Toxicity of muscimol and ibotenic acid containing mushrooms reported to a regional poison control center from 2002–2016

Background: Amanita muscaria (AM) and A. pantherina (AP) contain ibotenic acid and muscimol and may cause both excitatory and sedating symptoms. Gastrointestinal (GI) symptoms are not classically described but have been reported. There are relatively few reported cases of poisoning with these mushrooms in North America.

Methods: This is a retrospective review of ingestions of ibotenic acid and muscimol containing mushrooms reported to a United States regional poison center from 2002–2016. Cases were included if identification was made by a mycologist or if AM was clearly described.

Results: Thirty-four cases met inclusion criteria. There were 23 cases of AM, 10 AP, and 1 A. aprica. Reason for ingestion included foraging (12), recreational (6), accidental (12), therapeutic (1), self-harm (1), and unknown (2). Of the accidental pediatric ingestions 4 (25%) were symptomatic. None of the children with a symptomatic ingestion of AM required admission. A 3-year-old male who ingested AP had vomiting, agitation, and lethargy and received benzodiazepines. He was intubated and had a 3-day ICU stay. There were 25 symptomatic patients. All but one patient developed symptoms within 6?h. Six patients had symptoms for less than 6?h while 15 had symptoms lasting less than 24?h. Ingestions of AP were more symptomatic than AM with regard to the presence of any GI symptoms (80% vs. 35%), central nervous system (CNS) depression (70% vs. 35%), and CNS excitation (70% vs. 35%) respectively. Five patients were intubated. No patients experienced hypotension, seizures, acute kidney injury, or hepatotoxicity. No deaths were reported.

Discussion: Ingestion of ibotenic acid/muscimol containing mushrooms often produces a syndrome with GI upset, CNS excitation, and CNS depression either alone or in combination. Ingestion of AP was associated with a higher rate of symptoms compared to AM.     

Clinical and analytical features of severe suicidal quetiapine overdoses – a retrospective cohort study

Context. Detailed data on severe overdoses with quetiapine are relatively sparsely reported in the literature. Objective. To describe a cohort of 20 acute quetiapine overdoses and provide additional data on the pharmacokinetics and clinical features of intoxication with this drug. Material and methods. A retrospective study was conducted on patients with quetiapine poisoning admitted to our institution. We included moderate to severe overdoses between 2005–2011 who required admission to ICU. Results. Predominantly female patients (n = 17) ingested a median dose of 9.8 g quetiapine. Poison Severity Score was moderate in 9 patients, severe in 10 patients and in one case fatal. Quetiapine was analytically confirmed in all cases. Clinical manifestations included drowsiness or coma (all patients), tachycardia (12 patients) and hypotension (10 patients). Seizures and arrhythmia occurred in 4 patients, each. Intubation and mechanical ventilation was required in 14 patients due to seizures, respiratory depression or loss of airway protection and 15 patients developed pneumonia. Hypokalaemia and hyperglycaemia were present at admission in 10 and 5 patients, respectively. Despite frequent prolongation of the QT_c in 13 patients, QT interval was normal in most cases and QRS-interval was prolonged in only one patient. Presumably anticholinergic delirium was recognised in 8 patients and 6 patients received physostigmine with good clinical response. In 13 cases quetiapine was analysed quantitatively in serum with a relevantly prolonged half-life (16 ± 12 h) and a median peak serum concentration of 3074 ng/mL. In 4 of these 13 patients we observed an increase of quetiapine serum concentration in the further course. Conclusion. In this study, quetiapine overdoses were associated with significant toxicity and a fairly high number of complications. A careful and often prolonged clinical observation in the more severe cases of overdose seems mandatory.     

Fractures diagnosed in primary care – a five-year retrospective observational study from a Norwegian rural municipality with a ski resort

Abstract

Objective: The aim of this study was to characterize fractures recorded at a Norwegian primary care centre near a ski resort.

Design: A retrospective five-year observational study in the period 2010–2014.

Setting: A primary care centre equipped with an x-ray machine and located near a ski resort in a small rural municipality of 931 inhabitants in Norway. The X-ray images are digitalized and instantly transferred for assessment of a radiologist and/or an orthopedic surgeon both before and after treatment.

Subjects: All patients with radiologically confirmed fractures.

Results: A total of 1154 X-ray examinations were done, out of which 480 (41.6%) were fractures verified by a radiologist. The most frequent fractures were in the wrist (30%), collarbone (15%), shin (11%), humerus (9%) and ankle (8%). 316 (66%) of the fractures were in males and of these 225 were in age group 10–19?years. Males dominated among fractures in collarbone (92% males), finger (80% males), and foot (85% males). Women with fractures of the wrist, ankle, humerus and metacarpal bones, had a higher median age than men with similar fractures. Nonsurgical treatment with cast or braces was initially offered in 371 (77%) of the fracture-cases at the primary care level.

Conclusion: Young men acquired most of the fractures, predominantly in the wrist, and mostly during the winter sport season. Nearly eight of ten fractures were treated locally in primary care centre.

• Key points

• A large seasonal variation was found in number of patients with fractures.

• More than 60% had fractures in the wrist, collarbone, shin or ankle.

• More than half of the patients with a fracture were males and below 20 years old.

• Most fractures were ski-related.

     

Key issues and challenges in developing a pedagogical intervention in the simulation skills center – An action research study

Simulation skills centers (SSC) are considered important learning arenas for preparing and qualifying nursing students. Limited clinical placements and claims of diminished learning opportunities raise concerns that newly educated nurses lack proficiency in many psychomotor skills. Accordingly, there is an increased focus on learning in the SSC. However, it has been questioned if the pedagogical underpinning of teaching and learning in the SSC is missing or unclear. At a bachelor nursing education in Norway, there was a desire to change practice and enhance learning in the SSC by systematic use of The Model of Practical Skill Performance (Bjørk and Kirkevold, 2000). A participatory action research design was chosen. A pedagogical intervention was developed and implemented in 2010 in a cohort of eighty-seven first year bachelor nursing students during their basic nursing skill course. The intervention is shortly described. This article reports key issues and challenges that emerged during development of the new intervention. Data to inform the study were collected via thorough meeting minutes and the project leader's logbook, and analyzed using fieldnotes analysis. Six key issues and challenges were identified. These are presented and discussed consecutively in light of their importance for development and implementation of the new intervention.     

Ultrasonographically detected changes in Achilles tendons and self reported symptoms in elite gymnasts compared with controls – An observational study

There are no published data on the prevalence of Achilles tendinopathy in gymnasts. 40 elite gymnasts and 41 controls of mean (SD) age 16.3 (2.1) years had bilateral AT thickness (at 3 points along the tendon in longitudinal and transverse views) and abnormality measured using ultrasound (US). Data on a history of AT symptoms were gathered using a questionnaire.Among female gymnasts there were 17.5% of Achilles tendons (ATs) with current symptoms, compared with none of the controls (χ² = 6.2, p < 0.05). Similarly, among male gymnasts 12.5% of ATs were currently symptomatic, compared with none of the controls (χ² = 6.62, p < 0.01). US scanning showed gymnasts had significantly (p < 0.001 to p < 0.05) thicker ATs for 5 out of 6 measures, and had more irregular longitudinal AT thickness (p < 0.05). 32.5% of female gymnast ATs had US abnormalities, compared with 6.2% of female control ATs (χ² = 7.43, p < 0.01). Similarly, 35% of male gymnast ATs had US abnormalities, compared with 4% of male control ATs (χ² = 7.43, p = 0 < 01). There was no relationship between AT symptoms and US-detected abnormalities in the gymnasts. Achilles tendinopathy is a common problem in gymnasts. The poor correlation between signs and symptoms suggests pathology is not always symptomatic.     

Disparity between skin perfusion and sublingual microcirculatory alterations in severe sepsis and septic shock: a prospective observational study

OBJECTIVE: Measurement of central-to-toe temperature difference has been advocated as an index of severity of shock and as a guide for circulatory therapy in critically ill patients. However, septic shock, in contrast to other forms of shock, is associated with a distributive malfunction resulting in a disparity between vascular compartments. Although this disparity has been established between systemic and microcirculatory parameters, it is unclear whether such disparity exists between skin perfusion and microcirculation. To test this hypothesis of disparity, we simultaneously measured parameters of the two vascular compartments, in the early phase of sepsis. DESIGN: Prospective observational study in patients with severe sepsis/septic shock in the first 6 h of ICU admission. Simultaneous measurements of central-to-toe temperature difference and sublingual microcirculatory orthogonal polarization spectral imaging, together with parameters of systemic hemodynamics. SETTING: 22 bed mixed-ICU in a tertiary teaching hospital. PATIENTS: 35 consecutive patients in a 12-month period. MEASUREMENTS AND RESULTS: In 35 septic patients and a median APACHE II score of 20, no correlation between central-to-toe temperature gradient and microvascular flow index was observed (r (s) = -0.08, p =0.65). Also no significant correlation between temperature gradient/microvascular flow index and systemic hemodynamic parameters could be demonstrated. CONCLUSIONS: During the early phase of resuscitated severe sepsis and septic shock there appears to be no correlation between sublingual microcirculatory alterations and the central-to-toe temperature difference. This finding adds to the concept of a dispersive nature of blood flow under conditions of sepsis between microcirculatory and systemic hemodynamics.     

Accidental hypothermia: Factors related to a prolonged hospital stay – A nationwide observational study in Japan

BackgroundThe incidence of accidental hypothermia (AH) is low, and the length of hospital stay in patients with AH remains poorly understood. The present study explored which factors were related to prolonged hospitalization among patients with AH using Japan's nationwide registry data.MethodsThe data from the Hypothermia STUDY 2018, which included patients ≥18 years old with a body temperature ≤ 35 °C, were obtained from a multicenter registry for AH conducted at 89 institutions throughout Japan, collected from December 1, 2018, to February 28, 2019. The patients were divided into a “short-stay patients” group (within 7 days) and “long-stay patients” group (more than 7 days). A logistic regression analysis after multiple imputation was performed to obtain odds ratios (ORs) for prolonged hospitalization with age, frailty, location, causes underlying the hypothermia, temperature, pH, potassium level, and disseminated intravascular coagulation (DIC) score as independent variables.ResultsIn total, 656 patients were included in the study, of which 362 were eligible for the analysis. The median length of hospital stay was 17 days. Of the 362 patients, 265 (73.2%) stayed in the hospital for more than 7 days. The factors associated with prolonged hospitalization were frailty (OR, 2.11; 95% confidence interval [CI], 1.09–4.10; p = 0.027), the occurrence of indoor (OR, 3.20; 95% CI, 1.58–6.46; p = 0.001), alcohol intoxication (OR, 0.17; 95% CI, 0.05–0.56; p = 0.004), pH (OR, 0.07; 95% CI, 0.01–0.76; p = 0.029), potassium level (OR, 1.36; 95% CI, 1.00–1.85; p = 0.048), and DIC score (OR, 1.54; 95% CI, 1.13–2.10; p = 0.006).ConclusionsFrailty, indoor situation, alcohol intoxication, pH value, potassium level, and DIC score were factors contributing to prolonged hospitalization in patients with AH. Preventing frailty may help reduce the length of hospital stay in patients with AH. In addition, measuring the pH value and potassium level by an arterial blood gas analysis at the ED is recommended for the early evaluation of AH.     

The relationship of severe health disorders with bone loss,grip strength,and mobility in postmenopausal women – a 15-year follow-up study

Purpose: To investigate the relationships of severe health disorders (SHD) with bone loss, grip strength (GS) and mobility in postmenopausal women. Method: The study sample consisted of 2227 Finnish women (mean age 53.2) from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) cohort. Postal inquiries and clinical measurements were completed during the 15-year follow-up at 5-year intervals between 1989 and 2004. Femoral neck bone mineral density (BMD) and GS were measured. Life-style factors and mobility were obtained via postal inquiries. Work disability pension according to the ICD-9 was an indicator of a SHD. Results: At the baseline 242 women had SHD, 506 got late SHD during 1989–1995, whereas 1479 women had none until 1996. The women with baseline SHD had higher annual bone loss (0.44%) than those without SHD (0.34%) (p?Conclusion: Effects of SHDs on BMD, GS, and mobility are disease-specific. Thus, rehabilitation should be encouraged in postmenopausal women with SHD, especially in case of diseases of respiratory and nervous system.

• Implications for Rehabilitation

• Osteoporosis, muscle strength and co-morbidity

• Women with severe health disorders (SHD) leading to work disability have impaired musculoskeletal health.

• Active monitoring of the musculoskeletal health is advised for those with SHD.

• Women with SHD may benefit from rehabilitative treatment in order to avoid complications of musculoskeletal impairments.

     

Long-term follow-up of the original interferon-β1b trial in multiple sclerosis: Design and lessons from a 16-year observational study

Objective: This article describes the design of and difficulties inherent in the execution of a long-term, observational trial that sought to assess the validity of short-term measures of multiple sclerosis (MS) (eg, relapse rate, inflammatory lesions) for long-term disease outcomes.Methods: In the original double-blind, placebo-controlled interferon (IFN)-p1b study, 372 patients with relapsing-remitting MS (Expanded Disability Status Scale score 0.0–5.5) were randomly assigned to IFN-β1b 50 ug (n = 125), IFN-β1b 250 μg (n = 124), or placebo (n = 123) for 2 years. These patients were recruited 16 years later for participation in this long-term follow-up (LTF) study, which had no exclusion criteria or drug interventions.Results: The 11 centers identified 88.2% (328/372) of the original study patients at LTF; however, 10.8% (n = 40) refused to participate and 9.4% (n = 35) were deceased. Detailed evaluations were available for 260 patients, which included 7 deceased patients. No differences in demographic or baseline disease characteristics were found between individuals who did and did not participate in the LTF. More patients randomly assigned to placebo in the original trial were deceased (20/123 [16.3%]) than those assigned to IFN-β1b 50 ug (9/125 [7.2%]; uncorrected P = 0.044) or IFN-β1b 250 ug (6/124 [4.8%]; uncorrected P = 0.003).Conclusions: Although most patients (88.2%) were identified at LTF, ascertainment was incomplete. This was attributable to patients' refusal to participate, loss to follow-up, or death. Delays in the registration of death data and recent privacy legislation provided further barriers. Mortality was lower for patients originally randomized to receive IFN-β1b rather than placebo. We recommend that all short-term trials on chronic diseases include provisions for LTF.     

Serological response to tick-borne encephalitis (TBE) vaccination in the elderly – results from an observational study

Background: In the elderly, the incidence of tick-borne encephalitis (TBE) is higher than in younger individuals. At the same time, the responsiveness of the elderly to vaccination may be decreased. Product information for TBE vaccines therefore recommends determining antibody response after two of the three doses required for primary immunization in persons over 60. Objective: To determine the proportion of persons aged 60 years or older with insufficient antibody response after administration of two doses of TBE vaccine. Methods: A retrospective analysis of TBE-specific antibody levels as determined by Immunozym^® ELISA in serum samples of 185 vaccinees > 60 years of age after the first two of the three vaccinations required for primary immunisation. Patients received either FSME-IMMUN Adult or Encepur^® Adults at one vaccination centre in the Czech Republic. In a subset of 80 vaccinees, two additional ELISAs and a neutralization test (NT) were performed. Results: Overall, 33 of the 185 individuals (18%) included in the Immunozym analysis had antibody concentrations below putative protective levels after two doses. Geometric mean concentrations and seropositivity rates were higher in individuals vaccinated with FSME-IMMUN than in those vaccinated with Encepur^®. While the differences in mean antibody levels and/or seropositivity rates in ELISAs for the Neudörfl strain (used in FSME-IMMUN) were significant, no significant differences were obtained for Enzygnost, which uses the Karlsruhe strain (used in Encepur). Conclusions: After two doses of TBE vaccine, one in five persons aged 60 years or older may be without protective antibodies, confirming the importance of testing the antibody response after the second vaccination and administering an additional dose in the event of insufficient response.     

Predictors of response to therapy with omalizumab in patients with severe allergic asthma – a real life study

Objectives: Omalizumab is a recombinant humanized IgG1 monoclonal anti-IgE antibody, used for the treatment of severe refractory allergic asthma. However, not all patients with IgE levels within the limits of administration, respond to treatment. The aim of the present study, was to determine clinical and inflammatory characteristics that could predict response to omalizumab.

Methods: We studied retrospectively patients treated with omalizumab as per GINA guidelines in one asthma tertiary referral center. Demographic and functional characteristics, level of asthma control, fractional exhaled nitric oxide, blood and eosinophils and IgE level, induced sputum cell count, eosinophil cationic protein and Interleukin-13 in sputum supernatant were recorded. All measurements were performed before starting treatment with omalizumab. Response to treatment was evaluated according to the physician’s global evaluation of treatment effectiveness. Patients were characterized as early responders when improvement was achieved within 16 weeks and as late responders when improvement was achieved between 16 and 32 weeks. Patients who did not show any improvement after 32 weeks of therapy were considered as non-responders.

Results: Forty-one patients treated with omalizumab were included in the study. 28 (68.3%) patients were characterized as responders while 13 patients (31.7%) were considered as non-responders. Among responders, 25 (89%) were early responders and 3 (n = 11%) were late responders. Responders were characterized by lower baseline FEV₁ and FEV₁/FVC and higher IL-13 levels in induced sputum supernatant compared to non-responders. Late responders had higher serum IgE levels, shorter disease duration and higher number of blood eosinophils. Finally, using ROC curve analysis, the best predictors of response to omalizumab were FEV₁ (AUC = 0.718) and IL-13 in sputum supernatant (AUC = 0.709).

Conclusion: Lower baseline FEV₁ and higher IL-13 levels in induced sputum supernatant were predictors of response to omalizumab. Patients with higher baseline serum IgE levels, shorter disease duration and higher blood eosinophils may experience a late response and might benefit from a more prolonged treatment before being characterized as non-responders.     

Improvement of antibiotic therapy and ICU survival in severe non-pneumococcal community-acquired pneumonia: a matched case–control study

IntroductionWe aimed to compare intensive care unit mortality due to non-pneumococcal severe community-acquired pneumonia between the periods 2000–2002 and 2008–2014, and the impact of the improvement in antibiotic strategies on outcomes.MethodsThis was a matched case–control study enrolling 144 patients with non-pneumococcal severe pneumonia: 72 patients from the 2000–2002 database (CAPUCI I group) were paired with 72 from the 2008–2014 period (CAPUCI II group), matched by the following variables: microorganism, shock at admission, invasive mechanical ventilation, immunocompromise, chronic obstructive pulmonary disease, and age over 65 years.ResultsThe most frequent microorganism was methicillin-susceptible Staphylococcus aureus (22.1 %) followed by Legionella pneumophila and Haemophilus influenzae (each 20.7 %); prevalence of shock was 59.7 %, while 73.6 % of patients needed invasive mechanical ventilation. Intensive care unit mortality was significantly lower in the CAPUCI II group (34.7 % versus 16.7 %; odds ratio (OR) 0.78, 95 % confidence interval (CI) 0.64–0.95; p = 0.02). Appropriate therapy according to microorganism was 91.5 % in CAPUCI I and 92.7 % in CAPUCI II, while combined therapy and early antibiotic treatment were significantly higher in CAPUCI II (76.4 versus 90.3 % and 37.5 versus 63.9 %; p < 0.05). In the multivariate analysis, combined antibiotic therapy (OR 0.23, 95 % CI 0.07–0.74) and early antibiotic treatment (OR 0.07, 95 % CI 0.02–0.22) were independently associated with decreased intensive care unit mortality.ConclusionsIn non-pneumococcal severe community-acquired pneumonia , early antibiotic administration and use of combined antibiotic therapy were both associated with increased intensive care unit survival during the study period.