Dynamics of automatically generated body condition scores during early lactation and pregnancy at first artificial insemination of Holstein cows.

The objective of this study was to characterize the association between body condition score (BCS) and BCS change (ΔBCS), determined by an automated camera system at multiple time points, and the subsequent pregnancy per first artificial insemination (P/AI1) of Holstein cows. A retrospective observational study was completed using data collected from 11,393 lactations in 7,928 Holstein cows calving between April 2019 and March 2021 in a commercial dairy operation located in Colorado. Cows were classified as primiparous or multiparous. Scores generated by BCS cameras at dry-off, calving, 21 days in milk (DIM), 56 DIM, and first artificial insemination were selected for the analyses and subsequently categorized as low (≤lower quartile), moderate (interquartile range), and high (≥upper quartile). Changes in BCS were calculated by periods of interest as change from dry-off to calving (multiparous cows); change from calving to 21 DIM; change from calving to 56 DIM; and change from calving to first artificial insemination and assigned into categories as large loss of BCS (top 25% of cows losing BCS); moderate loss (bottom 75% of cows losing BCS); no change (ΔBCS = 0); or gain of BCS (ΔBCS > 0). Data were examined in primiparous and multiparous cows separately using logistic regression and time-to-event analyses. Initial univariable models were followed by multivariable models that considered calving season, occurrence of disease, and milk yield up to 60 DIM as covariables. The logistic regression analyses indicated that in both parity groups the associations between BCS category and P/AI1 were more evident at 21 DIM, 56 DIM, and first artificial insemination, with lower odds of P/AI1 in cows in the low BCS category. Likewise, cows with large loss in BCS between calving and 21 DIM, calving and 56 DIM, and calving and first artificial insemination had lower odds of P/AI1 compared with other categories of ΔBCS within the same period of interest. Similarly, survival analyses evidenced that cows in the low BCS category required more time to get pregnant. In agreement, differences in the dynamics of the average daily BCS during the first 90 DIM were evident when cows were grouped by first AI outcome (pregnant vs. nonpregnant) and by their time to pregnancy category (<90 DIM; 91-150 DIM; or >150 DIM), with cows with reduced fertility showing lower BCS up to 90 DIM. Overall, low BCS and more pronounced reductions in BCS occurring closer to first artificial insemination resulted in lower odds of pregnancy per artificial insemination.

[Requirements for long-term follow-up on efficacy and safety of advanced therapy medicinal products. Risk management and traceability]. / Regelungen zur Uberwachung von Wirksamkeit und Sicherheit nach der Zulassung. Risikomanagement und Rückverfolgbarkeit von Arzneimitteln für Neuartige Therapien.

Advanced therapy medicinal products (ATMPs) are an innovative treatment option. To promote timely access of the innovative medicinal product and to safeguard public health, new elements have been introduced into legislation. A key element of the ATMP regulation is the requirement for long-term follow-up on safety and efficacy of patients enrolled in clinical trials with ATMPs, which is beyond the routine requirements on pharmacovigilance. For gene therapy medicinal products, a guideline on long-term follow-up, which lays down the technical requirements, is available. A further key element of the ATMP regulation is the traceability of the starting materials used to manufacture the ATMP. A common European coding system is imperative to ensure the traceability of starting materials, especially across the borders of European Member States.

Higher doses of intraoperative analgesia are associated with lower levels of persistent pain and less analgesic consumption six months after total hip arthroplasty.

BACKGROUND: Persistent postoperative pain is a major health problem affecting nearly 30% of all patients undergoing total hip arthroplasty. Previous studies have demonstrated an association between the intensity of acute postoperative pain and persistent pain, but this association might be an epiphenomenon of insufficient intraoperative analgesia. In this study, we investigated the association between the intraoperative level of analgesia and the persistent postoperative pain 6 months after surgery. METHODS: We investigated 110 patients undergoing primary total hip arthroplasty under total intravenous general anaesthesia in a prospective cohort study. A highly standardized surgical and a standardized anaesthetic procedure were performed to reduce variability and psychosocial influences were investigated to adjust for confounders. Acute postoperative pain was controlled using patient-controlled analgesia pumps. Postoperative pain intensities and analgesic requirements were monitored for 6 months following surgery. RESULTS: Of 105 patients included in the analysis, 32% continued using daily pain medication 6 months after surgery and reported a median pain level of 4/10. Multivariate analyses confirmed that the amount of intraoperative analgesia is a significant predictor of regular analgesic use and pain intensity 6 months after surgery. CONCLUSIONS: Higher levels of intraoperative analgesia are associated with lower levels of persistent pain and less analgesic consumption 6 months after total hip arthroplasty. Persistent pain may be attributable to intraoperative nociception, which is likely not adequately assessed and suppressed using current clinical measures. SIGNIFICANCE: Our study suggests that lower doses of intraoperative analgesia are associated with higher levels of persistent postoperative pain. Persistent pain may be caused by intraoperative nociception, which is likely not adequately suppressed using current clinical standard analgesic measures.

Restriction pattern variability of respiratory syncytial virus during three consecutive epidemics in Denmark.

A PCR-based assay was used to distinguish between respiratory syncytial virus (RSV) group A and B in order to analyze their prevalence in Denmark in three consecutive epidemics during the winters of 1992/93, 1993/94 and 1994/95. A total of 96 RSV strains isolated from hospitalized children were examined, showing alternation of group prevalence. Furthermore, the genetic variability of the RSV isolates was illustrated by restriction enzyme analysis of PCR products originating from a part of the F and G proteins that has been reported to be highly variable. We found that, in general, different genome types predominated each year, some types being present in consecutive epidemics, indicating a contribution of strains circulating unattended between outbreak seasons, while others seemed to disappear or became undetectable, being replaced by emerging types. Some of the genome types found seemed related to strains isolated up to more than two decades ago in other parts of the world. This indicates that the temporal fluctuation in predominance of genome types presumably caused by selective pressure exerted by host immunity is due to the favoring of strains from a pool of globally circulating, genetically relatively stable genome types, rather than a molecular evolution in strains induced or directed by immunoselective pressure.

The fluctuating pattern of various genome types of respiratory syncytial virus in Copenhagen and some other locations in Denmark.

A semi-nested RT-PCR method based on a region of the F and G glycoprotein genes was established, allowing the simultaneous detection and differentiation of group A and group B isolates of respiratory syncytial virus (RSV). The PCR products were subjected to digestion with restriction endonucleases to further differentiate the isolates. Using, in addition, previously reported studies the prevalence of various genome types in the Copenhagen region over a period of 6 years was established. Furthermore, the prevalence of genome types was determined in a distant region in Denmark during the winters of 1996/97 and 1997/98, and in yet another distant region during the winter of 1997/98. It was shown that the different regions in Denmark to a large extent share the same pool of genome types of RSV. Yet, while the fluctuating patterns of the two groups and various genome types were almost identical at different hospitals in the Copenhagen region, they varied between the different regions. This suggests that epidemics in local communities primarily rely on region-specific herd immunity parameters and emerge from strains endemically circulating in these local communities. Group B strains in Copenhagen showed an overall predominance, being predominant in three of the six epidemic seasons studied, and of almost equal predominance in one season.

Severity of respiratory syncytial virus disease related to type and genotype of virus and to cytokine values in nasopharyngeal secretions.

BACKGROUND: Investigations concerning the severity of respiratory syncytial virus (RSV) disease as related to (1) RSV type and genotype determined respectively by PCR and restriction enzyme analysis and (2) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) values in samples of nasopharyngeal secretion (NPS) have not been previously reported. METHODS: We prospectively studied 105 RSV infections in the lower respiratory tract of infants and young children admitted to a pediatric department in Copenhagen during three winter seasons, 1993, 1994 and 1995. RSV strains were typed and genotyped, respectively, by PCR and nucleic acid restriction analysis and correlated to the severity of the disease. The ratio IL-6:TNF-alpha, determined from IL-6- and TNF-alpha values in samples of NPS, was related to the severity of the disease. Concentrations of IL-6 and of TNF-alpha were determined in serum samples taken during 5 weeks after the onset of illness. RESULTS: Type B infections produced more severe disease than did type A infections, as assessed on the length of the hospital stay, use of respiratory support and the presence of an infiltrate on a chest radiograph. This difference was age-related. It was observed in infants 0 to 5 months old, but not in older age groups. Type B genotype B1122 produced more severe disease than type A genotype A2311 in infants 0 to 11 months old. Increased serum concentrations of IL-6 and TNF-alpha were detected in samples taken 1 to 2 days after the onset of illness. Whereas TNF-alpha serum concentrations remained high, IL-6 serum concentrations decreased during the following 3 to 4 weeks. The IL-6:TNF-alpha ratio in samples of NPS was related to the severity of the disease. A high ratio was related to a low severity. CONCLUSIONS: The severity of disease in patients admitted with acute RSV infections can be correlated to the RSV type as determined by PCR, to the RSV genotype as determined by nucleic acid restriction analysis and to the ratio IL-6:TNF-alpha in NPS.

Rates for tic disorders and obsessive compulsive symptomatology in families of children and adolescents with Gilles de la Tourette syndrome.

The aim of this study was to assess rates for tic disorders and obsessive compulsive psychopathology in families of children and adolescents with Gilles de la Tourette syndrome (TS). Diagnoses were based on the DSM III-R criteria. Obsessive compulsive psychopathology, that did not fulfill the criteria for obsessive compulsive disorder (OCD) was additionally assessed and termed obsessive compulsive symptoms (OCS). The authors hypothesized that comorbid OCD or OCS in TS patients predicts a higher familial loading with obsessive compulsive symptomatology. The study cohort included 87 patients with TS who were evaluated clinically and with the use of a structured psychiatric interview. All available parents (152/174; 87%), several sibs (49/93; 53%) and some second degree relatives (27/659; 4.1%) were also interviewed. For other first and second degree relatives the family history method was used. Familial rates for TS were clearly elevated. Rates for chronic tic disorders (CT) were considerably lower than in previous studies. Additionally, tic disorders not otherwise specified (TDNOS) were diagnosed in a substantial number of first degree (15/267; 5.6%) and second degree relatives (36/659; 5.5%). OCD in parents (4/174; 2.3%) did not occur in an above baseline rate. However, both OCD (14/87; 16.1%) and OCS (15/87; 17.2%) were frequently associated with TS in index patients. Interestingly, 10 of 16 fathers with OCS also had a tic disorder. Obsessive compulsive psychopathology clustered in families. It is concluded that genetic studies in TS could profit from adhering to a conservative diagnostic approach to both tic disorders and OCD. The familial clustering of OCS/OCD in conjunction with the elevated paternal rate for the co-occurrence of tic disorders and OCS might indicate heterogeneity of TS.

Repeatability of methacholine challenges in 2- to 4-year-old children with asthma, using a new technique for quantitative delivery of aerosol.

To determine the repeatability of bronchial responsiveness in awake young children, two methacholine challenge tests were performed on separate days in 16 children with stable asthma (mean age, 3 3/4 years). Methacholine was administered using a new method for quantitative delivery of aerosol that eliminates the effect of dilution of the aerosol by entrainment of air and enables quantitative delivery of aerosol according to body weight. Respiratory function was monitored by measurement of respiratory resistance by the interrupter technique (Rint), respiratory resistance and reactance at 5 Hz (Rrs5, Xrs5) by the impulse oscillation technique, transcutaneous measurements of oxygen (PtcO2), and specific airway resistance (sRaw). Repeatability was evaluated by determining the provocative dose that caused a defined percentage of change relative to baseline (PD%: Rint PD30, Rrs5 PD30, Xrs5 PD80, PtcO2 PD10, and sRaw PD80. Repeatability was estimated from the difference between the PD% obtained at the time of the two tests. Using the numeric value of these differences, the repeatability of Xrs5 PD60, PtcO2 PD10, and sRaw PD50 was [mean (SD)]: [0.8 (0.5)] [0.5 (0.4)] and [0.7 (0.6)] doubling doses, respectively. Rint PD30 and Rrs5 PD30 proved to be less reproducible: [1.2 (1)] and [1.6 (0.9)] doubling doses, respectively. The new method of aerosol delivery offers a means of standardizing the bronchoconstrictor stimulus, and the results show that estimates of bronchial responsiveness in young children can be obtained reproducibly within one doubling dose of methacholine.

Measurement of lung function in awake 2-4-year-old asthmatic children during methacholine challenge and acute asthma: a comparison of the impulse oscillation technique, the interrupter technique, and transcutaneous measurement of oxygen versus whole-body plethysmography.

This study evaluated three techniques for testing of lung function in young awake children. We compared measurements by the forced or impulse oscillation technique (IOS), the interrupter technique (IT), and transcutaneous measurements of oxygen (tcPo2) with concomitant measurements of specific airway resistance (sRaw) during methacholine challenge in 20 stable asthmatic children, 2-4 years old. Measurements were performed with all techniques after each dose of methacholine and after inhalation of a bronchodilator. Measurements were carried out during tidal breathing using a face-mask with a built-in mouthpiece. The ranking of sensitivity was as follows: sRaw > IOS, respiratory reactance at 5 Hz (Xrs5) > tcPo2 > interrupter resistance (Rint) > IOS, respiratory resistance at 5 Hz (Rrs5). The sensitivity of sRaw and Xrs5 was not significantly different, but both were significantly more sensitive than Rint and Rrs5; the sensitivity of tcPo2, Rint, and Rrs5 was not significantly different. Measurements in eight of the subjects performed during an episode of acute asthma yielded comparable results in regard to the sensitivity of the techniques. Measurements improved significantly after bronchodilator administration; however, the response to bronchodilator tended to be less during acute asthma and was best demonstrated by a deterioration of tcPo2. All the evaluated techniques reliably reflect short-term changes in respiratory function and can provide clinically useful estimates of airway function. The techniques are non-invasive, are not dependent on the active co-operation or sedation of the subjects, and therefore are well suited for routine use in young children.

Specific airway resistance, interrupter resistance, and respiratory impedance in healthy children aged 2-7 years.

We report data on respiratory function in healthy children aged 2-7 years in whom we measured respiratory resistance by the interrupter technique (Rint); total respiratory impedance (Zrs), respiratory resistance (Rrs), and reactance (Xrs) by the impulse oscillation technique; and specific airway resistance (sRaw) by a modified procedure method in the whole body plethysmograph. Measurements were attempted in 151 children and were successfully obtained in 121 children with a mean (SD) age of 5.3 (1.5) years; no measurements were possible in 30 children (mean age 3 (0.9) years). The repeatability of measurements was independent of the age of the subjects, and the within-subject coefficient of variation was 11.1%, 8.1%, 10.8%, and 10.2% for sRaw, Rint, Zrs, and Rrs at 5 Hz (Rrs5), respectively. All lung function indices were linearly related to age, height, and weight. A significant negative correlation with age, height, and weight was found for Rint, Zrs, and Rrs5. Xrs5 was positively correlated to age and body size. The mean values of Rint, Rrs5, Xrs5, and Zrs in children younger and older than 5 years were 1.04, 1.38, -0.5, and 1.48 kPa x L(-1) x s and 0.9, 1.18, -0.37, and 1.23 kPa x L(-1) x s, respectively. sRaw showed no significant correlation with body size or age and the mean sRaw in children younger and older than 5 years was 1.09 and 1.13 kPa x s, respectively. None of the indices of respiratory function differed between boys and girls. Xrs and Rrs exhibited a significant frequency dependence in the range of 5-35 Hz. The techniques applied in this study require minimal cooperation and allow measurement of lung function in 80% of our population of awake young children. Further studies are needed to evaluate the potentials of the presently established reference values for clinical and epidemiological purposes.

[The Gianturco method of spiral embolisation of the renal artery (author's transl)]. / Spiralembolisation der Nierenarterie nach Gianturco.

Spiral embolisation of a renal artery by the Gianturco method was carried out in eight patients. Our early experience with this technique is described. In seven patients it was possible to occlude arterial flow to the kidney completely, or almost completely. In one patient, faulty technique lead to an avoidable complication resulting in dislocation of the spiral into the femoral artery. The Gianturco method has advantages compared with other embolisation techniques, being simple, rapid, complete and permanent. In addition to its pre-operative and therapeutic use with renal tumours, the method can be used to abolish function in one or both kidneys.

[Clinical pathway "laparoscopic prostatectomy". Analysis of anesthesiological procedures in a randomized study]. / Klinischer Behandlungspfad "laparoskopische Prostatektomie". Anästhesiologische Prozessanalyse in einer randomisierten Studie.

METHODS: In this study we investigated the anesthesiological module of a clinical pathway. We chose the pathway of "laparoscopic prostatectomy" as an example for time-consuming minimally invasive surgery and 40 patients were randomly assigned to 2 groups receiving either total intravenous anesthesia (TIVA) using propofol/ remifentanil or balanced minimal flow anesthesia using desflurane/ remifentanil. During this module the indicators of quality such as vigilance, pain, postoperative nausea and vomiting (PONV) and mobilization were measured. Costs were evaluated and analyzed by a bottom-up procedure. RESULTS: There were no anesthesia-related deviations from clinical pathways and both forms of anesthesia management were equally well tolerated by the patients. No significant difference was observed regarding hemodynamic measurements or PONV. The patients in the desflurane/ remifentanil group recovered more rapidly (p=0.037) and had more pain. The amount of analgesic agents given immediately following anesthesia was significantly higher than in the TIVA group (p=0.017). The median anesthesia costs per minute for laparoscopic prostatectomy in the propofol group were 2.79 EUR (minimum cost 2.41 EUR, maximum cost 3.21 EUR) and in the desflurane group 2.68 EUR (minimum cost 2.45 EUR, maximum cost 3.39 EUR). The total anesthesia costs for both groups were within the proceeds matrix range for diagnosis-related groups (DRG). However, the cost analysis for medication was slightly higher than the proceeds matrix range for DRGs. CONCLUSION: Both forms of anesthesia can be implemented for time-consuming surgical procedures and allow a cost-effective anesthesia management. Anesthesiological procedures must go hand-in-hand with the type of anesthesia selected. The prophylactic use of analgetics for desflurane/ remifentanil anesthesia should be given earlier and in higher doses than in propofol/ remifentanil anesthesia. The prophylactic use of antiemetics following laparoscopic procedures of long duration is indicated. Optimizing anesthesiological procedures could lead to a continuous improvement in the quality of therapeutic pathways.

Stability testing in Haemophilus influenzae type b conjugate vaccines.

Coupling T-cell-independent antigens such as the capsular-polysaccharide (PRP) of H. influenzae type b (HIB) to a T-cell-dependent protein-carrier enhances the immune response, particularly in individuals who are poor responders to such antigens. An adequate immunogenicity is dependent upon the characteristics of the PRP antigen, the protein carrier, the efficiency of conjugation and the stability of the conjugate. Since adequate immunogenicity tests are not available, stability studies in such products are essentially confined to molecular size distribution and determination of the degree of conjugation. A better understanding of the factors involved in stability and an improvement of the testing methods are highly desirable.