Bovine viral diarrhoea viruses from New Zealand belong predominantly to the BVDV-1a genotype.

AIM: To determine which genotypes of bovine viral diarrhoea virus (BVDV) circulate among cattle in New Zealand. METHODS: Samples comprised BVDV-1-positive sera sourced from submissions to veterinary diagnostic laboratories in 2019 (n = 25), 2020 (n = 59) and 2022 (n = 74) from both beef and dairy herds, as well as archival BVDV-1 isolates (n = 5). Fragments of the 5' untranslated region (5' UTR) and glycoprotein E2 coding sequence of the BVDV genome were amplified and sequenced. The sequences were aligned to each other and to international BVDV-1 sequences to determine their similarities and phylogenetic relationships. The 5' UTR sequences were also used to create genetic haplotype networks to determine if they were correlated with selected traits (location, type of farm, and year of collection). RESULTS: The 5' UTR sequences from New Zealand BVDV were closely related to each other, with pairwise identities between 89% and 100%. All clustered together and were designated as BVDV-1a (n = 144) or BVDV-1c (n = 5). There was no evidence of a correlation between the 5' UTR sequence and the geographical origin within the country, year of collection or the type of farm. Partial E2 sequences from New Zealand BVDV (n = 76) showed 74-100% identity to each other and clustered in two main groups. The subtype assignment based on the E2 sequence was the same as based on the 5' UTR analysis. This is the first comprehensive analysis of genomic variability of contemporary New Zealand BVDV based on the analysis of the non-coding (5' UTR) and coding (E2) sequences. CONCLUSIONS AND CLINICAL RELEVANCE: Knowledge of the diversity of the viruses circulating in the country is a prerequisite for the development of effective control strategies, including a selection of suitable vaccines. The data presented suggest that New Zealand BVDV are relatively homogeneous, which should facilitate eradication efforts including selection or development of the most suitable vaccines.

A meta-analysis comparing the diagnostic performance of abbreviated MRI and a full diagnostic protocol in breast cancer.

AIM: To undertake a meta-analysis of the diagnostic performance of abbreviated (ABB) magnetic resonance imaging (MRI) and full diagnostic protocol MRI (FDP-MRI) in breast cancer. MATERIALS AND METHODS: This meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy (PRISMA-DTA) guidelines. The PubMed and EMBASE databases were searched through August 2019 for studies comparing the diagnostic performance of ABB-MRI and FDP-MRI in the breast. Studies were reviewed by two authors independently according to eligibility and exclusion criteria and split into two subgroups (screening population studies and studies using cohorts enriched with known cancers) to avoid bias. Quality assessment and bias for diagnostic accuracy was determined with Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The diagnostic accuracy for each subgroup was pooled using a bivariate random effects model and summary receiver operating characteristic (sROC) curves produced. Sensitivities and specificities were compared using a paired t-test. RESULTS: Five screening (62/2,588 cancers/patients) and eight enriched cohort (540/1,432 cancers/patients) studies were included in the meta-analysis. QUADAS-2 assessment showed a low risk of bias in most studies. The pooled sensitivity/specificity/area under the receiver operating characteristic curve (AUC) for screening studies was 0.90/0.92/0.94 for ABB-MRI and 0.92/0.95/0.97 for FDP-MRI. The pooled sensitivity/specificity/AUC for enriched cohort studies was 0.93/0.83/0.94 for ABB-MRI and 0.93/0.84/0.95 for FDP-MRI. There was no significant difference in sensitivity or specificity using ABB-MRI or FDP-MRI (p=0.18 and 0.27, p=0.18 and 0.93, respectively). CONCLUSION: The diagnostic performances of the ABB-MRI and FDP-MRI protocols used in either screening or enriched cohorts were comparable. There was a large variation in patient population, study methodology, and abbreviated protocols reported.

A randomised study evaluating the use of pyridoxine to avoid capecitabine dose modifications.

BACKGROUND: Pyridoxine is frequently used to treat capecitabine-induced hand-foot syndrome (HFS), although the evidence of benefit is lacking. We performed a randomised placebo-controlled trial to determine whether pyridoxine could avoid the need for capecitabine dose modifications and improve outcomes. METHODS: A total of 106 patients planned for palliative single-agent capecitabine (53 in each arm, 65%/35% colorectal/breast cancer) were randomised to receive either concomitant pyridoxine (50 mg po) or matching placebo three times daily. RESULTS: Compared with placebo, pyridoxine use was associated with an increased rate of avoiding capecitabine dose modifications (37% vs 23%, relative risk 0.59, 95% CI 0.29, 1.20, P=0.15) and fewer grade 3/4 HFS-related adverse events (9% vs 17%, odds ratio 0.51, 95% CI 0.15-1.6, P=0.26). Use of pyridoxine did not improve response rate or progression-free survival. CONCLUSION: Pyridoxine may reduce the need for capecitabine dose modifications and the incidence of severe HFS, but does not impact on antitumour effect.

The influence of perceptions and beliefs of civilian physiotherapist working for the Ministry of Defence in their management of back pain: an exploratory study using mixed methods.

BACKGROUND: There is a high prevalence of Lower Back Pain (LBP) within military populations. Physiotherapeutic management has a primary role for patient care, but there is a need to establish the most effective management. Civilian physiotherapists provide the majority of clinical provision throughout the Defence Medical Rehabilitation Programme for British Armed Forces personnel. To date no study has been carried out looking at their perceptions and beliefs with regards to management of non-specific LBP and the potential impact this had on the delivery of rehabilitation across Defence. METHODS: This mixed methods exploratory study aimed to explore the potential complexities surrounding the decision making process with regards to management of non-specific LBP using semi-structured interviews with 14 MOD civilian physiotherapists. All interviews were transcribed verbatim. The transcribed data was then subjected to a categorical content analysis. RESULTS: The analysis of the interview data revealed four interrelated themes that influence civilian physiotherapists in their management of back pain in military personnel: the military environment, integration of military procedures, physiotherapist treatment approach and communication. DISCUSSION: This paper highlights the value civilian physiotherapists place on experience when managing non-specific LBP. This experience however was gained through 'patient mileage' rather than integration of best evidence into practice. Several problems were identified in patient management including specific types of patients and their expectations and the importance of the right communication between Health Care Professionals, but also with patients.

An outbreak of livestock-associated meticillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex 398 in a regional burns centre.

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) outbreaks have been reported previously in burns centres with resulting mortality and morbidity. This article describes the first human-associated outbreak in the UK caused by a strain of mupirocin-resistant (MuR) livestock-associated MRSA clonal complex 398 (LA-MRSA CC398) in an adult burns centre. The centre historically had a very low prevalence of MRSA infections. AIM: To describe the clinical and epidemiological context of how the outbreak was identified and contained using a range of infection prevention and control (IPC) measures guided by both traditional and genetic methods. METHODS: A cluster of MuR-MRSA led to an outbreak investigation. Cases were detected via retrospective search and real-time laboratory surveillance. Isolates were sent continuously for whole-genome sequencing (WGS). A live timeline of cases and interventions was produced throughout the period. FINDINGS: The outbreak consisted of 12 cases (seven males and five females) aged between 22 and 70 years. Patients were identified between May and October 2020. All patients were colonized rather than infected. The strain acquired the plasmid bearing MupA while colonizing the index case before dissemination. The index case was found to be a chicken farmer. This outbreak was eventually controlled using IPC measures, audits, and blind staff decolonization guided by insight from WGS. CONCLUSION: It was not possible to determine how the strain entered the centre, or if a staff carrier was involved. The outbreak demonstrated the potential for continued transmissions for months despite active surveillance and stringent control measures.

Ultrasound elastography as an adjuvant to conventional ultrasound in the preoperative assessment of axillary lymph nodes in suspected breast cancer: a pilot study.

AIMS: To compare the performance of ultrasound elastography with conventional ultrasound in the assessment of axillary lymph nodes in suspected breast cancer and whether ultrasound elastography as an adjunct to conventional ultrasound can increase the sensitivity of conventional ultrasound used alone. MATERIALS AND METHODS: Fifty symptomatic women with a sonographic suspicion for breast cancer underwent ultrasound elastography of the ipsilateral axilla concurrent with conventional ultrasound being performed as part of triple assessment. Elastograms were visually scored, strain measurements calculated and node area and perimeter measurements taken. Theoretical biopsy cut points were selected. The sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) were calculated and receiver operating characteristic (ROC) analysis was performed and compared for elastograms and conventional ultrasound images with surgical histology as the reference standard. RESULTS: The mean age of the women was 57 years. Twenty-nine out of 50 of the nodes were histologically negative on surgical histology and 21 were positive. The sensitivity, specificity, PPV, and NPV for conventional ultrasound were 76, 78, 70, and 81%, respectively; 90, 86, 83, and 93%, respectively, for visual ultrasound elastography; and for strain scoring, 100, 48, 58 and 100%, respectively. There was no significant difference between any of the node measurements CONCLUSIONS: Initial experience with ultrasound elastography of axillary lymph nodes, showed that it is more sensitive than conventional ultrasound in detecting abnormal nodes in the axilla in cases of suspected breast cancer. The specificity remained acceptable and ultrasound elastography used as an adjunct to conventional ultrasound has the potential to improve the performance of conventional ultrasound alone.

Yap regulates skeletal muscle fatty acid oxidation and adiposity in metabolic disease.

Obesity is a major risk factor underlying the development of metabolic disease and a growing public health concern globally. Strategies to promote skeletal muscle metabolism can be effective to limit the progression of metabolic disease. Here, we demonstrate that the levels of the Hippo pathway transcriptional co-activator YAP are decreased in muscle biopsies from obese, insulin-resistant humans and mice. Targeted disruption of Yap in adult skeletal muscle resulted in incomplete oxidation of fatty acids and lipotoxicity. Integrated 'omics analysis from isolated adult muscle nuclei revealed that Yap regulates a transcriptional profile associated with metabolic substrate utilisation. In line with these findings, increasing Yap abundance in the striated muscle of obese (db/db) mice enhanced energy expenditure and attenuated adiposity. Our results demonstrate a vital role for Yap as a mediator of skeletal muscle metabolism. Strategies to enhance Yap activity in skeletal muscle warrant consideration as part of comprehensive approaches to treat metabolic disease.

The impact of COVID-19 on rare metabolic patients and healthcare providers: results from two MetabERN surveys.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has caused disruption in all aspects of daily life, including the management and treatment of rare inherited metabolic disorders (IMDs). To perform a preliminary assessment of the incidence of COVID-19 in IMD patients and the impact of the coronavirus emergency on the rare metabolic community between March and April 2020, the European Reference Network for Hereditary Metabolic Diseases (MetabERN) has performed two surveys: one directed to patients' organizations (PO) and one directed to healthcare providers (HCPs). The COVID-19 incidence in the population of rare metabolic patients was lower than that of the general European population (72.9 × 100,000 vs. 117 × 100,000). However, patients experienced extensive disruption of care, with the majority of appointments and treatments cancelled, reduced, or postponed. Almost all HCPs (90%) were able to substitute face-to-face visits with telemedicine, about half of patients facing treatment changes switched from hospital to home therapy, and a quarter reported difficulties in getting their medicines. During the first weeks of emergency, when patients and families lacked relevant information, most HCPs contacted their patients to provide them with support and information. Since IMD patients require constant follow-up and treatment adjustments to control their disease and avoid degradation of their condition, the results of our surveys are relevant for national health systems in order to ensure appropriate care for IMD patients. They highlight strong links in an interconnected community of HCPs and PO, who are able to work quickly and effectively together to support and protect fragile persons during crisis. However, additional studies are needed to better appreciate the actual impact of COVID-19 on IMD patients' health and the mid- and long-term effects of the pandemic on their wellbeing.

High water vs. ad libitum water intake for autosomal dominant polycystic kidney disease: a randomized controlled feasibility trial.

BACKGROUND: Vasopressin stimulates cyst growth in autosomal dominant polycystic kidney disease (ADPKD) and is a key therapeutic target. Evaluation of high water intake as an alternative to pharmacological vasopressin blockade is supported by patients. However feasibility, safety and adherence-promoting strategies required to deliver this remain unknown. AIMS: Assess the feasibility of a definitive randomized high water intake trial in ADPKD. METHODS: In this prospective open-label randomized trial, adult ADPKD patients with eGFR ≥ 20 ml/min/1.73 m2 were randomized to prescribed high water (HW) intake targeting urine osmolality (UOsm) ≤270 mOsm/kg, or ad libitum (AW) intake (UOsm >300 mOsm/kg). Self-management strategies including home-monitoring of urine-specific gravity (USG) were employed to promote adherence. RESULTS: We enrolled 42 participants, baseline median eGFR (HW 68.4 [interquartile range (IQR) 35.9-107.2] vs. AW 75.8 [IQR 59.0-111.0 ml/min/1.73 m2, P = 0.22) and UOsm (HW 353 [IQR 190-438] vs. AW 350 [IQR 240-452] mOsm/kg, P = 0.71) were similar between groups. After 8 weeks, 67% in the HW vs. 24% in AW group achieved UOsm ≤270 mOsm/kg, P = 0.001. HW group achieved lower UOsm (194 [IQR 190-438] vs. 379 [IQR 235-503] mOsm/kg, P = 0.01) and higher urine volumes (3155 [IQR 2270-4295] vs. 1920 [IQR 1670-2960] ml/day, P = 0.02). Two cases of hyponatraemia occurred in HW group. No acute GFR effects were detected. In total 79% (519/672) of USG were submitted and 90% (468/519) were within target. Overall, 17% withdrew during the study. CONCLUSION: DRINK demonstrated successful recruitment and adherence leading to separation between treatment arms in primary outcomes. These findings suggest a definitive trial assessing the impact of high water on kidney disease progression in ADPKD is feasible.

Endothelin-1 activates ETA receptors to cause reflex scratching in BALB/c mice.

BACKGROUND AND PURPOSE: Endothelin-1 (ET-1) is present in murine and human skin and causes itch (pruritus) when injected in humans. This behavioural study examined the scratch reflex evoked by ET-1 in mice. EXPERIMENTAL APPROACH: An automated detector was used to determine whether ET-1 causes reflex scratching, the behavioural correlate of itching, in BALB/c mice. Selective agonists and antagonists were used to probe the ET receptor(s) involved. KEY RESULTS: ET-1 evoked dose-related reflex scratching lasting up to 20 min following intradermal injection (0.1-100 ng; 0.04-40 pmol). The ED(50) for ET-1 induced scratching was 2.1 ng and desensitization occurred with cumulative dosing. High doses of the ET(B) receptor agonist IRL1620 (10 microg; 5.5 nmol), also caused scratching (ED(50) 1.3 microg, 0.7 nmol). The ET(A) receptor antagonist BQ123 significantly reduced scratching evoked by ET-1 and IRL 1620, suggesting that both agonists caused scratching via an ET(A) receptor-dependent mechanism. The ET(B) receptor antagonist BQ788 significantly reduced scratching evoked by IRL1620 but had no effect on scratching evoked by ET-1. This indicated that activation of ET(B) receptors by high doses of ET(B) agonist, but not ET-1, can trigger scratching. CONCLUSION AND IMPLICATIONS: ET-1 is a potent endogenous activator of reflex scratching (itch). Mechanisms for ET-induced scratching are considered, including direct action of ET-1 on pruriceptive nerve endings and indirect actions via release of endogenous mediators such as histamine from mast cells. ET-1 and ET(A) receptors, possibly also ET(B) receptors, are potential targets for developing specific anti-pruritic drugs to treat pruritic skin disorders such as atopic dermatitis.

Effect of Dexamethasone and Fluticasone on Airway Hyperresponsiveness in Horses With Inflammatory Airway Disease.

BACKGROUND: Airway hyperresponsiveness (AWHR), expressed as hypersensitivity (PC75 RL ) or hyperreactivity (slope of the histamine dose-response curve), is a feature of inflammatory airway disease (IAD) or mild equine asthma in horses. Glucocorticoids are used empirically to treat IAD. OBJECTIVES: To determine whether dexamethasone (DEX) (0.05 mg/kg IM q24h) and inhaled fluticasone (FLUT) (3,000 µg q12h) administered by inhalation are effective in decreasing AWHR, lung inflammation, and clinical signs in horses with IAD. METHODS: A randomized crossover study design was used. Eight horses with IAD were assigned to a treatment group with either DEX or FLUT. Measured outcomes included lung mechanics during bronchoprovocative challenges, bronchoalveolar lavage fluid (BALF) cytology, and scoring of clinical signs during exercise. RESULTS: Dexamethasone and FLUT abolished the increase in RL by 75% at any histamine bronchoprovocative dose in all horses after the first week of treatment. However, after 2 weeks of FLUT treatment, 1 horse redeveloped hypersensitivity. There was a significant decrease in the number of lymphocytes after treatment with both DEX and FLUT (P = .039 for both) but no significant differences in other BALF cell types or total cell counts (P > .05). There was no difference in the scoring of the clinical signs during each treatment and washout period (P > .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Both DEX and FLUT treatments significantly inhibit airway hypersensitivity and hyperreactivity in horses with IAD. There are no significant effects on the clinical signs or the number of inflammatory cells (except lymphocytes) in BALF. The treatments have no residual effect 3 weeks after discontinuation.

The burden of healthcare-associated Clostridium difficile infection in a non-metropolitan setting.

OBJECTIVE: Healthcare-associated Clostridium difficile infection (HCA-CDI) remains a major cause of morbidity and mortality in industrialized countries. However, few data exist on the burden of HCA-CDI in multi-site non-metropolitan settings. This study examined the introduction of an antimicrobial stewardship programme (ASP) in relation to HCA-CDI rates, and the effect of HCA-CDI on length of stay (LOS) and hospital costs. METHODS: A comparative before-and-after intervention study of patients aged ≥16 years with HCA-CDI from December 2010 to April 2016 across the nine hospitals of a non-metropolitan health district in New South Wales, Australia was undertaken. The intervention comprised a multi-site ASP supported by a clinical decision support system, with subsequent introduction of email feedback of HCA-CDI cases to admitting medical officers. MAIN OUTCOME MEASURES: HCA-CDI rates, comparative LOS and hospital costs, prior use of antimicrobials and proton pump inhibitors, and appropriateness of CDI treatment. RESULTS: HCA-CDI rates rose from 3.07 to 4.60 cases per 10,000 occupied bed-days pre-intervention, and remained stable at 4 cases per 10,000 occupied bed-days post-intervention (P=0.24). Median LOS (17 vs six days; P<0.01) and hospital costs (AU$19,222 vs $7861; P<0.01) were significantly greater for HCA-CDI cases (N=91) than for matched controls (N=172). Half of the patients with severe HCA-CDI (4/8) did not receive initial appropriate treatment (oral vancomycin). CONCLUSIONS: HCA-CDI placed a significant burden on the regional and rural health service through increased LOS and hospital costs. Interventions targeting HCA-CDI could be employed to consolidate the effects of ASPs.

Determining "need" for a Removable Partial Denture: a qualitative study of factors that influence dentist provision and patient use.

OBJECTIVE: To identify factors that influence Removable Partial Denture (RPD) provision, and patient use of RPDs in the UK. DESIGN: Exploratory qualitative interview study. SUBJECTS: There were two sample groups. A purposive sample of 16 male and female dentists was categorised in terms of level of RPD provision, experience, and practice characteristics. A purposive sample of 17 male and female partially dentate patients was categorised in terms of RPD use and demographic characteristics. DATA COLLECTION: Semi-structured in-depth interviews. RESULTS: For dentists, RPD provision was indicated by patient demand and physical function of the remaining teeth, but was mediated by NHS fee structures and professional satisfaction. For patients, RPD use was influenced by the trade-off between improved appearance and the unpalatable presence of an RPD in their mouth. The location of the gap(s) was important, but other issues were relevant such as ability to "manage" without the RPD. CONCLUSION: When defining "need" for an RPD, dentists focused on physical function of the teeth whereas patients focused on social meanings of the mouth. These differing priorities may improve understandings of patient non-compliance in RPD use. Further research on the relationship between denture use and social identity could be beneficial.

Tracheobronchoscopic Assessment of Exercise-Induced Pulmonary Hemorrhage and Airway Inflammation in Barrel Racing Horses.

BACKGROUND: Poor performance is often suspected to be associated with EIPH in barrel racing horses; however, there are no published reports of EIPH for this discipline. The prevalence of EIPH in barrel racing horses is also unknown. OBJECTIVES: This study was performed to determine the prevalence of EIPH and signs of airway inflammation in barrel racing horses under normal racing conditions in Alberta. ANIMALS: About 170 barrel racing horses. METHODS: Observational cross-sectional study. Tracheobronchoscopic examinations were performed at least 30 minutes postrace. Video recordings were scored off-site independently by two observers for EIPH and tracheal mucus accumulation (TMA). Horses with an EIPH score ≥2 were not assessed for TMA. Interobserver agreement was calculated by weighted κ statistics. Run times, environmental variables, and clinical information were also recorded for analysis. RESULTS: 77/170 (45.3%) of horses examined showed evidence of EIPH (grade ≥ 1). Interobserver agreement was 0.94. 140/141 (99.3%) of horses assessed for TMA showed evidence of tracheal mucus accumulation (grade ≥ 1) with 104/141 (73.8%) having a TMA score ≥ 2. Interobserver agreement was 0.73. A weak positive association was found between EIPH scores and average run speed, the presence of cough at rest reported by the riders, increased recovery time, exercise intolerance, and outdoor pattern. CONCLUSIONS AND CLINICAL IMPORTANCE: The high prevalence of EIPH observed in the sampled population indicates that barrel racing induces substantial stress on the lungs. The presence of EIPH did not impact negatively on performance. Factors such as environmental dust and frequent traveling might have contributed to the high prevalence of TMA observed.

Relationships between chemical structure and inhibition of ADP-stimulated human thrombocyte release of serotonin and platelet factor 4.

The inhibitory potencies of carbamoylpiperidinoalkane and N-alkylnipecotoylpiperazine derivatives on ADP-stimulated human blood platelet aggregation, serotonin (5-HT) release and platelet factor 4 (PF-4) release were evaluated. The procedure was designed to allow concurrent determination of all three sets of values. Most compounds were more than twice as potent in blocking PF-4 (X = 91 +/- 1 (S.E., n = 7)%) compared to their inhibition of 5-HT (X = 38 +/- 1(S.E., n = 6)%) release; the one compound which failed to meet these criteria was still decidedly more powerful in impeding PF-4 than 5-HT release. Since the compounds' platelet aggregation-inhibitory values were within the same range as their 5-HT release-blocking potencies, but had a strikingly greater impact in arresting PF-4 release, it is suggested that the platelet plasma membrane and the lining enveloping the dense bodies may share certain commonalities, while the sheathing encasing the alpha-granules may differ from both in a tangible manner.

Relationships between chemical structure and inhibition of epinephrine-induced human blood platelet aggregation.

The effect of structural features in a series of carbamoylpiperidine and nipecotoylpiperazine congeners on epinephrine-induced aggregation of human blood platelets is examined. Epinephrine-induced primary aggregation is effectively inhibited by the nipecotoylpiperazine derivatives (culminating at an IPA50 of 11.9 microM). While among nipecotoylpiperazine as well as carbamoylpiperidine congeners there are potent inhibitors of ADP-stimulated platelet function (cresting at an IA50 of 12.4 and 11.4 microM, respectively), the carbamoylpiperidine analogs are much less active (e.g., IPA50 of 298.1), or practically inactive, in impeding epinephrine-induced primary aggregation (PA).

Selection of active drugs for ovarian cancer based on CA-125 and standard response rates in phase II trials.

PURPOSE: To determine whether precise definitions of response based on serial CA-125 levels can predict the activity of drugs in phase II trials for ovarian cancer as accurately as standard criteria. PATIENTS AND METHODS: Fourteen different drugs for relapsed ovarian cancer were analyzed in 25 treatment groups in 19 clinical trials. Response rates were estimated in 1,457 assessable patients according to standard criteria and in 1,092 assessable patients according to CA-125. For each drug trial, the observed response rates acted as the input data for an evaluation of how the two criteria would perform in a hypothetical Gehan two-stage phase II trial, accepting a target drug efficacy rate of 20% and a rejection error of 5%. RESULTS: CA-125 and clinical response criteria were concordant in 20 of the 25 groups, with less than 5% chance of rejecting the drug in nine groups and greater than 5% in 11 groups. In four groups, the drug had less than 5% chance of being rejected by CA-125 but greater than 5% chance of being rejected by standard criteria. The difference in the classification of drugs by the standard and CA-125 response criteria was not statistically significant (P =.38, McNemar's test). CA-125 response rates were slightly higher than standard response rates by a factor of 1.11. CONCLUSION: Definitions based on a 50% or 75% decrease of CA-125 levels accurately predicted which drugs in phase II trials for relapsed ovarian cancer were active and justified further investigation.

A repetitive movement detector used for automatic monitoring and quantification of scratching in mice.

We have designed an economical non-invasive movement detector for small animal studies and used it for monitoring and quantifying itch in mice. The system is based on a sensitive force transducer positioned below a recording platform holding a lightweight polystyrene recording box in which an animal is placed. A programmed micro-controller is used to discriminate between non-specific movement, grooming behaviour, and scratching movements made by the animal's hind limb. Following sub-dermal injection of histamine receptor agonists into the neck of a mouse, dose-related scratching occurred which was detected and quantified. There was 91% correlation between bouts of scratching as counted manually from playback of the video recording and recorded by the detector. The detector was also able rapidly to count the individual scratch movements of the hind limb that comprise a bout, with 95% accuracy in comparison with manual counting during slow motion playback of video tape, something that is impossible for an unaided observer to achieve because individual scratch movements are too fast to discriminate by eye. Separate detectors were used for the efficient non-invasive study of four animals simultaneously, and this number could easily be increased by adding more platforms. The system could also be modified to record the animal's position within the box, which would be of value in studies involving exploratory behaviour. In summary, the non-invasive multichannel repetitive movement detector will be very useful for accurate measurement of scratching during pruritus studies in small animals, with considerable savings in staff time and effort. It should therefore be a valuable tool for helping to investigate pruritus and in the evaluation of anti-pruritic drugs.