Changes In Clinical Evaluations Research Articles

Laboratory safety evaluation of bedinvetmab, a canine anti-nerve growth factor monoclonal antibody, in dogs

Nerve growth factor (NGF), a critical mediator of nociception, is a novel analgesic therapeutic target. Bedinvetmab, a canine monoclonal antibody (mAb), binds NGF and inhibits its interaction with tropomyosin receptor kinase A (trkA) and p75 neurotrophin receptor (p75NTR) receptors. The objective of three integrated laboratory studies was to demonstrate the safety of bedinvetmab in adult laboratory Beagle dogs. Daily health, veterinary, clinical pathology, systemic exposure, and anti-drug antibody evaluations were performed. Study 1 additionally included electrocardiography, neurologic, and ophthalmic assessments, and radiographic monitoring of joints of the appendicular skeleton. Study 2 evaluated T-lymphocyte-dependent immune function. Study 3 evaluated the safety of short-term concurrent administration of carprofen, a nonsteroidal anti-inflammatory drug (NSAID), with bedinvetmab. Studies 1 and 3 included terminal pathology and histopathology evaluations. Study designs and procedures included directed complementary morphologic and functional evaluations of a literature- and in vitro-based list of potential safety issues related to the NGF signaling pathway and characteristics engineered into this mAb. Screening-level general procedures evaluated effects associated with mAbs that target and inhibit soluble agonist cytokines.There were no treatment-related adverse changes in clinical evaluations, clinical neurological and ophthalmic examinations, joints, immune morphology or function, and no effects of short-term concurrent NSAID usage. Treatment-emergent immunogenicity was not observed. Bedinvetmab (1 mg/kg SC monthly; 3× and 10× dose multiples) was well tolerated in normal laboratory Beagle dogs for 6 months and with 2 weeks’ concurrent NSAID administration.

Serial lung and IVC ultrasound in the assessment of congestive heart failure

BackgroundManagement of congestive heart failure (CHF) is dependent on clinical assessments of volume status, which are subjective and imprecise. Point-of-care ultrasound (POCUS) is useful in the diagnosis of CHF, but how POCUS findings correlate with therapy remains unknown. This study aimed to determine whether the changes in clinical evaluation of CHF with treatment are mirrored with changes in the number of B lines on lung ultrasound (LUS) and inferior vena cava (IVC) size. In this prospective observational study, investigators performed serial clinical and ultrasound assessments within 24 h of admission (T1), day 1 in hospital (T2) and within 24 h of discharge (T3). Clinical assessments included an evaluation of the jugular venous distension (JVD), hepatojugular reflux (HJR), pulmonary rales and a clinical congestion score was calculated. Ultrasound assessment included the IVC size and collapsibility, and the number of B lines in an 8-point scan.ResultsFifty consecutive patients were recruited with a mean age of 71.2 years (SD 12.7). Mean clinical congestion score on admission was 5.6 (SD 1.4) and declined significantly over time to 1.3 (0.91), as did the JVP, HJR and pulmonary rales. No significant changes were found in the IVC size between T1 [1.9 (0.65)] and T3 [2.0 (0.50)] or in the IVC collapsibility index [T1 0.3 (0.19) versus T3 0.25 (0.16)]. The mean number of B lines decreased from 11 (6.1) at T1 to 8.3 (5.5) at T3, although this decrease did not reach statistical significance. Spearman correlation between JVP and HJR versus IVC collapsibility and total B lines did not yield significant results.ConclusionsClinical exam findings correlate over time during the management of CHF, whereas LUS and IVC results did not. The number of B lines did decrease with therapy, but did not reach statistical significance likely because the sampled population was small and had only mild heart failure. Further studies are warranted to further explore the use of lung ultrasound in this patient population.

Changes in interpretations of proverbs in schizophrenic patients

Two groups of male schizophrenic patients, n 15 and 42 respectively, were tested with a Swedish proverbs test before insulin coma treatment in the first group, neuroleptic pharmaca treatment in the second group was initiated. The proverbs test was repeated at the end of the treatment period. Simultaneously with the testings psychiatric status was evaluated and the behavior at the ward. Related to changes in clinical evaluations we found changes in interpretative level implying that the patients interpreted the proverbs more like normals do than before. The relation of “interpretative improvement” to levels of age and intelligence and the relation between magnitudes of interpretative and clinical improvements are discussed.