Multiple drivers of decline in the global status of freshwater crayfish (Decapoda: Astacidea)

International audienceRates of biodiversity loss are higher in freshwater ecosystems than in most terrestrial or marine ecosystems, making freshwater conservation a priority. However, prioritization methods are impeded by insufficient knowledge on the distribution and conservation status of freshwater taxa, particularly invertebrates. We evaluated the extinction risk of the world's 590 freshwater crayfish species using the IUCN Categories and Criteria and found 32% of all species are threatened with extinction. The level of extinction risk differed between families, with proportionally more threatened species in the Parastacidae and Astacidae than in the Cambaridae. Four described species were Extinct and 21% were assessed as Data Deficient. There was geographical variation in the dominant threats affecting the main centres of crayfish diversity. The majority of threatened US and Mexican species face threats associated with urban development, pollution, damming and water management. Conversely, the majority of Australian threatened species are affected by climate change, harvesting, agriculture and invasive species. Only a small proportion of crayfish are found within the boundaries of protected areas, suggesting that alternative means of long-term protection will be required. Our study highlights many of the significant challenges yet to come for freshwater biodiversity unless conservation planning shifts from a reactive to proactive approach

Inhaled dry powder apomorphine (VR040) for 'off ' periods in Parkinson's disease: an in-clinic double-blind dose ranging study

Background: ‘Off’ periods increase as Parkinson's disease (PD) progresses and the benefits of standard therapy wane. Subcutaneous apomorphine rescues ‘off’ periods, but patient self‐injection and adverse cutaneous effects are sometimes problematic. Methods: We assessed safety, tolerability and efficacy of inhaled dry powder apomorphine (VR040) in a double‐blind clinic‐based Phase II study. Of 48 patients recruited at nine sites, 47 were randomized 2:1 inhaled apomorphine/placebo. Respirable doses (drug predicted to reach the lung), ascending through 1.5, 2.3, 3.0 and 4.0 mg until efficacy was achieved, were administered to patients in a practically defined ‘off’ state. The primary endpoint was the response in unified PD rating scale Part 3 (UPDRS 3), at the highest dose received by the patient. Secondary endpoints included time to ‘on’, the proportion of patients converting from ‘off’ to ‘on’, and duration of ‘on’. Results: In the 47 intent‐to‐treat patients with PD, mean age 60.6 years, the mean UPDRS 3 improvement was significantly greater for VR040 at 26.8 points (standard deviation 12.0), vs 14.9 (16.3) for placebo (treatment difference 11.6, 95% confidence interval 2.3–20.9, P = 0.016). Rapid apomorphine absorption (2–7 min) translated to rapid (mean 10 min) reversal from the ‘off’ state. Adverse effects did not differ between VR040 and placebo; no patient discontinued due to an adverse event; one serious adverse event (constipation) in the VR040 group was considered unrelated to trial medication. Conclusions: Inhaled apomorphine shows significant promise as a replacement for intermittent subcutaneous injections; further studies are appropriate to optimize efficacy and tolerability

Phase IIa randomized double-blind, placebo-controlled study of inhaled apomorphine as acute challenge for rescuing 'off' periods in patients with established Parkinson's disease

Background and purpose: In this first study of inhaled apomorphine (VR040) in patients with Parkinson's disease, the primary objective was to find the minimum efficacious dose of apomorphine that was useful in rescuing patients during ‘off’ periods. Safety, tolerability and pharmacokinetics of inhaled apomorphine were assessed during the study. Methods: A double‐blind, placebo‐controlled, randomized trial of three escalating single doses of inhaled apomorphine (0.2, 0.5 and 0.8 mg fine particle dose) versus placebo (3 : 1 active:placebo) was performed. Parkinson's motor severity assessments by a clinician, and disease state assessment by the patient, were performed at baseline during an ‘off’ state, and at specified times after test drug administration. Safety assessments (including vital signs, electrocardiogram and forced expiratory volume) were performed, and plasma apomorphine levels measured. Results: All 24 patients completed the study, and considering the three dose levels together, inhaled apomorphine did not significantly increase the proportion of patients switching from ‘off’ to ‘on’ (0/6 at 0.2 mg, 3/6 at 0.5 mg and 2/6 at 0.8 mg vs. 1/6 for placebo), or decrease the time from ‘off’ to ‘on’ post‐treatment (10 min for 0.5 mg, 40 min for 0.8 mg, vs. 20 min for placebo). However, there was a suggestion of benefit at the higher doses (5/12 switched ‘on’ at the 0.5 or 0.8 mg doses, vs. 1/6 for placebo). There were no serious adverse events and treatment was well tolerated. Peak plasma concentration was 1–3 min post‐dose, and plasma level dose proportionality was observed. Conclusions: Inhaled apomorphine was safe and well tolerated at the doses tested for an acute challenge to rescue ‘off’ periods, but efficacy at these doses was limited. A follow‐up study at higher doses is appropriate given these initial findings

Measuring therapy adherence in Parkinson's disease: a comparison of methods

The objective of this study was to assess different methods of measuring therapy adherence in Parkinson's disease (PD). In a single centre observational study, 112 patients with idiopathic PD were randomised to a crossover trial of active monitoring (n = 69, simple tablet count and electronic monitoring), or to no monitoring (n = 43, control group). All patients completed a self report and visual analogue scale (VAS) indicating therapy intake. In the active monitoring group, 56 (81% of cases) used ⩾80% of their medication, and 13 (19% of cases) used <80%, based on electronic monitoring. Median adherence for self report was 100% (interquartile range (IQR) 100 to 100) and for VAS was 100% (IQR 95 to 100), in both active and control groups. Patients taking ⩾80% of prescribed medication had a median total adherence of 98% (IQR 93 to 101) by electronic monitoring, which was similar to that from other methods: self report 100%, IQR 100 to 100; VAS 100%, IQR 95 to 100; simple tablet count 98%, IQR 89 to 100. Median total adherence in patients taking <80% of medication was significantly lower by electronic monitoring (69%, IQR 44 to 74) than by other methods: self report 100%, IQR 100 to 100; VAS 100%, IQR 95 to 100; and simple tablet count 90%, IQR 78 to 100 (all p<0.0001). Sensitivities of self report (10%), VAS (17%), and simple tablet count (50%) were all low for detecting suboptimal medicine intake. Self report, VAS, and simple tablet counts are insensitive as predictors of suboptimal medicine usage in PD. How patients take their medicines influences interpretation of the therapy response and consequent management decisions, with implications for clinical trial analysis and clinical practice

Alpha-synuclein in peripheral tissues and body fluids as a biomarker for Parkinson's disease - a systematic review

Parkinson's disease (PD) is neuropathologically characterized as an alpha‐synucleinopathy. Alpha‐synuclein‐containing inclusions are stained as Lewy bodies and Lewy neurites in the brain, which are the pathological hallmark of PD. However, alpha‐synuclein‐containing inclusions in PD are not restricted to the central nervous system, but are also found in peripheral tissues. Alpha‐synuclein levels can also be measured in body fluids. The aim of this study was to conduct a systematic review of available evidence to determine the utility of alpha‐synuclein as a peripheral biomarker of PD. We searched PubMed (1948 to 26 May 2013), Embase (1974 to 26 May 2013), the Cochrane Library (up to 26 May 2013), LILACS (up to 26 May 2013) and CINAHL (up to 26 May 2013) for the studies of alpha‐synuclein in peripheral tissues or body fluids in PD. A total of 49 studies fulfilled the search criteria. Peripheral tissues such as colonic mucosa showed a sensitivity of 42–90% and a specificity of 100%; submandibular salivary glands showed sensitivity and specificity of 100%; skin biopsy showed 19% sensitivity and 80% specificity in detecting alpha‐synuclein pathology. CSF alpha‐synuclein had 71–94% sensitivity and 25–53% specificity for distinguishing PD from controls. Plasma alpha‐synuclein had 48–53% sensitivity and 69–85% specificity. Neither plasma nor CSF alpha‐synuclein is presently a reliable marker of PD. This differs from alpha‐synuclein in solid tissue samples of the enteric and autonomic nervous system, which offer some potential as a surrogate marker of brain synucleinopathy

Baseline [123I]FP-CIT SPECT (DaTSCAN) severity correlates with medication use at 3 years in Parkinson's disease

Background: Presynaptic dopaminergic deficiency on dopamine transporter imaging supports a clinical diagnosis of Parkinson's disease and correlates with the severity of rigidity and bradykinesia. Baseline dopaminergic deficiency predicts clinical severity, but the relationship with subsequent medication use has not been reported.&lt;p&gt;&lt;/p&gt; Methods: A randomly selected cross section of 83 Parkinson's disease (PD) patients who had [123I] FP-CIT SPECT at the time of clinical diagnosis was identified. Dopaminergic deficiency was graded 1, 2 or 3 with increasing severity using visual assessment and by semiquantitative analysis of putamen and caudate uptake. Antiparkinson medication usage and clinical severity by Hoehn and Yahr were noted annually to 3 years.&lt;p&gt;&lt;/p&gt; Results: In 83 patients (66% male, median age 65.0 years, IQ 55.4–71.8), [123I]FP-CIT SPECT was grade 1 in 20 (24%), grade 2 in 53 (64%) and grade 3 in 10 patients (12%). Dopamine transporter uptake ratios were inversely associated with antiparkinson medication usage (r = −0.26, P = 0.0201) and Hoehn Yahr stage (r = −0.32, P = 0.0029) at 3 years from baseline, but there was considerable variation in drug usage in individual patients. At 3 years, patients with grade 1 scans at baseline received a median dose of 325 levodopa equivalent units (LEU) (interquartile range 175–433); grade 2 scan patients 400 LEU (interquartile range 300–635); and grade 3 scan patients 460 LEU (interquartile range 252–658).&lt;p&gt;&lt;/p&gt; Conclusion: The degree of reduction in presynaptic dopaminergic uptake at baseline is associated with higher antiparkinson drug dosage at follow-up, but the wide variation means that the baseline FP-CIT SPECT does not reliably predict drug use in individual cases

Dopamine agonists and pathological gambling

No abstract available