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A 52-week postmarketing surveillance study was initiated to evaluate the safety and effectiveness of guselkumab, a human anti-interleukin 23 subunit p19 monoclonal antibody, in Japanese patients with psoriasis vulgaris, psoriatic arthritis, generalized pustular psoriasis, and erythrodermic psoriasis in real-world practice. Here, we report results of the 20-week interim analysis of the ongoing postmarketing surveillance study. Patients who received guselkumab between May 2018 (the date of commercial launch in Japan) and October 2020 were registered in this study. In total, 411 and 245 patients were included in the safety and effectiveness analysis sets, respectively. Adverse drug reactions (ADRs) occurred in 6.6% (27 of 411) and serious ADRs in 2.2% (nine of 411) of patients. The most frequent ADRs by System Organ Class were "Infections and infestations" (2.4%), with nasopharyngitis being the most frequently observed ADR (0.7%). The mean Psoriasis Area Severity Index score decreased from 11.6 at baseline to 6.5 at week 4 and 2.2 at week 20, with improvements achieving statistical significance at each time point. Clinical Global Impression, Dermatology Life Quality Index, and Nail Psoriasis Severity Index outcomesalso showed substantial improvements. Our findings demonstrate that guselkumab is well tolerated and effective in Japanese patients with psoriasis through 20 weeks of treatment in real-world clinical practice, showing significant effectiveness observed as early as 4 weeks. The study was officially registered with the University Hospital Medical Information Network Clinical Trials Registry with the identifier UMIN000032969., (© 2024 Janssen Pharmaceutical K.K. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Importance: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced disease severity in moderate to severe atopic dermatitis (AD) in 2 phase 3 monotherapy studies., Objective: To assess the efficacy and safety of 4 mg and 2 mg of baricitinib in combination with background topical corticosteroid (TCS) therapy in adults with moderate to severe AD who previously had an inadequate response to TCS therapy., Design, Setting, and Participants: This double-blind, placebo-controlled, phase 3 randomized clinical trial, BREEZE-AD7 (Study of Baricitinib [LY3009104] in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis) was conducted from November 16, 2018, to August 22, 2019, at 68 centers across 10 countries in Asia, Australia, Europe, and South America. Patients 18 years or older with moderate to severe AD and an inadequate response to TCSs were included. After completing the study, patients were followed up for up to 4 weeks or enrolled in a long-term extension study., Interventions: Patients were randomly assigned (1:1:1) to receive 2 mg of baricitinib once daily (n = 109), 4 mg of baricitinib once daily (n = 111), or placebo (n = 109) for 16 weeks. The use of low-to-moderate potency TCSs was allowed., Main Outcomes and Measures: The primary end point was the proportion of patients achieving a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear), with a 2-point or greater improvement from baseline at week 16., Results: Among 329 patients (mean [SD] age, 33.8 [12.4] years; 216 [66%] male), at week 16, a vIGA-AD score of 0 (clear) or 1 (almost clear) was achieved by 34 patients (31%) receiving 4 mg of baricitinib and 26 (24%) receiving 2 mg of baricitinib compared with 16 (15%) receiving placebo (odds ratio vs placebo, 2.8 [95% CI, 1.4-5.6]; P = .004 for the 4-mg group; 1.9 [95% CI, 0.9-3.9]; P = .08 for the 2-mg group). Treatment-emergent adverse events were reported in 64 of 111 patients (58%) in the 4-mg group, 61 of 109 patients (56%) in the 2-mg group, and 41 of 108 patients (38%) in the placebo group. Serious adverse events were reported in 4 patients (4%) in the 4-mg group, 2 (2%) in the 2-mg group, and 4 (4%) in the placebo group. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and folliculitis., Conclusions and Relevance: A dose of 4 mg of baricitinib in combination with background TCS therapy significantly improved the signs and symptoms of moderate to severe AD, with a safety profile consistent with previous studies of baricitinib in AD., Trial Registration: ClinicalTrials.gov Identifier: NCT03733301.

Background: Management of moderate-to-severe atopic dermatitis (AD) commonly requires long-term treatment., Objective: The aim of this study was to report the safety and efficacy of dupilumab treatment for up to 3 years in adults with moderate-to-severe AD., Methods: This ongoing, multicenter, open-label extension study (LIBERTY AD OLE; NCT01949311) assessed dupilumab treatment in adults previously enrolled in dupilumab trials. Patients received dupilumab 300 mg weekly up to 148 weeks. The primary outcome was safety., Results: Of 2677 patients enrolled and treated, 347 reached week 148. Mean self-reported drug compliance was 98.2%. Safety data were consistent with previously reported trials (270.1 adverse events [AEs]/100 patient-years; 6.9 serious AEs/100 patient-years) and the known dupilumab safety profile. Common AEs (≥ 5% of patients) included nasopharyngitis, AD, upper respiratory tract infection, conjunctivitis, headache, oral herpes, and injection-site reactions. AD signs and symptoms showed sustained improvements during treatment with mean (standard deviation, mean percentage change from parent study baseline) Eczema Area and Severity Index 1.4 (3.2, - 95.4%) and weekly Pruritus Numerical Rating Scale 2.2 (1.8, - 65.4%) at week 148., Limitations: No control arm; fewer patients at later time points; regimen different from the approved 300 mg every 2 weeks dose., Conclusion: These safety and efficacy results support dupilumab as a continuous long-term treatment for adults with moderate-to-severe AD., Trial Registration: ClinicalTrials.gov: NCT01949311. Dupilumab provides favorable safety and sustained efficacy for up to 3 years in an open-label study of adults with moderate-to-severe atopic dermatitis (MP4  139831 kb).

Brodalumab, an interleukin-17 receptor A inhibitor, demonstrated rapid and robust efficacy with a favorable safety profile in patients with moderate to severe plaque psoriasis. Here, we present data from a multicenter, open-label extension study in patients with plaque psoriasis with/without psoriatic arthritis who completed 64 weeks of treatment with brodalumab (140 or 210 mg, every 2 weeks [Q2W]). Patients were enrolled to evaluate the long-term safety and efficacy of a modified dose of brodalumab. Eligible patients were switched to a reduced dose of brodalumab (140 mg every 4 weeks on day 1) in the extension study; the dose and dosing interval were modified sequentially at the physician's discretion (minimum 140 mg every 8 weeks and maximum 210 mg Q2W) until drug approval, after which all patients were switched to 210 mg Q2W for postmarketing surveillance. Of the 129 patients enrolled, 107 (82.9%) completed the 108-week or more extension study. All patients had psoriasis that was well controlled with brodalumab treatment on day 1. Improvement in psoriasis-related symptoms, evaluated with the Psoriasis Area and Severity Index, Psoriasis Scalp Severity Index, Dermatology Life Quality Index, Nail Psoriasis Severity Index, and American College of Rheumatology 20, 50 and 70, was maintained during the 108-week extension study. Brodalumab treatment was well tolerated throughout, and no new safety signals were identified. The most commonly reported treatment-related adverse event was nasopharyngitis, followed by influenza and oral candidiasis. No cases of serious candida infection or Crohn's disease were observed in this study. Serious treatment-related adverse events, such as appendicitis, brain abscess, bacterial meningitis, colon cancer, immunoglobulin A nephropathy and tubulointerstitial nephritis, were reported in one patient each. No anti-brodalumab-binding antibodies or brodalumab-neutralizing antibodies were detected in any patient throughout the extension study. Overall, the long-term efficacy and safety of brodalumab were demonstrated over 108 weeks., (© 2020 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Objectives: To determine long-term safety and efficacy of sarilumab as monotherapy or with non-methotrexate (MTX) conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in Japanese patients with active rheumatoid arthritis (RA). Methods: In this double-blind, randomized study (NCT02373202), patients received subcutaneous sarilumab 150 mg q2w (S150) or 200 mg q2w (S200) as monotherapy or with non-MTX csDMARDs for 52 weeks. The primary endpoint was safety. Results: Sixty-one patients received monotherapy (S150, n  = 30; S200, n  = 31) and 30 received combination therapy (S150 + csDMARDs, n  = 15; S200 + csDMARDs, n  = 15). Rates of treatment-emergent adverse events (TEAEs) were 83.3%/90.3%/93.3%/86.7% for S150/S200/S150 + csDMARDs/S200 + csDMARDs, respectively. Nasopharyngitis and neutropenia were the most frequently reported TEAEs. One serious infection was reported in each monotherapy group and in the S200 + csDMARDs group. There were no cases of grade 4 neutropenia; no patients with grade 3 neutropenia experienced associated serious infection. Improvements in ACR20/50/70 response rates were generally similar between the two monotherapy groups and between the two combination groups; improvements in physical function (Health Assessment Questionnaire-Disability Index, HAQ-DI) and DAS28-CRP were observed at weeks 24 and 52 (all groups). Conclusion: The safety profile of sarilumab was consistent with known class effects of interleukin-6 signaling blockade therapeutics. Sarilumab as mono- or combination therapy improved clinical signs/symptoms and physical function in Japanese RA patients.

Previous studies demonstrated that delgocitinib ointment, a novel topical Janus kinase inhibitor, rapidly improved clinical signs and symptoms of atopic dermatitis (AD) in Japanese adult patients. We sought to evaluate the long-term safety and efficacy of delgocitinib 0.5% ointment in a 52-week study (QBA4-2). Japanese patients aged 16 years or older with AD received delgocitinib 0.5% ointment b.i.d. for up to 52 weeks. Topical corticosteroids for the treatment of worsening of AD could be used at the investigators' discretion during the treatment period. Safety end-points included the incidence and severity of adverse events (AEs). Pooled safety analyses included the data from the other long-term study (QBA4-1). Efficacy end-points included the percentage change from baseline in the modified Eczema Area and Severity Index (mEASI). A total of 506 patients were included in the pooled safety population. Overall, AEs were reported in 69.0% of patients; most AEs were mild and unrelated to delgocitinib ointment. The most common AE was nasopharyngitis, followed by contact dermatitis, acne, and application site folliculitis. No skin atrophy or telangiectasia was found at the application sites of delgocitinib ointment. Application site irritation symptoms were infrequent (<2%) and mild. The incidence of AEs did not increase over time, except for seasonal diseases. The improvement effects on AD as assessed by mEASI were maintained throughout the treatment period. Delgocitinib 0.5% ointment was well tolerated and effective when administrated to Japanese adult patients with AD for up to 52 weeks., (© 2019 Japan Tobacco Inc. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd.)

Psoriasis is a chronic, recurrent, inflammatory, and proliferative skin disease. Its etiology has not yet been fully assessed, but undoubtedly it is a multifaceted disease. The key role in its pathomechanism is played by genetic, immunologic, and environmental factors and stress. If traditional methods of psoriasis treatment (phototherapy, methotrexate, retinoids, cyclosporine A) fail, we reach for the following biopharmaceuticals - infliximab, etanercept, adalimumab, or ustekinumab. However, genetic engineering progress discovers new possibilities - the pending clinical trials involve IL-17, IL-23 antagonists, PDE4 and -3 and -1. Psoriasis etiopathogenesis mainly involves the IL-17A, IL-17F, and IL-17A/F subtypes, which affect the keratinocytes. The biological therapy molecularly oriented with the antagonists of interleukin 17 is based mainly on the influence onto the cytokine in the manner that prevents it from binding with the receptor. Three biopharmaceuticals are currently under third phase studies: two fully humanized antibodies neutralizing IL-17 - ixekizumab and secukinumab, and one human monoclonal antibody, brodalumab. The below work will be devoted to the analysis of possible undesirable symptoms, which were observed during the studies. We will try to review the latest literature concerning the most important clinical trials conducted in many centers., (© 2019 The International Society of Dermatology.)

Objectives: We aimed to assess the effects of short-term and long-term exposure to ambient fine particle matter (PM 2.5 ) on acute nasopharyngitis., Methods: A total of 9468 participants aged 18 years and above were recruited from 10 communities in four cities of Guangdong, China during the baseline survey in 2014, and they were followed-up from January 2015 to December 2016. Air pollution exposure was assessed based on the daily concentrations (short-term) and annual concentrations (long-term) of the nearby air monitoring station and the survey date. A mixed-effect logistic model and Cox proportional hazards model were used to quantify the short-term and long-term associations after adjustment for potential confounding factors., Results: Significantly positive associations were found between both short-term and long-term exposures of PM 2.5 and acute nasopharyngitis. The adjusted odds ratio was 1.15 (95% CI: 1.07, 1.23) for each 10 μg/m 3 increase in daily PM 2.5 at lag2 day (short-term effects), and the hazard risk was 1.18 (95% CI: 1.10, 1.25) for each 10 μg/m 3 increase in annual PM 2.5 (long-term effects). Stronger associations between short-term PM 2.5 exposure and acute nasopharyngitis were observed among men (OR = 1.10; 95% CI: 1.04, 1.17) and participants aged above 65 years (OR = 1.13; 95% CI: 1.04, 1.23) in the stratified analyses. No significant association was found in women (OR = 1.00; 95% CI: 0.92, 1.10) or young participants ≤65 years (OR = 0.96; 95% CI: 0.88, 1.04). However, for the long-term exposure, the hazard risk was higher for participants younger than 65 years (OR = 1.22; 95% CI: 1.12, 1.32) than the older group (OR = 1.11; 95% CI: 1.00, 1.24)., Conclusion: This study indicates that both short-term and long-term exposures to higher concentrations of PM 2.5 could increase the risk of acute nasopharyngitis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To evaluate the long-term safety (primary objective) and efficacy (secondary objective) of antimuscarinic add-on therapy in patients receiving mirabegron., Methods: During a 2-week screening period, patients (aged ≥20 years, mirabegron treatment for ≥6 weeks, residual overactive bladder symptoms) received mirabegron 50 mg once daily. These patients were subsequently randomized to 52 weeks' treatment with mirabegron 50 mg/day plus an antimuscarinic (solifenacin 5 mg, propiverine 20 mg, imidafenacin 0.2 mg, or tolterodine 4 mg) with the potential to double the antimuscarinic dose (except for tolterodine) at week 8. Safety assessments included treatment-emergent adverse events, vital signs, 12-lead electrocardiograms, post-void residual volume, and laboratory evaluations. Efficacy was assessed using changes from baseline in overactive bladder symptom score total score; overactive bladder questionnaire short form score; micturitions, urgency episodes, urinary incontinence episodes, and urgency urinary incontinence episodes/24 h; mean volume voided per micturition; and number of night-time micturitions., Results: Overall, 80.2% of patients (88.1% women, mean age 65 years) experienced at least one treatment-emergent adverse event, with similar rates for all treatments. The adverse events most commonly reported were dry mouth, nasopharyngitis, and constipation. No marked change was observed in systolic or diastolic blood pressure for any treatment, although pulse rate increased slightly in the mirabegron and propiverine, and mirabegron and tolterodine groups. For all treatments, significant improvements were observed in all efficacy parameters, including overactive bladder symptom score total and questionnaire short form scores., Conclusions: Antimuscarinic add-on therapy is well tolerated and effective after initial treatment with mirabegron in patients with overactive bladder symptoms., (© 2018 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.)

Objective: The present study aimed to assess the long-term safety and tolerability of valsartan in hypertensive children aged 6-17 years, with or without chronic kidney disease (CKD)., Methods: This was an 18-month, open-label, multicentre, prospective study conducted in 150 patients with history of hypertension with or without CKD. The primary endpoint was long-term safety and tolerability of valsartan and valsartan-based treatments, assessed in terms of adverse events (AEs), serious AEs, laboratory measurements, estimated glomerular filtration rate (eGFR), urinalysis and electrocardiogram., Results: Of 150 enrolled patients, 117 (78%) completed the study. At week 78, a clinically and statistically significant reduction in mean sitting systolic and diastolic blood pressures was observed in all patients (- 14.9 mmHg and - 10.6 mmHg, respectively). Within the first 3 months of treatment, mean urine albumin creatinine ratio decreased in CKD population, which was sustained. A higher percentage of CKD patients had at least one AE compared to non-CKD patients (85.3% vs. 73.3%, respectively). The majority of AEs were mild (50.7%) or moderate (18.7%) in severity. As expected, in patients with underlying CKD, increases in serum potassium, creatinine and blood urea nitrogen were more commonly reported compared to non-CKD patients. A > 25% decrease in Schwartz eGFR was observed in 28.4% of CKD patients and 13.5% of non-CKD patients., Conclusions: Valsartan was generally well tolerated, with an AE profile consistent with angiotensin receptor blockers in the overall population and in patients with underlying CKD. Long-term efficacy was maintained and a beneficial effect on proteinuria was observed.

Background: Adalimumab (Humira ® , AbbVie Inc., North Chicago, IL, U.S.A.) is a fully human monoclonal antibody specific for tumour necrosis factor-α that is approved to treat adults with moderate-to-severe chronic plaque psoriasis., Objectives: To assess long-term safety for patients with psoriasis receiving adalimumab in clinical studies., Methods: Adalimumab safety data from adults with psoriasis who received at least one adalimumab dose in 18 clinical trials were evaluated. Adalimumab was delivered subcutaneously in all treatment regimens. Treatment-emergent adverse events (AEs) were collected from the first dose to 70 days after the last dose or cut-off date (31 December 2015). AE incidence rates were expressed as events per 100 patient-years (E/100 PYs) of adalimumab exposure. Standardized incidence ratios (SIRs) for malignancies and standardized mortality ratios (SMRs) were calculated., Results: Cumulative exposure was 5429·7 PYs in 3727 patients. Overall, there were 16 536 AEs (304·6 E/100 PYs). The most common AEs were nasopharyngitis, upper respiratory infection and headache (23·7, 12·9 and 7·9 E/100 PYs, respectively). Incidence rates for serious infections, tuberculosis and opportunistic infections were 1·8, 0·3 and 0·02 E/100 PYs, respectively. Incidence of malignancy excluding nonmelanoma skin cancer (NMSC) was 0·8 E/100 PYs [SIR 0·86, 95% confidence interval (CI) 0·58-1·23]. Incidences of NMSC and melanoma were 0·6 and 0·2 E/100 PYs, respectively. The SIR was 1·55 (95% CI 1·10-2·13) for NMSC and 3·04 (95% CI 1·11-6·62) for melanoma. The SMR was 0·34 (95% CI 0·16-0·65)., Conclusions: AE rates remained stable in this analysis of patients with psoriasis receiving adalimumab; no new safety signals were identified compared with earlier analyses., (© 2018 British Association of Dermatologists.)

A phase 3, multicenter, open-label, 52-week study investigated the efficacy and safety of adalimumab 80 mg at week 0 followed by adalimumab 40 mg every other week (option to escalate to 80 mg when necessary) in Japanese patients with generalized pustular psoriasis (GPP). Adults (aged 15-75 years) with GPP, total skin score (overall erythema area, erythema area with pustules, and edema area) of 3 or more, and erythema with pustules (skin score, ≥1) based on the 2014 Japanese Dermatological Association severity index of GPP were enrolled. The primary efficacy end-point was clinical response at week 16 (non-responder imputation), defined as achieving remission (total skin score, 0) or improvement from baseline (reduction of ≥1 point from a baseline total skin score of 3 or ≥2 points from a baseline total skin score of ≥4). Of 10 enrolled patients (mean disease duration, 10.6 years), seven patients, including three with the dose escalated to 80 mg every other week before week 15, achieved clinical response at week 16, and five achieved clinical response at week 52. Mean change from baseline total GPP score was -4.6 at week 16 (n = 8) and -6.0 at week 52 (n = 5); change in total skin score was -3.1 (n = 8) and -4.2 (n = 5), respectively. Nine patients experienced one or more adverse events and three experienced serious adverse events. The most common adverse events were nasopharyngitis, pruritus and hypoalbuminemia. In conclusion, adalimumab was effective and well tolerated for up to 52 weeks in the treatment of Japanese patients with GPP., (© 2018 AbbVie. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Previous global studies of guselkumab have demonstrated clinical benefits in patients with psoriasis. The aim of this 52-week, phase 3 study was to evaluate efficacy and safety of guselkumab in Japanese patients with moderate to severe plaque-type psoriasis. Patients randomly received guselkumab 50 mg or 100 mg at weeks 0, 4 and every 8 weeks, or placebo with cross-over to guselkumab 50 mg or 100 mg at week 16. Co-primary end-points were the proportion of patients achieving Investigator's Global Assessment (IGA) cleared/minimal (0/1) and 90% or more improvement in Psoriasis Area and Severity Index (PASI-90) at week 16. Overall, 192 patients were randomized to placebo, guselkumab 50 mg or 100 mg. At week 16, patients in the placebo group were crossed over to guselkumab 50 mg or 100 mg. At week 16, a significantly (P < 0.001) higher proportion of patients receiving guselkumab 50 mg and 100 mg versus placebo achieved IGA 0/1 (92.3% and 88.9% vs 7.8%) and PASI-90 (70.8% and 69.8% vs 0%). Patients in guselkumab 50 mg and 100 mg groups achieved significant improvement versus placebo in PASI-75 (89.2% and 84.1% vs 6.3%, P < 0.001) at week 16; improvement was maintained through week 52. Incidences of treatment-emergent adverse events were comparable among the groups through week 16; the most commonly reported was nasopharyngitis. No new safety concerns were observed until week 52. In conclusion, guselkumab treatment demonstrated superior efficacy over placebo and was well tolerated in Japanese patients with moderate to severe plaque-type psoriasis., (© 2018 Janssen Pharmaceutical K.K. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Background and Aims: Vedolizumab, a humanised monoclonal antibody for the treatment of inflammatory bowel disease, selectively blocks gut lymphocyte trafficking. This may reduce the risk of respiratory tract infections [RTIs] compared with systemic immunosuppressive therapies. To assess this possibility, we evaluated the rates of RTIs in clinical trials of vedolizumab., Methods: Patient-level data from Phase 3 randomised controlled trials [RCTs] of vedolizumab in ulcerative colitis [UC; GEMINI 1] and Crohn's disease [CD; GEMINI 2], and a long-term safety study [UC and CD] were pooled. Cox proportional hazards models were used to estimate the incidence of upper RTIs [URTIs] and lower RTIs [LRTIs] with adjustment for significant covariates., Results: In the RCTs [n = 1731 patients], the incidence of URTIs was numerically higher in patients receiving vedolizumab compared with those receiving placebo, although this difference was not statistically significant (38.7 vs 33.0 patients per 100 patient-years; hazard ratio [HR] 1.12; 95% confidence interval [CI]: 0.83-1.51; p = 0.463). The rate of LRTIs, including pneumonia, was numerically lower in the vedolizumab versus the placebo group: this difference was not statistically significant (7.7 vs 8.5 per 100 patient-years [HR 0.85; 95% CI: 0.48-1.52; p = 0.585]). Both URTIs and LRTIs were more frequent in patients with CD compared with UC. Most RTIs in patients receiving vedolizumab were not serious and did not require treatment discontinuation., Conclusions: Vedolizumab therapy was not associated with an increased incidence of respiratory tract infection compared with placebo.

Generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP) are the rare and severe subtypes of psoriasis, which are often difficult to treat. The aim of this phase 3, open-label study was to evaluate efficacy and safety of guselkumab, a human interleukin-23 monoclonal antibody, in Japanese patients with GPP and EP. Guselkumab 50 mg was administrated to GPP (n = 10) and EP (n = 11) patients at weeks 0, 4 and thereafter every 8 weeks (q8w). Beginning at week 20, patients were escalated to 100 mg q8w if they met the dose escalation criteria. The primary end-point was the proportion of patients achieving treatment success (Clinical Global Impression score of "very much improved", "much improved" or "minimally improved") at week 16. Safety evaluations included assessment of treatment-emergent adverse events (TEAE) through week 52. At week 16, the proportions of GPP and EP patients achieving treatment success were 77.8% (7/9) and 90.9% (10/11), respectively. Furthermore, guselkumab treatment consistently showed improvement in responses of secondary end-points such as Psoriasis Area and Severity Index, Investigator's Global Assessment, Japanese Dermatological Association severity index and improvement in body surface area involvement. Improvements in quality of life, as assessed by the Dermatology Life Quality Index, were also observed through week 52. The most commonly reported TEAE was nasopharyngitis (28.6%, 6/21). Safety findings were consistent with those observed previously in other studies. In conclusion, guselkumab treatment demonstrated efficacy and showed no safety concerns in Japanese patients with GPP and EP through week 52., (© 2018 Janssen Pharmaceutical K.K. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, works intracellularly within immune cells to regulate inflammatory mediators. This phase 2b randomized, placebo-controlled study evaluated efficacy and safety of apremilast among Japanese patients with moderate to severe plaque psoriasis. In total, 254 patients were randomized to placebo, apremilast 20 mg b.i.d. (apremilast 20) or apremilast 30 mg b.i.d. (apremilast 30) through week 16; thereafter, all placebo patients were re-randomized to apremilast 20 or 30 through week 68. Efficacy assessments included achievement of 75% or more reduction from baseline in Psoriasis Area and Severity Index score (PASI-75; primary) and achievement of static Physician Global Assessment (sPGA; secondary) score of 0 (clear) or 1 (minimal) at week 16. Safety was assessed through week 68. At week 16, PASI-75 response rates were 7.1% (placebo), 23.5% (apremilast 20; P = 0.0032 vs placebo) and 28.2% (apremilast 30; P = 0.0003 vs placebo); sPGA response rates (score of 0 or 1) were 8.8% (placebo), 23.9% (apremilast 20; P = 0.0165 vs placebo) and 29.6% (apremilast 30; P = 0.0020 vs placebo). Responses were maintained with apremilast through week 68. Most common adverse events (AEs) with placebo, apremilast 20 and apremilast 30 (0-16 weeks) were nasopharyngitis (8.3%, 11.8%, 11.8%), diarrhea (1.2%, 8.2%, 9.4%), and abdominal discomfort (1.2%, 1.2%, 7.1%), respectively. Exposure-adjusted incidence of these AEs did not increase with continued apremilast treatment (up to 68 weeks). Apremilast demonstrated efficacy and safety in Japanese patients with moderate to severe plaque psoriasis through 68 weeks that was generally consistent with prior studies., (© 2017 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Clinical experience has shown that allergic and non-allergic respiratory, metabolic, mental, and cardiovascular disorders sometimes coexist with bronchial asthma. However, no study has been carried out that calculates the chance of manifestation of these disorders with bronchial asthma in Saarland and Rhineland-Palatinate, Germany. Using ICD10 diagnoses from health care institutions, the present study systematically analyzed the co-prevalence and odds ratios of comorbidities in the asthma population in Germany. The odds ratios were adjusted for age and sex for all comorbidities for patients with asthma vs. without asthma. Bronchial asthma was strongly associated with allergic and with a lesser extent to non-allergic comorbidities: OR 7.02 (95%CI:6.83-7.22) for allergic rhinitis; OR 4.98 (95%CI:4.67-5.32) allergic conjunctivitis; OR 2.41 (95%CI:2.33-2.52) atopic dermatitis; OR 2.47 (95%CI:2.16-2.82) food allergy, and OR 1.69 (95%CI:1.61-1.78) drug allergy. Interestingly, increased ORs were found for respiratory diseases: 2.06 (95%CI:1.64-2.58) vocal dysfunction; 1.83 (95%CI:1.74-1.92) pneumonia; 1.78 (95%CI:1.73-1.84) sinusitis; 1.71 (95%CI:1.65-1.78) rhinopharyngitis; 2.55 (95%CI:2.03-3.19) obstructive sleep apnea; 1.42 (95%CI:1.25-1.61) pulmonary embolism, and 3.75 (95%CI:1.64-8.53) bronchopulmonary aspergillosis. Asthmatics also suffer from psychiatric, metabolic, cardiac or other comorbidities. Myocardial infarction (OR 0.86, 95%CI:0.79-0.94) did not coexist with asthma. Based on the calculated chances of manifestation for these comorbidities, especially allergic and respiratory, to a lesser extent also metabolic, cardiovascular, and mental disorders should be taken into consideration in the diagnostic and treatment strategy of bronchial asthma., Bronchial Asthma: PREVALENCE OF CO-EXISTING DISEASES IN GERMANY: Patients in Germany with bronchial asthma are highly likely to suffer from co-existing diseases and their treatments should reflect this. Quoc Thai Dinh at Saarland University Hospital in Homburg, Germany, and co-workers conducted a large-scale study of patients presenting with bronchial asthma in the Saarland region between 2009 and 2012. Patients with asthma made up 5.4% of the region's total population, with a higher prevalence occurring in females. They found that bronchial asthma was strongly associated with allergic comorbidities such as rhinitis. Indeed, asthmatic patients had a seven times higher chance to suffer from allergic rhinitis than the rest of the population, and were at higher risk of respiratory diseases like pneumonia and obstructive sleep apnea syndrome. Further associations included cardiovascular, metabolic and mental disorders. Dinh's team call for asthma treatments to take such comorbidities into account.

Background: Influenza virus is a major health care burden and is associated with significant morbidity and mortality. Data on morbidity and complications (pneumonia, otitis media) related to influenza virus infection in primary care settings are limited with reports mainly obtained from hospital settings. We assessed the prevalence of complications from viral/bacterial infections in influenza- positive compared with influenza- negative children presenting with influenza-like illness (ILI) in a primary care setting., Methods: This retrospective, practice-based chart review studied complications from viral/bacterial infections in 255 children and adolescents (females/males, 1-21 years) who presented with ILI. We also compared the prevalence of complications by influenza vaccination status between influenza positive (N = 32/121) and influenza negative (N = 50/134) cases (2013-2015). Comparisons for categorical variables were made using chi-squared tests., Results: The prevalence of complications was similar in influenza positive (18/121) and influenza negative (22/134) patients (P = NS). Patients presenting with ILI, who were vaccinated, were less likely to test positive for influenza compared with patients who were not vaccinated (P = 0.064). However, prevalence of infections was similar in both groups based on vaccination status. We did not find any effect of type of health insurance on influenza status (P > 0.05) CONCLUSION: Common respiratory complications of seasonal influenza did not differ in influenza positive compared with influenza negative patients. Vaccination with influenza vaccine may result in decreased duration or severity of symptoms, and remains an important public health intervention. In primary care settings, determination of influenza status may be an important tool for clinicians to predict the likelihood of complications.

Objective: To systematically review the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on two common respiratory system adverse events (RSAE: nasopharyngitis and upper respiratory tract infection) among type 2 diabetes (T2DM)., Methods: Medline, Embase, Clinical trials and Cochrane library were searched from inception through May 2015 to identify randomized clinical trials(RCTs) assessed safety of GLP-1RAs versus placebo or other anti-diabetic drugs in T2DM. Network meta-analysis within a Bayesian framework was performed to calculate odds ratios for the incidence of RSAE., Results: In the study, 50 RCTs were included, including 13 treatments: 7 GLP-1RAs (exenatide, exenatide-long-release-agent, liraglutide, lixisenatide, taspoglutide, albiglutide and dulaglutide), placebo and 5 traditional anti-diabetic drugs(insulin, metformin, sulfonylureas, sitagliptin and thiazolidinediones ketones). Compared with insulin, taspoglutide significantly decreased the incidence of nasopharyngitis (OR=0.67, 95%CI: 0.46-0.96). Significant lowering effects on upper respiratory tract infection were found when taspoglutide versus placebo (OR=0.57, 95%CI: 0.34-0.99) and insulin (OR=0.39, 95%CI: 0.23-0.73). The result from the network meta-analysis based on Bayesian theory could be used to rank all the treatments included, which showed that taspoglutide ranked last with minimum risk on nasopharyngitis and upper respiratory tract infection., Conclusion: Taspoglutide was associated with significantly lowering effect on RSAE.

The objective of the present retrospective study based on the analysis of 791 medical cards was to investigate microflora localized at the pharyngeal tonsil surface in the children living in the city of Chelyabinsk and presenting with exacerbation of chronic adenoiditis. 66% of the patients with this condition were 4-6 year old children. The most commonly documented were the associations composed of resident species S. alpha-haemoliticus and S. epidermidis together with pathobiontic S. aureus. S. beta-haemoliticus and S. pneumoniae occurred most frequently whereas H. influenza and some representatives of the genus Enterobacteriaceae were less numerous. Fungi of the genus Candida were identified in 25.4% of the samples at a titer above 10^4. In 23.7% of the cases, these fungi were found in the associations with S. aureus which resulted in mutual potentiation of the pathogenicity factor.

The most common diseases of the upper respiratory tract in children treated by ear-nose-throat (ENT) specialists in ambulatory practice are infections, such as colds, rhinitis, sinusitis and pharyngitis, very frequently accompanied and promoted by chronic nasal obstructions of various etiology. These diseases, when treated incorrectly or for too long, cause frequent school absenteeism and may also lead to hearing disorders linked with acute or suppurative otitis. They may also habitually perpetuate abnormal breathing and result in occlusal disorders. The aim of this study was to assess the incidence and type of upper respiratory tract diseases in children, depending on age and sex of patients and on the seasons. We also discussed the role of the ENT specialist in the diagnosis and treatment of certain diseases. In the study we analyzed the medical records of patients of preschool and school age treated in the ENT outpatient clinic over one calendar year. It was found that the largest group of patients comprised children of 3-7 years of age, and most children visited the outpatient clinic in the period March-May. The most common main disorder, according to ICD-10, was acute nasopharyngitis (J00) and vasomotor and allergic rhinitis (J30). Among the comorbid disorders H65 and H66 were the most frequent. No significant gender differences were noted in the frequency of particular types of disease.

The objective of the present study was to improve the effectiveness of medicamental therapy of exudative otitis media in the children with recurrent and chronic adenoiditis. It was shown that the use of fluifort (carbocysteine lysine salt) for the treatment of exudative otitis media in the children presenting with chronic adenoiditis is a more effective approach in comparison with the expectant management. It is concluded that the application of carbocysteine lysine salt in combination with the mometasone furoate nasal spray ensures the rapid elimination of the symptoms of adenoiditis and significantly accelerates the resolution of exudative otitis media compared with the monotherapeutic treatment.

Aim: This Phase IIb, randomized, double-blind, placebo-controlled trial evaluated the efficacy, safety, tolerability and pharmacokinetics of empagliflozin in patients with type 2 diabetes., Methods: Four hundred and eight patients (treatment-naïve or after a 4-week wash-out period) were randomized to receive empagliflozin 5, 10 or 25 mg once daily, placebo or open-label metformin for 12 weeks. The primary endpoint was change in haemoglobin A1c (HbA1c) after 12 weeks., Results: After 12 weeks' treatment, empagliflozin showed dose-dependent reductions in HbA1c from baseline [5 mg: -0.4%, 10 mg: -0.5%, 25 mg: -0.6%; all doses p < 0.0001 vs. placebo (+0.09%)]. Fasting plasma glucose (FPG) decreased with empagliflozin [5 mg: -1.29 mmol/l, 10 mg: -1.61 mmol/l, 25 mg: -1.72 mmol/l; all doses p < 0.0001 vs. placebo (+0.04 mmol/l)]. Body weight decreased in all empagliflozin groups (all doses p < 0.001 vs. placebo). The incidence of adverse events (AEs) was similar in the placebo (32.9%) and empagliflozin (29.1%) groups. The most frequently reported AEs on empagliflozin were pollakiuria (3.3% vs. 0% for placebo), thirst (3.3% vs. 0% for placebo) and nasopharyngitis (2.0% vs. 1.2% for placebo). AEs consistent with urinary tract infections (UTIs) were reported in four (1.6%) patients on empagliflozin vs. one (1.2%) on placebo. Genital infections were reported in five (2%) patients on empagliflozin vs. 0% on placebo. No UTIs or genital infections led to premature discontinuation., Conclusions: In patients with type 2 diabetes, empagliflozin resulted in dose-dependent, clinically meaningful reductions in HbA1c and FPG, and reductions in body weight compared with placebo. Empagliflozin was well-tolerated with a favourable safety profile., (© 2013 Blackwell Publishing Ltd.)

Background: Unnecessary use of resources for common illnesses has substantial effect on patient care and costs. Evidence-based guidelines do not recommend antibiotics or imaging for uncomplicated upper respiratory infections (URIs). The objective of the current study was to examine medical care providers' compliance with guidelines in treating uncomplicated URIs in emergency departments (EDs) in the US., Methods: Nationally representative data from the NHAMCS 2007 and 2008 were used. Uncomplicated URIs were identified through ICD-9 codes of nasopharyngitis, laryngitis, bronchitis, URI not otherwise specified and influenza involving upper respiratory tract. Exclusion criteria were concurrent comorbidities, follow-up visits, and age < 18 or >64 years. Most frequently prescribed classes of antibiotics were identified. Multivariate analyses were conducted to identify the factors associated with the prescribing of antibiotics and use of imaging studies., Results: In 2007 and 2008, there were 2.2 million adult uncomplicated URI visits without any other concurrent diagnoses in EDs in the US. Approximately 52% were given antibiotic prescriptions, over one-third of which were macrolides, and nearly half of the visits performed imaging studies. About 51% had a diagnosis of bronchitis, 35% URI NOS, 9% nasopharyngitis, laryngitis or influenza, and 4% multiple URI diagnoses. The diagnosis of bronchitis, fever at presentation, older ages, male gender, longer waiting time, and metropolitan areas were associated with a greater likelihood of prescribing antibiotics or imaging studies, controlling for confounding factors., Conclusion: Despite the recommendations and campaign efforts by the CDC and many medical associations, the prescribing of antibiotics in treating uncomplicated URIs in the EDs remains prevalent. Furthermore, overutilization of imaging studies is prevalent. Changes at levels of health care system and hospitals are needed to avoid unnecessary resource utilization. In addition, further patient education about antibiotic use in the community may greatly facilitate the transition out of an antibiotic-dependent consumer culture.

De novo high-throughput pyrosequencing was used to detect and characterize 2009 pandemic influenza A (H1N1) virus directly in nasopharyngeal swabs in the context of the microbial community. Data were generated with a prior sequence independent amplification by 454 pyrosequencing on GS-FLX platform (Roche). Influenza A assembled reads allowed near full-length genome reconstruction with the simultaneous analysis of site-specific heterogeneity. The molecular approach applied proved to be a powerful tool to characterize the new pandemic H1N1 influenza virus in clinical samples. This approach could be of great value in identifying possibly new reassortants that may occur in the near future.

Background: This study examined the efficacy and safety of quetiapine in combination with lithium or divalproex compared with placebo with lithium or divalproex in the prevention of recurrent mood events in bipolar I patients, most recent episode mania, depression, or mixed., Methods: Patients received open-label quetiapine (400-800 mg/day; flexible, divided doses) with lithium or divalproex (target serum concentrations 0.5-1.2 mEq/L and 50-125 microg/mL, respectively) for up to 36 weeks to achieve at least 12 weeks of clinical stability. Patients were subsequently randomized to double-blind treatment with quetiapine (400-800 mg/day) plus lithium/divalproex or placebo plus lithium/divalproex for up to 104 weeks. The primary endpoint was time to recurrence of any mood event., Results: Treatment with quetiapine in combination with lithium/divalproex significantly increased the time to recurrence of any mood event compared with placebo plus lithium/divalproex. The proportion of patients having a mood event was markedly lower in the quetiapine than in the placebo group (18.5% versus 49.0%). The hazard ratio for time to recurrence of a mood event was 0.28 (P<0.001), a mania event 0.30 (P<0.001), and a depression event 0.26 (P<0.001) corresponding to risk reductions of 72%, 70%, and 74%, respectively. During the randomization phase, the most common adverse events occurring in > or =5% in the quetiapine group were somnolence, nasopharyngitis, and headache. Insomnia was more common in the placebo group. During the randomization phase, there was an increase in weight of 0.5 kg in the quetiapine group and a reduction of 1.9 kg in the placebo group. The incidence and incidence density of a single emergent fasting blood glucose value> or =126 mg/dL was higher with quetiapine than with placebo (9.3% versus 4.1%; 17.6 versus 9.5 patients per 100 patient-years)., Limitations: This was an enriched sample of patients with bipolar I disorder responding to treatment with quetiapine plus lithium/divalproex., Conclusions: Maintenance treatment with quetiapine in combination with lithium/divalproex significantly increased time to recurrence of any event (mania, depression, or mixed) irrespective of the polarity of the index episode compared with placebo with lithium/divalproex. Long-term treatment with quetiapine was generally well-tolerated. Quetiapine with lithium/divalproex can provide an effective long-term treatment option for bipolar I disorder to prevent recurrences not only of mania but also depression.

Infants at day care centers tend to contract repetitive upper respiratory infections and prolonged otitis media. The increase in antimicrobial-resistant bacteria, particularly in infants, has given rise to a stubborn therapeutic problem. We studied the nasopharyngeal carriage and drug resistance to Haemophilus influenzae (H. influenzae) and Streptococcus pneumoniae (S. pneumoniae), the most common pathogens of upper respiratory infections, in infants at day care centers. Nasopharyngeal cultures of infants between the ages of 0 and 6 years were conducted at two day care centers in July 2004 ("summer"; n=183), and in February 2005 ("winter"; n=182). Isolated H. influenzae and S. pneumoniae were subjected to antibiotic susceptibility tests by broth microdilution. We also conducted an otolaryngological examination and a survey on past and life histories. H. influenzae in summer (38.3%) increased significantly in winter (57.7%). Beta-lactamase-negative and positive ampicillin-resistant H. influenzae (BLNAR+ BLPAR) in summer decreased significantly in winter. S. pneumoniae did not differ in summer (42.1%) or in winter (43.4%). Penicillin-resistant and intermediate S. pneumoniae (PRSP+PISP) was 41.3% in summer and decreased significantly to 19.0% in winter. BLNAR + BLPAR and PRSP + PISP differed with the day care center. In otolaryngological examination, rhinosinusitis was commonest (28.4% in summer and 30.8% in winter), followed by allergic rhinitis (8.7% in summer and 6.0% in winter) and otitis media (8.2% in summer and 6.0% in winter). Tonsillitis was minor (0.5% in both seasons). Rhinosinusitis in winter was significantly higher in carriers of H. influenzae and/or S. pneumoniae than in non carriers (36.4% versus 16.0%). Breast-fed infants tended to have less otitis media than bottle-fed infants (38.2% versus 52.9%). H. influenzae and/or S. pneumoniae plateaued (75-80%) after 12 months in day care centers. These results suggest that infants attending day care centers are immediately colonized by H. influenzae and S. pneumoniae in the nasopharynx after entering the centers. Nasopharyngeal drug-resistant H. influenzae and S. pneumoniae varied during the seasons and between day care centers. Further prospective studies are needed to determine upper respiratory tract infection in infants at day care centers and to evaluate carriage, epidemiology, and the drug-resistance rates of these pathogens.

A closed population of juveniles was studied to follow-up manifestations of primary rheumatic fever. In line with other unfavourable factors, the onset of the disease within the first 6 months of the observation was due to cross streptococcal infection (foci of chronic nasopharyngeal infection were detected in 68.6% examinees, rheumatism debut after acute nasopharyngeal infection was in 91.0% patients). Persistence of streptococci was established in many blood counts in immunofluorescence reaction in 88.2% patients in acute disease, in more patients with lingering rheumatic process. Clinical manifestations include, aside from arthritis and rheumocarditis, frequent thyroid and gastrointestinal lesions. It is thought valid to raise the dose and duration of administration of penicillin in patients with primary rheumatic fever as it eradicates chronic infection foci, prevents recurrences, reduces the number of patients with a lingering course of the disease, with recurrences and valvular defects of the heart.

Unlabelled: Penicillin resistant Streptococcus pneunmoniae poses an increasing problem in paediatrics, particularly in less developed countries. Outside of South Africa, little is known about S. pneumoniae susceptibilities in Sub-Saharan Africa. The objective of this study was to determine the prevalence of pneumococcal colonization and antimicrobial susceptibility among children in urban Ghana., Methods: Nasopharyngeal pneumococcal colonization was examined in 311 children attending a polyclinic for sick children and an immunization clinic in Kumasi, Ghana. Isolates were tested for antibiotic susceptibility to penicillin, tetracycline, erythromycin, chloramphenicol, cefuroxime, cefotaxime, ceftriaxone, and trimethoprim-sulfamethoxazole., Results: Over half (51.4%) of subjects were colonized with S. pneumoniae and 17% of isolates were resistant to penicillin, all demonstrating intermediate resistance. S. pneumoniae strains were also frequently resistant to trimethoprim-sulfamethoxazole and tetracycline, less so to chloramphenicol and cefuroxime and were almost uniformly sensitive to cefotaxime, cefriaxone and erythromycin., Conclusions: Our study shows a high rate of pneumococcal nasopharyngeal colonization and a concerning level of penicillin resistance although at a less alarming rate than seen in some other countries. Multiple antimicrobial resistance was also noted especially among drugs readily available and commonly used. These data impact treatment choices in pneumococcal disease. Vaccine may play an important role in disease limitation. An effort to curtail the misuse of antibiotics, by prescription and otherwise, may prevent further increases in resistance rates.

Allergic rhinitis (AR) is rarely found in isolation and needs to be considered in the context of systemic allergic disease associated with numerous comorbid disorders, including asthma, chronic middle ear effusions, sinusitis, lymphoid hypertrophy with obstructive sleep apnea, disordered sleep, and consequent behavioral and educational effects. The coexistence of AR and asthma is complex. First, the diagnosis of asthma may be confounded by symptoms of cough caused by rhinitis and postnasal drip. This may lead to either inaccurate diagnosis of asthma or inappropriate assessment of asthma severity with over treatment of the patient. The term "cough variant rhinitis" is therefore proposed to describe rhinitis that manifests itself primarily as cough that results from postnasal drip. AR, however, also has a causal role in asthma; it appears both to be responsible for exacerbating asthma and to have a role in its pathogenesis. Postnasal drip with nasopharyngeal inflammation leads to a number of other conditions. Thus sinusitis is a frequent extension of rhinitis and is one of the most frequently missed diagnoses in children. Allergen exposure in the nasopharynx with release of histamine and other mediators can cause Eustachian tube obstruction possibly leading to middle ear effusions. Chronic allergic inflammation of the upper airway causes lymphoid hypertrophy with prominence of adenoidal and tonsillar tissue. This may be associated with poor appetite, poor growth, and obstructive sleep apnea. AR is therefore part of a spectrum of allergic disorders that can profoundly affect the well being and quality of life of a child. Prospective cohort studies are required to assess the disease burden caused by AR in childhood and to further assess the potential educational impairment that may result. Because AR is part of a systemic disease process, its management requires a coordinated approach rather than a fragmented, organ-based approach.

While upper respiratory tract infections (URTIs) cause much infectious morbidity in infants and young children, adolescents are not immune to infections. Adolescents experience two to four episodes of viral nasopharyngitis annually. In addition to group A streptococcus (GAS), pharyngitis may occur with other streptococci, Arcanobacterium haemolyticum, Epstein-Barr virus, Neisseria gonorrhoeae, and other pathogens. Uvulits, typically in association with GAS, occurs occasionally. Peritonsillar abscess is the most common deep neck space infection seen in adolescents, but retropharyngeal and parapharyngeal abscesses also occur, causing major morbidity. Adolescents experience fewer cases of otitis media than younger children. Rhinosinusitis occurs commonly in adolescents, occasionally leading to chronic sinusitis and serious sequelae such as osteomyelitis. This article reviews the major URTIs likely to be encountered by physicians caring for adolescents. For each entity there is a brief description of the epidemiology, morbidity, microbiology, clinical and laboratory features, treatment, and prevention.

The terminology used to describe upper respiratory tract infections (URTIs) in children can be based on the symptomatic picture, the aetiological agents or anatomical features involved, or classical disease descriptions. However, there is a lack of precision in the epidemiology and nosology of nasopharyngitis and acute otitis media (AOM) in children. Moreover, there are differences between European countries in diagnostic and therapeutic measures. The aim of this broad survey was to record all items potentially relating to URTIs in children and, therefore, to refine the classification of nasopharyngitis and AOM, as well as to clearly define their medical and economic consequences as observed in normal medical practice. Specifically, the objectives can be summarised as follows: to define nasopharyngitis as a clear-cut entity and thus provide a standard for clinical trials; to identify different definitions of AOM and compare them with Paradise's algorithm; to establish a profile of patients at risk of recurrences; to assess therapeutic habits; and to determine the cost of illness. The survey involved 328 European physicians (general practitioners, paediatricians, ear, nose and throat specialists), who recorded spontaneous medical visits of 2007 children presenting with a first episode of nasopharyngitis or AOM during November and December 1996. These children were then followed up until April 1997 so that any recurrent episodes could be recorded. A parent questionnaire focusing on burden of illness for the family was also included. Demographic characteristics at inclusion and the first data on the multifactorial correspondence analysis for nasopharyngitis at inclusion are available and have been presented.

The authors present the results of the immuno-epidemiological studies of two collective bodies -- over 2000 persons in all -- equal by age composition and physical load, who were under the same sanitary-hygienic conditions. Observations were carried out from the time of formation of these collective bodies in November and were continued for a period of 6 months; they differed by the epidemic situation in respect to the meningococcus infection, i.e. cases of this disease and carriers were present in the first, and carriers only in the second group. The collective bodies were subjected to complete bacteriological examination (at the time of formation and in 3 and 6 months); blood was studied for the presence of antibodies to the complex meningococcus antigens of groups A, B and C (in the passive hemagglutination test.) There proved to be a marked increase in the percentage of positive tests with the A- and C-antibodies in both collective bodies and an increase in the number of positive tests with B-antibodies only in the collective body with no meningococcus cases. Since in the first collective body the percentage of generalized meningococcus infection cases was insignificant (about 0.85%) and there were no cases in the second collective body, a conclusion could be drawn that changes in the immunological indices among persons in these groups were caused by carrier state. Thus, the effect of meningococcus carrier state on the formation of immunological indices of collective bodies was revealed.

The epidemiological characteristics of meningococcal infection in Uzbekistan during the period of 8 years since its last epidemic rise in 1972 is presented. Differences in the intensity of the epidemic process among the urban and rural population due to a considerable isolation of most of the rural populated localities from the district centers and the low population density in the republic have been established. The seasonal distribution of the infection had a winter-spring character in urban areas and a spring character in rural areas. 63.4% of all cases were children under 14 years. In cities a high morbidity level among adolescents and young people was determined mainly by visitors from rural areas. A high epidemiological importance of healthy carriers, predominantly schoolchildren and young people was established. The immunological studies of humoral immunity in different groups of the population indicate that the process of immunization was more rapid in cities.

The authors report a series of 37 cases presenting with tuberculosis of the mucosa of the upper naso-pharynx. The localization broke down as: 5 cases of tuberculosis of naso-sinuses, 6 of the buccal cavity, 3 of the cavum, 10 of the oro-pharynx, 1 of the hypopharynx, and 12 of the larynx. -- The male-female ratio was unequal (2:1 M:F) -- The mean age was 52.5 years -- Most patients were European. The 3 rhinopharyngeal cases were in North Africans. -- Macroscopically the lesions were of a malignant character in 70%. -- There was palpable lymphadenopathy in 56% of patients. The most commonly involved chain was the jugulo-carotid, especially the subdigastric group. -- There was tuberculosis in the entourage in 20/37 cases. CXR was normal in 17 cases. On hospitalisation active T.b. was discovered in 15 cases. -- Biopsy confirmed a definitive diagnosis in every case. -- All patients were treated medically. There were no cases of resistant organisms. The results were excellent.

The authors present characteristics of meningococcus infection epidemic process in case of sporadic cases and under epidemic conditions (1965--1976). A scheme of epidemiological analysis suggested by the authors permitted to differentiate and to record the incidence of various clinical forms of meningococcus infection, to present data on the age, seasonal characteristics, focality, etc. Comparison of intensive morbidity indices for 10 years, both at the individual administration territories and in the Republic as a whole demonstrated morbidity level of 1.5--2.0 to be one of prognostic signs of the beginning epidemic. The main features differentiating the sporadic and epidemic morbidity periods were revealed. The presence of group diseases, a greater percentage of children among those who fell ill, and marked signs of seasonality and territorial difference characterized the period of rise caused by meningococcus of serological group A.

Against the backcloth of te quantitative picture of general practice activity described in the companion paper (Beaumont and Pike, Ecol. Dis. 2, 45, 1983), the question of health-environment interaction is addressed. To this end morbidity analyses of a number of environmentally distinct sub-areas of the general practice facilitate investigation of the geography of morbidity at the primary care level. Despite the inherent spatial variations in environmental conditions within the practice, no significant environmental effect or morbidity is identifiable; even in the most deprived areas minimum sanitary conditions are fulfilled.

The results of serological surveys, carried out with a view to the detection of capsular meningococcal polysaccharides in the passive hemagglutination (PHA) test and covering 1,289 patients with systemic meningococcal infection, 221 patients with bacteriologically confirmed meningococcal nasopharyngitis, 2,820 persons in organized groups of children and adults with different epidemiological situation (including 650 carriers) and 4,050 residents of 8 cities with different morbidity levels, were analyzed. The patients, the carriers and the members of organized groups underwent multiple surveys. As shown in this study, the confirmation of the meningococcal etiology of the systemic forms of meningococcal infection (meningitis, meningococcemia) in all cases with the exception of children under 1 year of age, as well as the determination of the groups of meningococci, could be achieved in the PHA test twice as frequently, i.e. in 60-70% of cases, as with the use of the bacteriological method. The same regularities were observed in nasopharyngitis. The conclusion was made on the possibility of using the PHA test for more exact determination of the group of meningococci, prevailing at the initial stage of diseases, this determination playing an essential role in the epidemiological surveillance. The data obtained as the result of serological surveys in organized groups may lead to conclusions on the circulation of meningococci and their group composition, thus showing the necessity of profound epidemiological study with ensuring epidemic-control measures. The selective serological study of some hundreds of donor sera is not expedient in big cities, as it provides no data on the circulation of meningococci there.(ABSTRACT TRUNCATED AT 250 WORDS)