New approaches for diagnosis of dry eye disease

We reviewed the literature for different diagnostic approaches for dry eye disease (DED) including the most recent advances, contradictions and promising diagnostic tools and technique. We performed a broad literature search for articles discussing different methods for diagnosis of DED including assessment of tear osmolarity, tear film stability, ocular biomarkers and others. Articles indexed in PubMed and google scholar were included. With the growing cosmetic industry, environmental pollution, and booming of digital screens, DED is becoming more prevalent. Its multifactorial etiology renders the diagnosis challenging and invites the emergence of new diagnostic tools and tests. Diagnostic tools can be classified, based on the parameter they measure, into tear film osmolarity, functional visual acuity, tear volume, tear turnover, tear film stability, tear film composition, ocular biomarkers and others. Although numerous methods exist, the most accurate diagnosis can be reached through combining the results of more than one test. Many reported tests have shown potential as diagnostic/screening tools, however, require more research to prove their diagnostic power, alone or in combination. Future research should focus on identifying and measuring parameters that are the most specific to DED diagnosis.     

Acute,sub-acute and general pharmacological evaluation of 5-(3,4-methylenedioxyphenyl)-4-ethyl-2E,4E-pentadienoic acid piperidide (SK-20): A novel drug bioavailability enhancer

An efflux pump inhibitor, SK-20 (5-(3,4-methylenedioxyphenyle)-4 ethyl-2E,4E-pentadienoic acid piperidide), was assessed for its toxicity at three different pharmacological profiles: acute, sub-acute and general pharmacology with pharmacokinetics. In acute study, the SK-20 was found safe up to a dose of 2000 mg/kg (b.wt.); and at sub-acute, dosages of 50 and 100 mg/kg (b.wt.) were found to be safe. However, dosages of 200 mg or above per kg (b.wt.) showed some morphological alterations in cellular architecture of both liver and kidneys in both sexes, viz., mild vascular congestion along with sporadic hemorrhages and infiltration into renal and hepatic parenchyma by mononucleate cell. General pharmacological studies did not result into any alterations in analgesic, convulsions, rectal temperatures and in the rhythm or the rate of the intestinal motility or the secretion of the bile. While the respiratory and the cardiac rate remained normal, the only parameter to show was the blood pressure, which at all the doses tested, showed a tendency toward reduction. Characteristically, the SK-20 at all doses influenced pentobarbital-induced hypnosis positively and negatively to spontaneous motor activity in a dose dependent manner. Pharmacokinetics of SK-20 revealed it to have retention time at 10.2 min and half life 2.47 h.     

A Phase II Study of Biodegradable Stents Plus Palliative Radiotherapy in Oesophageal Cancer

AimsSelf-expanding metal stents provide rapid improvement of dysphagia in oesophageal cancer but are associated with complications. The aim of the present study was to test the effectiveness of an alternative treatment of combining biodegradable stents with radiotherapy.Materials and methodsA Simon two-stage single-arm prospective phase II trial design was used to determine the efficacy of biodegradable stents plus radiotherapy in patients with dysphagia caused by oesophagus cancer who were unsuitable for radical treatment. Fourteen patients were recruited and data from 12 were included in the final analyses.ResultsFive of 12 patients met the primary end point: one stent-related patient death; four further interventions for dysphagia within 16 weeks of stenting (41.7%, 95% confidence interval 15.2–72.3%). The median time to a 10-point deterioration of quality of life was 2.7 weeks. Nine patients died within 52 weeks of registration. The median time to death from any cause was 15.0 weeks (95% confidence interval 9.6–not reached).ConclusionThe high re-intervention observed, which met the pre-defined early stopping criteria, meant that the suggested alternative treatment was not sufficiently effective to be considered for a larger scale trial design. Further work is needed to define the place of biodegradable stents in the management of malignant oesophageal strictures.     

Evaluation of an internet-based speech-in-noise screening test for school-age children

Objective: To evaluate a Dutch online speech-in-noise screening test (in Dutch: “Kinderhoortest”) in normal-hearing school-age children. Sub-aims were to study test–retest reliability, and the effects of presentation type and age on test results. Design: An observational cross-sectional study at school. Speech reception thresholds (SRTs) were obtained through the online test in a training condition, and two test conditions: on a desktop computer and smartphone. The order of the test conditions was counterbalanced. Study sample: Ninety-four children participated (5–12 years), of which 75 children were normal-hearing (≤25?dB HL at 0.5?kHz,?≤20?dB HL at 1–4?kHz). Results: There was a significant effect for test order for the two test conditions (first or second test), but not for presentation type (desktop computer or smartphone) (repeated measures analyses, F(1,75)?=?12.48, p?F(1,75)?=?0.01, p?=?0.982). SRT significantly improved by age year (first test: 0.25?dB SNR, 95% CI: –0.43 to –0.08, p?=?0.004. Second test: 0.29?dB SNR, 95% CI: –0.46 to –0.11; p?=?0.002). Conclusions: The online test shows potential for routine-hearing screening of school-age children, and can be presented on either a desktop computer or smartphone. The test should be evaluated further in order to establish sensitivity and specificity for hearing loss in children.     

Circulating microRNAs: A Potential Role in Diagnosis and Prognosis of Acute Myocardial Infarction

Rapid and correct diagnosis of acute myocardial infarction (AMI) plays a crucial role in saving patients'' life. Although some biomarkers (such as cardiac troponin and creatine kinase) are available for AMI diagnosis so far, there is still a clinical need for novel biomarkers, which can reliably rule in or rule out AMI immediately on admission. Circulating microRNAs (miRNAs) are a potential choice for novel biomarkers in AMI diagnosis and prognosis with high sensitivity and specificity. Circulating microRNAs are endogenous miRNAs that are detectable in whole blood, serum, or plasma in a highly stable form. Until now, around 20 circulating miRNAs were reported to be closely associated with AMI. In this minireview, we summarized recent available data on the correlation between circulating miRNAs and AMI. Some miRNAs, such as miR-208, miR-499, miR-133, and miR-1, were given special attention, since they may have a potential prospect in diagnosis and prognosis of AMI.     

EAACI guidelines on allergen immunotherapy: Prevention of allergy

Allergic diseases are common and frequently coexist. Allergen immunotherapy (AIT) is a disease‐modifying treatment for IgE‐mediated allergic disease with effects beyond cessation of AIT that may include important preventive effects. The European Academy of Allergy and Clinical Immunology (EAACI) has developed a clinical practice guideline to provide evidence‐based recommendations for AIT for the prevention of (i) development of allergic comorbidities in those with established allergic diseases, (ii) development of first allergic condition, and (iii) allergic sensitization. This guideline has been developed using the Appraisal of Guidelines for Research & Evaluation (AGREE II) framework, which involved a multidisciplinary expert working group, a systematic review of the underpinning evidence, and external peer‐review of draft recommendations. Our key recommendation is that a 3‐year course of subcutaneous or sublingual AIT can be recommended for children and adolescents with moderate‐to‐severe allergic rhinitis (AR) triggered by grass/birch pollen allergy to prevent asthma for up to 2 years post‐AIT in addition to its sustained effect on AR symptoms and medication. Some trial data even suggest a preventive effect on asthma symptoms and medication more than 2 years post‐AIT. We need more evidence concerning AIT for prevention in individuals with AR triggered by house dust mites or other allergens and for the prevention of allergic sensitization, the first allergic disease, or for the prevention of allergic comorbidities in those with other allergic conditions. Evidence for the preventive potential of AIT as disease‐modifying treatment exists but there is an urgent need for more high‐quality clinical trials.     

Preoperative Cell-Mediated Immune Status of Patients with Malignant Glial Tumors

The leukocyte adherence inhibition assay (LAI) was used to measure cell-mediated immunity in 26 patients with malignant glial neoplasms and in 41 control subjects. A significant inhibition of leukocyte adherence was observed in 21 out of 26 (80%) patients with malignant astrocytic gliomas in the presence of a 3M KC1 extract of glioma tissue compared to that of normal brain extract. Among the control group, no significant difference in the percentage of nonadherent leukocytes (NAL) was noted in the presence of either antigen. To study the specificity of the reaction, 3M KC1 extracts of meningioma, pituitary tumor, carcinoma of breast, carcinomas of lung, melanoma, brain, and heart tissues were employed as nonspecific antigens. Such studies revealed significantly lower values of NAL.

These data indicate that patients with malignant glial neoplasms manifest a cellular-immune response to glioma-associated antigens that can be measured by the tube LAI assay and that LAI assay may render additional useful information in the diagnostic and prognostic evaluation of malignant glial neoplasms.     

Differences in mean and variability of heart rate and ambulatory rate-pressure product when valsartan or carvedilol is added to lisinopril

Guidelines recommend combining β-blockers and angiotensin-converting enzyme (ACE) inhibitors in high-risk heart disease but not in the initial treatment of hypertension. The mechanism of this benefit has not been determined. After 3 weeks of lisinopril (L, 40 mg/day) run-in, 30 subjects entered a single-blinded, forced-titration, crossover study in which carvedilol (C, 20 then 40 mg/day) or a control renin-angiotensin blocker, valsartan (V, 160 then 320 mg/day) were added to L. Ambulatory blood pressure (ABP) and heart rate monitoring was performed at the end of each period. Rate-pressure product (RPP, systolic BP × heart rate, an indicator of cardiac oxygen consumption) was measured over 24 hours, daytime (6 am to midnight), and nighttime (midnight to 6 am) periods. Variability (standard deviation and range) of RPP, BP, and heart rate was also investigated. After 4 weeks, mean 24-hour systolic BP was about 8 mm Hg lower when either V or C was added to L (P < .01 each). Heart rate was consistently lower with C (8 beats/min over 24 hours, P < .000) but was slightly increased with V (about 2 beats/min, P = NS). Consequently, C lowered RPP to a greater degree than V over 24 hours (about 8% vs. 2%, P < .000) and during daytime and nighttime periods (P < .000 each). In addition, RPP variability (SD but not range) was consistently lower on C than V. When added to L, C reduces the mean and variability (SD) of 24-hour heart rate and cardiac workload to a greater degree than valsartan. These effects may contribute to the outcome benefits observed with β-blocker–ACE inhibitor combinations.