in completed suicides could be observed in Frankfurt am Main during the early pandemic.

HPA-axis regulation at in-patient admission is associated with antidepressant therapy outcome in male but not in female depressed patients.

A concatenation of data implicates a hyperactivity of the hypothalamus pituitary adrenal (HPA)-axis in the pathogenesis of depression and its normalization as a necessary predecessor of clinical response to antidepressant drugs. In addition, regulation of the HPA-axis has been shown to be dependent on sex hormones. We therefore investigated gender differences in HPA-axis regulation in depression and its normalization during remission of clinical symptoms. We used the combined dexamethasone suppression/CRH stimulation (Dex-CRH) test to evaluate the degree of HPA-axis dysregulation in 194 in-patients with unipolar depression from the Munich Antidepressant Response Signature (MARS) study at both admission and discharge. The Hamilton Depression (HAM-D) Rating Scale was used to monitor clinical response to antidepressant treatment. For both genders, we observed a normalization of HPA-axis dysregulation in remitters but not in non-remitters, both after 5 weeks of treatment and at discharge. The pattern of HPA-axis normalization with remission of depressive symptoms, however, showed gender-specific differences. In male patients, remission after 5 weeks of in-patient treatment was associated with a significantly higher cortisol response in the Dex-CRH test at admission. In female patients, 5-week remitters and non-remitters had a comparable cortisol response at admission. Cortisol response at admission was not correlated with gonadal steroid levels at this time point and the results were similar for pre-menopausal women vs. post-menopausal women. Gender-associated biological characteristics, likely independent of circulating gonadal steroids, thus seem to influence HPA-axis regulation in depression. In male patients, a single measure of HPA-axis dysregulation at admission may serve as a predictor of response to antidepressant treatment in addition to the previously reported repeated measure of the Dex-CRH test.

Out-of-equilibrium dynamics of a fractal model gel.

Using molecular dynamics computer simulations we investigate the dynamics of a gel. We start from a fractal structure generated by the diffusion limited cluster aggregation-deflection algorithm, onto which we then impose an interaction potential consisting of a short-range attraction as well as a long-range repulsion. After relaxing the system at zero temperature, we let it evolve at a fixed finite temperature. Depending on the temperature T we find different scenarios for the dynamics. For T approximately > 0.2 the fractal structure is unstable and breaks up into small clusters which relax to equilibrium. For T approximately < 0.2 the structure is stable and the dynamics slows down with increasing waiting time. At intermediate and low T the mean squared displacement scales as t(2/3) and we discuss several mechanisms for this anomalous time dependence. For intermediate T, the self-intermediate scattering function is given by a compressed exponential at small wave vectors and by a stretched exponential at large wave vectors. In contrast, for low T it is a stretched exponential for all wave vectors. This behavior can be traced back to a subtle interplay between elastic rearrangements, fluctuations of chainlike filaments, and heterogeneity.

Bladder scan accuracy in pediatric patients: Does patient position matter?

INTRODUCTION: Despite its widespread use in pediatric urology clinics, portable bladder scanning is an insufficiently studied tool that lacks standardized protocols. Workflow at the present clinic can be impeded by scanning in the supine position, due to multiple trips to the restroom and back to the exam room. OBJECTIVE: The current study sought to test accuracy of bladder scanning, and hypothesized that it would be equally accurate in the standing versus traditional supine position in children, given the intra-abdominal location of their bladders. DESIGN: Sixty children from the bladder/bowel clinic were prospectively recruited. Patients had a formal supine renal/bladder ultrasound and pre-void and/or post-void assessment with scans in both the standing and supine positions. The methods were compared using repeated measures one-way ANOVA. RESULTS: Mean age was 9.2 years. The majority (85%) were female. All bladder scan estimates except for post-void supine significantly correlated with ultrasound volume. Pre-void standing had the strongest correlation (r = 0.83). There was no difference between ultrasound and standing estimates for pre-void volumes, but supine underestimated volumes by 44.8 ml (P < 0.01) (Summary Figure). Sub-group analysis of children aged <10 years showed that pre-void scans in both positions significantly underestimated volume (12% of estimated bladder capacity for standing, 24% for supine, P < 0.05). For post-void volumes, both standing and supine overestimated measurements by 29.4 ml and 18.3 ml, respectively (both P < 0.001). Sub-group analysis based on age yielded comparable results. DISCUSSION: It is believed that this is the first study to examine bladder scanning in different positions. Limitations included small sample size, and the study fell short of cost-effectiveness and outcome analysis to assess the real-life impact of the proposed use of standing bladder scanning in the clinic. CONCLUSION: Standing bladder scanning may be used in place of supine. However, bladder scanning generally appeared to have poor accuracy, especially in younger children, and thus should be used with caution. In practical terms, it may decrease specificity of detecting elevated post-void residuals compared to ultrasound.

Caring for urologic transition patients: Current practice patterns and opinions.

INTRODUCTION: Congenitalism is an emerging field that recognizes the complex needs of adult patients with congenital urologic issues. Despite the onset of transitional care clinics, these patients remain difficult to care for due to resource availability, insurance coverage, and multi-disciplinary needs. OBJECTIVE: The current study sought to characterize practice patterns and opinions regarding care for urologic transition patients. DESIGN: An anonymous 20-question survey was sent to members of the Society of Pediatric Urology listserv. Questions pertained to physician background, practice demographics, clinic structure, and quality. Five-point Likert scales were used to assess quality markers (5 = most/best). Data were analyzed in R, and subgroup analyses were performed. Subgroups included presence of formal transition clinic, city size, and practice type. RESULTS: The response rate was 53%, with 124 respondents. A formal transition clinic was reported by 32%. Those with formal clinics reported higher enthusiasm (3.9 vs 3.4, P < 0.01) for care of these patients and believed they provided better care compared to other institutions (P < 0.001) Summart Table. There was no significant difference in perceived quality between respondents in academic vs other practices. There was a small trend towards higher-quality ratings in smaller cities (3.8 vs 3.5, P = 0.13). The majority (64%) felt that transition patients are best cared for by specialized adult providers; however, these formalized clinics found to be staffed primarily by pediatric providers (54%). DISCUSSION: This study supported the general consensus in the literature that transition clinics improve care for urologic transition patients, while underlining discordance between current practice patterns and recommendations for optimal care. CONCLUSION: The majority of practices appeared to lack a formal transition clinic, and there was variation in their structure. Those with formal clinics tended to rate themselves as providing higher-quality care. The majority of respondents believed that adult specialists in either reconstructive or neuro-urology are best suited to care for these complex patients.

Pharmacological and nonpharmacological factors influencing hypothalamic-pituitary-adrenocortical axis reactivity in acutely depressed psychiatric in-patients, measured by the Dex-CRH test.

The most consistent biological findings in patients with depression are abnormalities in the hypothalamic-pituitary-adrenal (HPA)-axis, which can be measured using the combined dexamethasone-suppression/CRH-stimulation (Dex-CRH) test. The reactivity of the HPA-axis in this test, however, ranges over several orders of magnitude in depressed patients with comparable severity of symptoms. In this present study, we investigate which factors influence the magnitude of the response in the Dex-CRH test in 235 acutely depressed in-patients. We first examined the effects of common confounders shown to influence the HPA-axis, such as caffeine and nicotine consumption, acute stressors during the test, weight, gender, and age. Of all these variables, only female sex and nicotine consumption were positively correlated with the cortisol or ACTH response, respectively. As for the effects of psychopharmacological treatment, only the intake of carbamazepine and the fact of having relapsed under an established pharmacotherapy significantly increased the response in the Dex-CRH test, whereas the presence or absence of antidepressant treatment, the type of antidepressant treatment, or the number of ineffective antidepressant treatment trials during the index episode up to admission did not have any effect. We also found a positive correlation of the number of previous episodes, the overall HAM-D score and the severity of somatic/vegetative symptoms with the results in the Dex-CRH test. These results underline that in depressed patients this test is not majorly influenced by disease-unrelated factors. In addition, current antidepressant treatment does not appear to affect test outcome in the absence of clinical response. The influence of the number of previous episodes and relapse under pharmacotherapy suggests that HPA-axis reactivity may be altered by repetitive states of hypercortisolemia or continuous antidepressant treatment. Finally, more severe vegetative symptoms are associated with an enhanced HPA-axis activity.

Obstructive sleep apnea treated by independently adjusted inspiratory and expiratory positive airway pressures via nasal mask. Physiologic and clinical implications.

Treatment of obstructive sleep apnea with nasal continuous positive airway pressure mandates simultaneous increases of both inspiratory and expiratory positive airway pressures to eliminate apneas as well as nonapneic oxyhemoglobin desaturation events. We hypothesized that the forces acting to collapse the upper airway during inspiration and expiration are of different magnitudes and that obstructive sleep-disordered breathing events (including apneas, hypopneas and nonapneic desaturation events) could be eliminated at lower levels of EPAP than IPAP. To test these hypotheses, a device was built that allows the independent adjustment of EPAP and IPAP (nasal BiPAP). Our data support the hypotheses that expiratory phase events are important in the pathogenesis of OSA and that there are differences in the magnitudes of the forces destabilizing the upper airway during inspiration and expiration. Finally, applying these concepts, we have shown that by using a device that permits independent adjustment of EPAP and IPAP, obstructive sleep-disordered breathing can be eliminated at lower levels of expiratory airway pressure compared with conventional nasal CPAP therapy. This may reduce the adverse effects associated with nasal CPAP therapy and improve long-term therapeutic compliance.

CPAP therapy via oronasal mask for obstructive sleep apnea.

STUDY OBJECTIVE: To determine the effectiveness of oronasal masks for positive pressure therapy in alleviating obstructive sleep apnea (OSA). METHODS AND PROCEDURES: Polysomnographic records of all 245 patients with OSA who underwent therapeutic trials of either continuous positive airway pressure (CPAP) or bilevel positive airway pressure between January 1991 and December 1992 were reviewed. Thirty patients who had been prescribed positive pressure therapy employing an oronasal mask were identified. Two patients known to be successfully treated with CPAP via oronasal mask underwent repeat polysomnography. The initial portion of the study was a diagnostic evaluation during which the patients were untreated. During the second portion of the study, both patients used CPAP via an oronasal mask while wearing a mouthpiece designed to maintain oral patency. RESULTS: The 30 patients with OSA who were identified in this study had significant amelioration of OSA while receiving positive pressure therapy via oronasal mask compared with the baseline, diagnostic polysomnogram (apnea index: 55.3 +/- 36.9-->1.6 +/- 3.7, p < 0.001; hypopnea index: 21.2 +/- 20-->2.7 +/- 4.9, p < 0.001; nadir of SaO2: 72.5 +/- 13.9-->87.1 +/- 4.3, p < 0.001, mean +/- SD). Improvement of OSA did not depend on maintenance of a closed mouth, as evidenced by elimination of sleep-disordered breathing in the two patients receiving positive pressure via oronasal mask while wearing a mouthpiece to keep the mouth open. CONCLUSION: Oronasal masks are a viable alternative interface for alleviating OSA with positive pressure therapy in those patients who are unwilling or unable to tolerate conventional nasal interfaces. Although there were no adverse consequences associated with the use of oronasal masks in our patients, appropriate safety precautions should be taken to minimize the possibility of aspiration of gastric contents and avoid untoward sequelae due to positive pressure device failure.

Accuracy of end-tidal and transcutaneous PCO2 monitoring during sleep.

STUDY OBJECTIVE: Although it is intuitively desirable, the measurement of arterial carbon dioxide tension (PaCO2) during diagnostic polysomnography and nocturnal trials of positive pressure therapy is invasive and potentially expensive. The accuracy of end-tidal carbon dioxide tension (PETCO2) and transcutaneous carbon dioxide (tcPCO2) monitoring in these contexts has not been systematically evaluated. This investigation was undertaken to evaluate the accuracy of PETCO2 and tcPCO2 in patients undergoing polysomnography. METHODS AND PROCEDURES: Values of PETCO2 were compared with PaCO2 in 19 patients spontaneously breathing room air (condition 1), in 13 patients receiving supplemental oxygen via nasal cannula (condition 2), and in 22 patients receiving nocturnal positive pressure ventilatory assistance (all but one with continuous positive airway pressure or bilevel positive airway pressure) (condition 3). The accuracy of tcPCO2 monitoring during sleep was also examined by comparing tcPCO2 values with simultaneously recorded PaCO2 values obtained during sleep in patients undergoing nocturnal polysomnography. Data were collected using three commercially available brands of tcPCO2 monitors (capnograph R, n = 17 patients; capnograph S, n = 17; and capnograph N, n = 15). RESULTS: Accuracy of PETCO2--There was significant scatter in the PaCO2 vs PETCO2 relationship such that only 23 percent of the variability in PaCO2 was explained by variation of PETCO2 during condition 1 and only 15 percent and 20 percent of the variability in PaCO2 was explained by variation of PETCO2 during conditions 2 and 3, respectively. 21.3 percent of patients had average PETCO2 values in error by > 10 mm Hg during condition 1, while during conditions 2 and 3, 46.2 and 63.7 percent of patients had average values in error by > 10 mm Hg, respectively. Accuracy of tcPCO2--While capnographs S and N generally overestimated PaCO2 with a wide scatter, capnograph R tended to have offsetting overestimations and underestimations of PaCO2 with a wide scatter. With each capnograph, a relatively small portion of the variability of the PaCO2 was explained by variability of the tcPCO2 (r2 = 0.2, 0.45 and 0.64 for capnographs S, N, and R, respectively). Across the three capnographs, 43.1 to 66.7 percent of measurements were in error by > 10 mm Hg, and 5 to 20 percent of measurements reflected errors > 20 mm Hg. There was no consistent relationship between the tcPCO2 error and the level of PaCO2, nor was the tcPCO2 error consistent in individual patients. There was no relationship between tcPCO2 accuracy and body mass index. CONCLUSION: Neither PETCO2, measured within a face mask, nor tcPCO2 is a consistently accurate reflection of PaCO2. This limits the utility of these variables in monitoring patients during diagnostic and therapeutic sleep studies, and in particular, during trials of nocturnal ventilatory assistance where adequate levels of support are to be established and unacceptable hyperventilation and respiratory alkalosis must be recognized.

Two-dimensional viscous froth model for foam dynamics.

The two-dimensional viscous froth model is a simple tractable model for foam rheology and coarsening. It includes, but is not confined to, the quasistatic regime. Here we present a detailed analysis and implementation of the model, illustrated with various examples. With certain simplifying assumptions, it provides significant insight into strain-rate-dependent effects in foam rheology and elsewhere, particularly in relation to recent experiments.

Kinetics of intravenous L-lactic acid in anaesthetized minipigs under normoxic/normocapnic/normohydrogenaemic conditions.

A mild and transitory increase in L-lactic acid (LAC) levels can be achieved by LAC infusion under normoxic/normocapnic/normohydrogenaemic conditions. This increase is probably sufficient to confer some protection to cholinesterases from inhibition by organophosphates.

L-lactate reduces in vitro the inhibition of butyrylcholinesterase (BChE) by paraoxon (E 600).

Intoxication with the organophosphorus compound paraoxon (POX), an inhibitor of serine hydrolases, is frequent. Oximes are the only enzyme reactivators clinically available. Serendipitous observation led us to the hypothesis that lactate might attenuate some of the POX effects. In vitro effects of lactate on the inhibition of butyrylcholinesterase (BChE) by POX were assessed in plasma of 12 healthy human volunteers. The determinations were repeated using different lactate and different POX concentrations. The BChE activity determinations were performed in the following settings: (i) baseline untreated plasma (BL); (ii) after addition of POX to plasma (pl+POX); (iii) after POX and plasma were incubated and then lactate was added (pl+POX/lact); (iv) after addition of lactate to plasma (pl+lact); (v) after lactate and plasma were incubated and then POX was added (pl+lact/POX); (vi) after lactate and POX were incubated and then added to plasma (lact+POX/pl). In the micro- and millimolar ranges, lactate is able to abolish in vitro the inhibition of BChE by POX in human plasma when added to plasma prior to POX or when incubated with POX prior to addition to plasma. Lactate added to plasma after POX has no protective effect. In a second set of experiments, the effect of lactate on BChE activity was determined. At high millimolar concentrations, lactate itself inhibits BChE to an extent comparable to POX. Lactate is a mixed inhibitor of BChE, being able to interfere with the enzyme-substrate complex (inhibition constant for the enzyme-inhibitor-substrate complex K'I(EIS) = 81 mM) and the enzyme (inhibition constant for the enzyme-inhibitor complex K(I) (EI) = 26 mM).

Diagnosis of sleep-disordered breathing by half-night polysomnography.

We hypothesized that sleep-disordered breathing (SDB), defined by the apnea index (AI), the apnea + hypopnea index (A + H/I), or the desaturation event frequency (number of desaturations greater than 5%/h slept) (DEF), could be diagnosed after less than full-night polysomnography (PSG). Forty-eight consecutive full-night PSG sessions were evaluated by separately analyzing the first half (PSG-1/2) and the total (PSG-T) sleep time: 134.42 +/- 35.7 and 277.15 +/- 56.5 min (mean +/- SD), respectively. PSG-1/2 and PSG-T were not different with respect to AI. The DEF was statistically but not clinically higher during PSG-1/2 (41.72 +/- 41 versus 37.95 +/- 35.8, p = 0.04). Sensitivities, specificities, and predictive values of each PSG-1/2 parameter were determined by comparing the values with those measured during PSG-T, using cutoff frequencies of both 5 and 10 events/h slept to define SDB. At a cutoff frequency of 10, sensitivities and positive predictive values were high for all PSG-1/2 parameters (range, 94.6 to 96.9%). The specificities of the DEF and AI during PSG-1/2 were also high (93.75 and 95%, respectively), but the negative predictive value of the DEF was substantially better (93.75 versus 83.3%). With SDB defined by 5 events/h slept, there also were high sensitivities (87.9 to 93%), positive predictive values (93.6 to 100%), and specificities (86.7 to 100%) for all parameters. Negative predictive values, however, were substantially reduced (62.5 to 76.5%). We conclude that PSG during 2 h of sleep is an appropriate method for evaluating SDB.(ABSTRACT TRUNCATED AT 250 WORDS)

Paraoxon sensitive phenylvalerate hydrolase in assessing the severity of acute paraoxon poisoning.

INTRODUCTION: Intoxications with organophosphorous compounds, especially paraoxon, are frequent. Organophosphorous compounds inhibit serine hydrolases such as acetylcholine, butyrilcholine, and carboxyl esterases although acetylcholine and butyrylcholine are too sensitive to paraoxon to be useful markers of severity. They cannot show a dose-dependent inhibition during an acute organophosphorous compounds exposure because maximal enzyme inhibition is reached at very low organophosphorous compounds concentrations. PURPOSE: To determine in vitro the dose-effect relationship between the activity of the paraoxon-sensitive phenylvalerate hydrolase, a member of the carboxvl esterases family, and the paraoxon dose, and to assess its utility as a putatively less sensitive enzyme marker to monitor the severity of an acute paraoxon intoxication. MATERIALS AND METHODS: Phenylvalerate hydrolase and butyrylcholine activities were determined in serum of nine healthy human volunteers before and after addition of different concentrations of paraoxon. The determination of phenyl-valerate hydrolase activity was carried out using a modification of the method described by Johnson. A commercially available kit was used to measure butyrylcholine activity. RESULTS: Paraoxon inhibits phenyl-valerate hydrolase activity at concentrations above 10 M. Maximal inhibition (approximately 50% of baseline) is achieved at concentrations above 2.5 x 10(-7) M. The IC50 value of paraoxon for phenyl-valerate hydrolase is 34+/-2 nM. The uninhibited phenyl-valerate hydrolase activity is due to paraoxon-resistent isoforms. Paraoxon begins inhibiting butyrylcholine activity at concentrations above 10(-9) M. At concentrations above 5 x 10(-5) M, no butyrylcholine activity is measulrable. The IC50 value of paraoxon for butyrylcholine is 150+/-23 nM. CONCLUSION: The paraoxon-sensitive subunit of phenyl-valerate hydrolase shows dose-dependent inhibition when exposed to paraoxon in vitro, but it is even more sensitive than butyrylcholine to paraoxon inhibition. Determinations of phenyl-valerate hydrolase activity to assess the severity of an acute organophosphorous compounds poisoning cannot be recommended, but phenyl-valerate hydrolase may have utility in worker surveillance.

Adequacy of prescribing positive airway pressure therapy by mask for sleep apnea on the basis of a partial-night trial.

We tested the hypothesis that a prescription for positive-pressure therapy (including pressure level, patient-device interface, and positive-pressure modality, e.g., CPAP or BiPAP) for obstructive sleep apnea (OSA) can be developed on the same night as the polysomnographic (PSG) diagnosis is made. Fifty consecutive patients with OSA in whom a partial-night PSG diagnosis was made (PSGD) underwent a therapeutic trial of positive-pressure therapy during the remainder of the night (PSG-PPP). The average apnea index during PSGD was 54.96 +/- 36.3 (mean +/- SD). On a subsequent full-night PSG (PSG-PPF), the prescription was tested. Thirty-one of the 50 patients were satisfactorily treated with CPAP, without variation of the interface during both PSG-PPP and PSG-PPF. In these patients the average pressure prescription while receiving PSG-PPF was statistically higher than during PSG-PPP (11.77 +/- 3.6 versus 10.56 +/- 3.6 cm H2O, respectively, p = 0.002). In 14 of these 31 patients (45%) some alteration in pressure requirement was necessary during PSG-PPF. Eleven patients required 2.5 cm H2O higher pressure and three patients required 5 cm H2O higher pressure during PSG-PPF than during PSG-PPP. There was a change of interface across the two therapeutic trials in 15 patients.(ABSTRACT TRUNCATED AT 250 WORDS)