The role of QT-prolonging medications in a forensic autopsy study from Western Denmark.

Medication-induced prolongation of the QT-interval (miQTP) can lead to cardiac arrhythmia. Our aim was to investigate the prevalence of forensic autopsy cases where fatal cardiac arrhythmia related to treatment with QT-prolonging medications (QT-PMs) could be suspected. We performed a cross-sectional study of 741 forensic autopsies undertaken at our institution in non-drug addicts aged 15 years or above from 2017 to 2019. We defined a high risk of miQTP by one detected QT-PM in a concentration above therapeutic level, or two or more detected QT-PMs in post mortem blood. We reviewed the autopsy reports from cases with a high miQTP-risk to identify cases with no other apparent cause of death. We discarded suicides and cases with lethal levels of QT-PMs. We identified 167 cases (22.5%) with high risk of miQTP, and discarded 36 suicides (4.9%) and 7 (0.9%) with lethal levels of QT-PMs. Apart from a high risk of miQTP, no other apparent explanation of the cause of death was present in seven (0.9%). In 18 cases (2.4%) with high miQTP-risk, the cause of death was primarily attributed to cardiac changes other than acute cardiovascular events. In conclusion, 22.5% had a high risk of miQTP, and fatal cardiac arrhythmia related to treatment with QT-PMs could be suspected in 0.9%. However, a genetic pro-arrhythmic background could not be excluded in our study. Furthermore, it is possible that QT-PMs could have played a role in some of the 2.4% of cases where the cause of death was mainly attributed to cardiac changes and the risk of miQTP was high.

Fatal poisoning in drug addicts in the Nordic countries in 2017.

This study is the seventh report on fatal poisonings among drug addicts in the Nordic countries. In this report, we analyse data from the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. Data on gender, number of deaths, places of deaths, age, main intoxicants and substances detected in blood were recorded to obtain national and comparable Nordic data, and to allow comparison with earlier studies conducted in 1984, 1991, 1997, 2002, 2007 and 2012. The death rate (number of deaths per 100,000 inhabitants) was highest in Iceland (6.58) followed closely by Sweden (6.46) and then lowest in Denmark (4.29). The death rate increased in Finland (5.84), Iceland and Sweden and decreased in Denmark compared to earlier studies. The death rate in Norway, which has decreased since 2002, has stabilised around 5.7 as of 2017. Women accounted for 7-23% of the fatal poisonings. The percentage was lowest in Iceland and highest in Finland and Norway. The age range was 14-70 years. The median age (41 years) was highest in Denmark and Norway. The other countries had a median age between 33 and 35 years. Opioids were the main cause of death. Methadone remained the main intoxicant in Denmark, while heroin/morphine was still the main intoxicant in Norway, as was buprenorphine in Finland. However, the picture has changed in Sweden compared to 2012, where heroin/morphine caused most deaths in 2017. Sweden also experienced the highest number of deaths from fentanyl analogues (67 deaths) and buprenorphine (61 deaths). Deaths from fentanyl analogues also occurred in Denmark, Finland and Norway, but to a smaller extent. Over the years, the proportion of opioid deaths has decreased in all countries except Sweden, which has experienced an increase. This decline has been replaced by deaths from CNS stimulants like cocaine, amphetamine and methylenedioxymethamphetamine (MDMA). Cocaine deaths have occurred in all countries but most frequently in Denmark. MDMA deaths have increased in all countries but mostly in Finland. Poly-drug use was widespread, as seen in the earlier studies. The median number of detected drugs per case varied from 4-6. Heroin/morphine, methadone, buprenorphine, cocaine, amphetamine, methamphetamine, MDMA, tetrahydrocannabinol (THC) and benzodiazepines were frequently detected. Pregabalin and gabapentin were detected in all countries, especially pregabalin, which was detected in 42% of the Finnish cases. New psychoactive substances (NPS) occurred in all countries except Iceland.

Pulmonary apelin levels and effects in rats with hypoxic pulmonary hypertension.

BACKGROUND: The peptide apelin is localised in the vascular endothelium and highly expressed in pulmonary tissue. The aim of this study was to investigate whether apelin could be a potential lung-derived plasma marker for pulmonary hypertension, and study the effect of apelin in pulmonary arteries. METHODS: Apelin protein levels were measured in the lung, right ventricle, and plasma from normoxic and chronic hypoxic rats with pulmonary hypertension. Isolated intrapulmonary arteries were mounted in microvascular myographs and the effect of apelin investigated. Finally, the distribution of apelin receptors in pulmonary tissue was visualised by immunohistochemistry. RESULTS: Total pulmonary apelin content was not changed by hypoxia. Right ventricular apelin concentrations and content were lower than in the lung, but increased substantially in hypoxia in correlation with right ventricular pressure. Plasma apelin did not reflect pulmonary or right ventricular apelin levels. In pulmonary arteries from normoxic rats, apelin inhibited vasoconstriction to endothelin-1 and angiotensin-II. However, in arteries from hypoxic rats, apelin failed to inhibit contraction to angiotensin-II and endothelin-1. No difference in immunoreaction for apelin receptors was found in lung sections and arteries from normoxic versus chronic hypoxic rats. CONCLUSIONS: Apelin changes in the right ventricle seem more specific for pulmonary hypertension than do changes in pulmonary tissue, which does not speak in favour of apelin as a lung-derived marker for this disease. During normoxic conditions, apelin has a modulating effect on vasoconstriction which is lost in chronic hypoxia. This may reflect alterations in the signal transduction downstream of the apelin receptor.

Retinal detachment after cataract extraction in myopic eyes.

PURPOSE: To determine the incidence of retinal detachment (RD) after cataract extraction in people 40 years of age or older with axial myopia (i.e., axial length > or = 25.5 mm). SETTING: Fifteen Danish eye clinics. METHODS: Two hundred forty-five eyes had cataract extraction performed at 15 eye clinics; 237 eyes had extracapsular cataract extraction (ECCE) and 8 eyes, intracapsular cataract extraction (ICCE). Postoperative data were reported by the practicing ophthalmologists. Mean follow-up was 27 months (range 14 to 32 months). RESULTS: Five RDs occurred in the 245 eyes (2.0%). Excluding the ICCE cases and the two cases of combined cornea transplantation and ECCE, RD occurred in 4 of the 235 eyes that had ECCE (1.7%). The incidence after ECCE with posterior chamber lens implantation was 1.4%. Complete postoperative status was reported on 158 eyes. Forty-eight eyes (30.4%) had a neodymium:YAG capsulotomy and 3 (6.0%) developed an RD 1, 3.5, and 21 months after the capsulotomy. CONCLUSION: The RD incidence after ECCE with posterior chamber lens implantation was low but higher than that in unselected populations. The incidence increased after laser capsulotomy.

[Risk of cataract surgery in patients with myopia. A prospective Danish multicenter study with special reference to a complication]. / Risiko ved operation for grå staer hos naersynede. En prospektiv dansk multicenterundersøgelse med soerligt henblik på komplikationen nethindeløsning.

A prospective Danish multicentre study was conducted to evaluate the incidence of retinal detachment after cataract extraction in myopic eyes (axial length, > or = 25.5 mm). Two hundred and forty-seven cataract extractions in myopic eyes were reported during a period of 13 months. Two hundred and forty-one eyes underwent extracapsular and six eyes intracapsular cataract extraction. The mean follow-up time for 158 eyes was seven months (ranging from 1-30 months). In five cases a retinal detachment was observed, one case was probably present preoperatively, this person had undergone intracapsular cataract extraction. The incidence of retinal detachment was thus 1.62-2.02% in the total material and 1.66% in eyes operated with extracapsular cataract extraction.

Some metabolic changes during human corneal organ culture.

In order to evaluate the changes in medium composition during closed system corneal organ culture at 30 degrees C, pH, pO2, glucose and lactate was measured 1 to 7, 14 and 28 days after incubation of a total of 49 human corneas. During organ culture pO2 decreased from 17.3 kPa to 8.8 kPa at day 28. The average oxygen consumption was initially 0.16 mumole/h/cm2, but decreased rapidly to an average of 0.04 mumole/h/cm2 during the first weeks of incubation. The glucose concentration fell from 5.1 mM to 0.25 mM after 28 days, and the lactate concentration rose from 2.5 mM to 11 mM. The concentration changes were for both substances highest during the first 14 days of organ culture. The pH fell from 7.36 to 6.64 after 28 days. These findings indicate that the cultured human cornea predominantly metabolizes glucose anaerobically, and that the metabolic activity decreases during incubation. The limiting metabolic factors for prolonging the culture period seem to be development of severe acidosis and glucose depletion in the medium.

Computerised intraocular lens calculation: clinical results and predictability.

The predictability of a theoretical, computer-assisted IOL calculation method and of the Sanders-Retzlaff-Kraff (SRK) method was evaluated from pre- and postoperative biometry in 110 cataractous patients subjected to a routine IOL calculation. With the theoretical method and the preoperative data the refraction was on the average 0.72 D (SD 0.78) more myopic than expected, an error which could be corrected for by (1) substituting the assumed postoperative chamber depth by the actual mean value and (2) adding 0.16 mm to the preoperative axial length. With the postoperative data the error was 0.05 D (SD 0.78) (p greater than 0.05). By the SRK method the refraction was 0.15 D (SD 0.71) and 0.37 D (SD 0.69) more hyperopic than expected with the pre- and the postoperative data respectively. These offset errors could be corrected for in either case by adjusting the assumed A constant in the SRK formula. With appropriate empirical corrections for offset errors the theoretical and the SRK method were similar in accuracy, that is, about 82% of the predictions within +/- 1 D, 99% within +/- 2 D, and 100% within +/- 3 D error. The variation in postoperative refraction after computerised IOL calculation was about one-third of the variation previously seen after implantation of standard power IOL.

Double-blind study of naproxen vs placebo in the treatment of acute migraine attacks.

Naproxen was compared with placebo in a double-blind, crossover trial in classic and common migraine. The trial was terminated at a fixed date; 37 patients had entered, 5 of whom were excluded. Naproxen was given as 750 mg at the first symptom of the attack, a total of 1250 mg per 24 h was allowed. Patients were followed for six attacks or three months in each phase, whichever came first. The severity of the headache was significantly less with naproxen in the first 2 h of the attack (p = 0.047), whereas there was no difference when the whole attack was considered. Significantly more patients preferred naproxen (p = 0.042). Side effects occurred in five patients, causing withdrawal of one patient while on naproxen.

Amaurosis fugax in a Danish community: a prospective study.

A prospective study of amaurosis fugax was carried out in a Danish community (population 481,000); case ascertainment was based on the collaboration of practicing ophthalmologists and general practitioners. Over a 3-year period we registered 131 cases; the annual incidence of "first amaurosis fugax episodes coming to medical attention" was 8.6 and 6.2 per 100,000 population for men and women, respectively. On the basis of a comparison of the age-incidence curves for cerebral and retinal ischemic attacks, the "true" incidence of amaurosis fugax is estimated to be approximately 14/100,000/yr, or 25-30% of the reported incidence of transient ischemic attacks. Clinical and/or radiologic signs of a carotid lesion on the appropriate side were present in 56% of the patients, and an additional 27% had symptoms or signs of other organic cardiovascular disorders. Forty-three (68%) of the 63 patients who underwent arteriography had an atheromatous lesion apparently amenable to carotid endarterectomy. In spite of the case-finding procedures employed in the study, cases of amaurosis fugax suitable for carotid surgery were thus ascertained at a rate of only 3/100,000/yr. This suggests that surgical treatment of patients with retinal ischemic attacks is of minor importance as a preventive measure against stroke in the community.