In utero exposure to selective serotonin reuptake inhibitors and development of mental disorders: a systematic review and meta-analysis.

OBJECTIVE: Several studies have investigated whether in utero exposure to selective serotonin reuptake inhibitors (SSRIs) is associated with increased risk of developing mental or behavioural disorders. The aim of this study was to perform a systematic review and meta-analysis based on this literature. METHODS: A systematic search of eligible literature in PubMed, EMBASE, and PsycINFO and subsequent meta-analysis was conducted in adherence with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. RESULTS: A total of 20 studies were included in the review, and results from 18 of these were meta-analyzed. We found a statistically significant positive association between in utero exposure to SSRIs and mental or behavioural disorders such as autism spectrum disorder (hazard ratio (HR) = 1.27; 95% confidence interval (CI) = 1.10-1.47), attention-deficit/hyperactivity disorder (HR = 1.33; 95% CI = 1.06-1.66) and mental retardation (HR = 1.41; 95% CI = 1.03-1.91). Confounding by indication was identified in five of seven studies investigating this aspect. CONCLUSION: Exposure to SSRIs in utero is associated with increased risk of developing mental or behavioural disorders. However, these associations do not necessarily reflect a causal relationship since the results included in this meta-analysis are likely affected by residual confounding by indication, which is likely to account for some (or all) of the positive association.

Non-traumatic spinal cord injury in Norway 2012-2016: analysis from a national registry and comparison with traumatic spinal cord injury.

STUDY DESIGN: Registry-based cross-sectional study. OBJECTIVES: To describe and analyze epidemiological and demographic characteristics of non-traumatic spinal cord injury (NTSCI) and to compare persons with NTSCI and traumatic spinal cord injury (TSCI). SETTING: A total of 225 non-traumatic and 349 traumatic SCI patients were admitted for primary rehabilitation at one of the three specialized SCI departments in Norway (located in Bergen, Trondheim, and Oslo) from 2012 to 2016. Patients who consented to registration in the Norwegian Spinal Cord Injury Registry (NorSCIR) were included. METHODS: Data were collected using the International SCI Core Data Set, as recommended by the International Spinal Cord Society (ISCoS). Demographics and injury characteristics were analyzed descriptively. The NTSCI and TSCI groups were compared using a Mann-Whitney U test and chi-square test. RESULTS: The mean age of the NTSCI patients was 55 years, and 59% were male. The incidence of NTSCI was 7.7-10.4 per million person-years, which is lower than the incidence of TSCI. NTSCI individuals were older, less severely injured, and their length of stay at the hospital was shorter than the TSCI individuals. The results may be influenced by the inclusion criterion in the registry. This makes the analyzed sample for NTSCI less complete. However, the majority of patients with nonprogressive NTSCI are included in the NorSCIR. CONCLUSION: For the first time, we are able to provide the national epidemiological status on NTSCI based on available data from the national registry. Further studies are required to improve the capture of NTSCI for future incidence studies.

Epidemiology of traumatic spinal cord injury in Norway in 2012-2016: a registry-based cross-sectional study.

STUDY DESIGN: A registry-based cross-sectional study. OBJECTIVES: To analyse the epidemiological and demographic characteristics of persons with traumatic spinal cord injury (TSCI) in Norway. SETTING: TSCI patients admitted for primary rehabilitation to one of the three specialised spinal cord injury (SCI) departments (located in Bergen, Trondheim, and Oslo) and consented to the Norwegian Spinal Cord Injury Registry (NorSCIR). METHODS: Analysis of data from NorSCIR during a 5-year period (2012-2016) was performed. Data were collected by using the International SCI Core Data Set as recommended by the International Spinal Cord Society (ISCoS). RESULTS: The lowest incidence of TSCI was 11.4/million (2012), and the highest incidence was 15.9/million (2014). In the study period, 349 individuals were registered with TSCI. In total, 76% were male, and the mean age was 47 (SD ± 19) years. We observed dominance in the 60-74 years age group. The distribution between tetraplegia and paraplegia was 48%/42%. For those initially classified as American Spinal Cord Injury Association Impairment Scale (AIS) grade A (complete injury), 77% remained grade A at discharge. Considerable changes during primary rehabilitation after incomplete lesions were observed. Most patients (68%) were discharged home after primary rehabilitation. Falls were the main cause of TSCI (47%) and occurred more often during the weekend. CONCLUSION: Through a National Medical Quality Registry based on internationally provided data sets, we are able to present systematic and updated data from Norway.

High number of kinome-mutations in non-small cell lung cancer is associated with reduced immune response and poor relapse-free survival.

Lung cancer is the leading cause of cancer related death, and the past years' improved insight into underlying molecular events has significantly improved outcome for specific subsets of patients. In particular, several new therapies that target protein kinases have been implemented, and many more are becoming available. We have investigated lung cancer specimens for somatic mutations in a targeted panel of 612 human genes, the majority being protein kinases. The somatic mutation profiles were correlated to profiles of immune cell infiltration as well as relapse-free survival. Targeted deep sequencing was performed on 117 tumour/normal pairs using the SureSelect Human Kinome kit (Agilent Technologies), with capture probes targeting 3.2 Mb of the human genome, including exons and untranslated regions of all known kinases, kinase receptors and selected cancer-related genes (612 genes in total). CD8 staining was determined using Ventana Benchmark. Survival analyses were performed using SPSS. The number of mutations per sample ranged from 0 to 50 (within the 612 genes tested), with a median of nine. The prognosis was worse for patients with more than the median number of mutations. A significant correlation was found between mutations in one of selected DNA-repair genes and the total number of mutations in that tumour (p < 0.001). There was a significant inverse correlation between the number of infiltrating stromal CD8+ lymphocytes and the presence of EGFR mutations.

Analgesia for labour: a survey of Norwegian practice - with a focus on parenteral opioids.

BACKGROUND: During the last two decades, epidural analgesia has become 'a gold standard' for labour pain in most Western countries. Newer short-acting opioids given systemically represent an alternative for adequate pain relief without using regional techniques. With this survey, we wish to explore how Norwegian hospitals practice labour analgesia, especially their use of systemic opioids. METHODS: A questionnaire was sent to the head of all 46 registered Norwegian labour units in 2005. The questionnaire focused on epidural and the use of systemic opioids. In 2008, the same questionnaire was sent to the 19 largest units reporting >1000 births a year, seeking updated information. RESULTS: Forty-three of the 46 original questionnaires were returned. An epidural frequency of 25.9% was registered. For epidural treatment, bupivacaine was the preferred local anaesthetic, while sufentanil was the opioid of choice for the majority of units. Pethidine was the most commonly used opioid for systemic administration (77%). All units reported nurse administration of systemic opioids. The intramuscular route was most commonly used, either alone (58%) or in combination with an intravenous (i.v.) administration (34%). Only one unit used i.v. fentanyl. There were only minor changes with the repeated survey, except for one large unit, which reported over a 50% increase in the epidural frequency. CONCLUSION: In Norway, the frequency of epidural for labour analgesia is still relatively low, but seems to be increasing. Systemic opioids are often used instead of or as a supplement. Clinical practice seems to be conservative, and newer short-acting opioids are seldom used systemically.

Role of anticardiolipin antibodies in young persons with migraine and transient focal neurologic events: a prospective study.

Anticardiolipin antibodies (aCL) are a risk factor for cerebral ischemia. In migraine, the association is controversial, with widely varying results in different small series. The controversy in part may be due to the inherent difficulty in distinguishing the transient focal neurologic events (TFNE) of migraine from TIA. To assess the frequency of aCL in migraine, we prospectively evaluated consecutive adults under 60 years of age with migraine without aura and with recent TFNE (<24-hour duration) clinically suggestive of either migraine with aura or TIA. We concomitantly enrolled persons with no CNS disease. Each person was interviewed and had blood drawn for solid-phase ELISA with IgG and IgM aCL isotyping. Neuroradiologic studies were reviewed. Patients with TFNE were followed every 6 months for the duration of the 3-year study. The frequency of aCL positivity (IgG >20, IgG >40, IgM >7.5) for the 645 patients with TFNE (8.8, 3.1, 4.2%), the 518 persons in the TFNE subgroup with migraine with aura (8.9, 3.3, 4.1%), the 497 persons with migraine without aura (7.0, 2.0, 3.6%), and the 366 control subjects (9.3, 3.6, 3.9%) did not differ significantly between groups. In TFNE patients with elevated aCL titer, the association was positive with diabetes mellitus, TFNE duration <15 minutes, and diplopia and was negative with hemiparesis, tinnitus, and family history of stroke. Findings on imaging consistent with cerebral ischemia were more frequent in aCL-positive persons. The short-term risk of stroke was uniformly low. In young persons, aCL is not associated with migraine or with TFNE, although diabetes mellitus, negative family history of stroke, and brief duration of symptoms (including diplopia) may predict immunoreactivity. Imaging studies suggest an ischemic etiology of TFNE in this cohort.

Parent perceptions of the integration transition process; overcoming artificial barriers.

The parents of 14 students with disabilities participated in interviews to evaluate the support they received during their child's transition to an integrated educational placement, to explore their concerns, and to discuss the effects of integration. Although parents identified areas of concern, they consistently expressed satisfaction regarding the outcomes of integrating their child, including professional and personal support. Responses emphasized the importance of commitment from local school districts and professionals, an individualized approach to parent involvement, and ongoing communication with parents.

[Unilateral ectopic twin pregnancy]. / Unilateral ektopisk tvillingegraviditet.

A case of a 12 week unilateral ectopic twin pregnancy is presented. The condition is rare with less than one hundred reported cases. Only three reported cases of unilateral ectopic twin pregnancy have been diagnosed sonographically. In this case the diagnosis of ectopic pregnancy was made by ultrasound, but, despite the length of the pregnancy only one fetus was seen.

[Appendicitis in pregnancy. Complications and treatment]. / Appendicitis i graviditeten. Komplikationer og behandling.

In order to establish guidelines for the management of a pregnancy that is complicated by acute appendicitis we carried out a retrospective review of 16 patients that had their appendix removed at the Department of Obstetrics and Gynaecology, Rigshospitalet, University of Copenhagen in the period 1974-1988. The diagnostic accuracy was 12/16 (75%). The signs and symptoms were classic. Uterine contractions may occur. There was one foetal death in a case complicated by an intraperitoneal abscess, and two patients delivered prematurely. Three patients had infectious complications, none of these patients were given prophylactic antibiotics. In all uncomplicated cases the pregnancy proceeded to term and the deliveries were normal. The pregnancy ought not to divert the surgeon's attention from performing prompt appendectomy once the diagnosis is suspected. Prophylactic antibiotics and tocolytic drugs should be used in all cases. Simultaneous caesarean section should be performed only on obstetric indications.

[Cesarean section. Changes in frequency and indications in the county of South Jutland during a 10-year period]. / Kejsersnit. Aendringer i frekvens og indikationer i Sønderjyllands Amt i en 10 års periode.

During recent years, the frequency of Caesarean section has changed everywhere. Changes during a ten-year period in the Department of Gynaecology in Sønderborg Hospital were registered and involve mainly the groups of imminant foetal death, previous Caesarean section, foeto-pelvic disproportion and placental insufficiency. Alterations in the obstetric services in the County of South Jutland and improved neonatal service have played an important part in development of the frequency of Caesarean section of Sønderborg Hospital.

Efficacy and side effects of intravenous remifentanil patient-controlled analgesia used in a stepwise approach for labour: an observational study.

BACKGROUND: Remifentanil has a suitable pharmacological profile for labour analgesia. In this prospective, observational study, intravenous patient-controlled analgesia with remifentanil, using stepwise bolus doses without background infusion, was examined during the first and second stages of labour. Outcomes were pain reduction, maternal satisfaction, maternal and neonatal side effects and remifentanil metabolism in the neonate. METHODS: Parturients with normal term singleton pregnancies were recruited. The initial remifentanil bolus dose was 0.15 µg/kg, increasing in steps of 0.15 µg/kg, with a 2-min lock-out. Pain scores using a 100 mm visual analogue scale, systolic and diastolic blood pressures, respiratory rate and maternal sedation were recorded every 15 min. Maternal oxygen saturation and heart rate were monitored continuously. Neonatal data included Apgar scores, clinical examination, naloxone use, resuscitation, umbilical cord blood gases and remifentanil concentrations. RESULTS: Forty-one parturients were enrolled. Pain scores were significantly reduced in the first 3 h of patient-controlled analgesia use compared to baseline, and at the end of the first and second stages of labour (P<0.05). Maximal pain reduction was 60% (P<0.01). One patient had inadequate pain relief and converted to epidural analgesia. The mean highest dose of remifentanil was 0.7 µg/kg [range 0.3-1.05]. Ninety-three percent of patients were satisfied with their analgesia. The lowest oxygen saturation was 91% and the lowest respiratory rate was 9 breaths/min. Eleven parturients (27%) received supplemental oxygen due to oxygen saturations <92%. Maternal sedation was moderate, and neonatal data reassuring. CONCLUSIONS: Remifentanil intravenous patient-controlled analgesia provides adequate pain relief and high maternal satisfaction during the first and second stages of labour. Maternal sedation and respiratory depression may occur, but no serious neonatal side effects were recorded. Careful monitoring is mandatory.

Fibrin content of carotid thrombi alters the production of embolic stroke in the rat.

BACKGROUND AND PURPOSE: Mechanical denudation of the endothelium of the carotid artery in animals produces a nonocclusive thrombus, but the brains of these animals have not been examined for the presence of embolic stroke. METHODS: The endothelium of the right carotid artery of 16 Wistar rats was denuded using a balloon catheter. Phosphotungstic acid hematoxylin (PTAH) staining and scanning electron micrographs of the nonocclusive thrombi in the carotid arteries were compared with those produced by photochemical methods, and brains were examined for infarcts. RESULTS: Although nonocclusive thrombi were present in the carotid arteries of 4 of 4 rats killed at 4 hours and in 8 of 12 killed at 24 hours, neither cerebral infarcts nor emboli were seen in the 14 brains evaluated by light microscopy. PTAH demonstrated a high fibrin content in the thrombus produced by the endothelial denudation, with almost no fibrin seen in photochemically induced thrombi. Scanning electron microscopy confirmed dense networks of fibrin in the thrombi produced by balloon denudation. CONCLUSIONS: The composition of a nonocclusive thrombus may determine the embolic potential of this thrombus. A low fibrin content in a nonocclusive platelet thrombus may enhance the embolic potential. This suggests that platelet inhibition may also be indicated in patients with carotid artery disease who are being treated with anticoagulant.

Lignocaine gel used for lubrication of intranasal and endotracheal tubes in premature neonates.

In this study, we have measured the plasma concentration of lignocaine and its metabolite, monoethylglycinxylidin, in 19 premature neonates (gestational age < or = 33 weeks) when lignocaine gel was used for lubrication of an intranasal tube (during continuous positive airway pressure treatment) or an endotracheal tube (for intubation). We did not find any correlation between plasma concentration of lignocaine or monoethylglycinxylidin and weight of the infant (range 795-2530 g). None of the neonates had toxic levels of lignocaine. One neonate had an exceptionally high but not toxic plasma level of monoethylglycinxylidin. However, this neonate had been treated for severe seizures with an iv infusion of lignocaine up to 13 h before the study. In conclusion, we found it safe to use moderate amounts of lignocaine (i.e. 0.3 ml/kg of lignocaine gel 20 mg/ml) for lubricating both intranasal and endotracheal tubes.

Acute appendicitis in pregnancy: complications and subsequent management.

OBJECTIVE: To establish guidelines for the management of a pregnancy that is complicated by acute appendicitis. DESIGN: Retrospective study. SETTING: University Hospital, Copenhagen, Denmark. SUBJECTS: 16 patients operated on for symptoms of acute appendicitis during the 15 year period 1974-1988. RESULTS: In 12 patients (75%) the diagnosis was confirmed histologically. The signs and symptoms were classic, and three patients had contractions. One fetus died, in a patient with appendicitis complicated by intraperitoneal abscess. In all uncomplicated cases the pregnancy proceeded to term and the deliveries were normal. CONCLUSIONS: Pregnancy should not deter a surgeon from removing an appendix, once the diagnosis is suspected; no pregnancy was affected by removal of a normal appendix. We recommend that prophylactic antibiotics and tocolytic drugs be given in all cases. Simultaneous caesarean section should be done only if there are obstetric indications.

[Appendicitis in pregnancy]. / Appendicitis i svangerskabet.

The incidence, symptoms, clinical and paraclinical findings, and complications of appendicitis during pregnancy is reviewed. The symptoms and signs do not differ from those in non-pregnant women with the disease. Uterine contractions may occur. The pregnancy ought not to divert the clinicians attention from the disease which is complicated by a considerable foetal mortality, premature labour and abortion. These complications are especially connected with perforated appendicitis. The perforation frequency is related to the delay prior to operation. Immediate appendectomy is recommended as soon as the disease is suspected, making use of prophylactic tocolytic therapy. Antibiotics should be administered according to the usual recommendations. Abdominal delivery should be reserved for obstetric indications only.

Intramuscular ephedrine reduces emesis during the first three hours after abdominal hysterectomy.

BACKGROUND: We tested the hypothesis that intramuscularly administered ephedrine prevents postoperative nausea and vomiting. Ephedrine is cheap, and for this indication poorly documented. METHODS: One hundred and nine patients undergoing elective abdominal hysterectomy under general anaesthesia were studied in a randomized, double-blind placebo-controlled study. Ten minutes before the end of the procedure patients received either ephedrine 0.5 mg/kg i.m. or placebo. The patients were closely observed for 24 h for postoperative nausea or vomiting (PONV) and received a standardized two-step antiemetic treatment of i.v. metoclopramide 10 mg, supplemented with ondansetron 4 mg i.v. if needed. RESULTS: The ephedrine treated patients had significantly less nausea, retching and vomiting, and need of antiemetic rescue during the first 3 h postoperatively compared with the placebo patients. No difference between the groups was evident in the 3-24 h postoperative observation period. All the patients with PONV during 0-3 h experienced PONV in the 3-24 h period. Treatment or prophylaxis with one drug was less efficient than two or more drugs combined. No significant differences in hypotension, tachycardia or other side-effects between the groups were noted. CONCLUSION: Ephedrine 0.5 mg/kg i.m. administered at the end of abdominal hysterectomy has a significant antiemetic effect during the first 3 h after administration with no evident side-effects.

Treatment type and amount influenced human immunodeficiency virus seroprevalence of patients with congenital bleeding disorders.

Two hundred and eighty-two patients with congenital bleeding disorders received blood component replacement therapy between January 1979 and April 1985, were followed-up by the Puget Sound Blood Center's Hemophilia Care Program, and were tested for antibody to human immunodeficiency virus (HIV). Serologic results were obtained at least 1 year after the last exposure to volunteer donor products that were prepared before donor HIV screening or after the last exposure to concentrates produced before the manufacturer's use of treatment methods for inactivation of HIV. In all, 106 patients were anti-HIV positive. The risk of HIV infection was greater in patients with more severe bleeding tendencies, greater exposure to components, and exposure to lyophilized concentrates from large pools of donors. Of 100 patients with hemophilia A who only received cryoprecipitate from volunteer donors from Washington State (during the 6.3-year period), 14% had become anti-HIV positive. Of 27 patients receiving mostly cryoprecipitate but also being exposed to a single lot of concentrate during the same period, 13 (48%) were positive. Of 49 patients treated predominantly or solely with factor VIII concentrates during this period, 43 (88%) were anti-HIV positive. Of 29 patients with von Willebrand disease, four were anti-HIV positive, including 2 of 26 receiving only cryoprecipitate and two of three who had received a single dose of factor VIII concentrate. Of 19 patients who were treated solely with volunteer donor plasma, all remained anti-HIV negative. Of 47 patients exposed to factor IX concentrate, 28 (60%) were positive. Data relevant to the risk of HIV transmission subsequent to screening of the volunteer donor population were also obtained. Treatment records of 55 hemophilia A patients who have remained anti-HIV negative through at least June 1990 showed exposure to 71,173 screened donors from May 1985 through December 1989, and all 55 patients have remained anti-HIV negative.

Growth kinetics of four human breast carcinomas grown in nude mice.

The immune-deficient nude mouse with human tumor xenografts is an appropriate model system for performing detailed growth kinetic examinations. In the present study one estrogen and progesterone receptor-negative (T60) and three receptor-positive (Br-10, MCF-7, T61) human breast cancer xenografts in nude mice were investigated. The proliferative tumor characteristics were examined by growth curves, thymidine labelling technique, and flow cytometric DNA analysis performed on fine-needle aspirations. The results showed that the tumors had growth kinetics comparable to other human tumor types with cell generation times of 42 to 60 hours. The three receptor-positive tumors had slower growth rate, larger tumor volume doubling time, and smaller growth fraction and labelling index than the receptor-negative tumor. However, no single proliferation parameter was sufficient to characterize the growth kinetics of individual tumors or to describe proliferative differences between the tumors.