Economic Consequences of the Overuse of Short-Acting ß-Adrenergic Agonists in the Treatment of Asthma in Spain.

BACKGROUND AND OBJECTIVE: To determine the relationship between short-acting ß-adrenergic agonist (SABA) overuse and health care resource use and costs in asthma patients in routine clinical practice. METHODS: A longitudinal retrospective study was conducted in Spanish primary and specialized care centers using the BIG-PAC medical records database. The study population comprised asthma patients ≥12 years of age who attended ≥2 consultations during 2017 and had 1-year follow-up data available. The main outcomes were demographics, comorbidities, medication, and clinical and health care resource use and costs. The relationship between SABA overuse and health care costs and between asthma severity and health care costs was determined. RESULTS: The SABA use IN Asthma (SABINA) study included 39 555 patients, with a mean (SD) age of 49.8 (20.7) years (64.2% female). The Charlson comorbidity index was 0.7 (1.0). SABA overuse (≥3 canisters/y) was 28.7% (95%CI, 27.7-29.7), with a mean of 3.3 (3.6) canisters/y. Overall, 5.1% of patients were prescribed ≥12 canisters/y. SABA overuse was correlated with health care costs (ρ=0.621; P<.001). The adjusted mean annual cost/patient according to the Global Initiative for Asthma (GINA 2019) classification of asthma severity was €2231, €2345, €2735, €3473, and €4243 for steps 1-5, respectively (P<.001). Regardless of asthma severity, SABA overuse yielded a significant increase in health care costs per patient and year (€5702 vs €1917, P<.001) compared with recommended use (<2 canisters/y). CONCLUSION: SABA overuse yields high costs for the Spanish National Health System. Costs increased with severity of asthma.

Clinical characteristics, management, and one-year risk of complications among patients with heart failure with and without type 2 diabetes in Spain.

OBJECTIVE: This work aims to describe the clinical characteristics and therapeutic management and to determine cardiovascular outcomes after one year of follow-up in a contemporaneous population with heart failure (HF) with and without type 2 diabetes in Spain. These factors were also analyzed in the DAPA-HF-like population (patients who met most inclusion criteria of the DAPA-HF trial) and in patients treated with SGLT2 inhibitors at baseline. METHODS: This work is an observational, retrospective, population-based study using the BIG-PAC database. The index date was January 1, 2019. People aged ≥ 18 years who received care for HF in 2019 were selected. Events that occurred in 2019 were analyzed. RESULTS: We identified 21,851 patients with HF (age 78.0 ± 11.3 years, 53.0% men, 50.9% with HF with reduced left ventricular ejection fraction, 44.5% in NYHA functional class II). HF prevalence was 1.88% and incidence was 2.83 per 1,000 person-years. Regarding HF treatments, 66.1% were taking renin-angiotensin system inhibitors, 69.4% beta blockers, 31.2% aldosterone antagonists, and 7.5% sacubitril/valsartan. During the year of follow-up, 29.8% had HF decompensation which led to hospitalization (mean time to first event of 120.9 ± 72.5 days), 12.3% died, and 8.1% died during hospitalization. Events were more common among patients with type 2 diabetes. Hospitalizations for HF were more common in the DAPA-HF-like population. CONCLUSIONS: In Spain, the population with HF is elderly and has many comorbidities. Approximately half of patients have HF with reduced left ventricular ejection fraction. There is room for improvement in HF management, particularly through the use of drugs that reduce both HF hospitalization and mortality, in order to reduce the burden of HF.

A randomized controlled trial to evaluate propylene glycol alone or in combination with dextrose as a treatment for hyperketonemia in dairy cows.

Our objective was to investigate the effect of i.v. dextrose as an adjunct therapy to oral propylene glycol on the resolution of hyperketonemia (HYK; blood ß-hydroxybutyrate ≥1.2 mmol/L), disease incidence, and early lactation milk yield. Cows (n = 1,249) between 3 and 16 d in milk (DIM) from 4 New York dairy farms were screened once weekly for HYK for 2 wk. Those with HYK and no previous history of retained placenta, metritis, or HYK were randomly assigned to 1 of 3 treatment groups: 300 mL of oral 100% propylene glycol for 3 d (PG3); 300 mL of oral 100% propylene glycol for 3 d plus 500 mL i.v. 50% dextrose on d 1 (PG3D1); or 300 mL of oral 100% propylene glycol for 3 d plus 500 mL i.v. 50% dextrose on all 3 d (PG3D3). Cows with a blood ß-hydroxybutyrate <1.2 mmol/L at initial screening were re-screened the following week and randomly assigned to the above treatment groups if blood ß-hydroxybutyrate was ≥1.2 mmol/L. Cows were assessed for post-treatment HYK resolution 1 and 2 wk after initial HYK diagnosis. We collected farm-diagnosed occurrence of adverse events (sold, died, metritis, displaced abomasum, or ketosis) during the first 60 DIM and milk yield data from the first 10 wk of lactation from herd management software. We used mixed-effects multivariable Poisson regression models to assess the risk of post-treatment HYK resolution at 1 and 2 wk following initial HYK diagnosis and adverse event occurrence among treated cows. We used repeated-measures ANOVA to assess differences in average daily milk yield between treatments. The overall HYK incidence was 30.1% (n = 373). Sixty-four percent of cows (n = 237) were assigned to a treatment group in the first week (3 to 9 DIM), and 36% (n = 136) assigned the second week (10 to 16 DIM). The incidence of 1 or more adverse events during the first 60 DIM was 9.4% (n = 35). We found no effect of treatment on risk of post-treatment HYK resolution at wk 1 (PG3 56.9%, PG3D1 45.0%, PG3D3 50.0%) or wk 2 (PG3 60.0%, PG3D1 52.1%, PG3D3 59.5%) following initial diagnosis, or for risk of adverse event occurrence (PG3 7.4%, PG3D1 8.0%, PG3D3 12.6%). Average daily milk yield (mean ± SE) was similar between treatment groups (PG3: 42.7 ± 0.6 kg/d, PG3D1: 42.4 ± 0.6 kg/d, PG3D3: 42.6 ± 0.6 kg/d). The addition of dextrose for 1 or 3 d provided no improvement in resolution of ketosis assessed once weekly, reduction in adverse events during the first 60 d of lactation, or a difference in average daily milk yield during the first 10 wk of lactation.

The microbiome of Escherichia coli and culture-negative nonsevere clinical mastitis: Characterization and associations with linear score and milk production.

Culture-negative and Escherichia coli cases are uncommonly treated in pathogen-based protocols for nonsevere mastitis. High-throughput 16S rRNA sequencing might reveal the presence of other pathogens and can provide information on microbial diversity. The objective was to explore the milk microbiome at the time of the mastitis event (enrollment) and its association with survival in the herd, milk production, and postevent linear score (LS) for cows with clinical mastitis characterized as negative or E. coli by culture. Fifty E. coli-positive and 35 culture-negative samples from cases were enrolled. No cases were treated with antimicrobials. All E. coli-positive quarters were characterized as transient; microbiological culture of samples taken 15 d postmastitis were negative for this organism. However, a difference in α-diversity (Shannon index) was present between enrollment and follow-up samples (3.8 vs. 5.1). When α-diversity was explored for enrollment E. coli samples, no relationship was observed between the Shannon indices of these samples and postmastitis LS. Alpha-diversity of the enrollment samples was lower for E. coli-positive cows that subsequently had greater losses in milk production. This difference was explained by a greater relative abundance of the family Enterobacteriaceae (67.8 vs. 38.4%) for cows that dropped in production. Analysis of composition of the microbiome identified one phylum, Proteobacteria, that differed between E. coli-positive cows that dropped in production and those that did not. Evaluation of ß -diversity found no statistical relationship between postmastitis LS and the microbiome. When evaluating α- and ß-diversities and composition of the microbiomes for culture-negative quarters, no associations were found for milk production changes and postmastitis LS. Three cows did not remain in the herd, limiting the ability to analyze survival. The findings suggest that a contributing factor to negative outcomes in E. coli-positive cows is relative abundance of this pathogen, and that no single or collective group of bacterial families is associated with milk production changes or postmastitis LS in culture-negative quarters. Although additional studies should be performed, the absence of associations between outcomes explored and microbial profiles in this study suggests that we are not missing opportunities by not treating nonsevere E. coli or culture-negative mastitis cases.

Is quality of life different between diabetic and non-diabetic people? The importance of cardiovascular risks.

BACKGROUND: To analyse and compare the impact of cardiovascular risk factors and disease on health-related quality of life (HRQoL) in people with and without diabetes living in the community. METHODS: We used data of 1,905 people with diabetes and 19,031 people without diabetes from the last Spanish National Health Survey (years 2011-2012). The HRQoL instrument used was the EuroQol 5D-5L, based on time trade-off scores. Matching methods were used to assess any differences in the HRQoL in people with and without diabetes with the same characteristics (age, gender, education level, and healthy lifestyle), according to cardiovascular risk factors and diseases. Disparities were also analysed for every dimension of HRQoL: mobility, daily activities, personal care, pain/discomfort, and anxiety/depression. RESULTS: There were no significant differences in time trade-off scores between people with and without diabetes when cardiovascular risk factors or established cardiovascular disease were not present. However, when cardiovascular risk factors were present, the HRQoL score was significantly lower in people with diabetes than in those without. This difference was indeed greater when cardiovascular diseases were present. More precisely, people with diabetes and any of the cardiovascular risk factors, who have not yet developed any cardiovascular disease, report lower HRQoL, 0.046 TTO score points over 1 (7.93 over 100 in the VAS score) compared to those without diabetes, and 0.14 TTO score points of difference (14.61 over 100 in the VAS score) if cardiovascular diseases were present. In fact, when the three risk factors were present in people with diabetes, HRQoL was significantly lower (0.10 TTO score points over 1 and 10.86 points over 100 in VAS score), obesity being the most influential risk factor. CONCLUSIONS: The presence of established cardiovascular disease and/or cardiovascular risk factors, specially obesity, account for impaired quality of life in people with diabetes.

Association between subclinical hypocalcemia in the first 3 days of lactation and reproductive performance of dairy cows.

The objective of this study was to determine the effects of subclinical hypocalcemia on reproductive performance in dairy cows. In a prospective cohort study, 97 cows on 2 dairy farms with automatic milking systems were monitored for subclinical hypocalcemia. Animals were enrolled 7 ± 3 days prior to estimated calving date and three parity groups were defined based on the lactation that the animals were going to start: lactation = 1, lactation = 2, and lactation ≥3. Serum calcium concentration (Ca) was measured in all animals in the first 3 DIM and subclinical hypocalcemia (SCH) was defined as Ca ≤ 8.6 mg/dL; animals that presented a low Ca level during all 3 days were classified as chronic SCH (cSCH). Return to cyclicity during the voluntary waiting period was analyzed based on weekly progesterone concentrations measured in serum. Information on reproductive outcomes (i.e., number of breedings, pregnancy status, days open, etc.), were collected from on-farm software after all study cows had completed their study period. Chronic SCH was present in all parity groups with higher incidence in multiparous animals (20% of parity = 1, 32% of parity = 2; and 46% of parity ≥ 3 animals). The cSCH animals took longer to show active ovaries when compared to eucalcemic and SCH animals. In a multivariable Cox's Proportional Hazard model animals with normal Ca were 1.8 times more likely to return to cyclicity by the end of the voluntary waiting period when compared to cSCH animals. Animals with cSCH also had 0.27 odds of being pregnant at first service compared to eucalcemic cows when analyzed by multivariable logistic regression. Subclinical hypocalcemia had a negative effect on return of ovarian function during the voluntary waiting period and decreased the odds of pregnancy at first service. Those cows with cSCH had an even more pronounced impaired reproductive function than those with one subclinical measurement.

Clinical outcome comparison of immediate blanket treatment versus a delayed pathogen-based treatment protocol for clinical mastitis in a New York dairy herd.

The purpose was to compare immediate intramammary antimicrobial treatment of all cases of clinical mastitis with a selective treatment protocol based on 24-h culture results. The study was conducted at a 3,500-cow commercial farm in New York. Using a randomized design, mild to moderate clinical mastitis cases were assigned to either the blanket therapy or pathogen-based therapy group. Cows in the blanket therapy group received immediate on-label intramammary treatment with ceftiofur hydrochloride for 5 d. Upon receipt of 24 h culture results, cows in the pathogen-based group followed a protocol automatically assigned via Dairy Comp 305 (Valley Agricultural Software, Tulare, CA): Staphylococcus spp., Streptococcus spp., or Enterococcus spp. were administered on-label intramammary treatment with cephapirin sodium for 1 d. Others, including cows with no-growth or gram-negative results, received no treatment. A total of 725 cases of clinical mastitis were observed; 114 cows were not enrolled due to severity. An additional 122 cases did not meet inclusion criteria. Distribution of treatments for the 489 qualifying events was equal between groups (pathogen-based, n = 246; blanket, n = 243). The proportions of cases assigned to the blanket and pathogen-based groups that received intramammary therapy were 100 and 32%, respectively. No significant differences existed between blanket therapy and pathogen-based therapy in days to clinical cure; means were 4.8 and 4.5 d, respectively. The difference in post-event milk production between groups was not statistically significant (blanket therapy = 34.7 kg; pathogen-based = 35.4 kg). No differences were observed in test-day linear scores between groups; least squares means of linear scores was 4.3 for pathogen-based cows and 4.2 for blanket therapy cows. Odds of survival 30 d postenrollment was similar between groups (odds ratio of pathogen-based = 1.6; 95% confidence interval: 0.7-3.7) as was odds of survival to 60 d (odds ratio = 1.4; 95% confidence interval: 0.7-2.6). The one significant difference found for the effect of treatment was in hospital days; pathogen-based cows experienced, on average, 3 fewer days than blanket therapy cows. A majority (68.5%) of moderate and mild clinical cases would not have been treated if all cows on this trial were enrolled in a pathogen-based protocol. The use of a strategic treatment protocol based on 24-h postmastitis pathogen results has potential to efficiently reduce antimicrobial use.

Palliative and supportive care in head and neck cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It provides recommendations on the assessments and interventions for this group of patients receiving palliative and supportive care. Recommendations • Palliative and supportive care must be multidisciplinary. (G) • All core team members should have training in advanced communication skills. (G) • Palliative surgery should be considered in selected cases. (R) • Hypofractionated or short course radiotherapy should be considered for local pain control and for painful bony metastases. (R) • All palliative patients should have a functional endoscopic evaluation of swallowing (FEES) assessment of swallow to assess for risk of aspiration. (G) • Pain relief should be based on the World Health Organization pain ladder. (R) • Specialist pain management service involvement should be considered early for those with refractory pain. (G) • Constipation should be avoided by the judicious use of prophylactic laxatives and the correction of systemic causes such as dehydration, hypercalcaemia and hypothyroidism. (G) • Organic causes of confusion should be identified and corrected where appropriate, failing this, treatment with benzodiazepines or antipsychotics should be considered. (G) • Patients with symptoms suggestive of spinal metastases or metastatic cord compression must be managed in accordance with the National Institute for Health and Care Excellence guidance. (R) • Cardiopulmonary resuscitation is inappropriate in the palliative dying patient. (R) • 'Do not attempt cardiopulmonary resuscitation' orders should be completed and discussed with the patient and/or the family unless good reasons exist not to do so where appropriate. This is absolutely necessary when a patient's care is to be managed at home. (G).

Randomized noninferiority trial comparing 2 commercial intramammary antibiotics for the treatment of nonsevere clinical mastitis in dairy cows.

The purpose was to evaluate 2 intramammary treatments for mild-to-moderate cases of clinical mastitis in a noninferiority comparison. Noninferiority trials are intended to show whether a given treatment, hetacillin potassium, has at least comparable efficacy as the reference treatment, ceftiofur hydrochloride. Treatments can be deemed inferior to the reference treatment by an amount less than the margin of noninferiority, or inconclusive if the confidence interval crosses the margin of noninferiority. Cows with clinical mastitis from 6 farms were considered for enrollment. Using a randomized design, cows with mild or moderate mastitis in 1 quarter were assigned to on-label treatment with either ceftiofur or hetacillin. A total of 596 cows met the criteria needed for continued enrollment. Treatment distribution resulted in 309 cows in the ceftiofur group and 287 cows in the hetacillin group. Mixed regression analysis was performed for the following outcomes: bacteriological cure, pathogen cure, clinical cure, postevent milk production and linear score, and survival to d 30 and 60. Cox proportional hazards analysis was used to describe treatment effect on survival and mastitis risks. Bacteriological cure, defined as absence of causative organism in samples retrieved at d 14 and 21 postmastitis, was similar between groups. No significant statistical differences were found in cure risk, and noninferiority of hetacillin relative to ceftiofur for bacteriological cure was conclusive (hetacillin=67%, ceftiofur=72%). Absence of a pathogen on both follow-up samples designated a cow as a pathogen cure. Pathogen cure was similar between treatment groups and noninferiority of hetacillin relative to ceftiofur was shown (hetacillin=35%, ceftiofur=32%). Clinical cure (hetacillin=68%, ceftiofur=64%), postevent milk production (hetacillin=37.0kg, ceftiofur=38.2kg), and linear scores (hetacillin=3.4, ceftiofur=3.1) were also not statistically different between treatment groups. Noninferiority of hetacillin relative to ceftiofur was shown for survival to d 30 and survival to d 60, whereas hetacillin was more likely to have a clinical cure than ceftiofur by d 4. No differences were seen between groups when Cox proportional hazards were performed, neither for exit from the herd in the 60 d following the event nor in the risk for a subsequent mastitis event. These findings can be used to develop farm-specific protocols for clinical mastitis treatment.

Effect of administration of recombinant bovine somatotropin on health and performance of lactating dairy cows diagnosed with hyperketonemia.

The effect of administering recombinant bovine somatotropin (rbST) to cows with hyperketonemia during the early postpartum period on health, metabolic parameters, milk production, and early reproductive performance was evaluated in a double-blinded clinical trial. Cows from 8 dairy herds in New York State were tested weekly between 3 and 16d in milk for elevated serum ß-hydroxybutyrate. Cows were enrolled in the study when blood ß-hydroxybutyrate was ≥1.3mmol/L for the first time. Enrolled cows were randomly assigned to a treatment (n=273) or placebo control (n=270) group. Treated cows were given 325mg of rbST subcutaneously on the day of enrollment and again 14d later. Control cows received the same regimen except the syringe contained only the carrier without somatotropin. After enrollment, blood samples were collected weekly for 4wk and submitted to the laboratory to be analyzed for selected metabolites. Risk ratios for clinical diseases subsequent to treatment were calculated using Poisson regression. Continuous data were analyzed using linear mixed models. Time to first insemination was assessed with survival analysis. In the 42d following the first administration of rbST, incidence risks of displaced abomasum, clinical ketosis, metritis, clinical mastitis, and lameness were not different between treatment groups. Cows treated with rbST had a slightly lower body condition score 28d after enrollment compared with control cows. In the 4wk following enrollment, serum nonesterified fatty acids and aspartate amino-transferase were slightly higher for treated than control cows, respectively. Serum glucose, calcium, haptoglobin, and ß-hydroxybutyrate were similar between groups. Treatment had no effect on resolution of hyperketonemia in any of the 4wk after enrollment. Milk production in either of the 2-wk periods after each treatment was not different between treated and control cows. Furthermore, milk production was not different between groups from enrollment to 98d in milk (42.6±0.6 and 42.1±0.7kg/d for treatment and control groups, respectively). Treatment had no effect on time to first insemination (83 and 74d in milk for treatment and control groups, respectively; hazard ratio=0.72) or first insemination pregnancy risk (27 and 29% for treatment and control groups, respectively; risk ratio=0.92). Based on the current results, it is not recommended to use a low dose of rbST as therapy for cows with hyperketonemia.

The association of subclinical hypocalcemia, negative energy balance and disease with bodyweight change during the first 30 days post-partum in dairy cows milked with automatic milking systems.

In a prospective cohort study, the daily bodyweight (BW) and milk production of 92 cows were recorded using automatic milking systems. The objectives were to characterize calcium serum concentration variability on days 1-3 post-partum and to evaluate the association between subclinical hypocalcemia (SHPC) and change in BW over the first 30 days in milk (DIM) in Holstein dairy cows, while controlling for concurrent disease and negative energy balance (NEB). SHPC was defined as total serum calcium concentration between 6 and 8 mg/dL, NEB was defined as non-esterified fatty acids (NEFA) > 0.7 mEq/L or ß-hydroxybutyrate (BHB) ≥ 1.2 mmol/L. The peak incidence of SHPC was at 1 DIM for all groups (11%, 42% and 60% for parities 1, 2, and ≥3, respectively). All parity groups lost weight (21, 33, and 34 kg) during the first 30 DIM. Parity 1 animals with disease compared with those without disease lost the most weight (2.6 kg/day BW loss vs. <1.9 kg/day, respectively). Normocalcemic parity 2 animals with either NEB or disease lost the most weight (>5 kg/day) compared with those in the SHPC group (≤4.5 kg/day). In parity ≥ 3 animals, SHPC was an important factor for BW loss; SHPC animals lost the most weight (>3.7 kg/day) vs. normocalcemic cows (≤3.3 kg/day) regardless of NEB or disease status. Even though all animals lost weight during early lactation the effect of disease, NEB, and SHPC on BW loss was different in each parity group.

Herd-level association of serum metabolites in the transition period with disease, milk production, and early lactation reproductive performance.

The objective was to identify herd-level indicators expressed as a proportion of sampled animals with increased nonesterified fatty acids (NEFA) or ß-hydroxybutyric acid (BHBA), or decreased calcium in wk -1 and wk +1 relative to calving that were associated with herd-level incidence of retained placenta, metritis and displaced abomasum, milk production, and probability of pregnancy at the first artificial insemination (AI). Fifty-five Holstein freestall dairy herds in the United States and Canada were visited weekly. Blood was collected from 2,365 cows around parturition, and serum concentrations of NEFA, BHBA, and calcium were determined. Different cow-level metabolite thresholds associated with detrimental health or productivity in previous studies were used to classify animals into high- and low-risk metabolite concentration groups. For wk -1 and wk +1 relative to calving, a herd-level threshold was determined as the proportion of sampled animals in the high-risk metabolite concentration groups with the strongest association with increased incidence of disease, milk loss, or decreased pregnancy at the first AI. The odds of displaced abomasum after calving were higher in herds that had ≥ 25% of the animals with BHBA ≥ 1,400 µmol/L in wk +1 [odds ratio (OR)=2.1; 95% confidence interval (CI)=1.0-4.2)] or ≥ 35% of the animals with calcium ≤ 2.1 mmol/L in wk +1 (OR=2.4; CI=1.3-4.3). Herd-level thresholds of ≥15% of the cows with BHBA ≥ 800 µmol/L in wk -1 and ≥ 15% of the cows with calcium ≤2.1mmol/L in wk +1 were associated with milk loss (±SE) of 4.4±1.7 and 3.8 ± 1.4 kg/d per cow, respectively. When only multiparous cows were considered, herds with ≥30% of the multiparous cows with NEFA ≥0.5 mEq/L in wk -1 were associated with a 3.0 ± 1.5 kg/d per cow milk loss. The odds of pregnancy at first AI were lower in herds that had ≥ 5% of the cows with calcium ≤ 2.1 mmol/L in wk -1 (OR=0.7; CI=0.5-1.0), or ≥ 30% of the cows with NEFA ≥ 1.0 mEq/L (OR=0.6; CI=0.4-0.9) or ≥ 25% of the cows with calcium ≤2.1 mmol/L in wk +1 (OR=0.7; CI=0.5-0.9). When only multiparous cows were considered, the odds of pregnancy at first AI were lower in herds that had ≥50% of multiparous cows with NEFA ≥0.5 mEq/L in wk -1 (OR=0.5; CI=0.2-0.9). In conclusion, several herd-level thresholds for the proportion of cows with increased NEFA or BHBA, or decreased calcium in the week before and after calving were associated with higher risk of displaced abomasum, milk loss at the first Dairy Herd Improvement Association test, and decreased pregnancy at first AI. The association found between precalving BHBA and milk production is promising due to the availability of several cow-side tests for measuring BHBA. Some of the herd-level associations differed from the previously described cow-level associations, suggesting the potential of interpreting periparturient metabolic challenges at the herd level, where changes in diet and management are generally implemented.

The association of serum metabolites in the transition period with milk production and early-lactation reproductive performance.

The objective was to examine the associations of peripartum concentrations of nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHBA), and calcium with milk production in early lactation and pregnancy at the first artificial insemination (AI) across different management systems. Fifty-five Holstein freestall dairy herds located across the United States and Canada were visited weekly for blood sample collection from 2,365 cows. For each week of sampling (from wk -1 through wk 3 relative to calving) and for each metabolite, serum concentrations were dichotomized at various thresholds to identify the thresholds with the best negative associations with milk production and pregnancy at first AI. These thresholds were used to categorize the serum concentrations into higher and lower risk categories. Repeated-measures ANOVA and multivariable logistic regression were conducted for milk production and pregnancy at the first AI data, respectively, considering cow as the experimental unit and herd as a random effect. In the week before calving, serum NEFA ≥ 0.5 mEq/L, BHBA ≥ 600 µmol/L, and calcium ≤ 2.1 mmol/L were associated with 1.6 to 3.2 kg/d milk loss across the first 4 Dairy Herd Improvement Association (DHIA) milk tests. High levels of NEFA and BHBA in wk 1 and 2 after calving (≥ 0.7 and ≥ 1.0 mEq/L for NEFA, and ≥ 1,400 and ≥ 1,200 µmol/L for BHBA), and low levels of calcium (≤ 2.1 mmol/L) in wk 1, 2 and 3 after calving were associated with milk loss at the first DHIA milk test. Serum concentrations of NEFA and BHBA were not associated with pregnancy at first AI in any sampling week, whereas calcium <2.2 to 2.4 mmol/L from wk 1 through wk 3 postpartum were associated with reduced pregnancy at first AI. In conclusion, high serum concentrations of NEFA, BHBA, and low concentrations of calcium around parturition were associated with early lactation milk loss, and low calcium concentration around parturition was associated with impaired early lactation reproduction.

The association of serum metabolites with clinical disease during the transition period.

The objective of this observational field study was to validate the relationship of serum concentrations of nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHBA), and calcium with disease in early lactation across different management systems. Fifty-five Holstein freestall dairy herds located across the United States and Canada were selected and visited weekly for blood sample collection from 2,365 cows. Only diseases that were consistently recorded across herds and blood samples collected before the disease occurred were considered. Metabolite concentrations in serum in wk -1 relative to calving were considered as predictors of retained placenta (RP) and metritis, and metabolite concentrations in serum in wk -1 and wk +1 relative to calving were considered as predictors of displaced abomasum (DA). For each disease, each metabolite, and week of sampling in the case of DA, a critical threshold was calculated based on the highest combined sensitivity and specificity and used to categorize the serum concentrations into high and low risk categories. Multivariable logistic regression models were built for each disease of interest and week of sampling, considering cow as the experimental unit and herd as a random effect. Cows with precalving serum NEFA concentrations ≥ 0.3 mEq/L were more likely to develop RP [odds ratio (OR) = 1.8; 95% confidence interval (CI) = 1.3 to 2.6] and metritis (OR = 1.8; 95% CI = 1.5 to 2.9) after calving than cows with lower NEFA concentrations. Precalving NEFA ≥ 0.5 mEq/L (OR = 2.4; 95% CI = 1.5 to 3.7), postcalving NEFA ≥ 1.0 mEq/L (OR = 2.7; 95% CI = 1.7 to 4.4), and postcalving calcium ≤ 2.2 mmol/L (OR = 3.1; 95% CI = 1.9 to 5.0) were associated with subsequent risk of DA. In conclusion, elevated serum NEFA concentrations within 1 wk before calving were associated with increased risk of RP, metritis, and DA after calving. Serum NEFA and calcium concentrations in the 2 wk around calving in combination were associated with the risk of DA.

[Assessment of the antibiotic allergy questionnaire in the medical history]. / Valoración del interrogatorio de la alergia a antibióticos en la historia clínica.

OBJECTIVES: Antibiotic allergy questionnaire is a useful tool for prescribing antibiotics. The objective of this study is to assess the prevalence and clinical reliability of antibiotic allergy in medical records. PATIENTS AND METHOD: Observational analysis of clinical records. Assessment of antibiotic allergy by direct interview conducted by the investigator. RESULTS: 610 medical records were evaluated. Antibiotic allergy was checked in 98%, mainly in medical wards. In 12 % of patients, antibiotic allergy was suspected, but after investigator interview only 5% of patients fulfilled clinical criteria for allergy. 44% of falses allergies were recorded. The most frequent cause of confusion was faint and gastric intolerance. CONCLUSIONS: The questionnaire about antibiotic allergy is present in almost all medical records. However its reliability is low, less than 50%. Prevalence of veritable antibiotic allergy is 5% in this study. Antibiotic allergy questionnaire in medical records is a practical tool. However periodical training about antibiotic allergy definition is necessary for nurses and medical staff.

Structural genomics: beyond the human genome project.

With access to whole genome sequences for various organisms and imminent completion of the Human Genome Project, the entire process of discovery in molecular and cellular biology is poised to change. Massively parallel measurement strategies promise to revolutionize how we study and ultimately understand the complex biochemical circuitry responsible for controlling normal development, physiologic homeostasis and disease processes. This information explosion is also providing the foundation for an important new initiative in structural biology. We are about to embark on a program of high-throughput X-ray crystallography aimed at developing a comprehensive mechanistic understanding of normal and abnormal human and microbial physiology at the molecular level. We present the rationale for creation of a structural genomics initiative, recount the efforts of ongoing structural genomics pilot studies, and detail the lofty goals, technical challenges and pitfalls facing structural biologists.