Immunogenicity and safety of an adjuvanted inactivated polio vaccine, IPV-Al, following vaccination in children at 2, 4, 6 and at 15-18 months.

BACKGROUND: Availability of affordable inactivated polio vaccines (IPV) is of major importance to meet the increasing global supply needs. The results presented here demonstrate non-inferiority of a reduced-dose, aluminium hydroxide-adjuvanted IPV (IPV-Al) to standard IPV. METHODS: A phase 3, observer-blinded, randomised, clinical trial was conducted in Panama in infants who received either IPV-Al (n = 400) or standard IPV (n = 400) at age 2, 4 and 6 months. In the booster trial, subjects received a single dose of IPV-Al at age 15-18 months. The primary endpoint was type-specific seroconversion, defined as an antibody titre ≥4-fold higher than the estimated maternal antibody titre and a titre ≥8, one month after the primary vaccination series. In the booster trial, the primary endpoint was the type-specific booster effects (geometric mean titre (GMT) post-booster (Day 28)/GMT pre-booster (Day 0). RESULTS: Seroconversion rates following primary vaccination with IPV-Al vs IPV were: 96.1% vs 100% (type 1); 100% vs 100% (type 2); and 99.2% vs 100% (type 3) respectively. IPV-Al was non-inferior to IPV, as the lower 95% confidence limits of the treatment differences were above the pre-defined -10%-point limit: 3.94% (-6.51; -2.01) for type 1; 0.0% (-1.30; -1.37) for type 2; -0.85 (-2.46; 0.40) for type 3. The booster effects for the group primed with IPV-Al versus the group primed with IPV were 25.3 vs 9.2 (type 1), 19.1 vs 6.5 (type 2) and 50.4 vs 12.5 (type 3). IPV-Al had a comparable safety profile to that of IPV. CONCLUSIONS: Non-inferiority of IPV-Al to standard IPV with respect to seroconversion after vaccination at 2, 4 and 6 months was confirmed for all three poliovirus serotypes. A robust booster response was demonstrated following vaccination with IPV-Al, regardless of the primary vaccine received. Both vaccines were well tolerated. ClinicalTrials.gov identifiers: NCT03025750 and NCT03671616. FUNDING: Bill & Melinda Gates Foundation.

Immunogenicity and safety of an adjuvanted inactivated polio vaccine, IPV-Al, compared to standard IPV: A phase 3 observer-blinded, randomised, controlled trial in infants vaccinated at 6, 10, 14 weeks and 9 months of age.

BACKGROUND: A dose-sparing inactivated polio vaccine (IPV-Al), obtained by adsorption of inactivated virus to an aluminium hydroxide adjuvant, can help mitigate global supply and the cost constraints of IPV. The objective of this trial was to demonstrate the non-inferiority of IPV-Al to standard IPV. METHODS: This phase 3, observer-blinded, randomised, controlled trial was conducted at 5 investigational sites in the Philippines. Infants not previously vaccinated with any polio vaccines were randomised to receive three IPV-Al (n = 502) or IPV vaccinations (n = 500) at 6, 10 and 14 weeks of age plus a booster vaccination at 9 months. The primary endpoint was type-specific seroconversion, defined as an antibody titre ≥4-fold higher than the estimated maternal antibody titre and a titre ≥8, one month after the primary vaccination series. RESULTS: Seroconversion rates following primary vaccination with IPV-Al (483 infants in the per-protocol analysis set) or IPV (478 infants) were: polio type 1, 97.1% versus 99.0%; type 2, 94.2% versus 99.0%; and type 3, 98.3% versus 99.6%. IPV-Al was non-inferior to IPV, as the lower 95% confidence limits of the treatment differences were above the predefined -10%-point limit: type 1, -1.85% (-3.85; -0.05); type 2, -4.75% (-7.28; -2.52); type 3, -1.24 (-2.84; 0.13). The booster effect (geometric mean titre (GMT) post-booster / GMT pre-booster) was: type 1, 63 versus 43; type 2, 54 versus 47; type 3, 112 versus 80. IPV-Al was well tolerated with a safety profile comparable to that of IPV. Serious adverse events were recorded for 29 infants (5.8%, 37 events) in the IPV-Al group compared to 28 (5.6%, 48 events) in the IPV group. CONCLUSION: Non-inferiority of IPV-Al to IPV with respect to seroconversion was confirmed and a robust booster response was demonstrated. Both vaccines had a similar safety profile. ClinicalTrials.gov identifier: NCT03032419.

Low-FODMAP diet reduces irritable bowel symptoms in patients with inflammatory bowel disease.

AIM: To investigate the effect of a low-FODMAP diet on irritable bowel syndrome (IBS)-like symptoms in patients with inflammatory bowel disease (IBD). METHODS: This was a randomised controlled open-label trial of patients with IBD in remission or with mild-to-moderate disease and coexisting IBS-like symptoms (Rome III) randomly assigned to a Low-FODMAP diet (LFD) or a normal diet (ND) for 6 wk between June 2012 and December 2013. Patients completed the IBS symptom severity system (IBS-SSS) and short IBD quality of life questionnaire (SIBDQ) at weeks 0 and 6. The primary end-point was response rates (at least 50-point reduction) in IBS-SSS at week 6 between groups; secondary end-point was the impact on quality of life. RESULTS: Eighty-nine patients, 67 (75%) women, median age 40, range 20-70 years were randomised: 44 to LFD group and 45 to ND, from which 78 patients completed the study period and were included in the final analysis (37 LFD and 41 ND). There was a significantly larger proportion of responders in the LFD group (n = 30, 81%) than in the ND group (n = 19, 46%); (OR = 5.30; 95%CI: 1.81-15.55, P < 0.01). At week 6, the LFD group showed a significantly lower median IBS-SSS (median 115; inter-quartile range [IQR] 33-169) than ND group (median 170, IQR 91-288), P = 0.02. Furthermore, the LFD group had a significantly greater increase in SIBDQ (median 60, IQR 51-65) than the ND group (median 50, IQR 39-60), P < 0.01. CONCLUSION: In a prospective study, a low-FODMAP diet reduced IBS-like symptoms and increased quality of life in patients with IBD in remission.

Osteochondrosis of the elbow joint in finishing pigs from three herds: associations among different types of joint changes and between osteochondrosis and growth rate.

Osteochondrosis (OC) is a degenerative condition of the cartilage seen in growing animals. The objective of the study was to investigate (1) the prevalence of macroscopically visible OC in the elbow of finishing pigs, (2) the relationship between changes in the surface of the articular cartilage and changes in the underlying cartilage and bone and the synovial membrane, and (3) the association between growth rate and the occurrence of OC in the elbow. The study used 9696 finishing pigs from three herds. After slaughter, the left elbow joint of each pig was examined, and macroscopically visible lesions in the articular cartilage, subchondral bone and synovial membrane were recorded. The highest prevalences of OC lesions were found in the humeral condyle with thickening of the articular cartilage (53%), irregularity of the articular cartilage (32%), lesions in the subchondral bone (26%), fissures under the cartilage (21%) and osteochondrosis dissecans (OCD) (14%). Irregularity of the articular cartilage was strongly associated with fissures under the cartilage and lesions in the subchondral bone (OR 13.7 and 5.8, respectively). Irregularity of the articular cartilage and OCD were associated with villous proliferation of the synovial membrane. For each additional 100 g of average daily gain in the weaner period or in the finishing period, the risk of irregularity in the articular cartilage and OCD increased by approximately 20% (ORs ranging between 1.14 and 1.20 for both weaners and finishers).

Antimicrobial use in Danish pig herds with and without postweaning multisystemic wasting syndrome.

A retrospective cohort study was performed on 130 pig herds in Denmark, to assess the effect of PMWS on the use of antimicrobial drug. The study comprised 65 herds diagnosed with PMWS during 2003-2004, and matched by the veterinary practitioner with 65 herds free from PMWS. Information on antimicrobial use 1 year before and 1 year after the diagnosis was achieved from the National Prescription Medicine Monitoring Database, VetStat, and summarized on quarter within age group and herd. The multiple linear regression analysis comprised antimicrobial use as the outcome variable with (1) quarter relative to diagnosis of PMWS in the positive herd (same date for the negative match), (2) diagnosis of PMWS (same date used for matched PMWS(-) herd), (3) season and (4) temporal trend as fixed effects. Relative to the unaffected herds, the antimicrobial use in the sow units in the PMWS(+) herds was elevated significantly by 35% in the last quarter and 43% in the fourth quarter before positive diagnosis in the herds (p<0.05). In weaner pigs, the antimicrobial use increased significantly two quarters before, and one quarter after the positive diagnosis, by 68%, 91% and 124% respectively. In weaner pigs, effects were seen of herd size and season. The study support that increased morbidity occur for an extended period prior to the diagnosis of PMWS, both in the sow units and the weaner pig units and further indicate that the syndrome cease after the diagnosis, with a decrease in need for antimicrobial treatment.

Diet quality: associations with health messages included in the Danish Dietary Guidelines 2005, personal attitudes and social factors.

OBJECTIVE: To study the association between diet quality and the new health messages in the Danish Dietary Guidelines 2005, i.e. 'Eat a varied diet', 'Engage in regular physical activity' and 'Maintain a healthy body weight'. DESIGN/SETTING/SUBJECTS: The study was cross-sectional, comprising a random sample of 3151 Danish adults aged 18-75 years. Dietary intake was estimated using a 7 d pre-coded food diary. Information on social background, leisure-time physical activity, height, body weight and intention to eat healthy was obtained by in-person interviews. Logistic regression models were used to explore the independent effects of energy intake, leisure-time physical activity, food variety, BMI, age, gender, education, household income, location of residence and intention to eat healthy on the likelihood to have high diet quality measured by an index based on the intake of dietary fibre and saturated fat. RESULTS: Greater food variety (OR = 1.32 for women, 1.13 for men), high leisure-time physical activity (OR = 2.20 for women, 1.91 for men), frequent intentions to eat healthy (OR = 8.19 for women, 5.40 for men) and low energy intake (OR=0.78 for women, 0.85 for men) were significantly associated with high diet quality. For women education was positively associated with diet quality. The study did not demonstrate any association between BMI and diet quality. CONCLUSION: The health behaviours 'Eat a varied diet' and 'Engage in regular physical activity' were positively associated with healthy eating. The dietary habits reported were strongly influenced by personal intentions. Thus, the biggest challenge for public health nutritionists will be to reach non-compliers who seldom have intentions to eat healthy.

Risk-based analysis of the Danish pork Salmonella program: past and future.

The Danish pork Salmonella control program was initiated in 1993 in response to a prominent pork-related outbreak in Copenhagen. It involved improved efforts at slaughter hygiene (postharvest) and on-farm (preharvest) surveillance and control. After 10 years, 95 million Euros, significant reductions in seropositive herds, Salmonella positive carcasses, and pork-attributable human cases (PAHC), questions have arisen about how best to continue this program. The objective of this study was to provide some analysis and information to address these questions. The methods used include a computer simulation model constructed of a series of Excel workbooks, one for each simulated year and scenario (http://www.ifss.iastate/DanSalmRisk). Each workbook has three modules representing the key processes affecting risk: seropositive pigs leaving the farm (Production), carcass contamination after slaughter (Slaughter), and PAHC of Salmonella (Attribution). Parameter estimates are derived from an extensive farm-to-fork database collected by industry and government and managed by the Danish Zoonosis Centre (http://www.food.dtu.dk). Retrospective (1994-2003) and prospective (2004-2013) simulations were evaluated. The retrospective simulations showed that, except for the first few years (1994-1998), the on-farm program had minimal impact in reducing the number of positive carcasses and PAHC. Most of the reductions in PAHC up to 2003 were, according to this analysis, due to various improvements in abattoir processes. Prospective simulations showed that minimal reductions in human health risk (PAHC) could be achieved with on-farm programs alone. Carcass decontamination was shown as the most effective means of reducing human risk, reducing PAHC to about 10% of the simulated 2004 level.

The intake of saturated fat and dietary fibre: a possible indicator of diet quality.

The aim of the present study was to assess if a simple dietary quality index (SDQI) is a useful indicator for nutritional quality in the Danish diet. Data from the Danish National Dietary Survey 2000-2 for adults (n 3151; age 18-75 years) were used to construct an SDQI based on the intake of dietary fibre and saturated fat. The SDQI was used to rank the individuals into three subgroups: the 25 % closest in meeting the recommended intakes of saturated fat and dietary fibre (compliers), the 25 % furthest away (non-compliers) and the 50 % in between (intermediates). Significant differences in food and nutrient intake between these subgroups were identified by intakes of food groups and intakes of nutrients followed by non-parametric tests. Compared with the Nordic Nutrition Recommendations 2004 and the Danish Dietary Guidelines 2005, compliers had a significantly better nutrient profile than intermediates and non-compliers, as the diet of compliers contained more whole-grain cereals, fruits, vegetables and fish, and more frequently low-fat dairy products, lean meats and boiled potatoes. The diet of all subgroups, especially non-compliers, had a high content of nutrient-poor, energy-dense foods, for example, salty snacks, confectionery, and beverages, for example, soft drinks and alcohol. The SDQI is a simple and useful tool to characterise the diet quality of Danish adults.

Determination of a saliva cotinine cut-off to distinguish pregnant smokers from pregnant non-smokers.

BACKGROUND: Objective validation of smoking status is necessary. Earlier studies have used saliva cotinine concentrations between 14.2 and 30 ng/ml as cut-off values to distinguish pregnant smokers from non-smokers. However, these cut-offs derive from studies including men and non-pregnant women. This constitutes a problem, as recent studies have reported an accelerated metabolism in pregnant smokers. The aim of this study was to determine the optimum cut-off cotinine level distinguishing pregnant smokers from pregnant non-smokers. METHODS: An observational study of 620 pregnant women, 359 self-reported smokers and 261 self-reported non-smokers, with complete data on smoking status and saliva cotinine. The study was conducted at a large university hospital in Copenhagen, Denmark. Saliva was sampled at the first antenatal visit to the midwife and analyzed for cotinine level by gas chromatography. Participants completed a questionnaire immediately after the first visit. RESULTS: A saliva cotinine cut-off level of 13 ng/ml, corresponding to a sensitivity of 0.99 and specificity 0.98, was found to be the optimum cut-off value separating pregnant smokers from non-smokers. The sum of the sensitivity and specificity was at its maximum, 1.981. A 95% bootstrap confidence interval for the optimum cut-off was (8-14 ng/ml). CONCLUSION: From the present data we recommend that in future studies on smoking cessation and pregnancy a cut-off level of 13 ng/ml should be applied to distinguish between pregnant smokers and non-smokers.

The effect of environmental tobacco smoke during pregnancy on birth weight.

BACKGROUND: This study explores whether pregnant nonsmokers' exposure to environmental tobacco smoke (ETS) affects the average birth weight at term. METHODS: The population studied consists of pregnant nonsmokers participating in a study called Smoke-free Newborn Study. The participants (n = 1612) answered a questionnaire during 12th to 16th gestational week about their exposure to ETS at home and outside the home. RESULTS: Pregnant nonsmokers exposed to ETS both at home and outside the home gave birth to children with a birth weight of 78.9 g (95% CI -143.7 to -14.1) (P=0.02) lower than the weight of children born to women unexposed to ETS. There was no significant reduction in birth weight among women exposed to ETS at home only or outside the home only. A nonsignificant dose-response association was seen between increasing daily exposure to ETS and reduction in birth weight. CONCLUSION: Nonsmoking pregnant women who were exposed to ETS at home as well as outside the home gave birth to children with a 79 g reduction in birth weight compared to children of unexposed women. The fact that exposure to ETS has an effect on the birth weight is regarded as essential. The authors recommend that pregnant women should not be exposed to passive smoking, and that it should be considered whether workplace legislation should be instituted in order to protect pregnant women against the adverse effects of passive smoking.

Quality control in boar semen production by use of the FACSCount AF system.

A simple and rapid flow cytometric method has recently been developed for simultaneous determination of sperm concentration and viability in semen from domestic animals. Use of SYBR-14 trade mark in combination with propidium iodide (PI) allows estimation of the proportion of live sperm (viability). An internal standard of fluorescent microspheres (beads) makes it possible to determine the sperm concentration during the same analysis. In the first experiment, the relationship between sperm viability and litter size was investigated. The second experiment explored whether a smaller variation in the number of motile sperm per insemination dose could be obtained using the FACSCount AF flow cytometer than using a spectrophotometer. Results in the first experiment show that sperm viability is closer related to litter size than is the traditionally used motility parameter. Although the flow cytometer is precise and objective, a limited effect on litter size should be anticipated if ejaculates are selected for insemination according to the percentage of viable sperm. However, the present trial used large insemination doses (2.3 x 10(9) motile sperm/dose) which partially compensate for the differences in motility and viability between boars and ejaculates. In the second experiment it was found that variation in the number of motile sperm per insemination dose could be reduced significantly if the FACSCount AF flow cytometer rather than the Corning 254 spectrophotometer was used for determination of sperm concentration in the raw semen. It is concluded that the FACSCount AF flow cytometer is a strong tool for improvement of the quality control in artificial insemination (AI) centres.

Multimodal intervention raises smoking cessation rate during pregnancy.

BACKGROUND: The aim was to study the effect of a multimodal smoking cessation intervention regimen on a number of pregnant smokers. METHODS: A prospective intervention study was designed where participants were allocated to intervention or control based on their birth date. The study included 647 pregnant smokers. The intervention group (n = 327) received initial individual smoking cessation counseling supplemented by an invitation to join, individually or in a group, a smoking cessation program with nicotine replacement therapy as a voluntary option. Intervention was designed as an integral part of the midwives' prenatal care. All pregnant smokers in the usual care group (n = 320) received standard counseling from a midwife. Outcome was self-reported smoking cessation in the 37th week of pregnancy and the reported cessation was validated by cotinine saliva concentration. RESULTS: Self-reported cessation rates during pregnancy were significantly higher in the intervention group (14%) than in the group receiving usual care (5.0%) (p < 0.0001) (Fisher's exact test). Cotinine-validated cessation rates during pregnancy were significantly higher among the former (7%) than the latter (2%) (p = 0.003). The adjusted odds ratio (OR) for smoking cessation was 4.20 (95% CI 2.13-8.03). Logistic regression analysis showed a significant positive association of smoking cessation with low caffeine consumption in pregnancy, many years in school, no exposure to passive smoking outside the home, and previous attempts to stop smoking. CONCLUSIONS: A multimodal intervention regimen with initial individual counseling supplemented by an invitation to join a smoking cessation program with nicotine replacement therapy as a voluntary option markedly increased cessation rates during pregnancy.