COVID-19 illness severity and 2-year prevalence of physical symptoms: an observational study in Iceland, Sweden, Norway and Denmark.

Background: Although the persistence of physical symptoms after SARS-CoV-2 infection is a major public health concern, evidence from large observational studies beyond one year post diagnosis remain scarce. We aimed to assess the prevalence of physical symptoms in relation to acute illness severity up to more than 2-years after diagnosis of COVID-19. Methods: This multinational study included 64,880 adult participants from Iceland, Sweden, Denmark, and Norway with self-reported data on COVID-19 and physical symptoms from April 2020 to August 2022. We compared the prevalence of 15 physical symptoms, measured by the Patient Health Questionnaire (PHQ-15), among individuals with or without a confirmed COVID-19 diagnosis, by acute illness severity, and by time since diagnosis. We additionally assessed the change in symptoms in a subset of Swedish adults with repeated measures, before and after COVID-19 diagnosis. Findings: During up to 27 months of follow-up, 34.5% participants (22,382/64,880) were diagnosed with COVID-19. Individuals who were diagnosed with COVID-19, compared to those not diagnosed, had an overall 37% higher prevalence of severe physical symptom burden (PHQ-15 score ≥15, adjusted prevalence ratio [PR] 1.37 [95% confidence interval [CI] 1.23-1.52]). The prevalence was associated with acute COVID-19 severity: individuals bedridden for seven days or longer presented with the highest prevalence (PR 2.25 [1.85-2.74]), while individuals never bedridden presented with similar prevalence as individuals not diagnosed with COVID-19 (PR 0.92 [0.68-1.24]). The prevalence was statistically significantly elevated among individuals diagnosed with COVID-19 for eight of the fifteen measured symptoms: shortness of breath, chest pain, dizziness, heart racing, headaches, low energy/fatigue, trouble sleeping, and back pain. The analysis of repeated measurements rendered similar results as the main analysis. Interpretation: These data suggest an elevated prevalence of some, but not all, physical symptoms during up to more than 2 years after diagnosis of COVID-19, particularly among individuals suffering a severe acute illness, highlighting the importance of continued monitoring and alleviation of these targeted core symptoms. Funding: This work was mainly supported by grants from NordForsk (COVIDMENT, grant number 105668 and 138929) and Horizon 2020 (CoMorMent, 847776). See Acknowledgements for further details on funding.

Psychobiological stress response to a lung cancer diagnosis: a prospective study of patients in Iceland and Sweden.

BACKGROUND: A diagnostic work-up leading to a lung cancer diagnosis is a severely stressful experience that may impact tumor progression. Yet, prospective data are scarce on psychological and biological components of stress at the time of lung cancer diagnosis. The aim of this study was to assess pre-to-post diagnosis change in psychological distress and urinary excretion of catecholamines in patients with suspected lung cancer. METHODS: Participants were 167 patients within the LUCASS study, recruited at referral for suspected lung cancer to University Hospitals in Iceland and Sweden. Patients completed questionnaires on perceived distress (Hospital Anxiety and Depression Scale, HADS) before and after diagnosis of lung cancer or a non-malignant origin. A subpopulation of 85 patients also provided overnight urine for catecholamine analysis before and at a median of 24 days after diagnosis but before treatment. RESULTS: A lung cancer diagnosis was confirmed in 123 (73.7%) patients, with a mean age of 70.1 years. Patients diagnosed with lung cancer experienced a post-diagnosis increase in psychological distress (p = 0.010), while patients with non-malignant lung pathology showed a reduction in distress (p = 0.070). Both urinary epinephrine (p = 0.001) and norepinephrine (p = 0.032) levels were higher before the diagnosis among patients eventually diagnosed with lung cancer compared to those with non-malignant lung pathology. We observed indications of associations between pre-to-post diagnosis changes in perceived distress and changes in urinary catecholamine levels. CONCLUSION: Receiving a lung cancer diagnosis is associated with an increase in psychological distress, while elevated catecholamine levels are evident already before lung cancer diagnosis.

Respiratory function and CT abnormalities among survivors of COVID-19 pneumonia: a nationwide follow-up study.

INTRODUCTION: Considering the pulmonary burden caused by acute COVID-19, questions remain of respiratory consequences after recovery. The aim of the study was to describe respiratory function of COVID-19 pneumonia survivors at mid-term follow-up (median 68 days) and assess whether impairments were predicted by acute illness severity or residual CT abnormalities. METHODS: Residents of Iceland that had COVID-19 and oxygen saturation ≤94% from 28 February 2020 to 30 April 2021 were offered a clinical follow-up visit with an interview, a 6 min walk test (6MWT), spirometry with gas exchange measurement and chest CT. The results of these examinations were described, grouped by the level of care during acute illness. The associations of disease severity and CT abnormalities at follow-up with subjective dyspnoea, 6MWT results and lung function test results were estimated with regression analyses. RESULTS: Of 190 eligible patients, 164 (86%) participated in the study. Of those, 32 had never been admitted to hospital, 103 were admitted to hospital without intensive care and 29 had required intensive care. At a follow-up, need for intensive care during acute illness was associated with shorter walking distance on 6MWT, lower oxygen saturation and lower DLCO. Imaging abnormalities at follow-up were observed for most participants (74%) and the magnitude of these changes was associated with decrements in 6MWT distance, oxygen saturation, forced vital capacity and DLCO. CONCLUSIONS: The findings show that impaired exercise capacity and lung physiology at follow-up were primarily observed for patients with COVID-19 pneumonia that required intensive care treatment and/or had persistent imaging abnormalities.

Optimal communication associated with lower risk of acute traumatic stress after lung cancer diagnosis.

PURPOSE: The aim of this study was to assess the role of the patient's background and perceived healthcare-related factors in symptoms of acute stress after lung cancer diagnosis. METHODS: The study population consisted of 89 individuals referred for diagnostic work-up at Landspitali National University Hospital in Iceland and subsequently diagnosed with lung cancer. Before diagnosis, the patients completed questionnaires on sociodemographic characteristics, pre-diagnostic distress (Hospital Anxiety and Depression Scale), social support, and resilience. At a median of 16 days after diagnosis, the patients reported symptoms of acute stress on the Impact of Event Scale-Revised (IES-R) and experience of communication and support from healthcare professionals and family during the diagnostic period. RESULTS: Patients were on average 68 years and 52% reported high levels of post-diagnostic acute stress (IES-R > 23) while 24% reported symptoms suggestive of clinical significance (IES-R > 32). Prior history of cancer (ß = 6.7, 95% CI: 0.1 to 13.3) and pre-diagnostic distress were associated with higher levels of post-diagnostic acute stress (ß = 8.8, 95% CI: 2.7 to 14.9), while high educational level (ß = - 7.9, 95% CI: - 14.8 to - 1.1) was associated with lower levels. Controlling for the abovementioned factors, the patients' perception of optimal doctor-patient (ß = - 9.1, 95% CI: - 14.9 to - 3.3) and family communication (ß = - 8.6, 95% CI: - 14.3 to - 2.9) was inversely associated with levels of post-diagnostic acute stress after lung cancer diagnosis. CONCLUSIONS: A high proportion of patients with newly diagnosed lung cancer experience high levels of acute traumatic stress of potential clinical significance. Efforts to improve doctor-patient and family communication may mitigate the risk of these adverse symptoms.

[Advances in lung cancer diagnosis and treatment - a review].

Lung cancer is the second and third most common cancer in Iceland for females and males, respectively. Although the incidence is declining, lung cancer still has the highest mortality of all cancers in Iceland. Symptoms of lung cancer can be specific and localized to the lungs, but more commonly they are unspecific and result in significant diagnostic delay. Therefore, majority of lung cancer patients are diagnosed with non-localized disease. In recent years, major developments have been made in the diagnosis and treatment of lung cancer. Positive emission scanning (PET) and both transbroncial (EBUS) or transesophageal ultrasound (EUS) biopsy techniques have resulted in improved mediastinal staging of the disease and minimal invasive video-assisted thoracic surgery (VATS) has lowered postoperative complications and shortened hospital stay. Technical developments in radiotherapy have benefitted those patients who are not candidates for curative surgery. Finally, and most importantly, recent advances in targeted chemotherapeutics and development of immunomodulating agents have made individual tailoring of treatment possible. Recent screening-trials with low-dose computed tomography show promising results in lowering mortality. This evidence-based review focuses on the most important developments in the diagnosis and treatment of lung cancer, and includes Icelandic studies in the field.

[Parenchymal lung changes on CT in patients with coronavirus disease 2019 (COVID-19)].

Introduction Infections due to COVID-19 can lead to life threatening pneumonia. Accompanying severe disease are more prominent pulmonary changes on Computed Tomography (CT) scan of the chest. The goal of this study was to describe pulmonary CT changes during acute COVID-19 and at follow up and whether the extent of changes correlate with severity of illness, demographics or other risk factors. Materials and methods Included in this study are all individuals that had confirmed COVID-19 and came for a follow up CT of the chest at Landspitali from May to September 2020. Information regarding medical history was obtained retrospectively from medical charts. All CT scans were reviewed using an international staging system to evaluate the extent of lung changes. Results Eighty-five patients with a mean age of 59 years were included in the study. Sixty patients (71%) were hospitalized during the acute phase and 18 (21%) were admitted to the ICU. During the acute phase more pronounced lung involvement was seen in males and patients admitted to the ICU. At follow-up females had less lung involvement but there was a significant relationship between a higher CT score and age, ICU admissions and days in the ICU. Full recovery was seen at follow-up CT in 31% of patients (median 68,5 days between acute and follow-up imaging). Conclusion Patients with severe COVID-19 have more pronounced lung involvement on CT than patients with milder disease during the acute phase and follow-up. Older patients and males are at greater risk of acute and persistent COVID-19 related lung changes.

Illness severity and risk of mental morbidities among patients recovering from COVID-19: a cross-sectional study in the Icelandic population.

OBJECTIVE: To test if patients recovering from COVID-19 are at increased risk of mental morbidities and to what extent such risk is exacerbated by illness severity. DESIGN: Population-based cross-sectional study. SETTING: Iceland. PARTICIPANTS: A total of 22 861 individuals were recruited through invitations to existing nationwide cohorts and a social media campaign from 24 April to 22 July 2020, of which 373 were patients recovering from COVID-19. MAIN OUTCOME MEASURES: Symptoms of depression (Patient Health Questionnaire), anxiety (General Anxiety Disorder Scale) and posttraumatic stress disorder (PTSD; modified Primary Care PTSD Screen for DSM-5) above screening thresholds. Adjusting for multiple covariates and comorbidities, multivariable Poisson regression was used to assess the association between COVID-19 severity and mental morbidities. RESULTS: Compared with individuals without a diagnosis of COVID-19, patients recovering from COVID-19 had increased risk of depression (22.1% vs 16.2%; adjusted relative risk (aRR) 1.48, 95% CI 1.20 to 1.82) and PTSD (19.5% vs 15.6%; aRR 1.38, 95% CI 1.09 to 1.75) but not anxiety (13.1% vs 11.3%; aRR 1.24, 95% CI 0.93 to 1.64). Elevated relative risks were limited to patients recovering from COVID-19 that were 40 years or older and were particularly high among individuals with university education. Among patients recovering from COVID-19, symptoms of depression were particularly common among those in the highest, compared with the lowest tertile of influenza-like symptom burden (47.1% vs 5.8%; aRR 6.42, 95% CI 2.77 to 14.87), among patients confined to bed for 7 days or longer compared with those never confined to bed (33.3% vs 10.9%; aRR 3.67, 95% CI 1.97 to 6.86) and among patients hospitalised for COVID-19 compared with those never admitted to hospital (48.1% vs 19.9%; aRR 2.72, 95% CI 1.67 to 4.44). CONCLUSIONS: Severe disease course is associated with increased risk of depression and PTSD among patients recovering from COVID-19.

Delirium and fever - a rare but dangerous cause - Case report

Fever complicated by delirium is a common problem in emergency departments and inpatient wards. There are various possible causes that must all be contemplated. Infections are prominent causes due to acuteness and severity, but when generating a differential diagnosis, other causes may be life-threatening and require swift diagnosis and management. We present here a case of a 58 year old man presenting at the emergency department with fever and delirium. After comprehensive history-taking and examination, alongside targeted testing, the correct diagnosis was ascertained, leading to appropriate treatment.

[The impact of lung diseases, smoking and e-cigarette use on the severity of COVID-19 illness at diagnosis].

INTRODUCTION: The COVID-19 pandemic has caused public health and economic turmoil across the globe. Severe COVID-19 disease most often presents with pneumonia and complications in acutely ill patients often stem from the lungs. The associations of lung disease, smoking and e-cigarette use with the incidence and severity of COVID-19 are unclear on a population level. METHODS: Data on 1761 patients from the Icelandic outpatient Landspitali COVID-19 Clinic were used. The prevalence of smoking, e-cigarette use and underlying lung diseases was calculated in the cohort, with stratification based on age groups and a clinical classification of symptom severity. It was tested whether these prevalences differed between age groups and classes of symptom severity. RESULTS: Most patients were in the age group between 35-54 years of age and a large majority had mild symptoms at diagnosis. The prevalence of smoking was 6% with the highest prevalence among 35-54 year olds. The prevalence of e-cigarette use was 4%. It was most prevalent in the age group between 18-34 years. There was no difference in the prevalence of smoking or e-cigarette use between classes of symptom severity. The prevalence of lung disease was 9%. It was higher among older patients and patients with more severe symptoms. CONCLUSION: The age distribution and prevalence of lung disease and their risk factors are described in the context of COVID-19 incidence and symptom severity in a whole-nation cohort of Icelanders. The cohort is younger and had less severe symptoms than in many previosly published studies of COVID-19. Interestingly, the prevalences of smoking and e-cigarette use were lower than in the Icelandic general population and they were not associated with symptom severity at diagnosis. To conclude, the results presented here indicate that underlying lung diseases are prevalent among people with severe COVID-19 symptoms but fail to demonstrate an association between cigarette smoking or e-cigarette smoking with COVID-19 severity.

Beta-Blocker Use and Lung Cancer Mortality in a Nationwide Cohort Study of Patients with Primary Non-Small Cell Lung Cancer.

BACKGROUND: ß-Adrenergic receptor blockers have been associated with improved survival among patients with different types of malignancies, but available data for patients with non-small cell lung cancer (NSCLC) are contradictory and limited to small hospital-based studies. We therefore aimed to investigate whether ß-blocker use at the time of cancer diagnosis is associated with lung cancer mortality in the largest general population-based cohort of patients with NSCLC to date. METHODS: For this retrospectively defined nationwide cohort study, we used prospectively collected data from Swedish population and health registers. Through the Swedish Cancer Register, we identified 18,429 patients diagnosed with a primary NSCLC between 2006 and 2014 with follow-up to 2015. Cox regression was used to estimate the association between ß-blocker use at time of cancer diagnosis ascertained from the Prescribed Drug Register and cancer-specific mortality identified from the Cause of Death Register. RESULTS: Over a median follow-up of 10.2 months, 14,994 patients died (including 13,398 from lung cancer). Compared with nonuse, ß-blocker use (predominantly prevalent use, 93%) was not associated with lung cancer mortality [HR (95% confidence interval): 1.01 (0.97-1.06)]. However, the possibility that diverging associations for specific ß-blockers and some histopathologic subtypes exist cannot be excluded. CONCLUSIONS: In this nationwide cohort of patients with NSCLC, ß-blocker use was not associated with lung cancer mortality when assessed in aggregate in the total cohort, but evidence for some ß-blockers is less conclusive. IMPACT: Our results do not indicate that ß-blocker use at lung cancer diagnosis reduces the cancer-specific mortality rate in patients with NSCLC.

Pulmonary carcinoid tumours: incidence, histology, and surgical outcome. A population-based study.

BACKGROUND: Pulmonary carcinoids (PCs) represent only a minority of all primary pulmonary malignancies but they are the most common type of pulmonary malignancy diagnosed in children and adolescents. In this nationwide study, we analyzed data on all PC tumours in the Icelandic population over a 60-year period and concentrated especially on incidence and patient outcomes. METHODS: We studied all cases of PCs diagnosed in Iceland in the period 1955‒2015. Histological specimens were re-evaluated and the tumours were staged according to the TNM system (seventh edition). Survival was estimated using the Kaplan-Meier method, with a mean follow-up of 15.7 years. RESULTS: Altogether, 88 patients (median age 51.0 years, 65.9% women) were diagnosed with PCs in the study period. The incidence increased from 0.19/100,000/year in the first decade (1955‒1964) to 0.58/100,000/year in the last decade (2005‒2015), with a mean increase of 29.0% per decade of the study period (p < 0.001). The rise in incidental detection was, however, not significant. The median tumour diameter was 2.2 cm (range 0.4‒7.0) and typical histology was seen in 74 patients (84.1%). The other 14 patients (15.9%) had atypical histology. In all, 90.9% of the patients underwent pulmonary resection, 81.2% of them with lobectomy, with all of them surviving at least 30 days postoperatively. Most patients (n = 52, 62.7%) were stage IA at diagnosis, 15 (18.1%) were stage IB, nine (10.8%) were stage IIA, and three were stage IIIA (3.6%). Four patients (4.8%) had distant metastases (stage IV), two of whom had typical histology. Five-year survival was 89.8% for all patients: 93.2% for patients with typical histology and 70.7% for those with atypical histology. CONCLUSION: The incidence of PCs in Iceland has increased significantly over the last six decades, which cannot be explained by a rise in incidental detection at chest imaging. Most patients have localized disease and a favourable histology, where the long-term outcome is excellent.

Mortality of lung cancer as a second primary malignancy: A population-based cohort study.

Lung cancer as a second primary malignancy (lung-2) is increasingly common, but its prognosis is poorly understood. This study aims to examine the overall and cancer-specific survival of patients diagnosed with lung-2 compared to lung-1. Primary lung cancer patients diagnosed from 1988 to 2014 in the Surveillance, Epidemiology, and End Results (SEER) program were included. Lung-2 was identified in patients with a previous diagnosis of nonlung primary malignancy in SEER. Hazard ratios (HRs) of overall and lung cancer-specific mortality were estimated among patients with lung-2 compared to lung-1, adjusting for age and calendar period at diagnosis, sex, race, socioeconomic status, tumor stage, histology, tumor grade, and treatment. A total of 679 541 and 85 758 patients were identified as lung-1 and lung-2, respectively. Compared to lung-1, patients with lung-2 were more likely to be diagnosed at localized stage, with smaller primary tumor, and treated with surgery. Lung-2 patients were at lower risk of lung cancer-specific mortality in the first 5 years (HR, 0.77; 95% CI, 0.76-0.78 at <1 year; HR, 0.87; 95% CI, 0.86-0.89 from 1 to <5 years) but at higher risk thereafter (HR, 1.32; 95% CI, 1.27-1.37 from 5 to 10 years), independent of tumor characteristics and cancer treatment. Similar pattern was found for overall mortality, although the survival benefit was restricted to the first year after diagnosis. Patients diagnosed with lung-2 face a favorable lung cancer-specific survival within the early period after diagnosis. A conservative approach to manage lung-2 solely based on malignancy history is not supported.

Association of BRCA2 K3326* With Small Cell Lung Cancer and Squamous Cell Cancer of the Skin.

Background: Most pathogenic mutations in the BRCA2 gene carry a high risk of hereditary breast and ovarian cancer (HBOC). However, a stop-gain mutation, K3326* (rs11571833), confers risk of lung cancer and cancers of the upper-aero-digestive tract but only a modest risk of breast or ovarian cancer. The Icelandic population provides an opportunity for comprehensive characterization of the cancer risk profiles of K3326* and HBOC mutations because a single mutation, BRCA2 999del5, is responsible for almost all BRCA2-related HBOC in the population. Methods: Genotype information on 43 641 cancer patients and 370 971 control subjects from Iceland, the Netherlands, and the United States was used to assess the cancer risk profiles of K3326* and BRCA2 999del5. BRCA2 expression was assessed using RNAseq data from blood (n = 2233), as well as 52 tissues reported in the GTEx database. Results: The cancer risks associated with K3326* are fundamentally different from those associated with 999del5. We report for the first time an association between K3326* and small cell lung cancer (odds ratio [OR] = 2.06, 95% confidence interval [CI] = 1.35 to 3.16) and squamous cell carcinoma of the skin (OR = 1.69, 95% CI = 1.26 to 2.26). Individuals homozygous for K3326* reach old age and have children. Unlike BRCA2 999del5, the K3326* allele does not affect the level of BRCA2 transcripts, and the allele is expressed to the same extent as the wild-type allele. Conclusions: K3326* associates primarily with cancers that have strong environmental genotoxic risk factors. Expression of the K3326* allele suggests that a variant protein may be made that retains the DNA repair capabilities important to hormone-responsive tissues but may be less efficient in responding to genotoxic stress.

[Fast diagnostic track for suspected lung cancer: A patient centered approach].

INTRODUCTION: The aim of this study is to describe the characteristics of patients who underwent a fast diagnostic track (FDT) due to suspected lung cancer at Landspitali University Hospital, Iceland. MATERIAL AND METHODS: Hospital records were reviewed on background characteristics, diagnosis, staging, waiting times and survival of all 550 patients (mean age 68.1 years, 57% female) that participated in the FDT from February 1, 2008 to January 31, 2015. Adjusting for clinical characteristics in a multivariate analysis, overall survival was compared for patients diagnosed with lung cancer within or outside the FDT in Iceland in 2014 (n=167, mean age 69.3 years, 61.7% female). RESULTS: Of the 550 FDT patients, 426 were diagnosed with lung cancer (77.5%); 346 of the non-small cell type (NSCLC) (81.2%). The proportion of patients receiving lung cancer diagnosis through the FDT increased from 23.3% in 2008 to 47.9% in 2014 (p<0.001). The waiting time from referral to diagnosis was 10 days median and 19 days from diagnosis to initiation of treatment. More patients with advanced disease were diagnosed outside the FDT (70.1% vs. 37.5%, p<0.05). When ad-- justed for age, sex, histology, stage at diagnosis and therapy, patients diagnosed with lung cancer outside the FDT had higher risk of all-cause mortality (HR 1.60; 95% CI: 0.95 - 2.71) although the difference was not statistically significant. CONCLUSION: An increasing proportion of lung cancer diagnosis in Iceland is made through a fast diagnostic track with potential benefits for patients. The waiting time from referral to diagnosis and treatment is in line with international guidelines. Key words: lung cancer, non-small cell lung cancer, diagnostic track, waiting times, survival. Correspondence: Hronn Hardardottir, hronnh@landspitali.is.

[Lung Transplantation in Icelanders].

INTRODUCTION: Lung transplantation is a treatment option for end-stage lung diseases, excluding lung cancer, when life expectancy is short and quality of life is poor. In most instances pulmonary function and quality of life improves after lung transplantation. Infections and rejection are the most common complications and limit the feasibility of lung transplantation. MATERIALS AND METHODS: Retrospective analysis of lung transplantations performed on Icelanders from February 1988 to January 2015. Clinical information was obtained from medical records and a database was created. Information on demographics, underlying lung disease, type of transplantation, immunosuppression, rejection and other complications was collected. RESULTS: A total of 21 lung transplantations were performed, one of which was a retransplantation. There were 9 females and 11 males and the mean age was 45 years (20-61 years). Most of the operations were done at the Sahlgrenska hospital in Gothenburg. Bilateral lung transplantion was the most common operation. COPD was the most common indication. Rejection and infections were the most common complications. Eight of 20 patients have had acute rejection and half of the patients chronic rejection. Six of 20 patients are deceased, three died from chronic rejection. Median survival is 8,5 years. Five-year survival is 74%. CONCLUSIONS: Lung transplantations are currently performed at the Sahlgrenska hospital in Gothenburg but follow-up is in the hands of specialized pulmonologists in Iceland. Complications and survival for Icelandic patients is similar to larger centers. Close cooperation with the transplanting center is essential. KEY WORDS: lung transplantation, Icelanders, indications, survival, complications.

[Pulmonary alveolar proteinosis - a case report]. / Próteinútfellingar í lungnablöðrum meðhöndlaðar með lungnaskoli.

Pulmonary alveolar proteinosis (PAP) is a rare lung disease of unknown origin, where an amorphous lipoprotein material accumulates in the alveoli of the lungs. We describe a young male with a four month history of progressive dyspnea, low grade fever, hypoxemia and weight loss. Chest X-ray showed diffuse interstitial and alveolar infiltrates in both lungs. The diagnosis of PAP was confirmed with trans-bronchial lung biopsy. Because of a deteriorating clinical course a whole lung lavage was performed. Under general anesthesia, both lungs were lavaged with warm saline in two different sessions with good results. Two years later the patient is almost free of symptoms and lung function has markedly improved.

[Lung cancer--review]. / Lungnakrabbamein--Yfirlitsgrein.

Lung cancer is the second most common cancer in Iceland and the most frequent cause of cancer related deaths. Smoking is by far the most important cause but familial factors also contribute. The symptoms of lung cancer are often subtle and the diagnosis, in about 70% of cases, is made when metastases have occurred. Curative surgical treatment is therefore only possible in about a third of the cases whereas other patients receive chemotherapy and/or radiation therapy. In recent years some important advances have been made in the diagnostic and therapeutic approaches to lung cancer. New imaging techniques have improved diagnosis and staging practices and consequently also treatment. Recent evidence suggests that screening with low dose CT may improve survival. New approaches to chemotherapy have been shown to improve survival and well being of patients with advanced disease. Chemotherapeutic agents are now being used in conjunction with surgery to reduce the risk of tumour spread. Furthermore, advances in surgical techniques have made resections possible in cases deemed inoperable in the past. In this review we present important advances in the diagnosis and treatment of lung cancer as reflected by recent literature that should be of interest to a wide variety of specialists.

Neuregulin 1 and susceptibility to schizophrenia.

The cause of schizophrenia is unknown, but it has a significant genetic component. Pharmacologic studies, studies of gene expression in man, and studies of mouse mutants suggest involvement of glutamate and dopamine neurotransmitter systems. However, so far, strong association has not been found between schizophrenia and variants of the genes encoding components of these systems. Here, we report the results of a genomewide scan of schizophrenia families in Iceland; these results support previous work, done in five populations, showing that schizophrenia maps to chromosome 8p. Extensive fine-mapping of the 8p locus and haplotype-association analysis, supplemented by a transmission/disequilibrium test, identifies neuregulin 1 (NRG1) as a candidate gene for schizophrenia. NRG1 is expressed at central nervous system synapses and has a clear role in the expression and activation of neurotransmitter receptors, including glutamate receptors. Mutant mice heterozygous for either NRG1 or its receptor, ErbB4, show a behavioral phenotype that overlaps with mouse models for schizophrenia. Furthermore, NRG1 hypomorphs have fewer functional NMDA receptors than wild-type mice. We also demonstrate that the behavioral phenotypes of the NRG1 hypomorphs are partially reversible with clozapine, an atypical antipsychotic drug used to treat schizophrenia.