Comparing Blind and Ultrasound-Guided Retrobulbar Nerve Blocks in Equine Cadavers: The Training Effect.

In standing ophthalmic surgery in horses, a retrobulbar nerve block (RNB) is often placed blindly for anesthesia and akinesia. The ultrasound (US)-guided RNB may have fewer complications, but the two techniques have only been compared once in equine cadavers. This study compares the techniques for success and complication rates and analyzes the effect of training on US guidance. Twenty-two equine cadavers were divided into three groups: blind RNBs were performed bilaterally in eight cadavers, US-guided RNBs were performed bilaterally in seven cadavers, and after US-guided training, blind RNBs were performed bilaterally in seven cadavers. All RNBs were performed by the same two inexperienced operators, and a combination of contrast medium (CM; 1.25 mL) and methylene blue dye (1.25 mL) were injected (2.5 mL total volume). Needle positioning in the periorbita and the distance of the CM to the optic foramen were assessed using computerized tomography (CT). Dye spreading was evaluated by dissection. In group 1, 37.5% of the injections were in the optimal central position in the periorbita; in group 2, 75% and in group 3, 71.4%. There was no significant difference between the groups regarding needle position (groups 1 and 2 p = 0.056; groups 1 and 3 p = 0.069, groups 2 and 3 p = 0.8). The mean CM distribution distance was not significantly different between all groups. Group 1 had 18.75% intraocular injections versus 0% in group 2 and 7.1% in group 3 (not significant). US guidance showed no significant increases in accuracy nor decreases in complications. However, the effects on accuracy showed a trend towards significant improvement, and larger scale follow-up studies might show significant training effects on US guidance.

Presumed cholesterinic granulomas detected on CT in horses are associated with increased lateral ventricle height and age.

Cholesterinic granulomas are mass-like lesions that form at the choroid plexus of the ventricular system. Large cholesterinic granulomas within the lateral ventricles have been reported to cause severe neurological signs. However, little data are available about their prevalence or appearance in the overall population. The objective was to report the prevalence of presumed cholesterinic granulomas on CT in a population of horses, and investigate associations between presumed cholesterinic granuloma presence, lateral ventricle size, age, and neurological signs. The study was cross sectional, CT scans of the head were assessed for presumed cholesterinic granuloma presence and size, and lateral ventricle height. Computed tomography findings and clinical information were compared using nonparametric testing. Computed tomography scans of 139 horses were included. Presumed cholesterinic granulomas were found in 22 horses (15.8%), nine were unilateral and 13 bilateral. A significant increase in prevalence was observed with age (P < .0001), with 38% of horses over 15 years old affected. The median volume of presumed cholesterinic granulomas was 242 mm3 with a range from 51 to 2420 mm3 . The mean lateral ventricle height was significantly increased in horses with presumed cholesterinic granulomas present (P = .004), with a median of 7.3 mm compared to 4.9 mm without. Neurological signs were not associated with presumed cholesterinic granuloma presence or lateral ventricle height. Fourth ventricle mineralizations were found in seven horses, which may represent cholesterinic granulomas. In conclusion, presumed cholesterinic granulomas occurred in a large proportion of the examined population and are associated with increased lateral ventricle dilation and advanced age.

Morphological variations of the infraorbital canal during CT has limited association with headshaking in horses.

Headshaking is a common problem in horses. The etiology is unknown but thought to involve sensory input from branches of the trigeminal nerve, some of which are within the infraorbital canal. The objective of this retrospective cross-sectional study was to describe the CT anatomy and variations of the infraorbital canal in horses with local disease processes and normal horses, and to examine associations between those findings and headshaking. Computed tomography scans were reviewed and morphological changes of the infraorbital canal were described. Presence of changes was then tested for association with headshaking prevalence, presence of disease processes in the region of the infraorbital canal, age, and sex. Nonparametric tests were used and a P-value of .05 was considered significant. A total of 218 horses were included, 9% of which had headshaking and 45% had CT lesions in the region of the infraorbital canal. Morphological changes to the bone of the infraorbital canal were found in 121 horses (56%) and included the following: increased mineralization 39 (18%), decreased mineralization 89 (41%), deformed shape 51 (23%), displaced position 43 (20%), and disruption 11 (5%). All changes of the infraorbital canal significantly increased in frequency with the presence of adjacent disease. Increased mineralization and disruption of the infraorbital canal were significantly associated with headshaking in horses with adjacent disease; the latter only reached significance after exclusion of dentally immature horses. No other changes were significantly associated with the presence of headshaking. No association was found between headshaking and the age or sex of the horse.

Caudal lumbar spinal cysts in two French Bulldogs.

BACKGROUND: Spinal cysts are rare findings in veterinary medicine, but they are increasingly recognized due to the availability of advanced imaging techniques. Extradural meningeal cysts in French Bulldogs have not been reported previously and arachnoid cysts (diverticula) have not been reported at the caudal lumbar (L6-L7) region in dogs. CASE PRESENTATION: Two French Bulldogs, aged 5 and 8 years, were referred for evaluation of lower back pain and bilateral hind limb neurological deficits. Neurologic examination revealed ataxia and postural deficits in both dogs. Magnetic resonance imaging (MRI) showed cauda equina compression due to a cyst-like lesion at the level of L6-L7 in both cases. The dogs underwent dorsal laminectomy and the meningeal cyst was completely removed in one dog and in the other dog the spinal arachnoid diverticula was marsupialized. In Case 1, histopathology of the cysts was performed and MRI was repeated. Both dogs were pain free during follow-up evaluations. CONCLUSIONS: Based on radiological, intra-operative and histopathological findings, the first case was diagnosed as a meningocele connected by a pedicle to the caudal tip of the dural sac forming a dural diverticulum categorized as an extradural spinal cyst type Ib, and Case 2 as a type III intradural arachnoid diverticula. It is concluded that spinal cysts should be included in the differential diagnosis of cauda equina syndrome and lower back pain in French Bulldogs. Results of these cases may be useful for diagnostic and treatment management.

Cheminformatics-aided pharmacovigilance: application to Stevens-Johnson Syndrome.

OBJECTIVE: Quantitative Structure-Activity Relationship (QSAR) models can predict adverse drug reactions (ADRs), and thus provide early warnings of potential hazards. Timely identification of potential safety concerns could protect patients and aid early diagnosis of ADRs among the exposed. Our objective was to determine whether global spontaneous reporting patterns might allow chemical substructures associated with Stevens-Johnson Syndrome (SJS) to be identified and utilized for ADR prediction by QSAR models. MATERIALS AND METHODS: Using a reference set of 364 drugs having positive or negative reporting correlations with SJS in the VigiBase global repository of individual case safety reports (Uppsala Monitoring Center, Uppsala, Sweden), chemical descriptors were computed from drug molecular structures. Random Forest and Support Vector Machines methods were used to develop QSAR models, which were validated by external 5-fold cross validation. Models were employed for virtual screening of DrugBank to predict SJS actives and inactives, which were corroborated using knowledge bases like VigiBase, ChemoText, and MicroMedex (Truven Health Analytics Inc, Ann Arbor, Michigan). RESULTS: We developed QSAR models that could accurately predict if drugs were associated with SJS (area under the curve of 75%-81%). Our 10 most active and inactive predictions were substantiated by SJS reports (or lack thereof) in the literature. DISCUSSION: Interpretation of QSAR models in terms of significant chemical descriptors suggested novel SJS structural alerts. CONCLUSIONS: We have demonstrated that QSAR models can accurately identify SJS active and inactive drugs. Requiring chemical structures only, QSAR models provide effective computational means to flag potentially harmful drugs for subsequent targeted surveillance and pharmacoepidemiologic investigations.

Guidelines for submitting adverse event reports for publication.

Publication of case reports describing suspected adverse effects of drugs and medical products that include herbal and complementary medicines, vaccines and other biologicals and devices is important for postmarketing surveillance. Publication lends credence to important signals raised in these adverse event reports. Unfortunately, deficiencies in vital information in published cases can often limit the value of such reports by failing to provide enough details for either (i) a differential diagnosis or provisional assessment of cause-effect association, or (ii) a reasonable pharmacological or biological explanation. Properly described, a published report of one or more adverse events can provide a useful signal of possible risks associated with the use of a drug or medical product which might warrant further exploration. A review conducted by the Task Force authors found that many major journals have minimal requirements for publishing adverse event reports and some have none at all. Based on a literature review and our collective experience in reviewing adverse event case reports in regulatory, academic and industry settings, we have identified information that we propose should always be considered for inclusion in a report submitted for publication. These guidelines have been endorsed by the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) and are freely available on the societies' web sites. Their widespread distribution is encouraged. ISPE and ISoP urge biomedical journals to adopt these guidelines and apply them to case reports submitted for publication. They also encourage schools of medicine, pharmacy, and nursing to incorporate them into the relevant curricula that address the detection, evaluation and reporting of suspected drug or other medical product adverse events.

Intranasally administered corticosteroids and neuropsychiatric disturbances: a review of the international pharmacovigilance programme of the World Health Organization.

BACKGROUND: The systemic use of corticosteroids is connected with a variety of psychiatric and neurologic effects. Corticosteroids for intranasal administration (INCs) are considered to act locally and to exert minimal systemic effects. An unexpected cluster of case reports of neuropsychiatric disorders during intranasal corticosteroid use was reported to the World Health Organization Uppsala Monitoring Centre. OBJECTIVE: To investigate the possible connection between intranasal corticosteroid use and the development of neuropsychiatric disorders, as reported to the International Pharmacovigilance Programme. METHODS: All reports containing adverse event terms indicating neuropsychiatric disturbances in suspected connection with intranasal corticosteroids were retrieved from Vigibase and evaluated (April 2006). The case reports are heterogeneous and vary regarding source, documentation quality, and relationship likelihood. RESULTS: A total of 429 reports were received from 16 countries (1980-April 2006), of neuropsychiatric events occurring in patients using INCs, representing 7.6% of the total of reports regarding these drugs in the same period. Frequently reported events were nervousness, anxiety, agitation, insomnia, emotional lability, depression, somnolence, confusion, convulsions, and migraine. Most reports concerned fluticasone propionate, beclometasone dipropionate, mometasone furoate, or budesonide. In 370 reports (86.2%), the INC was the sole suspect drug and in 220 (51.3%) it was the only drug used. In 97 of 108 patients who had discontinued use of the intranasal corticosteroid, the reaction abated. Of 41 patients, 32 had a relapse when the drug was reintroduced. CONCLUSIONS: The data collected by the International Pharmacovigilance Programme suggest that the intranasal use of corticosteroids can be complicated by neuropsychiatric adverse reactions. Further study is needed to confirm the connection and to determine the frequency and risk factors of such reactions.

Guidelines for submitting adverse event reports for publication.

Publication of case reports describing suspected adverse effects of drugs and medical products that include herbal and complementary medicines, vaccines, and other biologicals and devices is important for postmarketing surveillance. Publication lends credence to important signals raised in these adverse event reports. Unfortunately, deficiencies in vital information in published cases can often limit the value of such reports by failing to provide enough details for either (i) a differential diagnosis or provisional assessment of cause-effect association, or (ii) a reasonable pharmacological or biological explanation. Properly described, a published report of one or more adverse events can provide a useful signal of possible risks associated with the use of a drug or medical product which might warrant further exploration. A review conducted by the Task Force authors found that many major journals have minimal requirements for publishing adverse event reports, and some have none at all. Based on a literature review and our collective experience in reviewing adverse event case reports in regulatory, academic, and industry settings, we have identified information that we propose should always be considered for inclusion in a report submitted for publication. These guidelines have been endorsed by the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) and are freely available on the societies' websites. Their widespread distribution is encouraged. ISPE and ISoP urge biomedical journals to adopt these guidelines and apply them to case reports submitted for publication. They also encourage schools of medicine, pharmacy, and nursing to incorporate them into the relevant curricula that address the detection, evaluation, and reporting of suspected drug or other medical product adverse events.

Atypical antipsychotics and pituitary neoplasms in the WHO database.

Amisulpride and risperidone are potent dopamine D2 receptor blocking atypical antipsychotics that can cause hyperprolactinemia. Preclinical evidence shows that chronic administration of antipsychotics can cause pituitary adenomas in female mice. To investigate the clinical relevance in this finding, reports of pituitary neoplasms in the WHO adverse drug reaction (ADR) database were reviewed. Amisulpride and risperidone [corrected] had among the highest Information Component (IC) scores for benign pituitary neoplasm; amisulpride (IC = 3.31, IC025 = 1.83, 5 reports) and risperidone (IC = 4.03, IC025 = 3.33, 19 reports), and not otherwise specified (NOS) pituitary neoplasm: amisulpride (IC = 2.69, IC025 = 0.70, 3 reports) and risperidone (IC = 4.49, IC025 = 3.86, 23 reports). We conclude that there is a need for prospective studies to confirm causality and suggest that clinicians, until then, would consider a pituitary adenoma in patients experiencing severe hyperprolactinemia or associated symptoms when receiving potent D2 antagonists [corrected]

Botanical nomenclature in pharmacovigilance and a recommendation for standardisation.

Nomenclature of plants in pharmacology can be presented by pharmaceutical names or scientific names in the form of Linnaean binomials. In this paper, positive and negative aspects of both systems are discussed in the context of the scientific nomenclatural framework and the systems' practical applicability. The Uppsala Monitoring Centre (UMC) runs the WHO Programme for International Drug Monitoring and is responsible for the WHO Adverse Drug Reaction (ADR) database that currently contains 3.6 million records. In order for the UMC to monitor pharmacovigilance through ADRs to herbal medicine products the following nomenclatural criteria are important: (i) the name should indicate only one species of plant; (ii) the source for this name must be authoritative; (iii) the name should indicate which part of the plant is used. Based on these criteria, the UMC investigated four options: (i) adopt main names used in recognised (inter-) national pharmacopoeias or authoritative publications; (ii) adopt option 1, but cite the publication for all names in abbreviated form; (iii) three-part pharmaceutical names consisting of Latinised part name plus Latinised genus name, plus Latinised specific epithet; (iv) scientific binomial names, optionally with author and plant part used. The UMC has chosen the latter option and will at its adoption utilise the scientific botanical nomenclature as defined by the International Code of Botanical Nomenclature. This decision satisfies all criteria set by the UMC and renders the necessity of creating a new system or upgrading an old inconsistent system obsolete. The UMC has also issued an extensive synonymy checklist of vernacular, pharmaceutical and scientific names for the herbals in the WHO ADR database. We strongly recommend the adoption of scientific names to denote plant ingredients in medicine.

Botanical Nomenclature in Pharmacovigilance and a Recommendation for Standardisation.

Nomenclature of plants in pharmacology can be presented by pharmaceutical names or scientific names in the form of Linnaean binomials. In this paper, positive and negative aspects of both systems are discussed in the context of the scientific nomenclatural framework and the systems' practical applicability. The Uppsala Monitoring Centre (UMC) runs the WHO Programme for International Drug Monitoring and is responsible for the WHO Adverse Drug Reaction (ADR) database that currently contains 3.6 million records. In order for the UMC to monitor pharmacovigilance through ADRs to herbal medicine products the following nomenclatural criteria are important: (i) the name should indicate only one species of plant; (ii) the source for this name must be authoritative; (iii) the name should indicate which part of the plant is used. Based on these criteria, the UMC investigated four options: (i) adopt main names used in recognised (inter-) national pharmacopoeias or authoritative publications; (ii) adopt option 1, but cite the publication for all names in abbreviated form; (iii) three-part pharmaceutical names consisting of Latinised part name plus Latinised genus name, plus Latinised specific epithet; (iv) scientific binomial names, optionally with author and plant part used. The UMC has chosen the latter option and will at its adoption utilise the scientific botanical nomenclature as defined by the International Code of Botanical Nomenclature. This decision satisfies all criteria set by the UMC and renders the necessity of creating a new system or upgrading an old inconsistent system obsolete. The UMC has also issued an extensive synonymy checklist of vernacular, pharmaceutical and scientific names for the herbals in the WHO ADR database. We strongly recommend the adoption of scientific names to denote plant ingredients in medicine.

Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been associated with withdrawal symptoms. We investigated whether use of these drugs in pregnant women might cause neonatal withdrawal syndrome. METHODS: An association between paroxetine and neonatal convulsions was identified in December, 2001, by the data mining method routinely used to screen the WHO database of adverse drug reactions. An information component (IC) measure was used to screen for unexpected adverse reactions relative to the information in the database. We then assessed cases of neonatal convulsions and neonatal withdrawal syndrome associated with drugs included in the anatomical therapeutic chemical groups N06AB and N06AX. FINDINGS: By November, 2003, a total of 93 suspected cases of SSRI-induced neonatal withdrawal syndrome had been reported, and were regarded as enough information to confirm a possible causal relation. 64 of the cases were associated with paroxetine, 14 with fluoxetine, nine with sertraline, and seven with citalopram. The IC-2 SD for the group became greater than 0 in the first quarter of 1991, and the IC increased to 2.68 (IC-2 SD 0.32) by the second quarter of 2003. For each individual compound, the IC-2 SD was greater than 0. INTERPRETATION: SSRIs, especially paroxetine, should be cautiously managed in the treatment of pregnant women with a psychiatric disorder.