General health checks in adults for reducing morbidity and mortality from disease.

BACKGROUND: General health checks are common elements of health care in some countries. These aim to detect disease and risk factors for disease with the purpose of reducing morbidity and mortality. Most of the commonly used screening tests offered in general health checks have been incompletely studied. Also, screening leads to increased use of diagnostic and therapeutic interventions, which can be harmful as well as beneficial. It is, therefore, important to assess whether general health checks do more good than harm. OBJECTIVES: We aimed to quantify the benefits and harms of general health checks with an emphasis on patient-relevant outcomes such as morbidity and mortality rather than on surrogate outcomes such as blood pressure and serum cholesterol levels. SEARCH METHODS: We searched The Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Effective Practice and Organisation of Care (EPOC) Trials Register, MEDLINE, EMBASE, Healthstar, CINAHL, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) to July 2012. Two authors screened titles and abstracts, assessed papers for eligibility and read reference lists. One author used citation tracking (Web of Knowledge) and asked trialists about additional studies. SELECTION CRITERIA: We included randomised trials comparing health checks with no health checks in adults unselected for disease or risk factors. We did not include geriatric trials. We defined health checks as screening general populations for more than one disease or risk factor in more than one organ system. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the risk of bias in the trials. We contacted authors for additional outcomes or trial details when necessary. For mortality outcomes we analysed the results with random-effects model meta-analysis, and for other outcomes we did a qualitative synthesis as meta-analysis was not feasible. MAIN RESULTS: We included 16 trials, 14 of which had available outcome data (182,880 participants). Nine trials provided data on total mortality (155,899 participants, 11,940 deaths), median follow-up time nine years, giving a risk ratio of 0.99 (95% confidence interval (CI) 0.95 to 1.03). Eight trials provided data on cardiovascular mortality (152,435 participants, 4567 deaths), risk ratio 1.03 (95% CI 0.91 to 1.17) and eight trials on cancer mortality (139,290 participants, 3663 deaths), risk ratio 1.01 (95% CI 0.92 to 1.12). Subgroup and sensitivity analyses did not alter these findings.We did not find an effect on clinical events or other measures of morbidity but one trial found an increased occurrence of hypertension and hypercholesterolaemia with screening and one trial found an increased occurence of self-reported chronic disease. One trial found a 20% increase in the total number of new diagnoses per participant over six years compared to the control group. No trials compared the total number of prescriptions, but two out of four trials found an increased number of people using antihypertensive drugs. Two out of four trials found small beneficial effects on self-reported health, but this could be due to reporting bias as the trials were not blinded. We did not find an effect on admission to hospital, disability, worry, additional visits to the physician, or absence from work, but most of these outcomes were poorly studied. We did not find useful results on the number of referrals to specialists, the number of follow-up tests after positive screening results, or the amount of surgery. AUTHORS' CONCLUSIONS: General health checks did not reduce morbidity or mortality, neither overall nor for cardiovascular or cancer causes, although the number of new diagnoses was increased. Important harmful outcomes, such as the number of follow-up diagnostic procedures or short term psychological effects, were often not studied or reported and many trials had methodological problems. With the large number of participants and deaths included, the long follow-up periods used, and considering that cardiovascular and cancer mortality were not reduced, general health checks are unlikely to be beneficial.

Anti-interleukin-31-antibodies ameliorate scratching behaviour in NC/Nga mice: a model of atopic dermatitis.

BACKGROUND: Interleukin-31 (IL-31), a novel cytokine, is upregulated in atopic dermatitis skin lesions in humans and skin lesions in the NC/Nga mice, a murine model for atopic dermatitis. OBJECTIVE: Here, we investigated the effect of a monoclonal IL-31 antibody on scratching behaviour, weight gain and dermatitis in NC/Nga mice. METHODS: Mice were divided into three groups, n = 10 in each group. Mice were given monoclonal IL-31 rat-anti-mouse antibody 10 mg/kg or albumin intraperitoneally every fifth day for seven weeks. In addition, the mice in one group were not exposed to any form of intervention. The dermatitis score was clinically assessed twice a week. The scratching behaviour was automatically detected and objectively evaluated. RESULTS: Intervention with IL-31 antibody 10 mg/kg intraperitoneally every fifth day in NC/Nga mice from age 7 weeks reduced the scratching behaviour, but did not have any impact on weight gain or dermatitis. CONCLUSION: IL-31 antibody reduces scratching behaviour in an atopic dermatitis-like murine model during the onset of clinical skin manifestations. Our findings suggest IL-31 antibody as a new potential therapeutic approach for pruritus in atopic dermatitis and other pruritic diseases.

Continuing rise in oropharyngeal cancer in a high HPV prevalence area: A Danish population-based study from 2011 to 2014.

BACKGROUND: Human papillomavirus (HPV) is a critical element in the rising incidence of oropharyngeal squamous cell carcinoma (OPSCC), although whether this trend will continue, and the types of HPV responsible, are currently unknown. We previously demonstrated an increased incidence of HPV-related OPSCC in the high HPV prevalence area of Eastern Denmark from 2000 to 2010. Therefore, we investigated if the incidence for OPSCC continued to rise, the association to HPV and putative HPV-types in Eastern Denmark from 2011 to 14. We then projected the expected incidence of OPSCC versus cervical cancer through to 2020. PATIENTS AND METHODS: Patients with OPSCC (tonsillar squamous cell carcinoma [TSCC] and base of tongue squamous cell carcinoma [BSCC]) were identified via the Danish Head and Neck Cancer Group and the Danish Pathology Databank (n = 700). Tumours were re-reviewed and assessed using p16 immunohistochemistry, HPV DNA polymerase chain reaction (PCR), with genotyping by next generation sequencing. RESULTS: Sixty-two percent (432/700) of tumours were HPV-positive (HPV+). The total incidence rate (per 100.000) for OPSCC increased from 4.0 in 2011 to 4.5 in 2014, primarily due to a rise in HPV+ TSCCs and HPV+ BSCCs, although numbers of HPV-negative (HPV-) OPSCC also increased during the study period. The majority of HPV+ tumours were HPV16 DNA positive (86%), but we also identified HPV33 DNA (6%), HPV35 DNA (4%) and others (3%), including HPV18, 26, 31, 45, 56, 58, 59 and HPV67. CONCLUSION: An increasing incidence of OPSCC is driven primarily by HPV+ OPSCC. Sixty-two percent of tumours were HPV+, which is a high-prevalence, although the lower number of HPV- cases has yet to stabilise. HPV16 was the predominant genotype, although a significant proportion (14%) was of another genotype. Our projections suggest that the number of HPV+ OPSCC will exceed that of cervical cancer in 2016 in Eastern Denmark.

Immune cells and prognosis in HPV-associated oropharyngeal squamous cell carcinomas: Review of the literature.

Currently, oropharyngeal squamous cell carcinomas (OPSCC) are treated based on the traditional TNM-classification, although this scheme might be inadequate for the subgroup of human papillomavirus (HPV)-associated OPSCCs. It remains debatable whether this subgroup of patients with favorable prognosis should be offered altered treatment. Besides the well-known biomarkers of HPV and p16, new promising immune cells and markers might nuance the prognosis and treatment for patients with HPV+ OPSCC. We systematically reviewed the literature on immunological features of HPV-associated OPSCCs, and report that a high number of cytotoxic T cells (CD8s) and a low number of CD98 positive cells is associated with better outcome, while an increased CD4/CD8 ratio and a high human leukocyte antigen 1 (HLA1) intensity is most likely associated with worse outcome. These findings might contribute to future OPSCC staging and treatment.

Mesenchymal Stem Cell Therapy for the Treatment of Vocal Fold Scarring: A Systematic Review of Preclinical Studies.

OBJECTIVES: Therapy with mesenchymal stem cells exhibits potential for the development of novel interventions for many diseases and injuries. The use of mesenchymal stem cells in regenerative therapy for vocal fold scarring exhibited promising results to reduce stiffness and enhance the biomechanical properties of injured vocal folds. This study evaluated the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring. DATA SOURCES: PubMed, Embase, the Cochrane Library and Google Scholar were searched. METHODS: Controlled studies that assessed the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring were included. Primary outcomes were viscoelastic properties and mucosal wave amplitude. RESULTS: Seven preclinical animal studies (n = 152 single vocal folds) were eligible for inclusion. Evaluation of viscoelastic parameters revealed a decreased dynamic viscosity (η') and elastic modulus (G'), i.e., decreased resistance and stiffness, in scarred vocal folds treated with mesenchymal stem cells compared to non-treated scarred vocal folds. Mucosal wave amplitude was increased in scarred vocal folds treated with mesenchymal stem cells vs. non-treated scarred vocal folds. CONCLUSION: The results from these studies suggest an increased regenerative effect of therapy with mesenchymal stem cells for scarred vocal folds and are encouraging for further clinical studies.

Validation study of HPV DNA detection from stained FNA smears by polymerase chain reaction: Improving the diagnostic workup of patients with a tumor on the neck.

BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) often presents with cystic cervical metastasis and a small primary tumor localized in the palatine tonsils or base of the tongue, which is diagnostically challenging. Testing for HPV DNA in fine-needle aspiration (FNA) smears from metastases may facilitate a targeted diagnostic workup for identifying the primary tumor. This study was designed to assess the ability to detect HPV DNA in FNA smears with polymerase chain reaction (PCR). METHODS: May-Grünvald-Giemsa (MGG)-stained FNA smears from metastases and corresponding surgical specimens were collected from 71 patients with known HPV-positive OPSCC, 12 patients with oral squamous cell carcinoma (OSCC), 20 patients with branchial cleft cysts, and 20 patients with Warthin tumors. Thirty-eight patients with OPSCC and 7 patients with OSCC had FNA smears available from metastases and also surgical specimens from the primary tumor and the metastases. The scraped cell material from FNA smears and corresponding surgical specimens were analyzed for HPV DNA by PCR. p16 immunohistochemistry was performed on surgical specimens from the carcinomas. RESULTS: HPV DNA was detected in 68 of the 71 FNA smears from OPSCC metastases. All corresponding surgical specimens from primary tumors (n = 71) and metastases (n = 38) were p16- and HPV DNA-positive. All the surgical specimens and corresponding FNA smears from OSCCs, Warthin tumors, and branchial cleft cysts were HPV DNA-negative. The sensitivity and specificity were 94.7% and 100%, respectively. CONCLUSIONS: The detection of HPV DNA in MGG-stained FNA smears by PCR is a valid method that could be implemented in routine clinical practice. Cancer Cytopathol 2016;124:820-7. © 2016 American Cancer Society.

Developmentally Delayed Male with Mincer Blade Obstructing the Oesophagus for a Period of Time Suspected to Be 6 Months.

Introduction. Sharp, retained foreign bodies in the oesophagus are associated with severe complications. Developmentally delayed patients are especially subject to foreign objects. We describe a 37-year-old, developmentally delayed male with a mincer blade obstructing the oesophagus. Six months prior to surgical intervention, the patient was hospitalized in a condition of sepsis and pneumonia where the thoracic X-ray reveals a foreign body in the proximal oesophagus. When rehospitalized 6 months later, a mincer blade of the type used in immersion blenders was surgically removed. During these 6 months the patient's main symptoms were dysphagia, weight loss, and diarrhoea. When developmentally delayed patients present with dysphagia, we strongly encourage the awareness of the possible presence of foreign bodies. To our knowledge this is the first reported case of a mincer blade in the oesophagus.

A three-generation family with idiopathic facial palsy suggesting an autosomal dominant inheritance with high penetrance.

Idiopathic facial palsy (IFP), also known as Bell's palsy, is a common neurologic disorder, but recurrent and familial forms are rare. This case series presents a three-generation family with idiopathic facial palsy. The mode of inheritance of IFP has previously been suggested as autosomal dominant with low or variable penetrance, but the present family indicates an autosomal dominant trait with high or complete penetrance. Chromosome microarray studies did not reveal a pathogenic copy number variation, which could enable identification of a candidate gene.

Traumatic oesophageal perforation due to haematoma.

INTRODUCTION: Traumatic oesophageal perforation is a rare, life-threatening emergency that requires early recognition and prompt surgical management. PRESENTATION OF CASE: We present an unusual case of a patient on warfarin treatment developed an intramural oesophageal haematoma following blunt thoracic trauma leading to perforation on the 18th day. DISCUSSION: In treatment of oesophageal haematoma in patients on vitamin-K antagonists, strict control of the International Normalized Ratio (INR) is essential along with total parenteral nutrition therapy and refrainment through nasogastric tubes. Three explanations postulated to be the cause for late perforation which might be due to esophageal wall ischemia from pressure built up between the hematoma, azygos vein and the lower part of thoracic trachea; or could be an immediate rupture walled-off until the patient became symptomatic; or the intramural hematoma gradually lysed and causing late perforation. CONCLUSION: Although extremely rare, an oesophageal haematoma and late complications must be considered in patients on anti-coagulant therapy following blunt thoracic trauma and complaining only of chest pain.

Allergic rhinitis is often undiagnosed and untreated: results from a general population study of Danish adults.

INTRODUCTION: A few earlier studies have indicated that allergic rhinitis (AR) is underdiagnosed and undertreated. OBJECTIVE: To assess awareness, diagnosis and treatment of AR in a general population of Danish adults. METHODS: Between October 2007 and June 2008, a total of 1277 consecutive participants in a Danish general population study of 18- to 69-year olds were skin-prick-tested and asked about respiratory symptoms. AR was defined as a combination of self-reported rhinitis symptoms and skin-prick test reactivity against inhalant allergens. Participants reporting rhinitis symptoms completed an additional questionnaire on medication for rhinitis symptoms. RESULTS: The prevalence of AR was 23.1%. A total of 43.6% (n = 122/280) of persons with AR had not received any treatment in the previous 12 months, and only 56.6% (n = 163/288) had been given a diagnosis of hay fever by a doctor. Both AR and lower airway symptoms indicating more severe AR were reported in 48.5% (n = 143/295). These persons were significantly more likely to having received treatment in previous 12 months and a diagnosis of hay fever. CONCLUSION: Our results support that even in an affluent country like Denmark, AR is often undiagnosed and untreated. There appears to be a need for increased awareness of AR with regard to both diagnosis and treatment.

Regular health checks: cross-sectional survey.

OBJECTIVE: To investigate whether Danish providers of general health checks present a balanced account of possible benefits and harms on their websites and whether the health checks are evidence-based. METHODS AND DESIGN: Cross-sectional study. The search engines Google and Jubii (Danish) were in July and August 2009 used to identify 56 websites using Danish search terms for "health check" and "health examination". The content of the websites were evaluated using a checklist with 15 officially recommended information items. All tests offered through the websites were registered. The evidence for tests offered through at least 10% of the websites was identified in structured searches using PubMed and The Cochrane Library. RESULTS: We found 36 different tests on 56 websites offering health checks. Twenty one tests were offered on at least 10% of the websites. Seventeen (81%) of these tests were unsupported by evidence, or there was evidence against them for screening purposes. We found evidence supporting screening using body-mass-index, blood pressure, cholesterol, and faecal occult blood testing. None of the websites mentioned possible risks or harms. The websites presented a median of 1 of the 15 information items; the highest number from any provider was 2. CONCLUSIONS: Information from Danish providers of health checks was sparse and tests were often offered against existing evidence or despite lack of evidence. None of the included websites mentioned potential risks or harms.

General health checks in adults for reducing morbidity and mortality from disease: Cochrane systematic review and meta-analysis.

OBJECTIVES: To quantify the benefits and harms of general health checks in adults with an emphasis on patient-relevant outcomes such as morbidity and mortality rather than on surrogate outcomes. DESIGN: Cochrane systematic review and meta-analysis of randomised trials. For mortality, we analysed the results with random effects meta-analysis, and for other outcomes we did a qualitative synthesis as meta-analysis was not feasible. DATA SOURCES: Medline, EMBASE, Healthstar, Cochrane Library, Cochrane Central Register of Controlled Trials, CINAHL, EPOC register, ClinicalTrials.gov, and WHO ICTRP, supplemented by manual searches of reference lists of included studies, citation tracking (Web of Knowledge), and contacts with trialists. SELECTION CRITERIA: Randomised trials comparing health checks with no health checks in adult populations unselected for disease or risk factors. Health checks defined as screening general populations for more than one disease or risk factor in more than one organ system. We did not include geriatric trials. DATA EXTRACTION: Two observers independently assessed eligibility, extracted data, and assessed the risk of bias. We contacted authors for additional outcomes or trial details when necessary. RESULTS: We identified 16 trials, 14 of which had available outcome data (182,880 participants). Nine trials provided data on total mortality (11,940 deaths), and they gave a risk ratio of 0.99 (95% confidence interval 0.95 to 1.03). Eight trials provided data on cardiovascular mortality (4567 deaths), risk ratio 1.03 (0.91 to 1.17), and eight on cancer mortality (3663 deaths), risk ratio 1.01 (0.92 to 1.12). Subgroup and sensitivity analyses did not alter these findings. We did not find beneficial effects of general health checks on morbidity, hospitalisation, disability, worry, additional physician visits, or absence from work, but not all trials reported on these outcomes. One trial found that health checks led to a 20% increase in the total number of new diagnoses per participant over six years compared with the control group and an increased number of people with self reported chronic conditions, and one trial found an increased prevalence of hypertension and hypercholesterolaemia. Two out of four trials found an increased use of antihypertensives. Two out of four trials found small beneficial effects on self reported health, which could be due to bias. CONCLUSIONS: General health checks did not reduce morbidity or mortality, neither overall nor for cardiovascular or cancer causes, although they increased the number of new diagnoses. Important harmful outcomes were often not studied or reported. SYSTEMATIC REVIEW REGISTRATION: Cochrane Library, doi:10.1002/14651858.CD009009.

Long-term treatment with 0.1% tacrolimus ointment in adults with atopic dermatitis: results of a two-year, multicentre, non-comparative study.

Atopic dermatitis often requires long-term treatment. This European, multicentre, non-comparative, 24-month, follow-up study investigated the efficacy and safety of 0.1% tacrolimus ointment applied to adults with atopic dermatitis. Patients (n=672) applied a thin layer of 0.1% tacrolimus ointment twice daily for 3 weeks to all affected body areas. After 3 weeks, ointment was applied once daily. Clinical improvement became apparent after 2 weeks of treatment and 65.5% of patients had a rating of clearance, excellent or marked improvement by month 3. Skin burning (31.7%) was the most common causally-related adverse event, followed by pruritus (11.3%) folliculitis (6.4%), alcohol intolerance (5.7%), herpes simplex (5.7%), skin infection (4.6%), skin erythema (3.3%) and hyperaesthesia (2.4%). The most commonly reported infections were flu syndrome (12.9%), skin infection (9.8%), folliculitis (7.4%) and herpes simplex (7.0%). Long-term treatment up to 24 months with 0.1% tacrolimus ointment is safe and efficacious in adults with atopic dermatitis.