Antenatal cardiotocography in primary midwife-led care: a budget impact analysis.

OBJECTIVES: In many countries, the healthcare sector is dealing with important challenges such as increased demand for healthcare services, capacity problems in hospitals and rising healthcare costs. Therefore, one of the aims of the Dutch government is to move care from in-hospital to out-of-hospital care settings. An example of an innovation where care is moved from a more specialised setting to a less specialised setting is the performance of an antenatal cardiotocography (aCTG) in primary midwife-led care. The aim of this study was to assess the budget impact of implementing aCTG for healthy pregnant women in midwife-led care compared with usual obstetrician-led care in the Netherlands. METHODS: A budget impact analysis was conducted to estimate the actual costs and reimbursement of aCTG performed in midwife-led care and obstetrician-led care (ie, base-case analysis) from the Dutch healthcare perspective. Epidemiological and healthcare utilisation data describing both care pathways were obtained from a prospective cohort, survey and national databases. Different implementation rates of aCTG in midwife-led care were explored. A probabilistic sensitivity analysis was conducted to estimate the uncertainty surrounding the budget impact estimates. RESULTS: Shifting aCTG from obstetrician-led care to midwife-led-care would increase actual costs with €311 763 (97.5% CI €188 574 to €426 072) and €1 247 052 (97.5% CI €754 296 to €1 704 290) for implementation rates of 25% and 100%, respectively, while it would decrease reimbursement with -€7 538 335 (97.5% CI -€10 302 306 to -€4 559 661) and -€30 153 342 (97.5% CI -€41 209 225 to -€18 238 645) for implementation rates of 25% and 100%, respectively. The sensitivity analysis results were consistent with those of the main analysis. CONCLUSIONS: From the Dutch healthcare perspective, we estimated that implementing aCTG in midwife-led care may increase the associated actual costs. At the same time, it might lower the healthcare reimbursement.

Differences in Discounting Behavior and Brain Responses for Food and Money Reward.

Most neuroeconomic research seeks to understand how value influences decision-making. The influence of reward type is less well understood. We used functional magnetic resonance imaging (fMRI) to investigate delay discounting of primary (i.e., food) and secondary rewards (i.e., money) in 28 healthy, normal-weighted participants (mean age = 26.77; 18 females). To decipher differences in discounting behavior between reward types, we compared how well-different option-based statistical models (exponential, hyperbolic discounting) and attribute-wise heuristic choice models (intertemporal choice heuristic, dual reasoning and implicit framework theory, trade-off model) captured the reward-specific discounting behavior. Contrary to our hypothesis of different strategies for different rewards, we observed comparable discounting behavior for money and food (i.e., exponential discounting). Higher k values for food discounting suggest that individuals decide more impulsive if confronted with food. The fMRI revealed that money discounting was associated with enhanced activity in the right dorsolateral prefrontal cortex, involved in executive control; the right dorsal striatum, associated with reward processing; and the left hippocampus, involved in memory encoding/retrieval. Food discounting, instead, was associated with higher activity in the left temporoparietal junction suggesting social reinforcement of food decisions. Although our findings do not confirm our hypothesis of different discounting strategies for different reward types, they are in line with the notion that reward types have a significant influence on impulsivity with primary rewards leading to more impulsive choices.

Exploring vaginal discharge scoring to assess clinical metritis severity: Comparison between intrauterine dextrose and systemic antibiotics treatments.

The objectives of this study were to assess: 1) differences in the metabolic status, systemic inflammation, daily milk yield, and daily rumination time between Holstein dairy cows with different vaginal discharge scores (VDS) in the first 7±3 DIM, and 2) effects of intrauterine dextrose infusion on metabolic status, systemic inflammation, daily milk yield and daily rumination time in dairy cows with VDS4 and VDS5. Cows (n=641) from a farm located in central Pennsylvania were screened at 7±3 DIM (study d 0) to assess vaginal discharge scores. Vaginal discharge was scored using a five-point scale (i.e., 1- clear fluid, 2- <50% white purulent fluid, 3- >50% white purulent fluid, 4- red-brownish fluid without fetid smell, and 5- fetid red-brownish watery fluid). Cows with VDS4 and VDS5 were blocked by parity and randomly assigned to one of two treatment groups: 1) CONV (VDS4 n=15; VDS5 n= 23): two injections of ceftiofur (per label; 6.6 mg/Kg) 72 h apart; and 2) DEX (VDS4 n=15; VDS5 n=22): three intrauterine infusions of a 50% dextrose solution (1 L/cow) every 24 h. Cows that presented a VDS 1, 2, and 3 were categorized as normal vaginal discharge animals (NOMVDS; n=35) and were randomly selected and matched by parity to CONV and DEX cows. Daily milk yield and rumination time for the first 150 DIM were collected from on-farm computer records. Blood samples were collected to assess haptoglobin (HP) and ß-hydroxybutyrate (BHB) concentrations at study d 0, d 7, and d 14 relative to enrollment. Subclinical ketosis was defined as having a BHB concentration >1.2 mmol/dL at any of the sampling points. The data were analyzed using the MIXED and GLIMMIX procedures of SAS as a randomized complete block design. When comparing cows with different VDS (i.e., NOMVDS, VDS4, VDS5) separately, cows with VDS5 had the highest concentration of HP at enrollment compared to cows with VDS4 and NOMVDS; however, cows with VDS4 had higher concentrations of HP compared to cows with NOMVDS. Cows with VDS4 or VDS5 had a higher incidence of subclinical ketosis compared to cows with NOMVDS (p=0.005; VDS4= 62.08±9.16%; VDS5=74.44±6.74%; NOMVDS=34.36±8.53%). Similarly, daily milk yield (p<.0001; VDS4=30.17±1.32 kg/d; VDS5=27.40±1.27 kg/d; NOMVDS=35.14±1.35 kg/d) and daily rumination time (p=0.001; VDS4=490.77±19.44 min; VDS5=465±16.67 min; NOMVDS=558.29±18.80 min) was lower for cows with VDS4 and VDS5 compared to cows with NOMVDS at 7±3 days in milk. When analyzing HP concentration between treatment groups in cows with VDS4 (p=0.70), VDS5 (p=0.25), or VDS4 and VDS5 combined (p=0.31), there was no difference in HP concentration by study d 14 between treatment groups. Interestingly, when only cows with VDS4 were considered for treatment, both treatments, DEX and CONV, increased the daily milk yield to the levels of NOMVDS cows by 14 days in milk. On the other hand, when only cows with VDS5 were considered for treatment, cows treated with DEX produced, on average, 4.48 kg/d less milk in the first 150 days in milk compared to cows treated with CONV or cows that had NOMVDS. Similarly, when cows with either VDS4 or VDS5 were considered for treatment, DEX treatment also impaired milk yield. These results suggest that cows with either VDS 4 or 5 have an altered inflammatory status, and decreased milk yield and rumination compared to cows with NOMVDS. Furthermore, DEX treatment may have similar effects on daily milk yield and metabolic status compared to CONV in cows with VDS4, while DEX is not recommended for cows with VDS5.

Comparison of an oral mixed meal plus arginine and intravenous glucose, GLP-1 plus arginine to unmask residual islet function in longstanding type 1 diabetes.

Residual beta cells are present in most patients with longstanding type 1 diabetes but it is unknown whether these beta cells react normally to different stimuli. Moreover a defect in proinsulin conversion and abnormal alpha cell response are also part of the islet dysfunction. A three-phase [euglycemia, hyperglycemia, and hyperglycemia + glucagon-like peptide 1 (GLP-1)] clamp was performed in patients with longstanding type 1 diabetes. Intravenous arginine boluses were administered at the end of each phase. On another day, a mixed meal stimulation test with a subsequent intravenous arginine bolus was performed. C-peptide was detectable in a subgroup of subjects at baseline (2/15) or only after stimulation (3/15). When detectable, C-peptide increased 2.9-fold [95% CI: 1.2-7.1] during the hyperglycemia phase and 14.1-fold [95% CI: 3.1-65.2] during the hyperglycemia + GLP-1 phase, and 22.3-fold [95% CI: 5.6-89.1] during hyperglycemia + GLP-1 + arginine phase when compared with baseline. The same subset of patients with a C-peptide response were identified during the mixed meal stimulation test as during the clamp. There was an inhibition of glucagon secretion (0.72-fold, [95% CI: 0.63-0.84]) during the glucose clamp irrespective of the presence of detectable beta cell function. Proinsulin was only present in a subset of subjects with detectable C-peptide (3/15) and proinsulin mimicked the C-peptide response to the different stimuli when detectable. Residual beta cells in longstanding type 1 diabetes respond adequately to different stimuli and could be of clinical benefit.NEW & NOTEWORTHY If beta cell function is detectable, the beta cells react relatively normal to the different stimuli except for the first phase response to intravenous glucose. An oral mixed meal followed by an intravenous arginine bolus can identify residual beta cell function/mass as well as the more commonly used glucose potentiated arginine-induced insulin secretion during a hyperglycemic clamp.

Risks associated with antidepressants in patients with hypertension during pregnancy: a retrospective cohort study.

PURPOSE: In a cohort of pregnant women using antihypertensive drugs, we compared exposure to antidepressants versus no exposure and the possible association with birth weight, APGAR scores, NICU admission, and maternal admission to an obstetrical intensive care unit (OHC). It was hypothesized that pregnant women with hypertensive disorders using antidepressants are at greater risk of complications. METHODS: A retrospective cohort study in a general teaching hospital in Zwolle, in the Middle-Northern part of The Netherlands. Finally, 58 pregnancies in the exposed group and 273 pregnancies in the reference group met all inclusion and exclusion criteria. We compared the neonate's birthweight between the exposed to antidepressants group and the reference group as the primary outcome. Secondary outcomes were the APGAR score at 1 and 5 min and obstetric high care (OHC) admission of the mother and neonatal intensive care unit (NICU) admission of the child. RESULTS: We found no differences in birth weight in neonates of mothers with hypertensive disorders and whether or not to use antidepressants. Besides a possible higher risk of admission to an OHC in women with hypertension-complicated pregnancies using antidepressants, we found no other maternal or neonatal risks in this population. CONCLUSION: We found no additional maternal or neonatal risks of using antidepressants prescribed to women with hypertension disorders during pregnancy.

Antenatal cardiotocography in dutch primary midwife-led care: Maternal and perinatal outcomes and serious adverse events. A prospective observational cohort study.

PROBLEM: It is yet unknown whether shifting antenatal cardiotocography (aCTG) from obstetrician-led to midwife-led care leads to a safe reduction in referrals. BACKGROUND: ACTG is used to assess fetal well-being. In the Netherlands, the procedure has until now been performed as part of obstetrician-led care. Developments in E-health facilitates the performance of aCTG outside the hospital in midwife-led care, hereby increasing continuity of care. AIM: To evaluate 1) process outcomes of implementing aCTG for specific indications in primary midwife-led care; 2) maternal and perinatal outcomes of pregnant women receiving aCTG in midwife-led care; 3) serious adverse events (with outcomes, causes, avoidability, and potential prevention strategies) that have occurred during the innovation project 'aCTG in midwife-led care'. METHODS: Prospective observational cohort study and a case series study of serious adverse events. FINDINGS: A total of 1584 pregnant women with a specific aCTG indication were included in this cohort study for whom 1795 aCTGs were performed in midwife-led care. 1591 aCTGs(89.7%) were classified as reassuring. Referral to obstetrician-led care occurred for 234 women(13.0%) after an aCTG in midwife-led care of whom 202(86%) were referred back. Severe neonatal morbidity occurred in 27 neonates (1.7%). In the 5736 aCTGs included in the case series study, one case with a serious neonatal outcome was assessed as a serious adverse event attributable to human factors. DISCUSSION: ACTGs performed in midwife-led care increased continuity of care. In this innovation project, maternal and perinatal outcomes were in the expected range for women in midwife-led care.

The protective effects of hormonal suppression by a gonadotropin-releasing hormone agonist or an oral contraceptive on the decreased ovarian reserve in female rats exposed to isotretinoin.

OBJECTIVE: The objective of our study was to evaluate whether ovarian suppression by two different hormonal methods may spare the ovary the cytotoxic effects of isotretinoin in a rat model. MATERIALS AND METHODS: Four groups (n=8 Sprague-Dawley albino rats per group) were studied: control (Group I), 7.5 mg/kg/day isotretinoin (Group II), isotretinoin plus the combination of 0.030 mg ethinyl estradiol/0.15 mg levonorgestrel (combined oral contraceptive, COC), and isotretinoin plus 100 µg (microgram) leuprolide acetate (GnRHa) (Group III and IV, respectively). Four rats from each group were decapitated on the 30th day of treatment, and the remaining rats were decapitated on the 30th day of untreated follow-up. Serum anti-Mullerian hormone (AMH) concentrations, healthy and atretic follicle numbers, and apoptotic activity of follicles in oophorectomy specimens were compared between the groups. RESULTS: There were no significant differences in AMH levels among the study groups before, immediately after (first month), and one month after their last medication (second month) (p=0.08, 0.47, and 0.08, respectively). At the end of the first month, the control group had a higher median count of healthy primordial follicles compared to the study groups: 13.5 (8-22), 5.5 (3-11), 6 (2-13), and 1 (0-1) in control, isotretinoin, isotretinoin+COC, and isotretinoin+GnRHa groups, respectively (p=0.02). However, there was no statistically significant difference in the number of healthy primordial follicles between the groups one month after the last medication (p=0.33). The median atretic antral follicle counts in the first month were 2 (1-4), 3.5 (1-4), 0 (0-2), and 0 (0-0) in the control, isotretinoin, isotretinoin+COC, and isotretinoin+GnRHa groups, respectively (p=0.02). Otherwise, there were no significant differences in other types of follicles among the control and treated groups (p>0.05). There was also no statistical difference between the groups regarding immunostaining intensity for active caspase-3 evaluated in the first or second month of treatment (p=0.8 and 0.2, respectively). CONCLUSIONS: Our results show that GnRH agonists or COC have no protective effects on ovarian reserve when co-administered with isotretinoin in the rat model.

Clinical impact of an integrated e-health system for diabetes self-management support and shared decision making (POWER2DM): a randomised controlled trial.

AIMS/HYPOTHESIS: There is a lack of e-health systems that integrate the complex variety of aspects relevant for diabetes self-management. We developed and field-tested an e-health system (POWER2DM) that integrates medical, psychological and behavioural aspects and connected wearables to support patients and healthcare professionals in shared decision making and diabetes self-management. METHODS: Participants with type 1 or type 2 diabetes (aged >18 years) from hospital outpatient diabetes clinics in the Netherlands and Spain were randomised using randomisation software to POWER2DM or usual care for 37 weeks. This RCT assessed the change in HbA1c between the POWER2DM and usual care groups at the end of the study (37 weeks) as a primary outcome measure. Participants and clinicians were not blinded to the intervention. Changes in quality of life (QoL) (WHO-5 Well-Being Index [WHO-5]), diabetes self-management (Diabetes Self-Management Questionnaire - Revised [DSMQ-R]), glycaemic profiles from continuous glucose monitoring devices, awareness of hypoglycaemia (Clarke hypoglycaemia unawareness instrument), incidence of hypoglycaemic episodes and technology acceptance were secondary outcome measures. Additionally, sub-analyses were performed for participants with type 1 and type 2 diabetes separately. RESULTS: A total of 226 participants participated in the trial (108 with type 1 diabetes; 118 with type 2 diabetes). In the POWER2DM group (n=111), HbA1c decreased from 60.6±14.7 mmol/mol (7.7±1.3%) to 56.7±12.1 mmol/mol (7.3±1.1%) (means ± SD, p<0.001), compared with no change in the usual care group (n=115) (baseline: 61.7±13.7 mmol/mol, 7.8±1.3%; end of study: 61.0±12.4 mmol/mol, 7.7±1.1%; p=0.19) (between-group difference 0.24%, p=0.008). In the sub-analyses in the POWER2DM group, HbA1c in participants with type 2 diabetes decreased from 62.3±17.3 mmol/mol (7.9±1.6%) to 54.3±11.1 mmol/mol (7.1±1.0%) (p<0.001) compared with no change in HbA1c in participants with type 1 diabetes (baseline: 58.8±11.2 mmol/mol [7.5±1.0%]; end of study: 59.2±12.7 mmol/mol [7.6±1.2%]; p=0.84). There was an increase in the time during which interstitial glucose levels were between 3.0 and 3.9 mmol/l in the POWER2DM group, but no increase in clinically relevant hypoglycaemia (interstitial glucose level below 3.0 mmol/l). QoL improved in participants with type 1 diabetes in the POWER2DM group compared with the usual care group (baseline: 15.7±3.8; end of study: 16.3±3.5; p=0.047 for between-group difference). Diabetes self-management improved in both participants with type 1 diabetes (from 7.3±1.2 to 7.7±1.2; p=0.002) and those with type 2 diabetes (from 6.5±1.3 to 6.7±1.3; p=0.003) within the POWER2DM group. The POWER2DM integrated e-health support was well accepted in daily life and no important adverse (or unexpected) effects or side effects were observed. CONCLUSIONS/INTERPRETATION: POWER2DM improves HbA1c levels compared with usual care in those with type 2 diabetes, improves QoL in those with type 1 diabetes, improves diabetes self-management in those with type 1 and type 2 diabetes, and is well accepted in daily life. TRIAL REGISTRATION: ClinicalTrials.gov NCT03588104. FUNDING: This study was funded by the European Union's Horizon 2020 Research and Innovation Programme (grant agreement number 689444).

Maternal and neonatal outcomes after benzodiazepine and benzodiazepine agonist exposure during pregnancy in women with mental disorders.

AIMS: To compare the gestational age of neonates in utero exposed to benzodiazepines (BDZs) with nonexposed controls. Secondary objectives were birth weight, presence of congenital malformations, APGAR score and the need for >3 months (prolonged) maternal psychiatric care. METHODS: A retrospective cohort study of women and neonates from 2013 to 2021 with univariate and multivariable analysis to study the associations between BDZ exposure and gestational age compared to nonexposed women with mental health problems. RESULTS: We found that BDZ exposure was not associated with a lower gestational age. We found that women in the exposed group had an increased risk of psychiatric care (adjusted odds ratio 2.58 [95% confidence interval 1.71-3.91], P < .001). CONCLUSION: We found that in utero BDZ exposure was not associated with a significantly lower gestational age of the neonates and was associated with prolonged psychiatric care of their mothers.

Postpartum intrauterine dextrose infusion: Effects on uterine health, metabolic stress, systemic inflammation, and daily milk yield in clinically healthy dairy cows.

The objective of this study was to assess the effect of intrauterine dextrose infusion at 4 ± 1 d in milk (DIM) on the incidence of clinical metritis (CM), metabolic stress [i.e., body condition score (BCS), ß-hydroxybutyrate (BHB) concentration, and subclinical ketosis incidence], systemic inflammation (i.e., haptoglobin concentration), and daily milk yield in clinically healthy postpartum dairy cows. Cows (n = 245) from a dairy farm located in southwest Pennsylvania were screened at 4 ± 1 DIM using a Metricheck (Simcro Tech Ltd.) device to assess vaginal discharge. In addition, overall cow health (e.g., lameness, abnormal breathing) and rectal temperature were assessed at this time. Cows (n = 134) that presented a clear dense vaginal discharge, were in clinically good health status, and had a normal rectal temperature (i.e., <39.7°C) were blocked by parity (primiparous = 64; multiparous = 70) and randomly assigned to 1 of 3 groups: (1) SAL (n = 45): 1 intrauterine infusion of isotonic saline solution (1 L/cow); (2) DEX (n = 44): 1 intrauterine infusion of a 50% dextrose solution (1 L/cow), or (3) CON (n = 45): cows remained untreated. Cows were re-screened at 7 d after enrollment (11 ± 1 DIM) using the Metricheck device to assess CM incidence (research clinical metritis incidence; RCMI). On-farm computer records (i.e., Dairycomp 305) were also used to collect clinical metritis incidence (farm clinical metritis incidence; FCMI). In addition, BCS was assessed and blood samples were collected at enrollment and at study d 7, 14, and 21. Furthermore, daily milk yield and clinical disease events for the first 60 DIM were collected from on-farm computer records. The data were analyzed using the MIXED and GLIMMIX procedures of SAS (SAS Institute Inc.) as a randomized complete block design. Although not significant, the RCMI and FCMI in DEX and SAL cows were on average 14.5 and 18.1 percentage points higher, respectively, compared with CON cows. The SAL cows had higher BHB and haptoglobin concentrations and higher incidence of subclinical ketosis compared with CON cows on study d 7. With regard to daily milk yield, there was a day by treatment interaction, where CON cows produced more milk on certain days compared with DEX and SAL cows. Based on these findings, authors conclude that intrauterine dextrose infusion in clinically healthy postpartum cows with normal vaginal discharge may be prejudicial for cow health and performance.

Sleep duration and lipid metabolism in patients with diabetes mellitus: from the POWER2DM study.

This study assesses the association between sleep duration and plasma lipid profiles in people with diabetes mellitus (DM). Sleep duration data were obtained in 91 patients from the POWER2DM study (NCT03588104). The patients were divided in tertiles, based on their sleep duration, and blood samples were obtained at the beginning and after 9 months. Significant differences were found, specifically, patients in Tertile 3 (≥ 7.51 h) showed lower plasma levels of high-density lipoprotein cholesterol HDL-c (p < 0.05), apolipoprotein A1 (apo-A1; p < 0.05) and low HDL-c/apo-A1 ratio (p < 0.05). This study shows that sleep duration is associated with plasma lipid profiles in people with DM.

Case Report: Uterine Anomalies in Girls With a Congenital Solitary Functioning Kidney.

Unilateral renal agenesis and multicystic dysplastic kidney, resulting in a contralateral solitary functioning kidney (SFK), are part of the broad spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). In girls with SFK, screening for asymptomatic Müllerian anomalies of uterus and vagina is not yet routinely performed, and therefore often overlooked until clinical complications in the menstrual cycle or fertility process occur. In this case series, we report on four teenagers with congenital SFK presenting with menstrual problems due to a Müllerian anomaly. Routine peri-menarchal screening for Müllerian anomalies in girls with SFK may provide timely counseling, surgical treatment and prevention of associated complications such as endometriosis, infertility and miscarriages.

Bariatric Surgery in Youth: the Perspective of Dutch Pediatricians, Parents, and Adolescents.

BACKGROUND: Recent studies have indicated that bariatric surgery is effective for the treatment of youth with severe obesity. The attitudes of pediatricians, parents, and adolescents regarding this topic remain unclear. Therefore, the aim of this study was to assess the current thoughts and beliefs of Dutch pediatricians, parents, and adolescents regarding bariatric surgery in youth. METHODS: An online survey containing twenty questions on bariatric surgery in youth was distributed to pediatricians of the Dutch Society of Pediatrics. Parents and adolescents who participated in an interdisciplinary care program for overweight, obesity, and severe obesity filled out an online survey of twelve questions. RESULTS: One hundred and twenty-one pediatricians, 49 parents, and 19 adolescents completed the surveys. Seventy-two pediatricians (59.5%) considered bariatric surgery to be an effective treatment for youth with severe obesity when conventional treatment fails, and intend to refer patients for bariatric surgery. The most frequently suggested conditions for bariatric surgery were a minimum age of 16 years (n = 59, 48.7%), a BMI threshold of 40 kg/m2 (n = 51, 42.2%), and a minimum Tanner stage of IV (n = 59, 48.8%). Thirty parents (61.2%) and fourteen adolescents (73.7%) responded that bariatric surgery should become available for youth with severe obesity. CONCLUSION: Dutch pediatricians, parents, and adolescents increasingly accept bariatric surgery as a treatment modality in youth with severe obesity who do not respond successfully to lifestyle intervention. Whether pediatricians will actually refer youth for bariatric surgery remains to be seen when this treatment option will be implemented in the Netherlands.

Fasting parameters for estimation of stimulated ß cell function in islet transplant recipients with or without basal insulin treatment.

In order to assess ß cell secretory capacity after islet transplantation, standardized mixed meal stimulation tests are often used. But these tests are cumbersome and the effect of exogenous insulin on the test results is unclear. The aim of our study was to determine to what extent fasting glycemic indices can estimate stimulated ß cell function in islet transplant recipients with and without basal insulin. In total 100 mixed meal stimulation tests, including 31 with concurrent basal insulin treatment, were performed in 36 islet transplant recipients. In a multivariate model, fasting C-peptide and fasting glucose together estimated peak C-peptide with R2  = .87 and area under the curve (AUC) C-peptide with a R2  = .93. There was a larger increase of glucose during tests in which exogenous insulin was used (+7.9 vs +5.3 mmol/L, P < .001) and exogenous insulin use was associated with a slightly lower estimated peak C-peptide (relative change: -15%, P = .02). In islet transplant recipients the combination of fasting C-peptide and glucose can be used to accurately estimate stimulated ß cell function after a mixed meal stimulation test, whether exogenous basal insulin is present or not. These data indicate that graft function can be reliably determined during exogenous insulin treatment and that regular islet graft stimulation tests can be minimized.

Effects of postpartum acetylsalicylic acid on uterine diseases and reproductive performance in dairy cattle.

Uterine diseases are some of the most prevalent and costly diseases for the dairy industry. It has been reported that an exacerbated and prolonged inflammatory response around calving can increase the risk of developing metritis, which subsequently can impair production and fertility in dairy cows. The objective of this study was to assess the effects of 2 oral administrations of acetylsalicylic acid 24 h apart on the incidence of uterine diseases [i.e., retained fetal membranes, clinical metritis, clinical endometritis) and reproductive performance [i.e., days in milk to conception, number of services to conception, proportion of cows pregnant at first service, proportion of abortion at first service (ABRT)] in dairy cows after calving. Cows from one dairy farm (n = 246) located in central Pennsylvania were included in this study. Animals were blocked by parity and randomly assigned to 1 of 2 groups: (1) ASA (n = 121): within ~12 h after parturition, cows received 2 treatments with acetylsalicylic acid (ASA; 200 mg/kg, 4 boluses) 24 h apart; or (2) UNT (n = 125): cows remained untreated. Clinical metritis was assessed at 7 ± 3 and 14 ± 3 d in milk (DIM) using a Metricheck device (Simcro Tech Ltd., Hamilton, New Zealand). Cows that presented a fetid, red-brownish, watery vaginal discharge were classified as having clinical metritis. Clinical endometritis was assessed through ultrasonography and defined as presence of hyperechoic fluid (>3 mm) in the uterus lumen at 50 ± 10 DIM. The incidence of retained fetal membranes was defined as the failure of expulsion of the placenta within 24 h after calving and recorded by farm personnel. The data were analyzed using the MIXED and GLIMMIX procedures of SAS (SAS Institute Inc., Cary, NC) as a randomized complete block design. A lower proportion of cows treated with acetylsalicylic acid developed clinical metritis at 7 ± 3 DIM (ASA = 34.97 ± 5.57%; UNT = 57.21 ± 5.80%) and tended to develop clinical endometritis at 50 ± 10 DIM (ASA = 3.84 ± 2.67%; UNT = 13.61 ± 5.23%) compared with cows that remained untreated. Cows treated with acetylsalicylic acid tended to require 18 d less to conceive compared with UNT cows (ASA = 125.63 ± 8.21 d; UNT = 143.44 ± 6.28 d). Furthermore, there was a tendency for a treatment × ABRT interaction, whereby ASA cows that aborted at first service tended to conceive 35 d sooner compared with UNT cows that aborted at first service (ASA = 151.42 ± 15.90 d; UNT = 186.38 ± 11.84 d). Although there was no difference in pregnancy per AI at first service between treatment groups (ASA = 23.88 ± 7.92%; UNT = 17.93 ± 6.31%), the proportion of cows aborting at first service in the ASA group tended to be lower than that in the UNT group (ASA = 1.03 ± 1.06%; UNT = 6.04 ± 2.62%). Results from this study suggest that a short-duration acetylsalicylic acid treatment after calving may decrease the incidence of uterine diseases and improve reproductive success in cows that aborted at first service in dairy cattle.

Synthesis and characterization of SnO2 crystalline nanoparticles: A new approach for enhancing the catalytic ozonation of acetaminophen.

A novel sol-gel method was employed in this study to efficiently synthesize SnO2 nanoparticles to catalyze the ozonation of acetaminophen (ACT) from aqueous solutions. The influence of various parameters including Sn source, type of capping and alkaline agents, and calcination temperature on the catalytic activity of the SnO2 preparations was investigated. The SnO2 nanoparticles prepared by tin tetrachloride as Sn source, NaOH as gelatin agent, CTAB as capping agent and at calcination temperature of 550 °C (SnNaC-550) exhibited the maximum performance in the catalysis of ACT. The optimized catalyst (SnNaC-550) had spherical-homogeneous and cubic-shaped nanocrystalline particles with 5.5 nm mean particle size and a BET surface area of 81 m2/g, which resulted in 98% degradation and 84% mineralization of 50 mg/L ACT at 20 and 30 min reaction time, respectively when combined with ozonation (COP). Based on the radical scavenger experiments, •OH was the major oxidizing agent involved in the removal of ACT. LC/MS analysis showed that short-chain carboxylic acids were the main intermediates. Furthermore, the SnNaC-550 catalytic activity was preserved after four successive cycles. Collectively, the new method has the potential to efficiently synthesize stable and reusable SnO2 nanoparticles to catalyze the ozonation of ACT from aquatic environments.

Administration of acetylsalicylic acid after parturition in lactating dairy cows under certified organic management: Part I. Milk yield, milk components, activity patterns, fertility, and health.

Parturition is a natural process that gradually progresses from one stage to the next. However, around 5% of dairy cows will experience dystocia, which is considered to be a painful and stressful event. Studies have reported positive effects on cow performance and welfare after treatment with nonsteroidal anti-inflammatory drugs during the first postpartum days. The objectives were to assess the effects of acetylsalicylic acid administration after calving on (1) milk yield and components, (2) daily activity patterns, (3) reproductive performance, and (4) health in lactating dairy cows under certified organic management. Cows from 3 organic herds were enrolled. Within 12 h after parturition, cows were blocked by parity and calving ease and randomly assigned to 2 treatments: (1) aspirin (ASP; n = 278), in which cows received 4 consecutive treatments every 12 h with acetylsalicylic acid (100 mg/kg; 2 boluses) or (2) placebo (PLC, n = 285), in which cows received 4 treatments every 12 h with gelatin capsules (2 capsules) filled with water. Daily milk yield for the first 30 d in milk (DIM) and monthly milk yield, fat, protein, and somatic cell count (SCC) data from the first 5 Dairy Herd Improvement Association tests were collected. Activity patterns were measured using activity data loggers in the first 7 DIM. Clinical disease events (60 DIM) and fertility data were collected from on-farm computer records. Statistical analysis was performed using the MIXED (milk yield, components, and activity), LIFETEST (fertility), and GLIMMIX (health) procedures of SAS (SAS Institute Inc., Cary, NC). Overall, ASP cows produced 1.82 kg/d more milk than PLC cows during the first 30 DIM. Interestingly, cows that experienced dystocia and received ASP produced 4.48 kg/d more milk compared with cows in the PLC group that experienced dystocia. Cows treated with ASP had lower somatic cell count during the first 5 Dairy Herd Improvement Association tests. There were no differences in daily lying time, lying bouts, and lying bout duration between the ASP and PLC groups. However, cows in the ASP group had 587,64 steps/d more compared with PLC cows. In addition, ASP cows tended to require fewer days (ASP = 113.76 ± 4.99 d; PLC = 125.36 ± 4.74 d) and needed fewer services (ASP = 1.86 ± 0.21 services; PLC = 2.19 ± 0.24 services) to become pregnant compared with PLC cows. There were no differences in clinical disease events between treatments. Results from this study suggest that treating cows with ASP after calving may help improve milk yields and udder health, increase activity, and enhance fertility in dairy cattle under certified organic management.

Administration of acetylsalicylic acid after parturition in lactating dairy cows under certified organic management: Part II. Biomarkers of nociception, inflammation, and stress.

The objective was to assess the effect of oral administration of acetylsalicylic acid after calving on the concentrations of substance P (SP), haptoglobin (HP), and cortisol in lactating dairy cows. Holstein dairy cows (n = 152) from 3 organic herds were included. At parturition, cows were blocked by parity [multiparous (MULT) and primiparous (PRIM)] and calving ease [eutocia (EUT) and dystocia (DYS)] and were randomly assigned to 1 of 2 treatment groups: aspirin (ASP; n = 76), in which within 12 h after parturition cows received 4 treatments with acetylsalicylic acid (100 mg/kg; 2 boluses) at 12-h intervals, or placebo (PLC; n = 76), in which within 12 h after parturition cows received 4 consecutive treatments with gelatin capsules (2 capsules) containing water 12 h apart. Blood samples were collected immediately before treatment and at 12, 24, 36, 48, and 168 h (7 DIM) for assessment of circulating concentration of SP, HP, and cortisol. Based on farm records, cows were classified in the following clinical disease categories: no clinical disease event (NO-EVT), a single clinical disease event (SI-EVT), and more than 1 clinical disease event (MU-EVT). The study data were analyzed as a randomized complete block design using mixed multiple linear and logistic regression models. With regard to HP, there was a tendency for an interaction between treatment and parity, where MULT cows treated with ASP had lower concentration of HP compared with MULT cows treated with PLC (ASP = 124.33 ± 6.83 µg/mL; PLC = 143.9 ± 7.24 µg/mL). Analysis by calving ease showed that cows with DYS had higher concentrations of HP (DYS = 159.17 ± 5.97 µg/mL; EUT = 138.72 ± 6.22 µg/mL) and SP (only at 168 h; DYS = 64.99 pg/mL, 95% confidence interval, CI: 2.68-2.81; EUT = 60.33 pg/mL, 95% CI: 2.91-3.06) after calving compared with EUT cows. Regardless of treatment, PRIM cows had higher concentrations of SP (MULT = 55.11 pg/mL, 95% CI: 1.27-1.30; PRIM = 57.62 pg/mL, 95% CI: 1.99-2.06), HP (MULT = 134.14 ± 4.96 µg/mL; PRIM = 163.75 ± 7.76 µg/mL), and cortisol (MULT = 18.65 µg/mL, 95% CI: 1.02-1.05; PRIM = 21.92 µg/mL, 95% CI: 1.67-1.74) compared with MULT cows. In addition, cows that experienced SI-EVT or MU-EVT had higher concentrations of HP (NO-EVT = 134.13 ± 5.95 µg/mL; SI-EVT = 142.68 ± 7.32 µg/mL; MU-EVT = 170.03 ± 9.42 µg/mL) and cortisol (NO-EVT = 17.86 µg/mL, 95% CI: 1.20-1.24; SI-EVT = 21.01 µg/mL, 95% CI: 1.61-1.67; MU-EVT = 22.01 µg/mL, 95% CI: 2.08-2.18) compared with cows with NO-EVT recorded. Results from this study suggest that a short-duration anti-inflammatory therapy after calving reduced HP in MULT cows but may not have effects on SP and cortisol concentrations. Calving ease and parity affected the concentrations of markers of inflammation, nociception, and stress regardless of treatment. Further research is warranted to assess anti-inflammatory strategies aimed at decreasing inflammation and stress in DYS and PRIM cows and therefore improve welfare and performance of these high-priority groups.

Effects of postpartum acetylsalicylic acid on metabolic status, health, and production in lactating dairy cattle.

The transition period is one of the most challenging times for dairy cattle. Previous research suggests that treatment of postpartum cows with anti-inflammatory drugs may decrease pain and inflammation, enhancing cow welfare and performance during this challenging period. However, these strategies involve numerous time-consuming interventions, which require extra labor and do not fit modern farm logistics. The objective of this experiment was to assess the effects of acetylsalicylic acid (ASA) every 24 h for 2 d after calving on (1) daily milk yield, daily milk conductivity, and daily rumination during the first 60 days in milk (DIM), and 305-d mature-equivalent milk, milk fat, and milk protein yields, (2) body condition score, ß-hydroxybutyrate (BHB), and haptoglobin, and (3) incidence of clinical diseases during the first 60 DIM. Dairy cows (n = 246) from a dairy farm located in Pennsylvania were enrolled in this experiment. Cows were blocked by parity and assigned randomly to 1 of 2 treatments: (1) ASA (n = 121), in which cows received 2 treatments with ASA (200 mg/kg; 4 boluses), the first within 12 h after parturition and the second 24 h later; or (2) untreated (UNT; n = 125), in which cows remained untreated. Blood samples were collected at 30 ± 6 h, 7 ± 3 d, and 14 ± 3 d after calving to measure BHB and haptoglobin concentrations. Body condition score was assessed at enrollment, 7 ± 3 DIM, 14 ± 3 DIM, and 50 ± 10 DIM. Furthermore, incidences of diseases, daily rumination, daily milk yield, and daily milk conductivity during the first 60 DIM and 305-d mature-equivalent milk, milk fat, and milk protein yields were collected from on-farm computer records. The data were analyzed using mixed multiple linear and logistic regression models as a randomized complete block design. Multiparous cows treated with ASA produced 1.64 kg/d more milk compared with multiparous cows that remained untreated (ASA = 41.66 ± 0.88 kg/d; UNT = 40.02 ± 0.81 kg/d) during the first 60 DIM. There was no difference in daily milk conductivity and rumination between treatments. Cows treated with ASA had lower concentration of BHB (ASA = 1.16 ± 0.64 mmol/L; UNT = 1.23 ± 0.80 mmol/L) during the first 14 ± 3 DIM and had higher body condition score within the first 50 ± 10 DIM compared with cows that remained UNT. There were no differences in circulating concentrations of haptoglobin between treatments. These results support previous findings showing that the use of anti-inflammatory drugs after calving may increase milk production and affect the metabolic status of dairy cows.