From the Diabetes Trials Unit (R.R.H., S.K.P., M.A.B.), the Division of Public Health and Primary Health Care (H.A.W.N.), and the National Institute of Health Re- search (NIHR) School for Primary Care Research (H.A.W.N.), Oxford Centre for Diabetes, Endocrinology, and Metabo- lism (R.R.H., S.K.P., M.A.B., D.R.M., H.A.W.N.); and the NIHR Oxford Bio- medical Research Centre (R.R.H., D.R.M., H.A.W.N.) — both in Oxford, United Kingdom. Address reprint requests to Dr. Holman at the Diabetes Trials Unit, Ox- ford Centre for Diabetes, Endocrinology, and Metabolism, Churchill Hospital, Head- ington, Oxford OX3 7LJ, United Kingdom, or at rury.holman@dtu.ox.ac.uk. Background During the United Kingdom Prospective Diabetes Study (UKPDS), patients with type 2 diabetes mellitus who received intensive glucose therapy had a lower risk of microvascular complications than did those receiving conventional dietary therapy. We conducted post-trial monitoring to determine whether this improved glucose con- trol persisted and whether such therapy had a long-term effect on macrovascular outcomes. Methods Of 5102 patients with newly diagnosed type 2 diabetes, 4209 were randomly assigned to receive either conventional therapy (dietary restriction) or intensive therapy (either sulfonylurea or insulin or, in overweight patients, metformin) for glucose control. In post-trial monitoring, 3277 patients were asked to attend annual UKPDS clinics for 5 years, but no attempts were made to maintain their previously assigned thera- pies. Annual questionnaires were used to follow patients who were unable to attend the clinics, and all patients in years 6 to 10 were assessed through questionnaires. We examined seven prespecified aggregate clinical outcomes from the UKPDS on an intention-to-treat basis, according to previous randomization categories. Results Between-group differences in glycated hemoglobin levels were lost after the first year. In the sulfonylurea-insulin group, relative reductions in risk persisted at 10 years for any diabetes-related end point (9%, P = 0.04) and microvascular disease (24%, P = 0.001), and risk reductions for myocardial infarction (15%, P = 0.01) and death from any cause (13%, P = 0.007) emerged over time, as more events occurred. In the metformin group, significant risk reductions persisted for any diabetes-relat- ed end point (21%, P = 0.01), myocardial infarction (33%, P = 0.005), and death from any cause (27%, P = 0.002). Conclusions Despite an early loss of glycemic differences, a continued reduction in microvascu- lar risk and emergent risk reductions for myocardial infarction and death from any cause were observed during 10 years of post-trial follow-up. A continued benefit after metformin therapy was evident among overweight patients. (UKPDS 80; Current Controlled Trials number, ISRCTN75451837.)

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10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes

Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations.

In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease.

This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work.

The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available.

Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed.

The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients.

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Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)

Authors Jan L. Brozek, MD, PhD – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada Jean Bousquet, MD, PhD – Service des Maladies Respiratoires, Hopital Arnaud de Villeneuve, Montpellier, France, INSERM, CESP U1018, Respiratory and Environmental Epidemiology Team, France, and WHO Collaborating Center for Rhinitis and Asthma Carlos E. Baena-Cagnani, MD – Faculty of Medicine, Catholic University of Cordoba, Cordoba, Argentina Sergio Bonini, MD – Institute of Neurobiology and Molecular Medicine – CNR, Rome, Italy and Department of Medicine, Second University of Naples, Naples, Italy G. Walter Canonica, MD – Allergy & Respiratory Diseases, DIMI, Department of Internal Medicine, University of Genoa, Genoa, Italy Thomas B. Casale, MD – Division of Allergy and Immunology, Department of Medicine, Creighton University, Omaha, Nebraska, USA Roy Gerth van Wijk, MD, PhD – Section of Allergology, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands Ken Ohta, MD, PhD – Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan Torsten Zuberbier, MD – Department of Dermatology and Allergy, Charite Universitatsmedizin Berlin, Berlin, Germany Holger J. Schunemann, MD, PhD, MSc – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada

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Allergic Rhinitis and Its Impact on Asthma

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

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European Position Paper on Rhinosinusitis and Nasal Polyps 2020

ContextIn the intensive care unit (ICU), delirium is a common yet underdiagnosed
form of organ dysfunction, and its contribution to patient outcomes is unclear.ObjectiveTo determine if delirium is an independent predictor of clinical outcomes,
including 6-month mortality and length of stay among ICU patients receiving
mechanical ventilation.Design, Setting, and ParticipantsProspective cohort study enrolling 275 consecutive mechanically ventilated
patients admitted to adult medical and coronary ICUs of a US university-based
medical center between February 2000 and May 2001. Patients were followed
up for development of delirium over 2158 ICU days using the Confusion Assessment
Method for the ICU and the Richmond Agitation-Sedation Scale.Main Outcome MeasuresPrimary outcomes included 6-month mortality, overall hospital length
of stay, and length of stay in the post-ICU period. Secondary outcomes were
ventilator-free days and cognitive impairment at hospital discharge.ResultsOf 275 patients, 51 (18.5%) had persistent coma and died in the hospital.
Among the remaining 224 patients, 183 (81.7%) developed delirium at some point
during the ICU stay. Baseline demographics including age, comorbidity scores,
dementia scores, activities of daily living, severity of illness, and admission
diagnoses were similar between those with and without delirium (P>.05 for all). Patients who developed delirium had higher 6-month
mortality rates (34% vs 15%, P = .03) and spent 10
days longer in the hospital than those who never developed delirium (P<.001). After adjusting for covariates (including age,
severity of illness, comorbid conditions, coma, and use of sedatives or analgesic
medications), delirium was independently associated with higher 6-month mortality
(adjusted hazard ratio [HR], 3.2; 95% confidence interval [CI], 1.4-7.7; P = .008), and longer hospital stay (adjusted HR, 2.0;
95% CI, 1.4-3.0; P<.001). Delirium in the ICU
was also independently associated with a longer post-ICU stay (adjusted HR,
1.6; 95% CI, 1.2-2.3; P = .009), fewer median days
alive and without mechanical ventilation (19 [interquartile range, 4-23] vs
24 [19-26]; adjusted P = .03), and a higher incidence
of cognitive impairment at hospital discharge (adjusted HR, 9.1; 95% CI, 2.3-35.3; P = .002).ConclusionDelirium was an independent predictor of higher 6-month mortality and
longer hospital stay even after adjusting for relevant covariates including
coma, sedatives, and analgesics in patients receiving mechanical ventilation.

https://jamanetwork.com/journals/jama/articlepdf/198503/JCE30038.pdf

Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit

Background and aim: Perennial allergic rhinitis may impair social life. General scales of quality of life (QOL) are used to detect the importance of social life impairment, but the reliability and validity of QOL measures should be tested in patients with perennial allergic rhinitis. The extent to which QOL scores differ in patients with rhinitis and healthy subjects is unknown. Methods: A cross-sectional study was carried out in 111 patients with moderate to severe perennial allergic rhinitis and 116 healthy subjects to assess the validity of a general QOL scale, the SF-36 Health Status Questionnaire. This scale is based on 36 items selected to represent nine health concepts (dimensions). The internal reliability of each dimension of the questionnaire was examined. The differences in QOL scores between patients with rhinitis and healthy subjects were studied. Results: Most QOL scores were highly reliable. There was a significant impairment in eight of nine QOL dimensions in patients with perennial allergic rhinitis in comparison with healthy subjects. Conclusions: The SF-36 Health Status Questionnaire allows discrimination between patients with perennial allergic rhinitis and healthy subjects.

https://www.jacionline.org/article/0091-6749(94)90038-8/pdf

Assessment of quality of life in patients with perennial allergic rhinitis with the French version of the SF-36 Health Status Questionnaire

BACKGROUND AND AIM: Perennial allergic rhinitis impairs social life, but it is not known whether quality of life may be improved when patients are treated with an H 1 -blocker. A randomized, double-blind, placebo-controlled study was carried out with cetirizine to assess the effect of this drug on quality of life. METHODS: Two hundred seventy-four patients with perennial allergic rhinitis were tested. Quality of life was measured by using the Medical Outcome Study Short-Form Health Survey (SF-36) questionnaire. After a 2-week run-in period, cetirizine, 10 mg once daily, (136 patients) or placebo (138 patients) was given for the next 6 weeks. The SF-36 questionnaire was administered after the run-in period (at the start of treatment) and after 1 and 6 weeks of treatment. Symptom-medication scores were measured daily during the study. RESULTS: After the run-in period (baseline), there were no significant differences between the cetirizine and placebo groups in terms of symptoms or quality-of-life scores. After 6 weeks of treatment, percentage of days without rhinitis or with only mild rhinitis symptoms was significantly greater in the cetirizine group in comparison with the placebo group ( p p = 0.01 to p CONCLUSIONS: This study is the first to demonstrate that an H 1 -blocker, cetirizine, can improve quality of life for patients with perennial allergic rhinitis. (J ALLERGY CLIN IMMUNOL 1996;98:309-16.)

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Improvement of quality of life by treatment with cetirizine in patients with perennial allergic rhinitis as determined by a French version of the SF-36 questionnaire☆☆☆★

Objective

The aim of this study was to examine whether delirium has specific clinical subtypes.



Method

One hundred and eighty-three elderly subjects meeting DSM-IIIR criteria for delirium were evaluated using a 19-item symptom check-list assessing different dimensions of delirium symptomatology. Exploratory factor analysis was conducted in order to examine which symptoms clustered.



Results

Factor analysis confirmed the existence of two different clusters of symptoms: first, symptoms of hyperalert/hyperactive features (agitation, hyper-reactivity, aggressiveness, hallucinations, delusions); and second, symptoms of hypoalert/hypoactive features (decreased reactivity, motor and speech retardation, facial inexpressiveness).



Conclusion

This preliminary study seems to support the evidence of hypoactive and hyperactive subtypes of delirium, even though their aetiology and prognostic values need to be further examined. Copyright © 2000 John Wiley & Sons, Ltd.

Factor analysis supports the evidence of existing hyperactive and hypoactive subtypes of delirium.

Forty-five patients with residual or recurrent nasal polyposis after ethmoidectomy were treated with either cetirizine at twice the daily recommended (20 mg) dose or placebo for three months. The number and size of polyps remained unchanged during the study period. Cetirizine was found to reduce nasal sneezing and rhinorrhoea effectively. The drug also had a beneficial effect on nasal obstruction in the latter part of the study. The side effects of 20 mg (double the recommended daily adult dose) of cetirizine were few and comparable to placebo.

The effect of cetirizine on symptoms and signs of nasal polyposis

The SF-36 Health Status Questionnaire is a generic quality of life questionnaire based on 36 questions selected to represent nine health concepts. Perennial allergic rhinitis is a disease which causes variable restrictions on the physical, psychological and social aspects of patients' lives. According to the SF-36 questionnaire assessment, quality of life is impaired in these patients. Cetirizine, a potent, reliable histamine H1-receptor antagonist, has already been found to induce significant improvement in the quality of life of patients with chronic rhinitis, as assessed by the same SF-36 questionnaire after 1 and 6 weeks of treatment. This paper further investigates the extent to which cetirizine continues to improve quality of life after a long-term treatment (6 weeks) compared to a shorter treatment (1 week). The analyses show that, despite the significant improvement found after 1 week of treatment with cetirizine compared to placebo, a further 5-week course of therapy not only maintains this improvement but continues to enhance quality of life significantly above and beyond this.

Bernard Burtin

Papers

Assessment of quality of life in patients with perennial allergic rhinitis with the French version of the SF-36 Health Status Questionnaire

Improvement of quality of life by treatment with cetirizine in patients with perennial allergic rhinitis as determined by a French version of the SF-36 questionnaire☆☆☆★

Factor analysis supports the evidence of existing hyperactive and hypoactive subtypes of delirium.

The effect of cetirizine on symptoms and signs of nasal polyposis

Further improvement of quality of life by cetirizine in perennial allergic rhinitis as a function of treatment duration.