Polymorphism in interferon alpha/beta receptor contributes to glucocorticoid response and outcome of ARDS and COVID-19.

BACKGROUND: The use of glucocorticoids has given contradictory results for treating acute respiratory distress syndrome (ARDS). The use of intravenous Interferon beta (IFN ß) for the treatment of ARDS was recently tested in a phase III ARDS trial (INTEREST), in which more than half of the patients simultaneously received glucocorticoids. Trial results showed deleterious effects of glucocorticoids when administered together with IFN ß, and therefore, we aimed at finding the reason behind this. METHODS: We first sequenced the genes encoding the IFN α/ß receptor of the patients, who participated in the INTEREST study (ClinicalTrials.gov Identifier:  NCT02622724 , November 24, 2015) in which the patients were randomized to receive an intravenous injection of IFN ß-1a (144 patients) or placebo (152 patients). Genetic background was analyzed against clinical outcome, concomitant medication, and pro-inflammatory cytokine levels. Thereafter, we tested the influence of the genetic background on IFN α/ß receptor expression in lung organ cultures and whether, it has any effect on transcription factors STAT1 and STAT2 involved in IFN signaling. RESULTS: We found a novel disease association of a SNP rs9984273, which is situated in the interferon α/ß receptor subunit 2 (IFNAR2) gene in an area corresponding to a binding motif of the glucocorticoid receptor (GR). The minor allele of SNP rs9984273 associates with higher IFNAR expression, more rapid decrease of IFN γ and interleukin-6 (IL-6) levels and better outcome in IFN ß treated patients with ARDS, while the major allele associates with a poor outcome especially under concomitant IFN ß and glucocorticoid treatment. Moreover, the minor allele of rs9984273 associates with a less severe form of coronavirus diseases (COVID-19) according to the COVID-19 Host Genetics Initiative database. CONCLUSIONS: The distribution of this SNP within clinical study arms may explain the contradictory results of multiple ARDS studies and outcomes in COVID-19 concerning type I IFN signaling and glucocorticoids.

Feasibility and patient acceptability of a commercially available wearable and a smart phone application in identification of motor states in parkinson's disease.

In the quantification of symptoms of Parkinson's disease (PD), healthcare professional assessments, patient reported outcomes (PRO), and medical device grade wearables are currently used. Recently, also commercially available smartphones and wearable devices have been actively researched in the detection of PD symptoms. The continuous, longitudinal, and automated detection of motor and especially non-motor symptoms with these devices is still a challenge that requires more research. The data collected from everyday life can be noisy and frequently contains artefacts, and novel detection methods and algorithms are therefore needed. 42 PD patients and 23 control subjects were monitored with Garmin Vivosmart 4 wearable device and asked to fill a symptom and medication diary with a mobile application, at home, for about four weeks. Subsequent analyses are based on continuous accelerometer data from the device. Accelerometer data from the Levodopa Response Study (MJFFd) were reanalyzed, with symptoms quantified with linear spectral models trained on expert evaluations present in the data. Variational autoencoders (VAE) were trained on both our study accelerometer data and on MJFFd to detect movement states (e.g., walking, standing). A total of 7590 self-reported symptoms were recorded during the study. 88.9% (32/36) of PD patients, 80.0% (4/5) of DBS PD patients and 95.5% (21/22) of control subjects reported that using the wearable device was very easy or easy. Recording a symptom at the time of the event was assessed as very easy or easy by 70.1% (29/41) of subjects with PD. Aggregated spectrograms of the collected accelerometer data show relative attenuation of low (<5Hz) frequencies in patients. Similar spectral patterns also separate symptom periods from immediately adjacent non-symptomatic periods. Discriminative power of linear models to separate symptoms from adjacent periods is weak, but aggregates show partial separability of patients vs. controls. The analysis reveals differential symptom detectability across movement tasks, motivating the third part of the study. VAEs trained on either dataset produced embedding from which movement states in MJFFd could be predicted. A VAE model was able to detect the movement states. Thus, a pre-detection of these states with a VAE from accelerometer data with good S/N ratio, and subsequent quantification of PD symptoms is a feasible strategy. The usability of the data collection method is important to enable the collection of self-reported symptom data by PD patients. Finally, the usability of the data collection method is important to enable the collection of self-reported symptom data by PD patients.

Body movement as a biomarker for use in chronic pain rehabilitation: An embedded analysis of an RCT of a virtual reality solution for adults with chronic pain.

Introduction: Chronic low back pain (CLBP) is a major public health problem. Reliably measuring the effects of chronic pain on movement and activity, and any changes due to treatment, is a healthcare challenge. A recently published paper demonstrated that a novel digital therapeutic (DTxP) was efficacious in reducing fear of movement and increasing the quality of life of adult patients with moderate to severe CLBP. In this paper, we report a study of how data from wearable devices collected in this study could be used as a digital measure for use in studies of chronic low back pain. Methods: Movement, electrodermal recording, general activity and clinical assessment data were collected in a clinical trial of a novel digital therapeutic intervention (DTxP) by using the sensors in commercial Garmin Vivosmart 4, Empatica Embrace2 and Oculus Quest wearables. Wearable data were collected during and between the study interventions (frequent treatment sessions of DTxP). Data were analyzed using exploratory statistical analysis. Results: A pattern of increased longitudinal velocity in the movement data collected with right-hand, left-hand, and head sensors was observed in the study population. Correlations were observed with the changes in clinical scales (Tampa Scale of Kinesiophobia, EQ5D Overall health VAS, and EQ5D QoL score). The strongest correlation was observed with the increased velocity of head and right-hand sensors (Spearman correlation with increasing head sensor velocity and Tampa Scale of Kinesiophobia -0.45, Overall health VAS +0.67 and EQ5D QoL score -0.66). The sample size limited interpretation of electrodermal and general activity data. Discussion/Conclusion: We found a novel digital signal for use in monitoring the efficacy of a digital therapeutics (DTxP) in adults with CLBP. We discuss the potential use of such movement based digital markers as surrogate or additional endpoints in studies of chronic musculoskeletal pain. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04225884?cond=NCT04225884&draw=2&rank=1, identifier: NCT04225884.

Health-related Quality of Life in Intermediate- or High-risk Patients Treated With Radical External Radiotherapy and Adjuvant Docetaxel for Localized Prostate Cancer: A Randomized, Phase III SPCG-13 Study.

BACKGROUND/AIM: The goal of this study was to investigate whether health-related quality of life (HRQoL) was affected in patients with high- or intermediate-risk localized prostate cancer treated with docetaxel following radiation therapy (RT). PATIENTS AND METHODS: A total of 376 patients treated with RT and androgen deprivation were randomized to receive 6 cycles of docetaxel 75 mg/m2 (N=188, Arm A) or surveillance (N=188, Arm B). FACT-P HRQoL questionnaires were gathered at baseline, six months and 1, 2 and 4 years after randomization. The data were analysed using analysis of covariance. RESULTS: FACT-P scores decreased in Arm A at the end of treatment and remained unchanged in Arm B (p<0.0001). The HRQoL scores in Arm A matched Arm B in the 1-year follow-up (p=0.0528) and remained similar in further follow-up. CONCLUSION: Docetaxel transiently decreased HRQoL during chemotherapy but not after treatment for up to four years of follow-up.

Effect of Bifidobacterium animalis spp. lactis Bl-04 on Rhinovirus-Induced Colds: A Randomized, Placebo-Controlled, Single-Center, Phase II Trial in Healthy Volunteers.

BACKGROUND: This study was designed to assess the efficacy of Bifidobacterium animalis ssp. lactis (Bl-04) for prevention of rhinovirus colds and to explore the interactions between the probiotic, the viral infection, the host response and the host microbiome. METHODS: The effect of ingestion of the probiotic Bl-04 was evaluated in a randomized, double-blinded rhinovirus (RV) challenge study. Healthy volunteers recruited from a university community in USA were randomized 1:1 using a computer generated code to ingest either Bl-04 (n=165) or placebo (n=169) for 28 days and were then challenged with RV-A39, and followed for 14 days. All study interactions and sample collection occurred in dedicated clinical research space. The primary analysis was the effect of the probiotic on the incidence of RV-associated illness. (Trial registration: NCT02679807, study complete). FINDINGS: The first cohort of volunteers was randomized on March 14, 2016 and the last (5th) cohort was randomized on March 12, 2018. Sixty-three (56%, 95% CI [47%; 66%]) of the 112 subjects in the active group and 60 (50%,95% CI [41%; 59%]) of the 120 subjects in the placebo group had a protocol-defined rhinovirus-associated illness (χ2=0·91, p=0·34). The point estimate of the difference in illness (active-placebo) is 6.3% (95% CI -6.7;19.1). There were no adverse events that were judged as definitely or probably related to the study product. INTERPRETATION: In this study there was no effect of orally administered Bl-04 on the occurrence of RV-associated illness. FUNDING: Danisco Sweeteners Oy (now IFF Health & Biosciences).

Childbearing, the desire to have children, and awareness about the impact of age on female fertility among Finnish university students.

OBJECTIVE: To describe Finnish university students' childbearing histories, desires concerning childbearing, and awareness regarding the impact of age on female fertility. METHODS: A national survey of Finnish university students in 2008. A questionnaire was sent to 9,967 Finnish undergraduate university students aged less than 35 years. Altogether, the questionnaire was answered by 1,864 men and 3,222 women. The overall response rate was 51% (42% for men and 59% for women). Students were asked about their number of children, desired childbearing, and awareness of the effect of age on female fertility. RESULTS: Of the respondents, 8.25% had children, and 94.0% wanted to have children in the future. Female students were more aware of the impact of age on female fertility than were male students. Over half of the men and approximately one-third of the women thought that the marked decrease in female fertility begins after the age of 45 years. CONCLUSIONS: A vast majority of Finnish university students wanted to have children in the future. Their awareness of the natural, age-related decline in female fertility was insufficient. Sexual health education in schools and health care personnel's family planning counselling, for both men and women, should include information about the age-related drop in fertility.

Biweekly Cabazitaxel Is a Safe Treatment Option for Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients After Docetaxel - A Final Analysis of the Prosty II Trial.

BACKGROUND/AIM: Our phase III trial showed that biweekly docetaxel (D) is better tolerated than triweekly D in metastatic castration-resistant prostate cancer (mCRPC). The safety of biweekly cabazitaxel (CBZ) post-docetaxel was studied in mCRPC. PATIENTS AND METHODS: Altogether, 60 patients received CBZ 16 mg/m2 i.v. on day 1 and day 14 of a 4-week cycle. The mean serum PSA levels were 305 ng/ml, and the mean age 67 years. The primary endpoint was safety according to CTCAEv4.0. RESULTS: A total of 255 4-week cycles of CBZ were administered. The most common grade 3/4 adverse events were neutropenia (16.7%), pain (13.3%), fatigue (10.0%), anemia (5.0%) and non-neutropenic infection (10.0%). PSA responses occurred in 10 patients (16.7%). Clinical benefit rate was 38.3% and median survival 10 months. CONCLUSION: Biweekly CBZ is a well-tolerated treatment resulting in meaningful benefits for heavily pretreated mCRPC patients.

Quantification of tremor using consumer product accelerometry is feasible in patients with essential tremor and Parkinson's disease: a comparative study.

BACKGROUND: To quantify pharmacological effects on tremor in patients with essential tremor (ET) or Parkinson's Disease (PD), laboratory-grade accelerometers have previously been used. Over the last years, consumer products such as smartphones and smartwatches have been increasingly applied to measure tremor in an easy way. However, it is unknown how the technical performance of these consumer product accelerometers (CPAs) compares to laboratory-grade accelerometers (LGA). This study was performed to compare the technical performance of CPAs with LGA to measure tremor in patients with Parkinson's Disease (PD) and essential tremor (ET). METHODS: In ten patients with PD and ten with ET, tremor peak frequency and corresponding amplitude were measured with 7 different CPAs (Apple iPhone 7, Apple iPod Touch 5, Apple watch 2, Huawei Nexus 6P, Huawei watch, mbientlabMetaWear (MW) watch, mbientlab MW clip) and compared to a LGA (Biometrics ACL300) in resting and extended arm position. RESULTS: Both in PD and ET patients, the peak frequency of CPAs did not significantly differ from the LGA in terms of limits of agreement. For the amplitude at peak frequency, only the iPhone and MW watch performed comparable to the LGA in ET patients, while in PD patients all methods performed comparable except for the iPod Touch and Huawei Nexus. Amplitude was higher when measured with distally-located CPAs (Clip, iPhone, iPod) compared with proximally-located CPAs (all watches). The variability between subjects was higher than within subjects for frequency (25.1% vs. 13.4%) and amplitude measurement (331% vs. 53.6%). Resting arm position resulted in lower intra-individual variability for frequency and amplitude (13.4 and 53.5%) compared to extended arm position (17.8 and 58.1%). CONCLUSIONS: Peak frequencies of tremor could be measured with all tested CPAs, with similar performance as LGA. The amplitude measurements appeared to be driven by anatomical location of the device and can therefore not be compared. Our results show that the tested consumer products can be used for tremography, allowing at-home measurements, in particular in studies with a cross-over or intra-individual comparison design using the resting arm position. TRIAL REGISTRATION: This trial was registered in the Dutch Competent Authority (CCMO) database with number NL60672.058.17 on May 30th 2017.

Docetaxel Versus Surveillance After Radical Radiotherapy for Intermediate- or High-risk Prostate Cancer-Results from the Prospective, Randomised, Open-label Phase III SPCG-13 Trial.

BACKGROUND: Docetaxel combined with androgen deprivation therapy (ADT) has improved patient survival for advanced prostate cancer (PCa). OBJECTIVE: This randomised trial aimed to evaluate whether six courses of docetaxel improved biochemical disease-free survival (BDFS) after radical radiotherapy (RT) for intermediate- or high-risk PCa patients. DESIGN, SETTING, AND PARTICIPANTS: A total of 376 patients were randomised in this multinational phase III study, and received either six cycles of adjuvant docetaxel 75 mg/m2 every 3 wk without continuous prednisone (arm A, n = 188) or surveillance (arm B, n = 188) after RT (NTC006653848). Neoadjuvant/adjuvant ADT was mandatory for all the patients. The primary endpoint was rising prostate-specific antigen (PSA) ≥2 ng/ml above the nadir PSA value. Intermediate- or high-risk PCa was defined as T2 with a Gleason score (GS) of 4 + 3, PSA > 10; T2, GS 8-10, ≤ 70 ng/ml; or any T3. The patients were followed for 5 yr by assessing PSA levels every 3 mo for 2 yr and every 6 mo thereafter. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The study power was 89% to detect a difference in BDFS between groups, and the sample size calculation accounted for the T2/T3 distribution, where a 12%/15% difference in BDFS was assumed for the T2/T3 patients. RESULTS AND LIMITATIONS: All six cycles were completed in 147 (78%) of the patients in arm A. The median age was 67 yr in both treatment groups, 75% had T3 disease, and 47% had GS 8-10. The median follow-up was 59 mo (range 1-111 mo). The primary endpoint was observed for 58 patients in arm A (docetaxel) and for 57 patients in arm B (surveillance). The Kaplan-Meier analysis showed no difference in the BDFS curves (p = 0.6) between the treatment groups. The 5-yr estimated biochemical progression rates were 31% for arm A and 28% for arm B. Febrile neutropenia occurred in 16% of the docetaxel patients. No deaths were related to the docetaxel treatment. There were 43 deaths during the trial, including 20 in arm A and 23 in arm B, of which nine and seven, respectively, were due to PCa. The hazard ratio from Cox multivariate analysis for PSA progression of arm A (docetaxel) versus arm B (surveillance) was 1.14 (95% confidence interval 0.79-1.64, p = 0.5). CONCLUSIONS: Adjuvant docetaxel without prednisone did not improve BDFS after radical RT with ADT for intermediate- or high-risk PCa. PATIENT SUMMARY: We compared six cycles of adjuvant docetaxel given after radical external radiotherapy plus androgen deprivation therapy to surveillance in intermediate- and high-risk localised prostate cancer. We found no overall benefit in this setting.

Users and non-users of web-based health advice service among Finnish university students - chronic conditions and self-reported health status (a cross-sectional study).

BACKGROUND: The Internet is increasingly used by citizens as source of health information. Young, highly educated adults use the Internet frequently to search for health-related information. Our study explores whether reported chronic conditions or self-reported health status differed among Finnish university students using the Finnish Student Health Services web-based health advice service compared with those not using the service. METHODS: Cross-sectional study performed by a national postal survey in 2004. MATERIAL: A random sample (n = 5 030) of a population of 101 805 undergraduate Finnish university students aged 19-35. The response rate: 63% (n = 3 153). MAIN OUTCOME MEASURES: Proportion of university students reporting use a of web-based health advice service, diagnosed chronic conditions, and self-reported health status of users and non-users of a web-based health advice service. STATISTICAL METHODS: Data were presented with frequency distributions and cross-tabulations and the chi2 test was used. RESULTS: 12% (n = 370) of Finnish undergraduate students had used the web-based health advice service and were identified as 'users'. The proportion of male students reporting allergic rhinitis or conjunctivitis was greater among users than non-users (24%, n = 22 vs. 15%, n = 154, chi2, P = .03). The proportion of female students reporting chronic mental health problems was greater among users than non-users (12%, n = 34 vs. 8%, n = 140, chi2, P = .03). There was no statistical significance between the group differences of male or female users and non-users in self-reported health status (good or fairly good, average, rather poor or poor). CONCLUSION: Among young, highly educated adults the use of a web-based health advice service is not associated with self-reported health status. However, a web-based health advice service could offer support for managing several specific chronic conditions. More research data is needed to evaluate the role of web-based health advice services that supplement traditional forms of health services.

Effect of Adjuvant Trastuzumab for a Duration of 9 Weeks vs 1 Year With Concomitant Chemotherapy for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: The SOLD Randomized Clinical Trial.

Importance: Trastuzumab plus chemotherapy is the standard adjuvant treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. While the standard duration of trastuzumab treatment is 12 months, the benefits and harms of trastuzumab continued beyond the chemotherapy are unclear. Objective: To evaluate the efficacy and safety of adjuvant trastuzumab continued beyond chemotherapy in women treated with up-front chemotherapy containing a taxane and trastuzumab. Design, Setting, and Participants: Open-label, randomized (1:1) clinical trial including women with HER2-positive breast cancer. Chemotherapy was identical in the 2 groups, consisting of 3 cycles of 3-weekly docetaxel (either 80 or 100 mg/m2) plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide. Thereafter, no trastuzumab was administered in the 9-week group, whereas controls received trastuzumab to complete 1 year of administration. Disease-free survival (DFS) was compared between the groups using a Cox model and the noninferiority approach. The estimated sample size was 2168 patients (1-sided testing, with a relative noninferiority margin of 1.3). From January 3, 2008, to December 16, 2014, 2176 patients were accrued from 7 countries. Intervention: Docetaxel plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide in both groups. Controls continued trastuzumab to 1 year. Main Outcomes and Measures: The primary objective was DFS; secondary objectives included distant disease-free survival, overall survival, cardiac DFS, and safety. Results: In the 2174 women analyzed, median age was 56 (interquartile range [IQR], 48-64) years. The median follow-up was 5.2 (IQR, 3.8-6.7) years. Noninferiority of the 9-week treatment could not be demonstrated for DFS (hazard ratio, 1.39; 2-sided 90% CI, 1.12-1.72). Distant disease-free survival and overall survival did not differ substantially between the groups. Thirty-six (3%) and 21 (2%) patients in the 1-year and the 9-week groups, respectively, had cardiac failure; the left ventricle ejection fraction was better maintained in the 9-week group. An interaction was detected between the docetaxel dose and DFS; patients in the 9-week group treated with 80 mg/m2 had inferior and those treated with 100 mg/m2 had similar DFS as patients in the 1-year group. Conclusions and Relevance: Nine weeks of trastuzumab was not noninferior to 1 year of trastuzumab when given with similar chemotherapy. Cardiac safety was better in the 9-week group. The docetaxel dosing with trastuzumab requires further study. Trial Registration: ClinicalTrials.gov Identifier: NCT00593697.

Sexual intercourse and current contraceptive use among university students in Finland.

OBJECTIVE: To ascertain the current frequency of sexual intercourse, the current use of contraceptives, the ever use of emergency contraception, and the ever experience of condom failure among Finnish university students. STUDY DESIGN: The study population consisted of Finnish undergraduate university students (19-34 years of age) in 2004. The randomly selected sample comprised 5030 subjects. The data were collected by postal questionnaire, the response rate being 62.7%. Data were presented with frequency distributions and cross-tabulations. Chi-square test was used. Frequencies for women and men were presented and tested separately. RESULTS: A total of 80% of students were currently practicing sexual intercourse. Approximately half of the female students currently used hormonal contraception and one-third used a condom. Almost half of the men currently used a condom. The simultaneous use of condom and hormonal contraception was rare. Condom failure was common. The ever use of emergency contraception appeared to be associated with condom failure. CONCLUSION: Of Finnish university students 80% were sexually active and hormonal contraceptives were the most popular method of contraception among female students. The use of the condom should be practiced more often for prevention of sexually transmitted diseases.

Irritable bowel syndrome symptom severity improves equally with probiotic and placebo.

AIM: To determine the effects of Lactobacillus acidophilus NCFM on irritable bowel syndrome (IBS) symptoms and quality of life (QoL). METHODS: In this randomized triple-blind trial, adult IBS volunteers who were recruited according to Rome III criteria received 109 or 1010 colony-forming units of NCFM or placebo daily for 12 wk. IBS Symptom Severity Score (IBS-SSS), which constituted the primary outcome, and secondary outcomes, including individual IBS symptoms, IBS-related QoL questionnaire, anxiety and depression, defecation frequency, and stool consistency, were assessed at baseline at the end of the 8-wk run-in period, after 4 and 12 wk of intervention, and after a 4-wk washout. RESULTS: A total of 340 of 391 randomized volunteers completed the trial. IBS-SSS improved over 12 wk of treatment in all treatment groups, decreasing by a mean ± SD of 44.0 ± 80.2, 50.8 ± 82.4, and 48.3 ± 72.2 in the placebo, active low-dose, and active high-dose groups, respectively. Similarly, secondary outcomes did not differ between treatment groups. However, in a post hoc analysis of volunteers with moderate to severe abdominal pain at baseline (VAS > 35/100), the treatment significantly reduced the sensation of abdominal pain. Pain scores fell by 20.8 ± 22.8, 29.4 ± 17.9, and 31.2 ± 21.9 in the placebo, active low-dose, and active high-dose groups, respectively (P value for placebo vs combined active doses = 0.0460). CONCLUSION: NCFM alleviates moderate to severe abdominal pain, consistent with earlier observations of this strain mitigating visceral pain through increased analgesic receptor expression.

Bevacizumab Combined with Docetaxel or Paclitaxel as First-line Treatment of HER2-negative Metastatic Breast Cancer.

AIM: The study evaluated the efficacy of bevacizumab combined with a taxane-based treatment for advanced breast cancer. PATIENTS AND METHODS: In this non-randomized phase II study 65 patients received 10 mg/kg bevacizumab i.v. (days 1 and 15, q4w) plus either 50 mg/m2 docetaxel (days 1 and 15, q4w) or 90 mg/m2 paclitaxel (days 1,8 and 15, q4w) i.v. until disease progression, maximal response, unacceptable toxicity or the withdrawal of consent. Patients without progression continued bevacizumab at 15 mg/kg i.v. (q3w) alone, or with endocrine therapy. (NCT00979641). RESULTS: Progression-free survival was 11.3 months (95% confidence interval=9.7-16.0 months) and overall survival was 35.1 months (95% confidence interval=22.2-50.3 months). More than half of the patients (62%) responded at least partially. Bevacizumab-related serious adverse events occurred in 10.8% patients and one patient died because of gastrointestinal perforation. CONCLUSION: Treating advanced breast cancer with a bevacizumab-containing regimen as the first-line cytotoxic treatment resulted in excellent response rates and long survival.

Improving uptake of screening for colorectal cancer: a study on invitation strategies and different test kit use.

OBJECTIVE: The aim of this study was to compare the uptake of mail-delivered tests for colorectal cancer screening. We assessed the effect of an advance notification letter and a reminder letter, and analysed the proportion of inappropriately handled tests. MATERIALS AND METHODS: Fifteen thousand randomly selected residents of Latvia aged 50-74 years were allocated to receive one of three different test systems: either a guaiac faecal occult blood test (gFOBT) or one of two laboratory-based immunochemical tests (FIT) - FOB Gold or OC-Sensor. Half of the target population received an advance notification letter; all nonresponders were sent a reminder letter. RESULTS: The uptake of screening was 31.2% for the gFOBT, 44.7% for FOB Gold and 47.4% for the OC-Sensor (odds ratio 0.55; 95% confidence interval 0.51-0.60 for gFOBT vs. FOB Gold; odds ratio 0.90; 95% confidence interval 0.83-0.98 for FOB Gold vs. OC-Sensor). The uptake in the gFOBT group was improved by the advance notification letter (7.7%, P<0.0001). 30.9% returned tests were received after the reminder letter. The proportion of tests that could not be analysed because of inadequate handling was 0.9% for gFOBT, 4.4% for FOB Gold and 0.2% for the OC-Sensor (P=0.002 for gFOBT vs. OC-Sensor; P<0.001 for all comparisons vs. FOB Gold). CONCLUSION: The use of FIT resulted in higher uptake. Receipt of a reminder letter was critical to participation, but the use of an advance notification letter was important mainly for gFOBT. The proportion of inappropriately handled tests was markedly higher for FOB Gold.

Fixed-dose combination of tafluprost and timolol in the treatment of open-angle glaucoma and ocular hypertension: comparison with other fixed-combination products.

A new preservative-free fixed-dose combination of 0.0015% tafluprost, a prostaglandin F2α analog, and 0.5% timolol (TAF/TIM; Santen Oy, Tampere, Finland), a beta-adrenergic antagonist has recently been developed. The intraocular pressure (IOP) reduction with TAF/TIM in open-angle glaucoma and ocular hypertension is similar to that of other prostaglandin-timolol fixed-combination products. Patients with high IOP responded well to TAF/TIM with reductions of up to 40% (>13 mmHg) and beyond. Compared to previous controlled and double-masked clinical trials with DuoTrav(®) (Alcon, Fort Worth, USA) and Ganfort(®) (Allergan, Irvine, USA), TAF/TIM caused less superficial ocular side effects and less conjunctival hyperemia. Plausible explanations for the differences in side effects between the fixed-combination products are discussed.

Prevalence of Helicobacter pylori infection and atrophic gastritis in Latvia.

OBJECTIVES: Helicobacter pylori infection and atrophic gastritis are related to an increased risk for gastric cancer. There is a decrease in global H. pylori prevalence. We analyzed the prevalence of H. pylori infection in Latvia by the plasma IgG test and the presence of atrophy by means of pepsinogen testing. METHODS: This subanalysis was carried out on a randomly selected cross-sectional sample of a general population of adults to access cardiovascular risk factors. Plasma samples were screened for H. pylori IgG (cutoff value 24 U/ml), and pepsinogens (Pg) I and II. Pg cutoff values of PgI/PgII ≤ 3 and PgI ≤ 70 ng/ml were used to assess the prevalence of atrophy of any grade and PgI/PgII ≤ 2 and PgI ≤ 30 ng/ml for advanced atrophy. RESULTS: Altogether, 3564 serum samples were available for the study (2346 women, 1218 men; median age 54 years). Of the tested individuals, 79.21% were H. pylori positive, with no difference between sexes. The prevalence increased with age (P<0.001). Atrophy of any grade was identified in 1444 individuals (40.52%) and advanced atrophy in 475 individuals (13.33%). Linear association with age was present in both response types (P<0.001). The prevalence of atrophy of any grade was higher in women (41.73%) than in men (38.18%; P=0.04); this difference was lost for advanced atrophy (women 13.98%, men 12.07%; P=0.1). CONCLUSION: The prevalence of H. pylori infection or atrophy remains high in Latvia. Determining the right cutoff value is critically important for pepsinogen-based atrophy detection in Europe in order to objectively stratify gastric cancer risk.