Quality of life and fear of COVID-19 in 2600 baccalaureate nursing students at five universities: a cross-sectional study.

BACKGROUND: The COVID-19 pandemic has caused significant disruptions in the implementation of programs across educational institutions. Nursing students, being both young adults and by practical training, part of the health care system, may be particularly vulnerable during the COVID-19 pandemic. The purpose of this study was to explore the associations between self-reported fear of COVID-19, general health, psychological distress and overall quality of life (QoL) in a sample of Norwegian baccalaureate nursing students compared to reference data. METHODS: The survey targeted baccalaureate nursing students from five universities in February 2021. An electronic questionnaire consisted of the Fear of COVID-19 Scale (FCV-19S), the Hopkins Symptom Checklist 5 (SCL-5), one general health and one overall QoL question. The respondents' mean scores were compared to reference data. Hierarchical regression analyses were conducted, and effect sizes (Cohen's d) were evaluated. RESULTS: In total, 2605 out of 6088 (43%) students responded. Their FCV-19S scores (mean 2.45, CI 2.42, 2.48) were significantly higher than those of the reference population (mean 1.8, P < 0.001). Nursing students scores showed significantly lower general health (mean 3.50 ± 0.93 SD, population mean = 3.57, Cohen's d = 0.07), higher levels of psychological distress (mean 2.68 ± 1.03 SD, population mean = 2.12, Cohen's d = 0.55) and lower overall QoL (mean 5.50 ± 2.16 SD, population mean = 8.00, Cohen's d = 1.16) compared to pre-pandemic reference data. FCV-19S scores were significantly associated with levels of general health (Cohen's d = 0.26), psychological distress (Cohen's d = 0.76) and overall QoL (Cohen's d = 0.18). CONCLUSIONS: Baccalaureate nursing students reported worse outcomes during the Covid-19 pandemic on general health, psychological distress and overall QoL compared to the reference population. Level of fear of Covid-19, however, accounted for few of these differences. Other factors related to the pandemic may have reduced nursing students' overall QoL.

Does moderate intensity impact exercise and non-impact exercise induce acute changes in collagen biochemical markers related to osteoarthritis? - An exploratory randomized cross-over trial.

OBJECTIVE: To investigate acute changes in biochemical markers of cartilage turnover in response to moderate intensity exercise with and without joint impact in humans with knee osteoarthritis. DESIGN: We conducted a randomized, cross-over, exploratory clinical study. Twenty subjects with knee osteoarthritis (OA) were randomized, of which twenty completed 30 min of cycling and 15 completed 30 min of running on days 1 week apart. Fasting blood samples were taken before, immediately after and 1, 2, 3, and 24 h after activity was initiated. Midstream spot urine was sampled before and after activity. Serum samples were analyzed for concentrations of fragment of type II collagen degradation, C2M, fragment of type VI collagen degradation, C6M, cartilage oligomeric matrix protein, COMP, marker of type II collagen formation, PRO-C2, and urine for marker of crosslinked type II collagen degradation, CTX-II. To establish a reference, all subjects had similar samples taken during rest on a separate day. Data was analyzed in a restricted maximum likelihood based random effects linear mixed model. RESULTS: C2M trended to increase after cycling compared running (13.49%, 95%CI: -0.36-27.34%) and resting (12.88%, 95%CI: 0.2-25.6%) and the type II collagen formation/degradation ratio switched towards degradation after cycling, but not running. C6M trended to decrease after cycling (-8.1%, 95%CI: -14.8 to -1.4%) and running (-6.8%, 95%CI: -14.16-0.55%). CONCLUSION: In persons with knee OA moderate intensity exercise without joint impact may induce acute changes in circulating levels of biochemical markers reflecting type II and VI collagen degradation.

Can adenosine triphosphate be a proxy measure in evaluation of hand disinfection effect?

Contaminated hands may contribute to the transmission of pathogens. In the prevention of healthcare-associated infections the effect of disinfection methods should ideally be possible to measure in a simple way. Microbial cultivation is the reference standard, but it is a rather complicated and time-consuming procedure, and the use of swabs for measuring adenosine triphosphate (ATP) has become a much-used proxy measurement (bioluminescence). We evaluated the effect of three hand-disinfection methods on eradication of Escherichia coli from artificially contaminated hands, using cultivation and ATP measurements in parallel. ATP measurement was found to be an unsuitable method as this reflects the total amount of cellular material left on the hands, not only the viable bacteria.

Effects of hand disinfection with alcohol hand rub, ozonized water, or soap and water: time for reconsideration?

The effect of alcohol hand rub was tested in eradicating Escherichia coli, and compared with hand wash using ozonized tap water or soap and water. Alcohol eradicated all bacteria in 10 out of 35 participants, but with an average (SD) of 2330 (4227) cfu/mL left after disinfection, whereas ozonized water removed all bacteria in 10 out of 55 participants, with an average of only 538 (801) cfu/mL left (P = 0.045). Soap washing was the most effective with total removal of bacteria in six out of 20 participants, with an average of 98 (139) cfu/mL (P = 0.048 and 0.018 versus ozonized water and alcohol, respectively).

Gastropexy predicts lower use of acid-reducing medication after laparoscopic sleeve gastrectomy. A prospective cohort study.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) may induce gastro-oesophageal reflux disease and surgical techniques should be sought to reduce reflux after LSG. Gastropexy of the sleeve gastrectomy pouch to prevent kinks, torsion and intrathoracic sleeve migration was added to our standard LSG in 2012, and the aim of this study was to evaluate if adding gastropexy has influenced the occurrence of gastrooesophageal reflux symptoms (GORS) after LSG. METHODS: In this prospective two-cohort study, the group with LSG and gastropexy (G) was compared with a historical cohort who did not have gastropexy (NG). The use of acid-reducing medication (ARM) was used as a proxy measure of GORS. Gastropexy was performed by suturing the gastrocolic ligament (including the gastroepiploic arcade) to the staple line from the cardia to well below the incisura angularis. Non-resorbable sutures were used. Multiple logistic regression analysis was used to study differences in the use of ARM between the NG and G group two years after surgery. RESULTS: Patient characteristics as age, gender and BMI at baseline, and excess body mass index loss (EBMIL) and smoking at two years were similar between the NG group (n = 216) and G group (n = 116). The follow-up rate was 86.4% for the NG group and 85.3% for the G group. Adding gastropexy did not increase the morbidity rate. In the NG group, the number of patients using ARM was 21 (9.7%) preoperatively and 66 (30.6%) two years after surgery. In the G group, the number using ARM was 11 (10.4%) preoperatively and 18 (14.2%) two years after surgery. The adjusted odds ratio for postoperative GORS in group G compared to group NG was 0.32 (95% CI: 0.16-0.64, p < 0.001). CONCLUSION: Gastropexy may prevent postoperative reflux symptoms after LSG. We recommend to evaluate gastropexy in a randomized controlled trial.

The association of dietary animal and plant protein with putative risk markers of colorectal cancer in overweight pre-diabetic individuals during a weight-reducing programme: a PREVIEW sub-study.

PURPOSE: Diets with increased protein content are popular strategies for body weight regulation, but the effect of such diets for the colonic luminal environment is unclear. We aimed to investigate the associations between putative colorectal cancer-related markers and total protein intake, plant and animal proteins, and protein from red and processed meat in pre-diabetic adults (> 25 years). METHODS: Analyses were based on clinical and dietary assessments at baseline and after 1 year of intervention. Protein intake was assessed from 4-day dietary records. Putative colorectal cancer-related markers identified from 24-h faecal samples collected over three consecutive days were: concentration of short-chain fatty acids, phenols, ammonia, and pH. RESULTS: In total, 79 participants were included in the analyses. We found a positive association between change in total protein intake (slope: 74.72 ± 28.84 µmol per g faeces/E%, p = 0.01), including animal protein intake (slope: 87.63 ± 32.04 µmol per g faeces/E%, p = 0.009), and change in faecal ammonia concentration. For change in ammonia, there was a dose-response trend from the most negative (lowest tertile) to the most positive (highest tertile) association (p = 0.01): in the high tertile, a change in intake of red meat was positively associated with an increase in ammonia excretion (slope: 2.0 ± 0.5 µmol per g faeces/g/day, p < 0.001), whereas no such association was found in the low and medium tertile groups. CONCLUSION: Increases in total and animal protein intakes were associated with higher excretion of ammonia in faeces after 1 year in overweight pre-diabetic adults undertaking a weight-loss intervention. An increase in total or relative protein intake, or in the ratio of animal to plant protein, was not associated with an increase in faeces of any of the other putative colorectal cancer risk markers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01777893.

A systematic review of quality of life research in medicine and health sciences.

PURPOSE: Quality of life (QOL) is an important concept in the field of health and medicine. QOL is a complex concept that is interpreted and defined differently within and between disciplines, including the fields of health and medicine. The aims of this study were to systematically review the literature on QOL in medicine and health research and to describe the country of origin, target groups, instruments, design, and conceptual issues. METHODS: A systematic review was conducted to identify research studies on QOL and health-related quality of life (HRQOL). The databases Scopus, which includes Embase and MEDLINE, CINAHL, and PsycINFO were searched for articles published during one random week in November 2016. The ten predefined criteria of Gill and Feinstein were used to evaluate the conceptual and methodological rigor. RESULTS: QOL research is international and involves a variety of target groups, research designs, and QOL measures. According to the criteria of Gill and Feinstein, the results show that only 13% provided a definition of QOL, 6% distinguished QOL from HRQOL. The most frequently fulfilled criteria were: (i) stating the domains of QOL to be measured; (ii) giving a reason for choosing the instruments used; and (iii) aggregating the results from multiple items. CONCLUSION: QOL is an important endpoint in medical and health research, and QOL research involves a variety of patient groups and different research designs. Based on the current evaluation of the methodological and conceptual clarity of QOL research, we conclude that the majority QOL studies in health and medicine have conceptual and methodological challenges.

Ozonized water as an alternative to alcohol-based hand disinfection.

BACKGROUND: Hand hygiene plays a vital role in the prevention of transmission of micro-organisms. Ozone (O3) is a highly reactive gas with a broad spectrum of antimicrobial effects on bacteria, viruses, and protozoa. It can easily be produced locally in small generators, and dissolved in tap water, and quickly transmits into ordinary O2 in the surrounding air. AIM: To compare ozonized tap water and alcohol rub in decontamination of bacterially contaminated hands. METHODS: A cross-over study among 30 nursing students. Hands were artificially contaminated with Escherichia coli (ATCC 25922), then sanitized with ozonized tap water (0.8 or 4 ppm) or 3 mL standard alcohol-based rub (Antibac 85%). The transient microbes from fingers were cultivated and colony-forming units (cfu)/mL were counted. The test procedure was modified from European Standard EN 1500:2013. FINDINGS: All contaminated hands before disinfection showed cfu >30,000/mL. The mean (SD) bacterial counts in (cfu/mL) on both hands combined were 1017 (1391) after using ozonized water, and 2337 (4664) after alcohol hand disinfection. The median (range) values were 500 (0-6700) and 250 (0-16,000) respectively (non-significant difference). Twenty per cent of participants reported adverse skin effects (burning/dryness) from alcohol disinfection compared with no adverse sensations with ozone. CONCLUSION: Ozonized tap water is an effective decontaminant of E. coli, and it could be an alternative to traditional alcohol-fluid hand disinfectants both in healthcare institutions and public places. Ozonized water may be especially valuable for individuals with skin problems.

Physical activity preferences of 10-year-old children and identified activities with positive and negative associations to cardiorespiratory fitness.

AIM: This study investigated children's physical activity (PA) preferences, as these can aid the design of school-based interventions. METHODS: Data were collected in 2014 as a part of the Active Smarter Kids study and 1026 students (52% boys) from 57 Norwegian primary schools completed a questionnaire about their favourite physical activities at a mean age of 10.2 ± 0.3 years. We identified five patterns of PA and studied whether gender, cardiorespiratory fitness and abdominal adiposity were associated with these patterns. RESULTS: Soccer and slalom skiing were the favourite activities, and the most pronounced gender differences were for activities favoured by girls, which included dancing, gymnastics, exercising to music and jumping rope (p < 0.001). When the five component patterns were analysed using linear mixed-effect models, this showed a strong female preference for dancing, gymnastics, exercising to music and climbing. Cardiovascular fitness was negatively associated with frisbee, dodgeball, baseball and floorball, and positively associated with team handball, volleyball and basketball and with slalom skiing and cross-country skiing. It was interesting that the children's preferences were not related to their abdominal adiposity. CONCLUSION: The results showed different gender-based PA preferences and positive and negative associations with cardiovascular fitness, but no relationship with abdominal adiposity.

A review of systematic reviews on the effects of patient-reported outcome monitoring with clinical feedback systems on health-related quality of life-implications for a novel technology in obesity treatment.

Patient-reported outcome monitoring with clinical feedback systems (PRO/CFS) has been employed in many disease states to measure and improve health-related quality of life (HRQOL). Exploring the role of PRO/CFS in treatment for obesity may prove valuable. Systematic reviews were summarized to determine the effectiveness of PRO/CFS on HRQOL in any disease area. Primary studies evaluating the effect of PRO/CFS on HRQOL in treatment for obesity were also considered for inclusion. Systematic searches were performed in The Cochrane Library, PROSPERO, Epistemonikos, HTA, DARE, CINAHL, Medline, Embase, PsycINFO, BMJ Clinical Evidence, PDQ-Evidence and PubPsych. Two reviewers independently screened references until final inclusion and critically appraised included reviews using PRISMA checklist. Five systematic reviews and no primary studies met inclusion criteria. Although results were inconsistent, effectiveness of PRO/CFS on HRQOL was demonstrated in some diseases/treatments (e.g. psychiatric treatment; symptom burden in cancer treatment). No trials using PRO/CFS in treatment for obesity were identified. In some trials, PRO/CFS was not fully integrated into consultations, thereby PRO/CFS was not extensively studied. General effectiveness of PRO/CFS on HRQOL is inconclusive due to heterogeneous and statistically insignificant findings, and lack of stringency in conceptualization and execution of PRO/CFS. There are no data relevant to treatment for obesity. Future studies should use rigorous methodology to examine the effectiveness of PRO/CFS in treatment for obesity.

Small intestinal absorption in patients with chronic obstructive pulmonary disease complicated by cor pulmonale - A pilot study.

BACKGROUND: Cor pulmonale is a common complication to Chronic Obstructive Pulmonary Disease (COPD), and may result in increased pressure in the inferior caval vein and stasis of the liver. The chronic pulmonary hypertension may lead to stasis in the veins from the small intestine and thereby compromise absorption of nutrients. AIM: To investigate whether patients with pulmonary hypertension have reduced absorption capacity compared to COPD patients without cor pulmonale. METHODS: Absorption of d-xylose (25 g) and zinc (132 mg), administered as a single dose, was tested in 14 COPD patients, seven with and seven without cor pulmonale. The presence of cor pulmonale was determined by echocardiography. The concentration of d-xylose and zinc were measured in peripheral blood one, two and three hours after ingestion and used as markers of absorption. Furthermore, urine was collected for five hours to determine the amount of excreted d-xylose. RESULTS: No significant difference in absorption of d-xylose (p = 0.28) or zinc (p = 0.51) was found between the two groups. However, a trend towards a delay in d-xylose absorption, as assessed by time-to-peak concentration, was observed in patients with cor pulmonale (p = 0.08). There was no significant difference in the amount of excreted d-xylose in the urine between the groups (p = 0.52). No correlation was found between the tricuspid regurgitation gradient and the absorption of both test-markers (rs = 0.34 and rs = -0.25). Likewise, no correlations were found between the inferior caval pressure during the in- and expiration phases and the absorption of d-xylose (rs = -0.09 rs = 0.23) or zinc (rs = -0.39, rs = -0.39). CONCLUSION: We found no indications that small intestinal absorption is affected in a clinically relevant degree in patients with cor pulmonale.

A systematic review of reviews: exploring the relationship between obesity, weight loss and health-related quality of life.

This is the first systematic review of reviews to assess the effect of obesity and weight loss on health-related quality of life (HRQoL). We identified 12 meta-analyses/systematic reviews published between January 2001 and July 2016. They addressed the following themes: (i) the relationship between weight/body mass index and HRQoL (baseline/pre-intervention; n = 2). (ii) HRQoL after weight loss (varied interventions and/or study design; n = 2). (iii) HRQoL after weight loss (randomized controlled trials only; n = 2). (iv) HRQoL after bariatric surgery (n = 6). We found that in all populations, obesity was associated with significantly lower generic and obesity-specific HRQoL. The relationship between weight loss and improved HRQoL was consistently demonstrated after bariatric surgery, perhaps due to a greater than average weight loss compared with other treatments. Improved HRQoL was evident after non-surgical weight loss, but was not consistently demonstrated, even in randomized controlled trials. This inconsistency may be attributed to variation in quality of reporting, assessment measures, study populations and weight-loss interventions. We recommend longer-term studies, using both generic and obesity-specific measures, which go beyond HRQoL in isolation to exploring mediators of HRQoL changes and interactions with other variables, such as comorbidities, fitness level and body image.

Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future.

Osteoarthritis (OA) is the biggest unmet medical need among the many musculoskeletal conditions and the most common form of arthritis. It is a major cause of disability and impaired quality of life in the elderly. We review several ambitious but failed attempts to develop joint structure-modifying treatments for OA. Insights gleaned from these attempts suggest that these failures arose from unrealistic hypotheses, sub-optimal selection of patient populations or drug dose, and/or inadequate sensitivity of the trial endpoints. The long list of failures has prompted a paradigm shift in OA drug development with redirection of attention to: (1) consideration of the benefits of localized vs systemic pharmacological agents, as indicated by the increasing number of intra-articularly administered compounds entering clinical development; (2) recognition of OA as a complex disease with multiple phenotypes, that may each require somewhat different approaches for optimizing treatment; and (3) trial enhancements based on guidance regarding biomarkers provided by regulatory agencies, such as the Food and Drug Administration (FDA), that could be harnessed to help turn failures into successes.

Intensive lifestyle intervention provides rapid reduction of serum fatty acid levels in women with severe obesity without lowering omega-3 to unhealthy levels.

Serum fatty acid (FA) levels were monitored in women with severe obesity during intensive lifestyle intervention. At baseline, total FA levels and most individual FAs were elevated compared to a matching cohort of normal and overweight women (healthy controls). After 3 weeks of intensive lifestyle intervention, total level was only 11-12% higher than in the healthy controls and with almost all FAs being significantly lower than at baseline, but with levels of omega-3 being similar to the healthy controls. This is contrary to observations for patients subjected to bariatric surgery where omega-3 levels dropped to levels significantly lower than in the lifestyle patients and healthy controls. During the next 3 weeks of treatment, the FA levels in lifestyle patients were unchanged, while the weight loss continued at almost the same rate as in the first 3 weeks. Multivariate analysis revealed that weight loss and change of serum FA patterns were unrelated outcomes of the intervention for lifestyle patients. For bariatric patients, these processes were associated probably due to reduced dietary input and increased input from the patients' own fat deposits, causing a higher rate of weight loss and simultaneous reduction of the ratio of serum eicosapentaenoic to arachidonic acid.

Treatment of symptomatic knee osteoarthritis with oral salmon calcitonin: results from two phase 3 trials.

PURPOSE: To evaluate the structure-modifying and symptom efficacy, as well as safety and tolerability of oral salmon calcitonin (sCT) formulated with a 5-CNAC carrier (a molecule based on Eligen(®) technology), in osteoarthritis (OA) patients with moderate to severe knee pain and joint structural damage classified as Kellgren and Lawrence (KL)2-3. METHODS AND DESIGN: This is the combined reporting of two randomized, double-blind, multi-center, placebo-controlled trials (CSMC021C2301 and CSMC021C2302), evaluating the efficacy and safety of oral sCT in patients with painful knee OA with structural manifestations, enrolling 1176 and 1030 patients, respectively. Study subjects were randomized (1:1) to oral sCT 0.8 mg twice daily or placebo (PBO) for 24 months. The primary efficacy objectives were to examine the treatment effect compared to placebo on change over 24 months in joint space width (JSW) in the signal knee measured by X-ray, and to examine the change in pain and function using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) questionnaire. Other study parameters included patient and physician global assessment, and biochemical markers of bone (CTX-I) and cartilage degradation (CTX-II). RESULTS: At the 24 month endpoint there was no statistically significant treatment effect on joint space narrowing (JSN) in any of the two studies. In CSMC021C2301 there was a treatment effect on WOMAC (sum of pain, function, stiffness, and total scores) as well as on the biomarkers of bone and joint metabolism, but due to the hierarchical testing procedure the treatment effect was not claimed statistically significant. CONCLUSIONS: The present formulation of oral sCT did not provide reproducible clinical benefits in patients with symptomatic knee OA (NCT00486434, NCT00704847).

OA phenotypes, rather than disease stage, drive structural progression--identification of structural progressors from 2 phase III randomized clinical studies with symptomatic knee OA.

BACKGROUND/PURPOSE: The aim of this study was to identify key characteristics of disease progression through investigation of the association of radiographic progression over two years with baseline Joint Space Width (JSW), Kellgren-Lawrence (KL) grade, Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain, Joint Space Narrowing (JSN), and BMI. METHODS: Data from 2206 subjects (4390 knees) were combined for this post-hoc analysis of two randomized, double-blind, multi-center, placebo-controlled phase III trials (NCT00486434 and NCT00704847) that evaluated the efficacy and safety of 2-years treatment with oral salmon calcitonin of subjects with painful knee osteoarthritis (OA). RESULTS: There was a clear positive and significant correlation between KL grade and WOMAC pain and total WOMAC, albeit the variance in pain measures was from min-to-max for all KL categories, emphasizing the heterogeneity of this patient population and pain perception. 32% of target knees did not progress, and only 51% had changes over minimum significant change (MSC). BMI, KL-Score and WOMAC pain was diagnostic, but only KL-score and pain had prognostic value, albeit pain in a non-linear manner. CONCLUSION: These data clearly describe significant associations between KL grade, JSW, pain and BMI in patients with symptomatic knee OA. KL grade, BMI and WOMAC pain were diagnostically associated with OA based on JSW but only KL-score and pain in a non-linier fashion was prognostic. 50% of patients did not progress more than MSC, highlighting the importance for identification of structural progressors and the phenotypes associated with these. These results suggest that disease phenotypes, rather than disease status, are responsible for disease progression.

Impact of physical activity and diet on lipoprotein particle concentrations in severely obese women participating in a 1-year lifestyle intervention.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Physical activity and high aerobic fitness protects against cardiovascular disease and early death, besides having a very modest impact on lipoprotein-cholesterol in obese subjects. Physical activity has been shown to favourably alter lipoprotein particle concentrations and apolipoprotein B with minimal weight loss in overweight to moderately obese subjects. WHAT THIS STUDY ADDS: We studied the impact of physical activity on lipoprotein subclass particle concentrations in women with severe obesity. Increased physical activity duration was associated with favourable changes, whereas increased PA intensity was associated with adverse changes in some lipoprotein particle subclasses in severely obese women. Severely obese women that manage to increase their physical activity level can improve their lipoprotein profile, whether or not they lose fat mass Physical activity (PA) and high aerobic fitness protects against cardiovascular disease and early death possibly among others because of an anti-atherogenic impact on lipoprotein particle concentrations. The objective of this study was to determine the impact of PA and diet on lipoprotein particle concentrations. Thirty-one severely obese women (age 43.6 ± 10.2 years; body mass index 43.0 ± 6.3 kg m(-2) ) participated in a 1-year lifestyle intervention with repeated measurements of lipoprotein particle subclass concentrations and size of very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL), as well as fat mass, PA and diet. Multiple regression was used to determine associations with change (Δ) in two principal components (PCs) describing lipoprotein distributions: ΔPC 1 LIPO (dominated by VLDL and LDL) and ΔPC 2 LIPO (dominated by large HDL and mean HDL particle size). ΔPA duration was the only variable that was significantly related to ΔPC 1 LIPO (partial r = -0.40, P = 0.008), while ΔPA intensity was the only variable that was significantly related to ΔPC 2 LIPO (partial r = -0.43, P = 0.003) in adjusted models. Increased PA duration was associated with favourable changes, whereas increased PA intensity was associated with adverse changes in some lipoprotein particle subclasses in severely obese women.

Evaluation of the efficacy, safety and pharmacokinetic profile of oral recombinant human parathyroid hormone [rhPTH(1-31)NH(2)] in postmenopausal women with osteoporosis.

CONTEXT: Treatment of osteoporosis with subcutaneous (SC) injections of rhPTH(1-34) or rhPTH(1-84) is associated with significant improvements in BMD and reductions in osteoporotic fractures. However, subcutaneous injections can be associated with discomfort and thus deteriorating compliance. OBJECTIVE: The UGL-OR1001 trial aimed to establish the efficacy and safety parameters of a novel oral tablet formulation of rhPTH(1-31)NH(2) and matching placebo tablets and open-label teriparatide positive control in postmenopausal women with osteoporosis. DESIGN: 24 weeks of randomized, double-blind treatment with once daily doses of 5mg oral treatment or corresponding placebo, or open-label subcutaneous teriparatide. PATIENTS OR OTHER PARTICIPANTS: Women diagnosed with postmenopausal osteoporosis as detected by lumbar spine DXA, with an exclusion of those with prior treatment with bone active agents. INTERVENTION(S): Orally formulated recombinant human PTH(1-31)NH(2) and placebo, or open-label subcutaneous teriparatide as a positive control. MAIN OUTCOME MEASURE(S): The primary endpoint was to characterize the percent change from baseline in bone mineral density (BMD) at L1-L4 axial lumbar spine after 24 weeks in the rhPTH(1-31)NH(2) arm. Secondary and exploratory endpoints included safety and tolerability of the oral formulation, measurement of biochemical markers of bone turnover, and evaluation of the PK profile at first and last dose. The study was registered at ClinicalTrials.gov with the identifier: NCT01321723. RESULTS: The oral tablet formulation of rhPTH(1-31)NH(2) resulted in similar PK profiles at both timepoints with mean C(max) values similar to subcutaneous administration. In the rhPTH(1-31)NH(2) arm, a 2.2% increase in lumbar spine BMD was observed compared to baseline (p<0.001), while no change was observed in the placebo arm. Open-label teriparatide resulted in a 5.1% increase in LS BMD (p<0.001). In the oral PTH study arm, the bone formation marker osteocalcin was increased by 32%, 21% and 23% at Weeks 4, 12 and 24, respectively. There was no significant increase in the level of the bone resorption marker CTx-1. CONCLUSIONS: In summary, these data demonstrate that enteric-coated oral tablet formulation technology consistently generated robust levels of exposure of rhPTH(1-31)NH(2) leading to induction of bone formation without inducing bone resorption resulting in significantly increased levels of LS BMD. Few adverse events were observed, recommending this orally delivered drug candidate for further development.

Surface-catalysed reactions on pollutant-removing building products for indoor use.

In order to evaluate the potential for emission of secondary reaction products from building materials designed to remove pollutants from indoor air, four samples of ceiling tiles--three commercially available and one custom-made--were investigated in chamber experiments. The chambers were irradiated with artificial light simulating indoor conditions and formaldehyde as well as several VOCs (2-butanone, n-butanol, toluene, hexanal, n- butylacetate, 2-butoxyethanol, alpha-pinene, benzaldehyde, n-decane, limonene and 1,2-dichlorobenzene) were added. Depending on the individual substrate-substance combination, it was possible to identify secondary emissions, e.g. formaldehyde, furfural, acetophenone, n-butylbutyrate, n-butyl-i-butyrate, n-butylpropionate, 4-heptanone, acetic acid, i-butyraldehyde and crotonaldehyde. These were generated by cleavage, hydrolysis, rearrangement or radical reactions. Some of these reactions also occurred with samples not containing photocatalysts. All these secondary emissions have to be taken seriously into account when evaluating the performance of materials designed to remove pollutants from indoor air, as they can prove detrimental to human health.