The potential role of biological treatment of chronic rhinosinusitis with nasal polyps: a nationwide cohort study.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) can be a challenge to treat despite appropriate pharmacological therapy and endoscopic sinus surgery. With the introduction of biological treatment, costs will increase. In this study, we determine the number of patients with CRSwNP treated with endoscopic sinus surgery and revision surgery and thereby fulfil the main criterion for treatment with biologics in the newest European guidelines. Furthermore, we estimate a potential number of recipients of biologics nationwide. METHODS: All adult patients registered in the Danish National Patient Registry as having undergone first endoscopic sinus surgery for CRSwNP from 2012â€"2018 were included. The number of operations, surgery dates, and comorbidities were extracted. The Kaplan-Meier method was used to calculate the revision rate over time. Revision surgery was used as a surrogate to determine the pool of potential recipients of biologics, as these would fulfil the eligibility criteria and ensure the necessary cost-effectiveness. RESULTS: A total of 4667 operated patients with CRSwNP were included out of a population of 4.7 million adults (incidence 14/100,000 person-years). Approximately 18% (120 per year) was estimated to have revision surgery within seven years. The median time to revision surgery was 22 months. Of all analysed patients, 21% had registered asthma and/or allergic rhinitis, while these diseases were registered in 34% of patients treated with revision surgery. CONCLUSION: In Denmark, an average of 120 operated patients annually will have revision surgery within seven years and may benefit from treatment with biologics as an alternative option to revision surgery.

Personal UVR exposure of farming families in four European countries.

BACKGROUND: The main risk factor for skin cancer is ultraviolet radiation (UVR). Farming families living in rural areas with easy outdoor access may experience excessive UVR exposure. Differences between countries in latitude, altitude and sun behaviour could result in different personal UVR exposures. However, no studies have examined this until now. OBJECTIVES: To determine personal UVR exposure in work and leisure situations among farming families in Europe. METHODS: Prospective cohort study of farmers, their partners (spouses) and children in Denmark (DK), Poland (PL), Austria (AT), and Spain (ES) from 2009 to 2011. Personal UVR exposure and sun behaviour were recorded by dosimetry and diaries. RESULTS: Farmers' average daily UVR exposure on working days ranged from 1.4 SED (DK, AT) to 2.7 SED (ES). Corresponding figures for partners were: 0.6 SED (DK) to 1.9 SED (PL), and for children (day-care/school days): 0.7 SED (ES) to 1.3 SED (PL). DISCUSSION AND CONCLUSIONS: Farmers' UVR exposure was comparable to that of outdoor workers in previous studies and exceeded the recommended UVR exposure limits on 36% (DK, AT), 29% (PL) and 56% (ES) of their working days. Attention to sun protection for outdoor workers across Europe in preventing UVR-induced skin cancer is still needed.

Clinical and proctoscopic evaluation of topical formalin application in the treatment of chronic radiation proctitis.

BACKGROUND AND AIMS: Chronic radiation proctitis is a disease associated with radiotherapy of cancer in the pelvic region. The main symptom is rectal bleeding. Several treatment modalities have been attempted, but few have demonstrated satisfactory effects. We present our experience with formalin applied locally to the rectal mucosa in the treatment of chronic radiation proctitis. Furthermore, we assess possible complications, the gravest suggested being cancer. Previous studies on the subject have reported good results, but often with a somewhat vaguely defined follow-up. Our evaluation of the treatment was based on both subjective symptoms and proctoscopic findings. MATERIAL AND METHODS: A small study (N = 11) was conducted retrospectively. All patients treated for chronic radiation proctitis with formalin in our clinic were identified, and data concerning effect and complications were collected by studying the patients' records, with a questionnaire and a follow-up interview and proctoscopy. RESULTS: The study showed a marked decrease in bleeding and objective signs of proctitis in all patients. Complete cessation of bleeding was achieved in five patients. Possible complications to the treatment detected in our study were the following: anorectal pain, tenesmus, incontinence, diarrhea, and mucous rectal discharge. No signs of neoplasia were found. CONCLUSIONS: The formalin treatment had a very good effect on chronic radiation proctitis. Possible complications were detected. Except in the case of anorectal pain, these are all of a questionable nature and can possibly be attributed to chronic radiation proctitis itself rather than the formalin treatment. Further study is warranted to confirm long-term effects of the formalin and to exclude possible complications, especially secondary anorectal cancer.

Photodynamic therapy of actinic keratoses with 8% and 16% methyl aminolaevulinate and home-based daylight exposure: a double-blinded randomized clinical trial.

BACKGROUND: Photodynamic therapy (PDT) is an effective but time-consuming and often painful treatment for actinic keratosis (AK). Home-based daylight-PDT has the potential to facilitate treatment procedure and to reduce associated pain due to continuous activation of small amounts of porphyrins. Moreover, a reduced methyl aminolaevulinate (MAL) concentration may reduce associated inflammation, making the treatment more tolerable for the patients. OBJECTIVES: To compare response rates and adverse effects after PDT using conventional 16% and 8% MAL with home-based daylight exposure in treatment of AK. METHODS: Thirty patients with mostly thin-grade AK of the face or scalp were treated with 16% and 8% MAL-PDT in two symmetrical areas after application of sunscreen. Immediately after, patients left the hospital with instructions to spend the remaining day outside at home in daylight. Patients scored pain during treatment and light exposure was monitored with an electronic wristwatch dosimeter. RESULTS: The complete response rate after 3 months was 76.9% for 16% MAL and 79.5% for 8% MAL (P = 0.37). Patients spent a mean of 244 min outdoors and received a mean effective light dose of 30 J cm(-2). Light doses of 8-70 J cm(-2) induced similar response rates (P = 0.25). Patients experienced mild to moderate pain during daylight exposure (mean maximal pain score of 3.7). No differences in pain scores and erythema were seen between the areas treated with 16% MAL and with 8% MAL. CONCLUSIONS: Home-based daylight-mediated MAL-PDT was an effective and well-tolerated treatment for AK. No differences in response rates or adverse events were found between the areas treated with 16% MAL and with 8% MAL.

Continuous activation of PpIX by daylight is as effective as and less painful than conventional photodynamic therapy for actinic keratoses; a randomized, controlled, single-blinded study.

BACKGROUND: Photodynamic therapy (PDT) is a highly effective treatment for actinic keratoses (AK); however, it is time consuming and often painful for the patient. Daylight-PDT would make the treatment independent of the clinic and less painful due to the continuous activation of small amounts of porphyrins during its formation. OBJECTIVES: The objective of this randomized controlled study was to compare response rates and adverse effects after methyl aminolevulinate (MAL)-PDT using conventional red light-emitting diode (LED) light vs. daylight. PATIENTS/METHODS: Twenty-nine patients with AK of the face and scalp were treated with MAL-PDT in two symmetrical areas. One area was illuminated by red LED light (37 J cm(-2)) after 3-h incubation with MAL under occlusive dressing. The other area was treated with daylight for 2.5 h after the MAL cream had been under occlusion for half an hour. RESULTS: We found no significant difference in the treatment effect between the two treatments (P = 0.13), with a reduction of AK lesions of 79% in the daylight area compared with 71% in the LED area. Treatment response in the daylight area did not depend on the intensity of the daylight. Illumination with LED was more painful than daylight (P < 0.0001). Erythema and crusting occurred after both treatments and were similar in the two areas. CONCLUSIONS: PDT of AK by continuous activation of porphyrins by daylight proved to be as effective as conventional PDT. PDT using daylight activation will make the treatment of these extremely common premalignant tumours more time and cost effective, and more convenient for the patient.

Floc-forming properties of polyphosphate accumulating organisms in activated sludge.

The physico-chemical characteristics of polyphosphate-accumulating organisms (PAO) involved in enhanced biological phosphorus removal (EBPR) was investigated in order to find a novel method for phosphorus recovery. If the physico-chemical characteristics of PAO are different from those of other main floc components, it may be possible to enrich PAO in bulk water or in the floc material for improved recovery of phosphorus. A combination of shear tests, chemical manipulation, and quantification of PAO by fluorescence in situ hybridization was applied. The microcolony strength of both Rhodocyclus-related PAO and Actinobacteria-related PAO was generally high as no treatment could break up more than 20% of all PAO in microcolonies. In contrast, it was possible to remove 20-40% of the organic matter and other bacterial cells by applying a high pH value or adding EDTA. With that a selective enrichment of PAO in the remaining floc material was possible. The feasibility of applying this selective PAO enrichment in flocs remains to be evaluated in full-scale plants for P-recovery.

Risk factors among young women with endometrial cancer: a Danish case-control study.

OBJECTIVE: This study was undertaken to identify and quantify risk factors for endometrial cancer among young women. STUDY DESIGN: This case-control study included all Danish women <50 years old who had endometrial cancer diagnosed during the period 1987 to 1994. A total of 237 case patients and 538 population control subjects matched with the case patients for age and residence were included in the analysis. RESULTS: Women with a family history of endometrial cancer had an odds ratio for endometrial cancer of 2.1 (95% confidence interval, 1.1-3.8)). Completion of 1 term pregnancy implied an odds ratio of 0.6 (95% confidence interval, 0.3-1.1). The risk of endometrial cancer decreased significantly with increasing age at first birth and with the number of induced abortions. Use of oral contraceptives for 1 to 5 years decreased the risk of endometrial cancer (odds ratio, 0.2; 95% confidence interval, 0.1-0.3). The odds ratio for endometrial cancer among women who received hormone replacement therapy for 1 to 5 years was 3.1 (95% confidence interval, 1.4-7.0). Body mass index was not demonstrated to be an independent risk factor in this study. The protective impacts of the different exposures (risk factors) can be expressed as etiologic fractions, which indicate how much each exposure reduces the occurrence of endometrial cancer compared with a situation without the existence of that particular exposure. These fractions were as follows: oral contraceptive use for > or =1 year, -45%; 2 term pregnancies, -88%; age > or =30 y when giving birth for the first time, -38%; and a history of incomplete pregnancy, -16%. CONCLUSION: A number of risk factors for endometrial cancer are common to premenopausal and postmenopausal women: family history, reproductive history, hormone replacement therapy, and the use of oral contraceptives. Among young women reproductive variables imply the greatest prophylactic potential.

Comparison of models used for UV index calculations.

Eighteen radiative transfer models in use for calculation of UV index are compared with respect to their results for more that 100 cloud-free atmospheres, which describe present, possible future and extreme conditions. The comparison includes six multiple-scattering spectral models, eight fast spectral models and four empirical models. Averages of the results of the six participating multiple-scattering spectral models are taken as a basis for assessment. The agreement among the multiple-scattering models is within +/- 0.5 UV index values for more than 80% of chosen atmospheric parameters. The fast spectral models have very different agreement, between +/- 1 and up to 12 UV index values. The results of the empirical models agree reasonably well with the reference models but only for the atmospheres for which they have been developed. The data to describe the atmospheric conditions, which are used for the comparison, together with the individual results of all participating models and model descriptions are available on the Internet: http://www.meteo.physik.uni-muenchen.de/++ +strahlung/cost/.

Transvaginal ultrasound, endometrial cytology sampled by Gynoscann and histology obtained by Uterine Explora Curette compared to the histology of the uterine specimen. A prospective study in pre- and postmenopausal women undergoing elective hysterectomy.

BACKGROUND: The purpose of this study was to evaluate the diagnostic value of transvaginal ultrasound measurement of endometrial thickness, cytology obtained by Gynoscann, and histology of the endometrium sampled by Uterine Explora Curette compared with histology of the uterine specimen as the gold standard. METHODS: Consecutive patients admitted for hysterectomy had transvaginal ultrasound, sampling by Gynoscann, and Uterine Explora Curette done just before surgery, after informed consent. RESULTS: A total of 181 women entered the study. Sixteen had endometrial cancer, seven had atypical hyperplasia and nine had complex hyperplasia. A total of 168 patients had a transvaginal ultrasound done. At a cutoff limit of 4mm (endometrial thickness of 4mm or less indicating normal endometrium), the sensitivity was 90.3%, the specificity 24.8%, the positive predictive value 21.4% and the negative predictive value 91.9%. One endometrial cancer, one atypical and one complex hyperplasia were missed. The Gynoscann method showed a sensitivity of 62.5%, a specificity of 94.0%, a positive predictive value of 69.0% and a negative predictive value of 92.1%. Two cancers, three atypical and six complex hyperplasia were missed. The Uterine Explora Curette showed a sensitivity of 90.6%, a specificity of 100.0%, a positive predictive value of 100.0% and a negative predictive value of 98.0%. One endometrial cancer and two complex hyperplasia were missed. CONCLUSION: Transvaginal ultrasound is a reliable method in excluding endometrial pathology. The Uterine Explora Curette was superior to Gynoscann in diagnosing neoplasia of the endometrium. It was found to have the same diagnostic accuracy as conventional dilatation and curettage.

The importance of leukotrienes in airway inflammation in a mouse model of asthma.

Inhalation of antigen in immunized mice induces an infiltration of eosinophils into the airways and increased bronchial hyperreactivity as are observed in human asthma. We employed a model of late-phase allergic pulmonary inflammation in mice to address the role of leukotrienes (LT) in mediating airway eosinophilia and hyperreactivity to methacholine. Allergen intranasal challenge in OVA-sensitized mice induced LTB4 and LTC4 release into the airspace, widespread mucus occlusion of the airways, leukocytic infiltration of the airway tissue and broncho-alveolar lavage fluid that was predominantly eosinophils, and bronchial hyperreactivity to methacholine. Specific inhibitors of 5-lipoxygenase and 5-lipoxygenase-activating protein (FLAP) blocked airway mucus release and infiltration by eosinophils indicating a key role for leukotrienes in these features of allergic pulmonary inflammation. The role of leukotrienes or eosinophils in mediating airway hyperresponsiveness to aeroallergen could not be established, however, in this murine model.

Thermal artifacts and inter-gynecologist variation of laser cone biopsies of the cervix.

OBJECTIVE: To evaluate the extent of thermal artifacts and the inter-gynecologist variation in CO2 laser cone biopsies for cervical intraepithelial neoplasia (CIN) using high power density. METHODS: All 1180 histologic sections from 93 CO2 laser cone biopsies performed by nine gynecologists were evaluated by morphometry. Power density of 19,700 W/cm2 and spot size of 0.43 mm were used. The lengths of different epithelia, the distance from CIN to the excision margins, the thermal artifacts, and the extension of denudation were analyzed. Mean values and standard deviations were analyzed for all indices. The inter-gynecologist variation was analyzed using one-way analysis of variance, Tukey-Kramer Honestly Significant Difference test, and chi 2 contingency table analysis regarding cones classified as "good" or "not good". RESULTS: The mean length of analyzed surface per cone was 134 mm. In 3% of the sections, the sum of artifacts at the external excision margin exceeded the average "minimum free distance" from CIN to the margin (2.88 mm). At the endocervical excision margin, the free distance was exceeded in 17% of the sections. Eighteen percent of the cones had CIN at the excision margins, with no significant differences between gynecologists (P = .83). Differences existed between gynecologists regarding free minimum distance and minor thermal artifacts at the external margin, but when clinically relevant groups were applied, no significant differences were found (P > .05). CONCLUSION: We found that a high power density at CO2 laser cone biopsy resulted in specimens with minimal thermal artifacts compared to other authors who used low power density. No clinically relevant differences were found between the gynecologists regarding free margins or artifacts.

Outpatient CO2 laser excisional conization for cervical intraepithelial neoplasia under local anesthesia.

AIM AND OBJECTIVE: To evaluate the feasibility of CO2 laser excisional conization in patients with cervical intraepithelial neoplasia (CIN) in an outpatient setting under local anesthesia. DESIGN: A prospective study of women with cervical intraepithelial neoplasia over one year recording early and late complications, cure rate, and patients' compliance. The procedure was performed with a Coherent CO2 laser connected to the colposcope with a micromanipulator. The equipment attaining 19,700 W/cm2, spot diameter 0.43 mm, focus distance 300 mm, and continuous beam. RESULTS: The material included 81 women. Seventy-eight women were treated as outpatients, while three women were admitted for 24 hours observation due to surgical and technical complications during the treatment. Sixty-six percent of the women had bleeding less than 10 ml during the treatment. One woman was admitted 24 hours after surgery due to bleeding requiring suturing. Median operation-time was 11 minutes (range 3-60). All specimens contained CIN. In 76% of the cases the pre- and postoperative diagnosis were identical. Twelve specimens had CIN in one or both margins. Abnormal cytology after conization was found in three cases (4.2%). High patient compliance was found as 92% of the treated women would choose the same kind of treatment if it had to be repeated. CONCLUSION: High success rate, few complications and high patient compliance make the procedure adequate as a routine procedure in treatment and diagnosis of CIN.

[Acceptance of ambulatory laser conization under local anesthesia by Danish women]. / Danske kvinders accept af ambulant laserkonisation i lokalanaestesi.

The aim of the study was to evaluate the acceptability of CO2 laser excisional conization for cervical intraepithelial neoplasia under local anaesthesia in an outpatient setting. Seventy-seven patients, who underwent this procedure, were interviewed three months later concerning pain during treatment, pain and bleeding in the immediate postoperative period, and their general opinion about this procedure. The median duration of surgery was 11 minutes. The postoperative median observation time was 90 minutes. Seventy-one women experienced no discomfort during treatment. Thirty-one patients needed mild analgesics for an average of three days. Bleeding continued for a mean of 7.7 days after treatment and 73% experienced the bleeding as less, 8% as more as compared to menstrual bleeding. Ninety-two percent of the women would prefer this procedure if they had to undergo conization once again. In conclusion, we found a high acceptability in women treated with CO2 laser excisional conization under local anaesthesia in an outpatient setting.

Low-dose 17 beta-estradiol vaginal tablets in the treatment of atrophic vaginitis: a double-blind placebo controlled study.

The aim of the study was to investigate the effect of 25 micrograms 17 beta-estradiol administered as a small vaginal tablet (Vagifem, Novo Nordisk A/S) on the symptoms of the vagina related to atrophy. The study was designed as a double-blind randomized placebo controlled study running for 12 weeks. The women were treated once daily for 2 weeks with the active or the placebo tablet. During the subsequent 10 weeks the women were treated twice a week. One hundred and sixty-four women were included. Ten dropped out for minor reasons, most of these due to lack of effect in the placebo group. In the Vagifem group 78.8% were suffering from moderate to severe atrophy of the vagina, compared with 81.9% in the placebo group. After 2 weeks the percentages were 14.3 and 35.3, respectively. After 12 weeks of treatment, 10.7% in the Vagifem group compared with 29.9% in the placebo group had moderate to severe atrophy (P less than 0.0001). A substantial part of the women complained about subjective symptoms such as vaginal dryness and dyspareunia. After 12 weeks of treatment, a significant improvement was found in the Vagifem group (P less than 0.002). Before treatment 53.1% in the treatment group and 41.0% in the placebo group were suffering from urological symptoms. After 2 weeks, 60.5% of the women in the Vagifem group underwent a change for the better compared to 35.3% in the placebo group. After 12 weeks of treatment the percentages in the two groups feeling an improvement were 62.8% and 32.4%. In this study local low-dose treatment with 25 micrograms 17 beta-estradiol was found to have a significant effect on the postmenopausal urogenital symptoms related to atrophy.

Induction of labour: the effect of vaginal prostaglandin or i.v. oxytocin--a matter of time only?

Ninety-one pregnant women with unfavourable cervix (Bishop score no higher than 6) were randomly allocated to induction of labour with either prostaglandin E2 suppositories 2.5 mg 1-2 a day or i.v. oxytocin 4-32 mU/min. The induction procedure was carried on for 2 days. For statistical comparison of efficacy, life table analysis and the logrank test were used with vaginal delivery as the aimed 'event'. Prostaglandin suppositories were more efficient after 12 h (p less than 0.025) and 24 h (p less than 0.005), whereas no difference in efficacy was observed after 48 h. Vaginal delivery was obtained within 48 h in 74% of the women in the prostaglandin group and in 70% in the oxytocin group. No difference was observed in methods of delivery or neonatal Apgar scores, though, in neonates delivered vaginally within 2 days, lowered umbilical artery blood pH values were found after prostaglandin E2 suppositories (p less than 0.05). The patients attitude toward the method of induction was highly in favour of the prostaglandin suppositories. Prostaglandin E2 suppositories are considered excellent for induction of labour if delivery has to be within 24 h, whereas the two methods are equally effective after 48 h.

Lamicel does not promote induction of labour. A randomized controlled study.

Lamicel is a synthetic tent, which, when inserted in the cervical canal, dilates the cervix by osmosis. Lamicel as an adjunct to induction of labour with intravenous oxytocin or vaginal prostaglandin E2 has been examined in a randomized controlled trial. Ninety-one pregnant women with an unripe cervix participated in the study. No improvement in efficacy was observed in the Lamicel groups compared to the control groups, neither when induction of labour was performed with oxytocin nor with vaginal prostaglandin.