Exploring National Trends and Organizational Predictors of Violence and Mistreatment From Patients and Visitors.

GOAL: Rising incidents of violence and mistreatment of healthcare workers by patients and visitors have been reported. U.S. healthcare workers are five times more likely to experience nonfatal workplace violence (WPV) than workers in any other profession. However, less is known about the national trends in the incidence of violence and mistreatment in healthcare. The specific organizational and individual-level factors that relate to stress arising from these occurrences specifically by patients and family members are also not fully understood. The goals of this study were to examine national trends of violence toward healthcare workers, understand which populations are most vulnerable to stress from violence and mistreatment, and explore organizational factors that are related to these occurrences. METHODS: Data were collected from three sources: (1) The Bureau of Labor Statistics Intentional Injury by Another Person data for the period 2011-2020, (2) data from a large national workers' compensation claim services provider for the period 2018-2022, and (3) results from a survey distributed at a large medical center in June and July 2022. Data were represented graphically and analyzed using multivariate regression and dominance analysis to identify specific predictors of WPV and mistreatment among healthcare workers. PRINCIPAL FINDINGS: Of the total surveyed sample, 23.7% of participants reported mistreatment from patients or visitors as a major stressor and 14.6% reported WPV from patients or visitors as a major stressor. Stress from mistreatment and WPV was most frequently reported by nurses, employees aged 18 to 24 years other than nurses, those who identified as White, and those who identified as female or a gender minority. The emergency room (ER) showed the highest percentages of stress from mistreatment (61.8%) and violence (55.9%) from patients or visitors. The top predictors of stress from WPV and mistreatment by patients or visitors among healthcare workers ranked high to low were working in the ER, working as a nurse, a lack of necessary supplies or equipment, patient or visitor attitudes or beliefs about COVID-19, and working in a hospital-based unit. PRACTICAL APPLICATIONS: In addition to protecting employees as a moral imperative, preventing WPV is critical for organizational performance. Employee productivity is estimated to decrease up to 50% in the 6 to 18 weeks following an incident of violence, while turnover can increase 30% to 40%. An effective WPV prevention plan and a proactive approach to supporting the physical and mental health conditions that may result from WPV can mitigate the potential costs and exposures from these incidents. Organizations must also set clear expectations of behavior with patients and visitors by refusing to tolerate violence and mistreatment of caregivers. The impact of WPV can remain present and active for up to 8 years following an incident. Policy-level interventions are also needed. Currently, there are no federal protections for healthcare workers related to violence, though some states have made it a felony to abuse healthcare workers.

[Sepsis with hemolysis due to a liver abscess in a 60-year-old male patient]. / Sepsis mit Hämolyse im Rahmen eines Leberabszesses bei einem 60-jährigen Patienten.

Many cases of Clostridium perfringens sepsis prove to be fatal. We present a case of C. perfringens sepsis with a liver abscess as the focus of infection, which was successfully treated by an interdisciplinary intensive medical care management. The sepsis with this rare pathogen was favored by the presence of a bilioenteric anastomosis and immunosuppressive treatment of a pre-existing Crohn's disease. Antibiotic treatment with clindamycin and penicillin G was initiated and the abscess was drained. Hemodialysis with high cut-off filters was started because of acute kidney failure in the Acute Kidney Injury Network (AKIN) stage III, hemolysis and rhabdomyolysis. Therapeutic plasma exchange was performed due to sepsis and acute liver failure.

[Diagnosis and treatment of kidney involvement in plasma cell diseases : Renal involvement in multiple myeloma and monoclonal gammopathies]. / Diagnose und Therapie der Nierenbeteiligung bei Plasmazellerkrankungen : Renale Beteiligung bei multiplem Myelom und monoklonalen Gammopathien.

BACKGROUND: Kidney involvement is a common complication in patients with plasma cell diseases. OBJECTIVE: This article outlines the spectrum of renal involvement in plasma cell dyscrasia and describes diagnostic and therapeutic measures to guide clinical management. MATERIAL AND METHODS: Evaluation and discussion of the current literature as well as existing guidelines and recommendations of professional societies. RESULTS: The clinical manifestations of renal involvement in plasma cell disorders are heterogeneous and range from acute cast nephropathy in multiple myeloma to rare forms of glomerulonephritis. The term monoclonal gammopathy of renal significance (MGRS) was introduced to describe kidney involvement caused by monoclonal gammopathy but without evidence for underlying malignancy. Light chain cast nephropathy is the most common renal manifestation in multiple myeloma, whereas monoclonal immunoglobulin deposition disease (MIDD) and renal light chain (AL) amyloidosis can be found in multiple myeloma and MGRS. Decisive is the extended hematological diagnostics in order to exclude the presence of a hematological neoplasm. The treatment of renal involvement in monoclonal gammopathies involves the reduction of the plasma cell clone with cytoreductive treatment. The reduction of the monoclonal protein in serum is prognostically relevant for the renal response to treatment. In the case of histological evidence of a light chain cast nephropathy, high cut-off dialysis is recommended to reduce the free light chains in serum. CONCLUSION: The spectrum of renal manifestations in plasma cell dyscrasia has been expanded, particularly since the introduction of the term MGRS. Diagnostic and therapeutic management remain an interdisciplinary challenge.

[Fomepizole, ethanol or dialysis in the case of life-threatening ethylenglycol intoxication?] / Fomepizol, Ethanol oder Dialyse bei lebensbedrohlicher Ethylenglykolvergiftung?

The EXTRIP (EXtracorporeal Treatments In Poisoning) workgroup is a collaborative international effort of pharmacologists, toxicologists, critical care physicians and nephrologists reviewing all available evidence in extracorporeal procedures for the treatment of intoxications in a standardized way to distill treatment recommendations for the physician at the bedside. The second round of guidelines will include recommendations for ethylenglycol intoxication. The case reported here is of a 60-year old man with a body weight of 65 kg who ingested approximately half a bottle (500 mL) of Aral Antifreeze in a suicidal attempt and presented around 12 h later with severe metabolic acidosis (venous blood gas analysis: pH 7.13; lactate 30 mmol/l, anion gap 23.3 mmol/l). As fomepizole, the inhibitor of the alcohol dehydrogenase, was not readily available, therapy with intermittent hemodialysis was started, as well as ethanol infusion. The first available ethylenglycol concentration before prolonged intermittent hemodialysis was 1230 mg/L. The total removed amount of ethylenglycol during intermittent hemodialysis, as well as following prolonged intermittent renal replacement therapy, was quantified (102 and 65 g). Based on this case report, the new EXRIP recommendations for the role of extracorporeal treatment in the case of ethylenglycol intoxication are discussed.

Melkersson-Rosenthal syndrome in the context of sarcoidosis: a case report.

BACKGROUND: Melkersson-Rosenthal syndrome is a rare disease characterized by the triad of recurrent orofacial swelling with facial paralysis and fissured dorsal tongue. Histologically, noncaseating granulomatous inflammation occurs that confirms the diagnosis. Overlaps between granulomatous diseases such as sarcoidosis and Crohn's disease are described. Systemic corticosteroid therapy is the treatment of choice for acute attacks. CASE PRESENTATION: We here present a case of a 59-year-old White woman suffering from Melkersson-Rosenthal syndrome with a past history of sarcoidosis on therapy with leflunomide in combination with low-dose tacrolimus successfully treated with the anti-leprosy drug clofazimine after failure of systemic steroid therapy. CONCLUSIONS: We propose clofazimine as an alternative treatment in steroid-refractory cases.

Irradiation Effects in Glasses: Suppression by Synthesis under High-Pressure Hydrogen.

Glasses synthesized under high pressure of hydrogen showed resistance to certain effects of irradiation. Paramagnetic and light-absorption effects associated with irradiated glasses were diminished by a factor as large as 20 in some glasses. Irradiation increases the concentration of hydroxyl ions, as evidenced by increased absorption in the 2.7-micron (3700 cm(-1)) infrared region for hydrogen-silica glasses.

Pharmacophore-guided lead optimization: the rational design of a non-zinc coordinating, sub-micromolar inhibitor of the botulinum neurotoxin serotype a metalloprotease.

Botulinum neurotoxins, responsible for the neuroparalytic syndrome botulism, are the deadliest of known biological toxins. The work described in this study was based on a three-zone pharmacophore model for botulinum neurotoxin serotype A light chain inhibition. Specifically, the pharmacophore defined a separation between the overlaps of several different, non-zinc(II)-coordinating small molecule chemotypes, enabling the design and synthesis of a new structural hybrid possessing a Ki=600 nM (+/-100 nM).

Studies of fluoride-preactivated rabbit liver adenylyl cyclase.

Rabbit liver adenylyl (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) cyclase was stimulated by preincubation with F- and Mg2+ and the stimulation persisted despite extensive washing and/or detergent solubilization. Optimum preactivation conditions were found to be 4 mM NaF and 2 mM MgCl2; higher or lower concentrations produced submaximum stimulation regardless of preincub ation time. In addition to an enhanced catalytic acticity, the activated enzyme also exhibited different responses to Ca2+ and Cu2+ when compared to the basal enzyme. ATP caused a time-dependent inhibition that could be partially prevented or reversed by F-, but was not completely reversed by washing. This inhibition was not observed when 5'-adenosine(beta, gamma-imide) triphosphate blocks inhibition by ATP. The results support, but do not prove, the proposed molecular basis of F- activation which entails a phosphorylation-dephosphorylation mechanism.

[Successful hemodialysis for life-threatening carbamazepine drug overdose: Case-based introduction of new guidelines]. / Erfolgreiche Hämodialyse bei lebensbedrohlicher Carbamazepinintoxikation : Vorstellung neuer Leitlinien anhand eines Fallberichts.

BACKGROUND: Over the last decade, there has been a paradigm shift in the extracorporeal treatment of intoxications. The availability of new treatment options, especially new membranes has led to a decrease in the use of techniques like charcoal hemoperfusion, once considered the gold standard to eliminate highly protein bound substances. EXTRIP GUIDELINES: The EXtracorporeal Treatments In Poisoning (EXTRIP) workgroup is a collaborative international effort of pharmacologists, toxicologists, critical care physicians, and nephrologists that is reviewing all available evidence in extracorporeal procedures for the treatment of poisonings in a standardized way to distill treatment recommendations for the physician at the bedside. One of the first available EXTRIP guidelines summarizes treatment recommendations for severe carbamazepine intoxications. CASE REPORT: We report the case of a 43-year-old Caucasian woman with who ingested about 21 g carbamazepine in a suicidal attempt together with alcohol. Combining gastroscopic removal of carbamazepine and multiple dose activated charcoal with intermittent high-flux hemodialysis lowered the initial carbamazepine level of 56.5 mg/l (47 mg/l before dialysis) to 25 mg/l. The patient, who initially required mechanical ventilation could be transferred to the psychiatric ward 24 h after ICU admission.

Sequence and analysis of the DNA encoding protective antigen of Bacillus anthracis.

The nucleotide sequence of the protective antigen (PA) gene from Bacillus anthracis and the 5' and 3' flanking sequences were determined. PA is one of three proteins comprising anthrax toxin; and its nucleotide sequence is the first to be reported from B. anthracis. The open reading frame (ORF) is 2319 bp long, of which 2205 bp encode the 735 amino acids of the secreted protein. This region is preceded by 29 codons, which appear to encode a signal peptide having characteristics in common with those of other secreted proteins. A consensus TATAAT sequence was located at the putative -10 promoter site. A Shine-Dalgarno site similar to that found in genes of other Bacillus sp. was located 7 bp upstream from the ATG start codon. The codon usage for the PA gene reflected its high A + T (69%) base composition and differed from those of genes for bacterial proteins from most other sequences examined. The TAA translation stop codon was followed by an inverted repeat forming a potential termination signal. In addition, a 192-codon ORF of unknown significance, theoretically encoding a 21.6-kDa protein, preceded the 5' end of the PA gene.

Type A botulinum neurotoxin proteolytic activity: development of competitive inhibitors and implications for substrate specificity at the S1' binding subsite.

Type A botulinum neurotoxin (botox A) is a zinc metalloprotease that cleaves only one peptide bond in the synaptosomal protein, SNAP-25. Single-residue changes in a 17-residue substrate peptide were used to develop the first specific, competitive inhibitors of its proteolytic activity. Substrate analog peptides with P4, P3, P2' or P3' cysteine were readily hydrolyzed by the toxin, but those with P1 or P2 cysteine were not cleaved and were inhibitors. Peptides with either D- or L-cysteine as the N-terminus, followed by the last six residues of the substrate, were the most effective inhibitors, each with a Ki value of 2 microM. Elimination of the cysteine sulfhydryl group yielded much less effective inhibitors, suggesting that inhibition was primarily due to binding of the active-site zinc by the sulfhydryl group. Botox A displayed an unusual requirement for arginine as the P1' inhibitor residue, demonstrating that the S1' binding subsite of botox A is dissimilar to those of most other zinc metalloproteases. This characteristic is an important element in shaping the substrate specificity of botox A.

Passive immunization of Ebola virus-infected cynomolgus monkeys with immunoglobulin from hyperimmune horses.

A commercially available immunoglobulin G (IgG) from horses, hyperimmunized to Ebola virus, was evaluated for its ability to protect cynomolgus monkeys against disease following i.m. inoculation with 1 000 PFU Ebola virus (Zaire '95 strain). Six monkeys were treated immediately after infection by i.m. infection of 6.0 ml IgG; these animals developed passive ELISA titers of 1:160 to 1:320 to Ebola, two days afer inoculation. However, the beneficial effects of IgG treatment were limited to a delay in onset of viremia and clinical signs, in comparison with untreated controls. The six IgG recipients had no detectable viremia day 5, in contrast with three virus infected controls whose viremias exceeded 7.0 log10 PFU/ml that day. The controls died on days 6, 6, and 7, while two IgG recipients died day 7 and the remaining 4 died day 8, all with high viremias. These results document that passively acquired antibody can have a beneficial effect in reducing the viral burden in Ebola-infected primates; however, effective treatment of human patients may require antibodies with higher specific activities and more favorable pharmacokinetic properties than the presently available equine IgG.

In vivo spectrometric calcium flux recordings of intrinsic Caudate-Putamen cells and transplanted IMR-32 neuroblastoma cells using miniature fiber optrodes in anesthetized and awake rats and monkeys.

A method is described to enable the recording of transient intracellular calcium changes in deep brain structures in anesthetized and awake animals using a fluorescent indicator combined with in vivo optical detection methods. Optrodes were fabricated using a bifurcated fiber-optic cable with an attached infusion guide cannula. After intracranial implantation of an optrode, animals were prepared in the following manner, (1) rats (intra-striatal) and monkeys (intra-putamen) were infused with the fluorescent calcium indicator, Oregon Green, to load intrinsic cells; or (2) rats were intra-striatally transplanted with a slurry of dye-loaded IMR-32 neuroblastoma cells via pipette ejection. Excitation light from an argon-ion laser was launched through the optrode and passed into the tissue. The resulting calcium-induced fluorescence signals were captured by the optrode, then detected and processed by externalized photomultiplier- and CCD-based spectrometer electronics. In approximately 25% of all intrinsic cell recordings, the baseline fluorescence intensity was relatively stable over time whereas in the remainder, large amplitude oscillations were observed with a frequency in the range of 0.5-2 Hz. These Ca(2+) transients were inhibited by local infusion of 10 microM omega-conotoxin MVIIC and 1 microM TTX. Extracellular electrophysiological recordings that were made adjacent to the optrode tip revealed that the Ca(2+) oscillations were in phase with the burst firing of striatal neurons. This suggested that the optical signals had a neuronal origin, most likely from medium spiny neurons. Baseline fluorescence intensity increased during infusion of high [K(+)](o), the calcium ionophore, A-23187, or during temporary bilateral carotid artery occlusion. Monkey (Saimiri sciureus) putamen recordings also affirmed the presence of similar calcium-related transients in a non-human primate. In the transplant preparations, the IMR-32 cells displayed a stable, non-oscillating baseline fluorescence. They were similarly responsive to high [K(+)](o) challenge and appeared viable for at least several hours. Similar optical recording approaches might be applied to monitor other fluorescent, chemiluminescent or bioluminescent events from almost any brain structure. Moreover, transplanted transfected cells expressing a single specific receptor or ion-channel protein may effectively serve as biosensing elements for the measurement of extracellular neurochemical signaling.

Structure-function studies of waglerin I, a lethal peptide from the venom of Wagler's pit viper, Trimeresurus wagleri.

Waglerins are 22-24 residue lethal peptides, found in the venom of Trimeresurus (Tropidolaemus) wagleri. The effects upon lethality and immunoreactivity resulting from structural modifications of these peptides were studied. A synthetic analogue with alanine residues in place of the two half-cystines of native peptide was nontoxic, suggesting that the single intramolecular disulfide bond in waglerins is critical for bioactivity. Substituting glutamic acid for aspartic acid at residue 5 slightly diminished lethality. Analogues containing asparagine instead of aspartic acid at residue 5 and/or a carboxamide- instead of a carboxy-terminus were lethal, demonstrating that neither a negative charge on residue 5 nor on the carboxy-terminus was required for bioactivity. A proteolytic fragment of waglerin I containing residues 6-22 was isolated and proved nontoxic. Therefore, one or more of the first five residues were necessary for bioactivity. Antiserum against waglerin I bound strongly to waglerins I, II, and SL-I, and to various analogues, proteolytic fragments, and chemically modified waglerin I. These findings suggest that the antibodies might be directed mainly against short, linear epitopes, implying an extended conformation for waglerin I.

Purification, sequencing and characterization of pseudexin phospholipases A2 from Pseudechis porphyriacus (Australian red-bellied black snake).

Pseudexin is the name given to a mixture of toxic phospholipase A2 isoenzymes isolated from the venom of the Australian red-bellied black snake, Pseudechis porphyriacus. We found that this mixture consists of three components: pseudexins A, B and C, which we individually purified by reverse phase chromatography or by hydrophobic interaction chromatography. Pseudexins A and B had relatively low specific toxicities in mice (i.p. LD50 of 1300 and 750 micrograms/kg, respectively), while C was non-toxic. All three had similar phospholipase A2 activities (43-53 muequiv H+ released/min/mg protein). The complete amino acid sequences of pseudexins A and B were determined. Amino acids were identical at 91 of the 117 residues. The first 28 residues of pseudexin C were determined, sufficient to show that C is structurally similar to A and B, but not identical with either. As judged by reactions with antisera against several other snake phospholipase A2 toxins, pseudexins A, B and C have very similar antigenic structures. We noted extensive homology with other phospholipases.

Cloning and nucleotide sequences of crotamine genes.

A cDNA library containing snake toxin genes was constructed in bacteriophage lambda by using mRNA isolated from the glands of the South American rattlesnake, Crotalus durissus terrificus. The first high-density screening of 400,000 plaques for crotamine-containing genes yielded over 800 positives when a labeled cDNA probe with sequence homology to crotamine was used. Four of these clones with insert sizes from 270 to 400 base pairs were chosen and their inserts subcloned into pGEM-3Z and sequenced. Nucleotide sequence analysis of the cloned cDNAs predicted the existence of multiple variants of the crotamine toxin. The different forms, identified from the DNA sequences, displayed discrepancies in amino acid sequence for crotamine when compared with previously published reports. Direct amino acid sequencing of commercially purified crotamine and CNBr fragments thereof confirmed the structures predicted by the nucleic acid sequences.

Lethal toxins and cross-neutralization of venoms from the African water cobras, Boulengerina annulata annulata and Boulengerina christyi.

Venoms of the water cobras, Boulengerina, were assayed for lethality, proteolytic activity and protein content. Boulengerina annulata annulata and B. christyi venoms averaged 89% protein and lacked proteolytic activity. The murine i.p. LD50 of B. a. annulata and B. christyi venoms were 0.143 and 0.120 mg/kg, respectively. Polyvalent antivenom produced by the South African Institute of Medical Research neutralized 575 and 200 LD50 of B. a. annulata and B. christyi venoms/ml antivenom, respectively. Cation exchange chromatography resolved four lethal peaks from B. a. annulata venom and six lethal peaks from B. christyi venom. The major lethal peaks (about 12% of total venom protein) were purified further with molecular sieve chromatography and were characterized as 61 (B. a. annulata toxin) and 62 (B. christyi toxin) residue polypeptides with four half-cystines. Elucidation of the complete amino acid sequences indicated that these toxins belonged to the short-chain class of postsynaptic neurotoxins. Short-chain neurotoxins 1 from B. a. annulata and B. christyi had murine i.p. LD50 of 0.052 and 0.083 mg/kg, respectively, and showed over 80% homology with N. nigricollis alpha toxin. Reverse-phase analysis of another peak present in both venoms resolved a toxin that had an N-terminus identical to B. christyi short-chain neurotoxin 1. These fractions also contained toxins readily separable from the short-chain isotoxin by preparative reverse-phase chromatography. Amino acid sequencing of the first 28 residues indicated that both toxins were long-chain neurotoxins with identical N-termini. The LD50 of long-chain neurotoxins 2 from B. a. annulata and B. christyi venoms were 0.086 and 0.090 mg/kg, respectively. The venoms of these little-known elapids have the lowest LD50 of any African proteroglyph studied thus far and have high concentrations of potent postsynaptic neurotoxins.

Molecular properties and structure-function relationships of lethal peptides from venom of Wagler's pit viper, Trimeresurus wagleri.

Two new lethal peptides (waglerins) were purified from the venom of Trimeresurus wagleri, and sequenced. We found them to be analogs of lethal peptides (waglerins) I and II reported previously (Weinstein et al., Toxicon 29, 227-236, 1991), with an additional Ser-Leu on the amino terminus. Three of the four waglerins were synthesized and the products were chemically and biologically equivalent to the naturally occurring counterparts in venom. Murine i.p. LD50 for synthetic waglerins I, SL-I and II were 0.33, 0.22, and 0.51 mg/kg, respectively. The single, intramolecular disulfide bond in each synthetic peptide formed rapidly in high yield. The reduced (cysteine-containing) forms of the peptides appeared to have significant toxicities, even without prior disulfide bond formation, but synthetic analogs with serine substituted for cysteine were not toxic. The synthetic dimer of waglerin I, formed by two intermolecular disulfide bonds, was not toxic, but rapidly rearranged to lethal, monomeric waglerin I at alkaline pH upon the addition of 5 mM beta-mercaptoethanol. Waglerin I was inactivated by cleavage at Tyr-15 with chymotrypsin.

Characterization and amino acid sequences of two lethal peptides isolated from venom of Wagler's pit viper, Trimeresurus wagleri.

Two lethal toxins were isolated from Trimeresurus wagleri venom by fast protein liquid chromatography (molecular sieve) and high performance liquid chromatography (reverse phase). The toxins (termed peptide I and II) had mol. wt of 2504 and 2530, respectively, pIs of 9.6-9.9 and lacked phospholipase A, proteolytic, and hemolytic activity. Lethal peptide I had a murine i.p. LD50 of 0.369 mg/kg, while lethal II had a murine i.p. LD50 of 0.583 mg/kg. Peptide I retained full toxicity after autoclaving at 121 degrees C for 40 min. The lethal activity was found to represent less than 1% of the total venom protein, which was only 62-65% of crude venom. The amino acid sequence of peptide I revealed a proline-rich (over 30% of total sequence) sequence unique among snake venom toxins. Lethal peptide II showed the same sequence except for a second tyrosine in the position of histidine (residue No. 10) in peptide I. The toxin lacked antigenic identity with a number of representative neurotoxins and myotoxins. The crude venom shared at least one antigen with Crotalus scutulatus scutulatus venom. This antigen was not Mojave toxin. The toxin appears symptomatologically suggestive of a vasoactive peptide or neurotoxin.