Mortality in 497 patients with affective disorders attending a lithium clinic or after having left it

The impact of lithium prophylaxis on mortality has been studied in 497 patients, 405 bipolars and 92 unipolars, who attended the same out-patient lithium clinic for up to 30 years. In order to avoid preselection, no minimum period of lithium treatment was required in our study. Of a total of 6014 patient-years, 4330 were spent in regular contact with the study clinic. General mortality due to natural causes was not significantly increased; among cardiovascular diseases, only pulmonary embolism showed an excess mortality. No patients died of lithium intoxication or chronic renal insufficiency. Patients were divided into three groups: Group A, 277 patients, attended the study clinic until death or the end of the study, Group B, 86 patients, left the clinic but continued to take lithium, and Group C, 134 patients, both left the clinic and stopped taking lithium. Among bipolars, the suicide rate compared to the general population was in excess in all three groups. Among unipolars, suicides occurred only after the patients had left the study clinic and stopped taking lithium. A special analytical method was used for intergroup comparisons of suicide rates. Bipolars in Group A attending the study clinic regularly had a suicide rate of 3.5 per 1000 patient-years. The rate increased to 6.3 or by 80 % if patients had left the clinic and did not take lithium any longer as in Group C. The suicide rate in Group C increased by 45% compared to Group B, patients who left the clinic but continued to take lithium. Our results support the hypothesis that lithium has a significant antisuicidal effect in bipolars as well as in unipolars. The suicide mortality can be further reduced by regular attendance in a specialised mood disorder clinic.     

Impact of Length of Residence in the United States on Risk of Diabetes and Hypertension in Resettled Refugees

The relationship between resettlement and development of chronic disease has yet to be elucidated in refugees. We aimed to assess the relationship between length of residence in the US and development of diabetes and hypertension utilizing multivariable logistic regression models in a sample of former refugee patients seeking primary care services. Multivariable logistic regression models adjusting for age, gender, and country of origin showed significantly increasing odds of type 2 diabetes (OR 1.12, 95% CI 1.03–1.22, p?<?0.01) and hypertension (OR 1.07, 95% CI 1.00–1.14) with increasing length of stay in the US for resettled refugee adults. A significant proportion of diabetes (26.7%) and hypertension (36.9%) diagnoses were made within one year of arrival, highlighting the critical role of focusing diagnosis and prevention of chronic disease in newly resettled refugees, and continuing this focus throughout follow-up as these patients acculturate to their new homeland.     

ROTEM monitoring of activated and non-activated prothrombin complex concentrate correction of dilutional coagulopathy

Objectives Prothrombin complex concentrates have been used to correct dilutional coagulopathy, but many preparations contain anticoagulants, such as heparin, to counteract their prothrombotic effects. These anticoagulants can interfere with haemostatic assays. The aim of this study was to monitor two different prothrombin complex concentrates for the treatment of albumin dilution in vitro, using rotational thromboelastometry with or without the heparin-antagonising agent protamine. Methods Citrated blood from 10 healthy volunteers was, in vitro, diluted 1:1 with 5% albumin and then corrected with a four-factor prothrombin complex concentrate with heparin anticoagulant (Confidex®) corresponding to a clinical dose of 43?IU/kg. Blood samples were tested with or without protamine. An activated prothrombin complex concentrate (APCC) (FEIBA®) without heparin in doses of 50?IU/kg and 100?IU/kg was also tested. Thromboelastometry was performed after recalcification. Results Albumin dilution significantly affected all thromboelastometry parameters. The four-factor PCC had an additional anticoagulant effect when added to the albumin-diluted blood; it was partially corrected by protamine for all parameters except maximum clot firmness. The APCC significantly improved all parameters, with over-correction of clotting time but only partial correction of maximum clot firmness. Conclusions The anticoagulant content of many prothrombin complex concentrates needs to be considered when performing in vitro testing. A heparin-free APCC better corrected an in vitro albumin-induced dilutional coagulopathy than a four-factor PCC, despite of blocking heparin with protamine.     

EFFECT OF TRANSCUTANEOUS NERVE STIMULATION ON MICROCIRCULATION IN INTACT SKIN AND BLISTER WOUNDS IN HEALTHY VOLUNTEERS

Healthy non-smoking volunteers participated in two experimental studies in which the circulatory changes induced by transcutaneous nerve stimulation (TENS) were quantified by two different methods. In experimental series 1 (intact skin), nine volunteers were given TENS on the left lower leg for 60 minutes on three occasions at different frequencies each time (2 Hz, 100 Hz, and sham). Changes in blood flow were assessed by laser Doppler imaging technique every five minutes. The mean blood flow increased by 40% during low frequency TENS and by 12% during high frequency TENS. There was no change in mean blood flow during sham stimulation. In experimental series 2 (blister wound), the circulatory changes induced by TENS were studied by intravital video microscopy and computerised image analysis in standard blister wounds on the lower leg. The microcirculatory blood flow, measured as red blood cell velocity (RBC-V) in 5-14 individual capillaries in each wound, was assessed before and during 45 minutes of TENS (2 Hz and 100 Hz). Mean RBC-V increased by 23% during low frequency TENS (n = 6) and by 17% during high frequency TENS (n = 8). The results show that: laser Doppler imaging and intravital video microscopy techniques can be used to study events at the microcirculatory level; the blister wound is an interesting new standard wound for use in clinical studies; and TENS stimulates the peripheral cirulation.     

Adverse events related to the new psychoactive substance 3-fluorophenmetrazine – results from the Swedish STRIDA project

Background: New psychoactive substances (NPS) are often poorly pharmacologically documented and the production is unregulated, implying high risks for toxic side effects. This report from the STRIDA project describes analytically confirmed non-fatal intoxications involving the phenmetrazine analogue 3-fluorophenmetrazine (3-FPM).

Study design and methods: Observational case series of patients with suspected acute NPS exposure requiring hospital care. Blood and urine samples were collected from patients presenting in emergency departments (ED) or intensive care units (ICU), after consultation with the Swedish Poisons Information Centre (PIC). Laboratory analysis was performed by multi-component liquid chromatography–mass spectrometry. Clinical data were collected during PIC consultations and retrieved from medical records.

Results: From November 2014 to October 2015, eight cases were registered as 3-FPM or “phenmetrazine” intoxications at the PIC after consultation. During the same period, analysis of STRIDA project samples confirmed 3-FPM use in a total of 19 patients (84% men) aged 22–54 (median 30) years. 3-FPM was detected in 15 out of 19 serum (2.7–1416?ng/mL) and in 14 out of 14 urine (1.0–6857?μg/mmol creatinine) samples. All patients were also tested positive for other psychoactive substances, with benzodiazepines being most common (57% of the cases). Ten patients were monitored in the ED for <4?h, while six needed ICU monitoring of which five were graded as severe intoxications (Poisoning Severity Score 3). Prominent clinical signs were tachycardia (47%), depressed consciousness (42%), agitation/anxiety (37%), delirium (37%), dilated pupils (26%), and seizures (16%). All patients survived.

Conclusion: In 19 patients testing positive for 3-FPM, a high incidence of severe clinical features was demonstrated. However, as all patients had also used other psychoactive substances, it was difficult to identify a unique toxidrome for 3-FPM. The results further showed that many 3-FPM intoxications would have been missed, if relying solely on information from PIC consultations. These results emphasize the importance of performing bioanalytical investigation in cases of suspected NPS intoxication.