Prophylactic therapy with omeprazole for prevention of equine gastric ulcer syndrome (EGUS) in horses in active training: A meta-analysis.

BACKGROUND: Guidelines regarding the impact and value of prophylaxis or maintenance therapy in equine gastric ulcer syndrome (EGUS) are not well-established or defined. The merits and the magnitude of effects of prophylaxis for spontaneous or recurrent squamous gastric ulceration in horses in training are uncertain. OBJECTIVES: To pool data from randomised controlled trials (RCTs) to eliminate reporting bias and evaluate the efficacy of prophylactic omeprazole in the prevention of EGUS in training horses, and secondarily to compare prophylactic dosages of omeprazole. STUDY DESIGN: Meta-analysis. METHODS: This meta-analysis was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic literature search identified RCTs comparing omeprazole prophylaxis with sham in prevention of EGUS. Data were analysed using the Mantel-Haenszel test method to calculate risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs). Primary outcome was efficacy of prophylaxis. Secondary outcome was endoscopic severity of ulceration. The influence of study characteristics on the outcomes was examined by subgroup analyses. RESULTS: In preventing gastric ulcer occurrence, omeprazole prophylaxis was superior to sham in training horses (7 trials, 566 horses, RR 0.28, 95% CI 0.18-0.43; 23.4% in omeprazole prophylaxis vs. 77.2% in sham; high quality evidence). Prevalence of ulceration was 75.3 and 87.2% in the sham arms of the 1 mg/kg and 2 mg/kg omeprazole groups, respectively. Severity scores were significantly lower for omeprazole vs. sham (mean difference [MD] -1.05; 95% CI -1.35 to -0.69). Subgroup analyses comparing prophylactic omeprazole dosages resulted in a mean difference of -0.94 and -1.60 for the 1 and 2 mg/kg groups, respectively. MAIN LIMITATIONS: Studies showed heterogeneity with regard to prophylactic dose. CONCLUSIONS: Omeprazole prophylaxis in active training horses significantly reduces gastric ulceration compared with no prophylaxis (sham) with the absolute effect of 566 fewer ulcers per 1000 horses treated.

Inhibition of the phosphoinositide 3-kinase pathway for the treatment of patients with metastatic metaplastic breast cancer.

BACKGROUND: Mesenchymal/metaplastic breast cancers (MpBCs) are often triple-negative (TNBC), and chemo-refractory, and can harbor phosphoinositide 3-kinase (PI3kinase) alterations; thus, therapy with mTor inhibitors may demonstrate activity. PATIENTS AND METHODS: Patients with mesenchymal/MpBC treated with temsirolimus-based regimens were evaluated. Mutational analyses [polymerase chain reaction (PCR)-based DNA sequencing method, mass spectrometric detection (Sequenom MassARRAY), or next-generation sequencing] as well as loss of phosphatase and tensin homolog (PTEN) (immunohistochemistry) were performed (archived tissue when available). RESULTS: Twenty-three patients (one of whom was on two separate trials) were treated using temsirolimus-containing regimens: temsirolimus alone (n = 1 patient) or combined with the following: liposomal doxorubicin and bevacizumab (DAT, n = 18); liposomal doxorubicin (DT, n = 1); paclitaxel and bevacizumab (TAT, n = 2); paclitaxel (TT, n = 1); carboplatin and bevacizumab (CAT, n = 1). Response rate [complete response (CR) + partial response (PR)] was 25% across all regimens; 32% in the anthracycline-based regimens [DAT and DT (CR = 2, PR = 4; N = 19)]. An additional two patients achieved stable disease (SD) ≥6 months [total SD ≥6 months/CR/PR = 8 (33%)]. Molecular aberrations in the PI3K pathway were common: PIK3CA mutation = 6/15 (40%), PTEN mutation = 3/11 (27%), and PTEN loss = 2/11 (18%). A point mutation in the NF2 gene (K159fs*16; NF2 alterations can activate mTor) was found in one patient who attained CR (3+ years). Of the eight patients who achieved SD ≥6 months/CR/PR, all 4 patients with available tissue had a molecular aberration that activate the PIK3CA/Akt/mTOR axis: PIK3CA mutation = 2; PTEN loss = 1; NF2 aberration = 1. CONCLUSIONS: DAT has activity in MpBCs including complete CRs. Molecular aberrations that can activate the PI3 K/Akt/mTOR axis are common in MpBC.

Sporobolomyces roseus in the cerebrospinal fluid of an immunocompetent patient--to treat or not to treat?

We present the case of an immunocompetent male who presented with symptoms of meningitis. Yeasts were seen in two consecutive cerebrospinal fluid samples, which were identified by PCR as Sporobolomyces roseus. This yeast is rarely encountered in clinical settings, and has only previously been seen to cause infection in immunocompromised patients. This case highlights the challenges presented by the identification of an unusual pathogen in an unexpected clinical setting.

Stroke recurrence within the time window recommended for carotid endarterectomy.

OBJECTIVE: In the North Dublin Population Stroke Study, we investigated the risk of recurrent stroke within the 14-day time window recommended for endarterectomy. METHODS: In a population-based prospective cohort study, all ischemic stroke patients were identified over 1 year and categorized into those with (CS-positive) and without (CS-negative) ipsilateral carotid stenosis (CS) (≥50% lumen narrowing). Nonprocedural stroke recurrence was determined at 72 hours and 7 and 14 days. RESULTS: Of 365 ischemic stroke patients with carotid imaging, 51 were excluded due to posterior circulation or nonlateralizing stroke, ipsilateral carotid occlusion, or intracranial stenosis, leaving 314 included for analysis (36 CS-positive and 278 CS-negative). Recurrent stroke occurred in 5.6% (2/36) CS-positive and 0.4% (1/278) CS-negative patients by 72 hours of symptom onset (p =0.003), 5.6% (2/36) CS-positive and 0.7% (2/278) CS-negative patients (p =0.01) by 7 days, and in 8.3% (3/36) CS-positive and 1.8% (5/278) CS-negative patients by 14 days (p =0.02). On multivariable Cox regression analysis, CS was the only independent predictor of recurrence at 72 hours (adjusted hazard ratio [HR] 36.1, 95% confidence interval [CI] 1.6-837.5, p =0.03), and 7 days (HR 9.1, 1.1-79.2, p =0.05), with a trend at 14 days (HR 4.6, 0.9-22.8, p =0.06). CONCLUSIONS: Although only a minority of patients with symptomatic CS had a recurrent stroke within 14 days, early recurrent stroke risk was high, particularly within the first 72 hours. Earlier carotid revascularization or improved acute medical treatment may reduce recurrence in this high-risk group.

What is the benefit of bevacizumab combined with chemotherapy in patients with recurrent ovarian, fallopian tube or primary peritoneal malignancies?

The aim of this retrospective analysis was to investigate the efficacy and adverse effects of the monoclonal antivascular endothelial growth factor antibody bevacizumab (Avastin(R)) combined with chemotherapeutic agents in non-protocol patients with recurrent ovarian, fallopian tube, or primary peritoneal malignancies. Using our databases, we identified patients treated with bevacizumab combination therapy since June 2005. Responses were evaluated with Response evaluation Criteria in Solid tumors and serum CA125 Rustin criteria. Toxicity was assessed according to the Common toxicity Criteria (CTC) v.3.0. Data from 64 patients were included. The median patient age was 58 years, and they had undergone a median of 4.5 (range, 1-10) prior cytotoxic chemotherapy regimens. The median length of follow-up was 8 months (range, 2-29). The most commonly used combinations were bevacizumab plus taxanes (26.6%) and plus cyclophosphamide (26.6%). A median of 4 cycles of therapy with a median bevacizumab dose of 3,600 mg (range, 500-18,240) were administered. An overall response rate of 21.3% was observed in 13 patients with partial response, and another 42.6% of patients had stable disease. Among the patients with elevated pretreatment serum CA125 concentration, an overall response rate of 46.3% (25/54) was observed according to modification of the Rustin criteria. Fifteen (23.4%) patients had grades 3 or 4 adverse events. Gastrointestinal perforations occurred in 2 (3.1%) patients. Seventeen (26.6%) patients had improved performance status scores. Bevacizumab combined with chemotherapy showed promising clinical benefits, with significant response of serum CA125 concentration and moderate adverse effects.

Emergency stenting of an acute internal carotid artery occlusion from spontaneous dissection.

SUMMARY: Internal carotid artery (ICA) dissection is an important cause of stroke in the younger population. Carotid stenting with or without angioplasty is usually the preferred treatment for symptomatic patients who have failed medical therapy. We report a case of a symptomatic internal carotid artery dissection at the petrous segment of the ICA initially treated conservatively with anticoagulation and antiplatlet agents. Due to early clinical deterioration from near complete carotid occlusion without adequate cross over flow, the patient underwent emergency stenting of the ICA. Post procedure angiography demonstrated no residual stenosis of the ICA. The patient progressively improved and at six months followup, the patient had no further symptoms, a normal neurological examination and improvement in the imaging findings. The successful clinical result in our case of ICA stenting for dissection as a 'hemispheric rescue' contributes to the growing literature of endovascular management of carotid dissection. The excellent mid term follow-up confirms the efficacy of this treatment for a dominant ICA.

Circulating levels of beta2-glycoprotein I in thrombotic disorders and in inflammation.

Beta2-glycoprotein I (beta2GPI) is a plasma protein suspected to have a role in inhibition of thrombosis. This suspicion is reinforced by the observation that beta2GPI is the major target for autoantibodies in the antiphospholipid syndrome. However, little is known about its circulating levels in common thrombotic diseases or inflammation. We measured beta2GPI levels in 344 healthy controls, 58 normal pregnancies, 102 patients with non-haemorrhagic stroke, 121 patients with acute coronary syndrome and 200 patients with elevated C-reactive protein (CRP). In healthy individuals, we found a strong positive correlation between age and beta2GPI concentration (r = 0.274, P < 0.001) and that beta2GPI levels fall significantly after the eighth week of pregnancy (P = 0.002). We also found significantly reduced levels of beta2GPI in patients with stroke and in elderly patients with myocardial syndrome (P = 0.013 and 0.043). However, in neither group did beta2GPI levels change in the following six months, suggesting that the reduced levels were not a transient post-event phenomenon. In patients with inflammation, beta2GPI levels showed a significant negative correlation with CRP (r = -0.284, P < 0.001) and positively correlated with albumin and transferrin (r = 0.372 and 0.453, respectively with P < 0.001 for both). Furthermore, the largest reduction in beta2GPI levels occurred in patients with the highest CRP values (P < 0.001).

Patient and hospital delays in acute ischaemic stroke in a Dublin teaching hospital.

A limiting factor for thrombolysis in ischaemic stroke is delayed presentation to hospital. Prolonged A&E stay and delayed rehabilitation affects care. We evaluated the delay in presentation, A&E stay and rehabilitation delivery in 117 consecutive stroke patients. The mean presentation delay was 16.0 +/- 23.7 hours. A prior history of TIA or stroke, a reduced Glascow Coma Scale and larger strokes were associated with shorter delays to presentation. Longer delays occurred in patients living alone. The mean time spent in A&E was 11 hours, those with larger strokes spent shorter time. There were significant delays in referral to, and assessment by certain rehabilitation disciplines. Delayed presentation in stroke is a barrier to thrombolysis. Increasing public awareness may reduce this delay. In addition, prolonged A&E stay and delayed rehabilitation may adversely affect management, outcome and duration of hospital stay. Further study is required to investigate the reasons and possible solutions for such deficiencies.

Clinical outcomes of bacteremic pneumococcal pneumonia in the era of antibiotic resistance.

Limited data are available about the impact of antimicrobial resistance on clinical outcomes in cases of pneumococcal pneumonia. This was studied in 146 persons hospitalized with invasive pneumonia due to Streptococcus pneumoniae (minimum inhibitory concentration of cefotaxime, > or = .25 microg/mL) who were identified through population-based active surveillance for the period of November 1994 through April 1996. Compared with matched control subjects who had infection with more-susceptible S. pneumoniae, the proportion of subjects who died or who were admitted to an intensive care unit did not differ significantly. Multivariable analysis showed no significant contribution of antimicrobial resistance to mortality or the requirement for care in an intensive care unit. The ability to detect an effect of antimicrobial resistance on these important outcome measures may have been influenced by aggressive multidrug empirical therapy in this group of hospitalized patients. Factors other than resistance, such as severity of illness at presentation and advance directive status ("do not resuscitate" orders), appear to have a stronger influence on pneumococcal pneumonia outcomes.

Traumatic bilateral carotid dissection with concomitant cerebral infarction.

A 40-year-old man presented with a major nondominant hemisphere stroke syndrome after a road traffic accident. Cranial computed tomography scan revealed an extensive right hemisphere infarction involving the entire anterior and middle cerebral artery territories. Duplex Doppler ultrasound and cerebral angiography revealed bilateral internal carotid artery dissection with evidence of underlying fibromuscular dysplasia. Anticoagulation with heparin was commenced despite the coexisting large cerebral infarction, with the objective of protecting the uninjured but at-risk left cerebral hemisphere from ischemic injury. Patients with multiple cerebral arterial dissections complicated by cerebral infarction present a significant management dilemma. Our literature review revealed a lack of clear management guidelines for such cases.

Evaluation of stroke management in an Irish university teaching hospital: the Royal College of Physicians stroke audit package.

BACKGROUND: There are few data regarding the standard of stroke care in Ireland. AIM: To investigate the level of documentation for 13 key areas of stroke management. METHODS: Using a validated stroke audit package, this study reviewed the medical records of 100 consecutive patients hospitalised with acute stroke. RESULTS: Documentation of stroke symptoms, risk factors, general examination and investigations (cranial computer tomography [CT] and carotid Dopplers) were satisfactory. Neurological documentation was variable, with power (87%), sensation (70%) and eye movements (63%) being the most frequently recorded features, while cognition (3%), visual fields (13%), gait (7%), incontinence (1%) and swallowing (0%) were infrequently recorded. Diagnostic formulation and an acute management plan were documented in less than half of patients, whereas cranial CT (93%) and carotid Dopplers (93%) were well documented. Secondary preventive measures were documented in two-thirds of patients at follow-up. CONCLUSIONS: These results serve as a baseline from which to initiate and monitor improvements in the service at our hospital, including the involvement of neurologists in stroke care, and will also allow assessment of the impact of such changes.

The role of routine laboratory studies and neuroimaging in the diagnosis of dementia: a clinicopathological study.

OBJECTIVE: To determine the neuropathological diagnoses of longitudinally followed patients with potentially reversible causes of dementia and to examine the results of the "dementia work-up," especially neuroimaging, by comparison with the pathological diagnosis. DESIGN: A neuropathologic series of 61 consecutive patients, with review of clinical, laboratory, neuroimaging, and pathological results. RESULTS: Of the 61 patients, forty-eight (79%) had a clinical diagnosis of probable or possible Alzheimer's disease (AD). Compared with the pathological diagnosis, the sensitivity and specificity of the clinical diagnosis of AD were 96% and 79%, respectively. Of the 61 patients, 9 had abnormal laboratory tests, the correction of which did not improve the subsequent course. These patients were found to have AD8 and frontotemporal dementia on pathology. In two patients, neuroimaging was helpful in the clinical diagnoses of frontotemporal dementia and progressive supranuclear palsy (PSP). Neuroimaging revealed cerebrovascular disease in 18 patients, only two of whom were suspected clinically. Pathology confirmed AD in 17 and PSP in 1 of these patients. Sensitivity and specificity for the clinical diagnosis of cerebrovascular disease in comparison with pathology were 6% and 98%, respectively. With the added information from neuroimaging, that sensitivity increased to 59% and specificity decreased to 81%. CONCLUSIONS: All cases with abnormal laboratory or neuroimaging results had AD or some other neurodegenerative disease on pathology. The "dementia work-up" did not reveal any reversible causes for dementia in this group of patients. Neuroimaging may have a role, especially in the diagnosis of possible AD with concomitant cerebrovascular disease.

Frequency and clinical determinants of dementia after ischemic stroke.

OBJECTIVE: To investigate the frequency and clinical determinants of dementia after ischemic stroke. METHODS: The authors administered neurologic, neuropsychological, and functional assessments to 453 patients (age 72.0 +/- 8.3 years) 3 months after ischemic stroke. They diagnosed dementia using modified Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised criteria requiring deficits in memory and two or more additional cognitive domains as well as functional impairment. RESULTS: The authors diagnosed dementia in 119 of the 453 patients (26.3%). Regarding dementia subtypes, 68 of the 119 patients (57.1%) were diagnosed with vascular dementia, 46 patients (38.7%) were diagnosed with AD with concomitant stroke, and 5 patients (4.2%) had dementia for other reasons. Logistic regression suggested that dementia was associated with a major hemispheral stroke syndrome (OR 3.0), left hemisphere (OR 2.1) and right hemisphere (OR 1.8) infarct locations versus brainstem/cerebellar locations, infarcts in the pooled anterior and posterior cerebral artery territories versus infarcts in other vascular territories (OR 1.7), diabetes mellitus (OR 1.8), prior stroke (OR 1.7), age 80 years or older (OR 12.7) and 70 to 79 years (OR 3.9) versus 60 to 69 years, 8 or fewer years of education (OR 4.1) and 9 to 12 years of education (OR 3.0) versus 13 or more years of education, black race (OR 2.6) and Hispanic ethnicity (OR 3.1) versus white race, and northern Manhattan residence (OR 1.6). CONCLUSIONS: Dementia is frequent after ischemic stroke, occurring in one-fourth of the elderly patients in the authors' cohort. The clinical determinants of dementia include the location and severity of the presenting stroke, vascular risk factors such as diabetes mellitus and prior stroke, and host characteristics such as older age, fewer years of education, and nonwhite race/ethnicity. The results also suggest that concomitant AD plays an etiologic role in approximately one-third of cases of dementia after stroke.

Clinical outcomes of meningitis caused by Streptococcus pneumoniae in the era of antibiotic resistance.

Limited data are available on clinical outcomes of meningitis due to cefotaxime-nonsusceptible Streptococcus pneumoniae. We analyzed data from 109 cases of pneumococcal meningitis in Atlanta, Baltimore, and San Antonio, which were identified through population-based active surveillance from November 1994 to April 1996. Pneumococcal isolates from 9% of the cases were resistant to cefotaxime, and isolates from 11% had intermediate susceptibility. Children were more likely to have cephalosporin-nonsusceptible pneumococcal meningitis, but mortality was significantly higher among adults aged 18-64 years. Vancomycin was given upon admission to 29% of patients, and within 48 h of admission to 52%. Nonsusceptibility to cefotaxime was not associated with the following outcomes: increased mortality, prolonged length of hospital or intensive care unit (ICU) stay, requirement of intubation or oxygen, ICU care, discharge to another medical or long-term-care facility, or neurological deficit. Empirical use of vancomycin, current prevalence of drug-resistant S. pneumoniae, and degree of nonsusceptibility to cefotaxime may have influenced these findings.

The cognitive syndrome of vascular dementia: implications for clinical trials.

Dementia is common among patients with cerebrovascular disease, particularly in a setting of one or more clinically evident strokes. Prior cohort and case studies have suggested that the cognitive syndrome of vascular dementia is characterized by predominant executive dysfunction, in contrast to the deficits in memory and language function that are typical of patients with Alzheimer disease. The course of cognitive decline may also differ between those dementia subtypes, with many, but not all, patients with vascular dementia exhibiting a stepwise course of decline caused by recurrent stroke and most patients with Alzheimer disease exhibiting a gradually progressive course of decline. The findings of prior studies of the cognitive syndrome of vascular dementia must be interpreted with caution, however, because of (1) possible inaccuracies in the determination of the dementia subtype and the loss of precision that might result from pooling heterogeneous subgroups of patients with vascular dementia, (2) difficulties inherent in identifying a pattern of strengths and weaknesses in patients who are required to have memory impairment and other deficits to meet operationalized criteria for dementia, and (3) the use of limited test batteries whose psychometric properties are incompletely understood. Specific questions that should be addressed by future studies are discussed.

An outbreak of acute respiratory disease caused by Mycoplasma pneumoniae and adenovirus at a federal service training academy: new implications from an old scenario.

Outbreaks of Mycoplasma pneumoniae and adenovirus have been reported in military institutions for several decades. During a recent outbreak in a federal service training academy, we performed an epidemiological and laboratory investigation to better characterize and control the outbreak. Of 586 students responding to a questionnaire, 317 (54%) reported having a respiratory illness during the outbreak period. Among 42 students who underwent complete laboratory testing, 24 (57%) had evidence of M. pneumoniae infection, 8 (19%) had evidence of adenovirus infection, and 4 (10%) had evidence of both. Polymerase chain reaction testing of oropharyngeal swabs revealed more acute M. pneumoniae infections (57% positive) than did serology or culture. Multivariate analysis revealed that visiting the campus health clinic >3 times for a nonrespiratory condition, such as injury, was a significant risk factor for illness among freshmen early in the course of the outbreak, whereas having an ill roommate was a risk factor throughout the duration of the outbreak.