Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy.

BACKGROUND: Venous thromboembolism (VTE) often complicates the clinical course of cancer. The risk is further increased by chemotherapy, but the trade-off between safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. This is the second update of a review first published in February 2012. OBJECTIVES: To assess the efficacy and safety of primary thromboprophylaxis for VTE in ambulatory cancer patients receiving chemotherapy compared with placebo or no thromboprophylaxis. SEARCH METHODS: For this update the Cochrane Vascular Information Specialist searched the Cochrane Vascular Group Specialised Register (June 2016). In addition, the Information Specialist searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 5). Clinical trials registries were searched up to June 2016. SELECTION CRITERIA: Randomised controlled trials comparing any oral or parenteral anticoagulant or mechanical intervention to no thromboprophylaxis or placebo, or comparing two different anticoagulants. DATA COLLECTION AND ANALYSIS: We extracted data on methodological quality, participant characteristics, interventions, and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively. MAIN RESULTS: We identified five additional randomised controlled trials (2491 participants) in the updated search, considering in this update 26 trials with a total of 12,352 participants, all evaluating pharmacological interventions and performed mainly in people with locally advanced or metastatic cancer. The quality of the evidence ranged from high to very low across the different outcomes and comparisons. The main limiting factors were imprecision and risk of bias. One large trial of 3212 participants found a 64% (risk ratio (RR) 0.36, 95% confidence interval (CI) 0.22 to 0.60) reduction of symptomatic VTE with the ultra-low molecular weight heparin (uLMWH) semuloparin relative to placebo, with no apparent difference in major bleeding (RR 1.05, 95% CI 0.55 to 2.00). When compared with no thromboprophylaxis, LMWH significantly reduced the incidence of symptomatic VTE (RR 0.54, 95% CI 0.38 to 0.75; no heterogeneity, Tau2 = 0.00%) with a non-statistically significant 44% higher risk of major bleeding events (RR 1.44, 95% CI 0.98 to 2.11). In participants with multiple myeloma, LMWH was associated with a significant reduction in symptomatic VTE compared with the vitamin K antagonist warfarin (RR 0.33, 95% CI 0.14 to 0.83), while the difference between LMWH and aspirin was not statistically significant (RR 0.51, 95% CI 0.22 to 1.17). Major bleeding was observed in none of the participants treated with LMWH or warfarin and in less than 1% of those treated with aspirin. Only one study evaluated unfractionated heparin against no thromboprophylaxis but did not report on VTE or major bleeding. When compared with placebo, warfarin was associated with a non-statistically significant reduction of symptomatic VTE (RR 0.15, 95% CI 0.02 to 1.20). Antithrombin, evaluated in one study involving paediatric patients, had no significant effect on VTE or on major bleeding when compared with no antithrombin. The direct oral factor Xa inhibitor apixaban was evaluated in a phase II dose-finding study that suggested a low rate of major bleeding (2.1% versus 3.4%) and symptomatic VTE (1.1% versus 13.8%) in comparison with placebo. AUTHORS' CONCLUSIONS: In this second update, we confirmed that primary thromboprophylaxis with LMWH significantly reduced the incidence of symptomatic VTE in ambulatory cancer patients treated with chemotherapy. In addition, the uLMWH semuloparin, which is not commercially available, significantly reduced the incidence of symptomatic VTE. The risk of major bleeding associated with LMWH, while not reaching statistical significance, suggest caution and mandate additional studies to determine the risk-to-benefit ratio of LMWH in this setting. Despite the encouraging results of this review, routine prophylaxis in ambulatory cancer patients cannot be recommended before safety issues are adequately addressed. We need additional studies investigating targeted primary prophylaxis in people with specific types or stages of cancer associated with a higher risk of VTE.

A Comparison of Copromicroscopic and Molecular Methods for the Diagnosis of Cat Aelurostrongylosis.

The gold standard method for the diagnosis of cat aelurostrongylosis is the detection of Aelurostrongylus abstrusus first stage larvae with the Baermann's examination. Nevertheless, molecular assays have shown higher diagnostic performances compared to copromicroscopy. This study evaluated the usefulness of an A. abstrusus species-specific PCR on different biological samples collected in clinical settings from 100 privately-owned cats in Italy (n. 60) and Greece (n. 40). A fecal sample was collected from each animal and a pharyngeal swab was also obtained for cats from Italy. All stool samples were subjected to flotation and Baermann's test. The cats were categorized in three groups based on the results of copromicroscopy, i.e., Group A (n. 50 cats with A. abstrusus infection regardless of positivity for other helminths), Group B (n. 25 cats negative for A. abstrusus but positive for at least one of any other helminth), Group C (n. 25 cats negative for any helminth). DNA was extracted from individual aliquots of feces, flotation supernatant, Baermann's sediment and the pharyngeal swab and then subjected to a PCR specific for A. abstrusus. At least one fecal aliquot or the pharyngeal swab scored positive by the A. abstrusus-specific PCR for 48/50 (96%) cats enrolled in Group A; in particular, 38/50 (76%), 35/50 (70%), 41/50 (82%) and 21/25 (84%) DNA extracts from feces, flotation supernatant, Baermann's sediment and pharyngeal swabs were positive by PCR. These results confirm that molecular tools are highly sensitive and specific and indicate that pharyngeal swabs are the most suitable sample for molecular analysis in clinical settings.

Simultaneous Exposure to Angiostrongylus vasorum and Vector-Borne Pathogens in Dogs from Italy.

Several drivers have recently fostered the expansion of Angiostrongylus vasorum throughout Europe, where Vector-Borne Pathogens (VBPs) are also spreading. However, the level of simultaneous risk of infection is still unknown in canine populations. This study evaluated the simultaneous exposure to A. vasorum and major canine VBPs in dogs of Italy. Sera of 294 dogs were subjected to two ELISAs, detecting A. vasorum circulating antigens and antibodies against the parasite, and to the following assays: (i) SNAP® 4DX (IDEXX Laboratories Inc.) detecting Dirofilaria immitis antigens, and antibodies vs. Borrelia burgdorferi, Anaplasma spp. and Ehrlichia spp. and (ii) IFAT for the detection of antibodies vs. Leishmania infantum, Babesia canis and Rickettsia conorii. Twenty-two (7.5%, CI: 4.8-11.1%) and six (2%, CI: 0.7-4.4%) dogs scored positive for circulating A. vasorum antibodies and antigens, respectively. Seventeen dogs (5.8%, CI: 3.4-9.1%) were positive for A. vasorum antibodies + at least one VBP, three (1%, CI: 0.2-3%) for A. vasorum antigen + at least one VBP, while one dog (0.3%, CI: 0.01-1.88%) was positive for A. vasorum antigen + A. vasorum antibodies + B. canis antibodies. These results show that dogs living in different regions of Italy are at risk of simultaneous infections with both A. vasorum and VBPs. Despite the same scenario being likely in other countries of Europe, the current knowledge is scant. Therefore, further studies are warranted to amplify current epizootiological information and to understand whether control programs should be improved.

Highly Variable Clinical Pictures in Dogs Naturally Infected with Angiostrongylus vasorum.

Canine angiostrongylosis by Angiostrongylus vasorum is increasingly reported in both enzootic and previously free areas. The complex pathogenesis of the disease makes the clinical workup challenging. Infected dogs show highly variable clinical pictures, characterized by subclinical to life-threatening general, cardio-respiratory, neurological and/or gastrointestinal signs. The present study reports the high variability of clinical pictures from 36 dogs across central and southern Italy that were naturally infected by A. vasorum. Of them, 23 (63.9%) presented at least one clinical sign, while 13 (36.1%) were subclinically infected and apparently healthy. Overall, 19 dogs (52.8%) showed cardiorespiratory signs, 14 (38.9%) had non-specific abnormalities, 2 (5.6%) presented coagulation disorders and 1 (2.8%) had a severe neurological condition. Importantly, four dogs presenting with clinical signs had neither cough nor dyspnea. These results underline that angiostrongylosis should be included in the differential diagnosis, even when dogs display only non-specific clinical signs. The proportion of apparently healthy dogs highlights the relevance of routine copromicroscopic and/or antigenic tests in enzootic areas to avoid the sudden onset of potentially life-threatening signs.

Exposure to Major Vector-Borne Diseases in Dogs Subjected to Different Preventative Regimens in Endemic Areas of Italy.

Vector-borne diseases (VBDs) are globally widespread arthropod-transmitted diseases with a significant impact on animal and human health. Many drivers have recently spurred the geographic spread of VBDs in dogs. This study has evaluated the exposure to most important VBDs in dogs under different preventative treatments in different regions of Italy, i.e., Veneto, Friuli Venezia-Giulia, Umbria, Giglio Island (Tuscany), Abruzzo and Latium. Serological analyses were performed to detect antibodies against Leishmania infantum, Babesia canis, Anaplasma phagocytophilum/Anaplasma platys, Ehrlichia canis/Ehrlichia ewingii, Borrelia burgdorferi, Rickettsia conorii and the circulating antigen of Dirofilaria immitis. Dogs were categorized according to the treatment schedule usually received, and the association between seropositivity and possible risk factors was statistically evaluated. Overall, 124/242 (51.2%) dogs tested positive for at least one pathogen, while 34 (14.0%) were exposed to two or more pathogens. The most detected seropositivity was against R. conorii, followed by Anaplasma spp., L. infantum, B. canis, and the other pathogens under study. Significant statistical associations were found according to geographical provenance, history of tick infestation, lifestyle and inadequate prophylactic treatments. Random/irregular treatments have been identified as a clear risk factor. These results show that adequate prophylactic treatment protocols are overlooked by dog owners, despite the availability of several effective products, with possible implications in veterinary medicine and on public health.

Leishmania infantum Seroprevalence in Cats From Touristic Areas of Italy and Greece.

Leishmaniosis by Leishmania infantum is a major zoonotic Vector-Borne Disease (VBD) in terms of geographic distribution, pathogenicity and zoonotic potential. While dogs are the main reservoir of L. infantum, the infection in cats is poorly understood although increasingly reported from enzootic and non-enzootic areas. The Mediterranean basin is a key area for leishmaniosis and includes touristic spots that require continuous surveillance for VBDs in consideration of the growing tendency of tourists to travel with their pets. This study evaluated L. infantum seroprevalence in cats living in selected touristic localities of Italy and Greece. A total of 269 cat serum samples from three Sites i.e., 76, 40, and 153 from Adriatic Coast of Abruzzo, Italy (Site A), Giglio Island, Tuscany, Italy (Site B), and Mykonos Island, Greece (Site C), respectively, were included in the survey. Sera samples were subjected to an indirect immunofluorescence antibody assay for the detection of anti-L. infantum specific IgG. Associations between possible risk factors and seropositivity to L. infantum were statistically evaluated. Antibodies against L. infantum were detected in eight out of 269 (3.0%) cats tested i.e., 4/76 (5.3%), 1/40 (2.5%), and 3/153 (2.0%), from sites A, B, and C, respectively. A statistical association between anti-L. infantum antibodies and cohabitation with dogs was shown. This study indicates that feline populations living in the examined Italian and Greek touristic areas are exposed to L. infantum and that they may contribute to the circulation of L. infantum, enhancing the risk of infection for dogs and humans.

Occurrence of canine and feline extra-intestinal nematodes in key endemic regions of Italy.

Extra-intestinal nematodes of companion animals are of growing concern in veterinary medicine for their pathogenic potential and the current expansion throughout Europe. The present study has evaluated the occurrence of major canine and feline extra-intestinal nematodes in regions of Italy having epidemiological relevance. Associations of various recorded parameters related to the examined animals have been statistically evaluated, along with a comparative analysis with the most recent epidemiological data. Overall, 1055 dogs and 1000 cats were tested. Among extra-intestinal nematodes Angiostrongylus vasorum was the most common in dogs followed by Capillaria aerophila and Dirofilaria spp.; Aelurostrongylus abstrusus was the most recorded parasite in cats, followed by C. aerophila and Troglostrongylus brevior. The statistical analysis revealed that outdoor access is associated with A. vasorum, A. abstrusus and T. brevior infections, that were also more prevalent in animals with cardio-respiratory signs. Moreover, cats aged less than 12 months had more chances to be infected by lungworms. The data herein presented confirm the occurrence and the possible risk of expansion of different extra-intestinal parasitoses of dogs and cats in Italy, underlining the importance of a constant epidemiologic vigilance and of appropriate control methods.

Microfilaricidal efficacy of a single administration of Advocate(®) (Bayer Animal Health) in dogs naturally infected with Dirofilaria immitis or Dirofilaria repens.

The present study evaluated the microfilaricidal efficacy of a single application of the spot-on containing imidacloprid 10%/moxidectin 2.5% (Advocate(®), Bayer Animal Health) in dogs naturally infected either by Dirofilaria immitis or Dirofilaria repens. Dogs living in north-eastern and central-southern Italy, endemic for D. immitis and D. repens respectively, were randomly screened. Sixteen animals, eight infected with D. immitis and eight with D. repens, and fulfilling inclusion criteria were enrolled. Dogs infected with D. immitis received an adulticide treatment prior to the study and Advocate(®) 3 weeks after. The animals were divided in blocks of two (1:1, T1:T2) animals each, where Day 0 (D0) had an interval of 15days to compare T2 vs. T1 dogs during the first fortnight of examination (i.e. T2 dogs acted as control animals at each examination). At baseline (Days -15 and 0 for T2 and T1 dogs, respectively) the animals had a range of microfilaraemia of 180-99.700mff/ml (D. immitis) and 60-750 mff/ml (D. repens). All animals received a topical administration of Advocate(®) at D0 and were examined for microfilariae with microscopic and molecular tests at D15, D30, D60 and D90. All animals scored negative for mff at the first control post-treatment and throughout the study, with the exception of two D. immitis- infected animals that had a 2 mff/ml count at D15, and then become negative from Day 30 onwards. No adverse events were observed. The present study demonstrates the safety and the high microfilaricidal efficacy (99.97% and 100% for D. immitis and D. repens, respectively) of a single dose of moxidectin contained in Advocate(®) in naturally infected dogs.

Dementia in patients with atrial fibrillation and the value of the Hachinski ischemic score.

AIM: To assess the prevalence of vascular dementia, mixed dementia and Alzheimer's disease in patients with atrial fibrillation, and to evaluate the accuracy of the Hachinski ischemic score for these subtypes of dementia. METHODS: A nested case-control study was carried out. A total of 103 of 784 consecutive patients evaluated for cognitive status at the Ambulatory Geriatric Clinic had a diagnosis of atrial fibrillation. Controls without atrial fibrillation were randomly selected from the remaining 681 patients using a 1:2 matching for sex, age and education. RESULTS: The prevalence of vascular dementia was twofold in patients with atrial fibrillation compared with controls (21.4% vs 10.7%, P = 0.024). Alzheimer's disease was also more frequent in the group with atrial fibrillation (12.6% vs 7.3%, P = 0.046), whereas mixed dementia had a similar distribution. The Hachinski ischemic score poorly discriminated between dementia subtypes, with misclassification rates between 46% (95% CI 28-66) and 70% (95% CI 55-83). In patients with atrial fibrillation, these rates ranged from 55% (95% CI 32-77) to 69% (95% CI 39-91%). In patients in whom the diagnosis of dementia was excluded, the Hachinski ischemic score suggested the presence of vascular dementia in 11% and mixed dementia in 30%. CONCLUSIONS: Vascular dementia and Alzheimer's disease, but not mixed dementia, are more prevalent in patients with atrial fibrillation. The discriminative accuracy of the Hachinski ischemic score for dementia subtypes in atrial fibrillation is poor, with a significant proportion of misclassifications.