Essential Tremor Prevalence is Low in the Druze Population in Northern Israel

Background: Essential tremor (ET) and Parkinson's disease (PD) are probably the most common movement disorders. As ethnic differences have been reported in ET, we designed the present study to evaluate the prevalence of ET and that of Parkinson's disease (PD) in the Druze villages of northern Israel. Methods: A two-phase, door-to-door survey was undertaken. Residents aged &ge;51 years who agreed to participate and answered &ldquo;yes&rdquo; to tremor or PD-related screening questions and 3% of subjects who screened negative were evaluated. Diagnostic criteria for ET were similar to those used in Sicilian and Spanish studies. PD was diagnosed according to Gelb's criteria. Results: The target population consisted of 9,086, the study cohort of 3,980 residents. Tremor was observed in 36 subjects. In 27, the tremor fully met the criteria for ET. The prevalence of ET (age &ge;65) was 1.49% (95% CI 0.91&ndash;2.07%). PD was diagnosed in 23 subjects. The prevalence of PD (age &ge;65) was 1.13 (95% CI 0.62&ndash;1.64%). Leucine-rich repeat protein kinase 2 (G2019S mutation) was evaluated in subjects diagnosed with tremor PD and those screened for assessment of the validity of the questionnaire. None carried the mutation. Discussion: The prevalence of ET in the Druze population is low and similar to the prevalence of PD.</div

Long-term effectiveness of unboosted atazanavir plus abacavir/lamivudine in subjects with virological suppression

Effectiveness data of an unboosted atazanavir (ATV) with abacavir/lamivudine (ABC/3TC) switch strategy in clinical routine are scant. We evaluated treatment outcomes of ATV + ABC/3TC in pretreated subjects in the EuroSIDA cohort when started with undetectable plasma HIV-1 viral load (pVL), performing a time to loss of virological response (TLOVR 50 copies/mL. We included 285 subjects, 67% male, with median baseline CD4 530 cells, and 44 months with pVL ≤50 copies/mL. The third drug in the previous regimen was ritonavir-boosted atazanavir (ATV/r) in 79 (28%), and another ritonavir-boosted protease inhibitor (PI/r) in 29 (10%). Ninety (32%) had previously failed with a PI. Proportions of people with virological success at 48/96/144 weeks were 90%/87%/88% (TLOVR) and 74%/67%/59% (snapshot analysis), respectively. The rates of VF were 8%/8%/6%. Rates of adverse events leading to study discontinuation were 0.4%/1%/2%. The multivariable adjusted analysis showed an association between VF and nadir CD4+ (hazard ratio [HR] 0.63 [95% confidence interval [CI]: 0.42-0.93] per 100 cells higher), time with pVL ≤50 copies/mL (HR 0.87 [95% CI: 0.79-0.96] per 6 months longer), and previous failure with a PI (HR 2.78 [95% CI: 1.28-6.04]). Resistance selection at failure was uncommon. A switch to ATV + ABC/3TC in selected subjects with suppressed viremia was associated with low rates of VF and discontinuation due to adverse events, even in subjects not receiving ATV/r. The strategy might be considered in those with long-term suppression and no prior PI failure

Aging and the evolution of comorbidities among HIV-positive individuals in a European cohort

Objectives: To describe changes in the prevalence of comorbidities and risk factors among HIV-positive individuals in the EuroSIDA study. Design: Comparison of two cross-sectional cohorts of HIV-positive adults under active follow-up in 2006 and 2014. Methods: Baseline demographics and prevalence of comorbidities were described. Factors associated with the prevalence of chronic kidney disease (CKD) and cardiovascular disease (CVD) were assessed by logistic regression modelling using generalized estimating equations. Results: Nine thousand, seven hundred and ninety-eight individuals were under active follow-up in EuroSIDA during 2006 and 12 882 during 2014. Compared with study participants in 2006, those in 2014 were older [median age 48.6 years (IQR 40.3-55.1) vs. 43.1 years (37.2-50.0) in 2006] and had higher prevalence of hypertension (59.6 vs. 47% in 2006), diabetes (6.3 vs. 5.4%), CKD (6.9 vs. 4.1%) and CVD (5.0 vs. 3.7%). Individuals in the 2014 cohort had higher odds for CKD (unadjusted OR 2.62, 95% CI 2.30-2.99, P &lt; 0.0001) and CVD (OR 1.88, CI 1.68-2.10, P &lt; 0.0001), but after multivariable adjustment for age group, comorbidities and other factors, year of cohort was no longer significantly associated with the odds of CKD [adjusted OR (aOR) 0.97, CI 0.52-1.82, P = 0.92) or of CVD (aOR 0.94, CI 0.54-1.63, P = 0.82). Conclusion: Between 2006 and 2014, the population aged and experienced an overall higher prevalence of non-AIDS comorbidities, including CKD and CVD. The increase in CVD could be explained by the aging population, and the increase in CKD by aging and changes in other factors. Treatment strategies balancing HIV outcomes with long-term management of comorbidities remain a priority.</p

Comparable long-term efficacy of Lopinavir/Ritonavir and similar drug-resistance profiles in different HIV-1 subtypes.

BACKGROUND: Analysis of potentially different impact of Lopinavir/Ritonavir (LPV/r) on non-B subtypes is confounded by dissimilarities in the conditions existing in different countries. We retrospectively compared its impact on populations infected with subtypes B and C in Israel, where patients infected with different subtypes receive the same treatment. METHODS: Clinical and demographic data were reported by physicians. Resistance was tested after treatment failure. Statistical analyses were conducted using SPSS. RESULTS: 607 LPV/r treated patients (365 male) were included. 139 had HIV subtype B, 391 C, and 77 other subtypes. At study end 429 (71%) were receiving LPV/r. No significant differences in PI treatment history and in median viral-load (VL) at treatment initiation and termination existed between subtypes. MSM discontinued LPV/r more often than others even when the virologic outcome was good (p = 0.001). VL was below detection level in 81% of patients for whom LPV/r was first PI and in 67% when it was second (P = 0.001). Median VL decrease from baseline was 1.9±0.1 logs and was not significantly associated with subtype. Median CD4 increase was: 162 and 92cells/µl, respectively, for patients receiving LPV/r as first and second PI (P = 0.001), and 175 and 98, respectively, for subtypes B and C (P<0.001). Only 52 (22%) of 237 patients genotyped while under LPV/r were fully resistant to the drug; 12(5%) were partially resistant. In48%, population sequencing did not reveal resistance to any drug notwithstanding the virologic failure. No difference was found in the rates of resistance development between B and C (p = 0.16). CONCLUSIONS: Treatment with LPV/r appeared efficient and tolerable in both subtypes, B and C, but CD4 recovery was significantly better in virologically suppressed subtype-B patients. In both subtypes, LPV/r was more beneficial when given as first PI. Mostly, reasons other than resistance development caused discontinuation of treatment

Viral load and CD4 counts at the beginning and the end of the study.

<p>Patients were grouped as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086239#pone-0086239-t003" target="_blank">Table 3</a>. The median of the individual CD4 changes, ΔCD4, was calculated for each group (rather than the difference between the medians of CD4 counts). Selected <i>p</i>-values between relevant groups are shown. Significant differences between groups in other parameters were not found.</p><p>Abbreviations: 1st_PI – patients receiving LPV/r as first PI; 2nd _PI – patients receiving LPV/r as second or higher-order PI; B – patients with HIV subtype B; C – patients with HIV subtype C; C_M – male patients with subtype C; F –female; F-UP – follow up, time from diagnosis to start of the study, in years; M– male; MSM – men who have sex with Men; non-BC- patients with HIV subtype other than subtype B or C; PI – protease inhibitor; VL – viral load; a</p><p><i>p</i> values were calculated between groups in the box. The C or non-BC groups were compared to the B group.</p>b<p>the median values of the individual ΔCD4 values of patients.</p

Clinical outcome of LPV/r treatment of patients stratified according to different VL and CD4 levels at baseline.

<p>Patients were stratified according to VL: above 100,000 cp/ml; between 10 and 100 thousands cp/ml and below 10,000 cp/ml when starting LPV/r. Each group was further divided according to baseline CD4 count: below 200 cells/µl; between 200 and 500 cells/µl and above 500 cell/µl, creating altogether 9 groups. Group 9 (VL below 10,000 cp/ml and CD4 counts more than 500 cell/µl) was significantly different from the other groups in two parameters: shorter time on LPV/r treatment and lower percent of patients receiving LPV/r as first PI. As the median VL of this group was initially below detection level and baseline CD4 count above 700, no further decline in viral load could be observed and the lack of further increase in CD4 was also expected.</p><p>cp/ml – copies/ml; Gr – group; VL –Viral Load.</p

Side effects and other reasons for stopping LPV/r treatment.

<p>(A) Reasons for stopping LPV/r treatment as reported by physicians. Although samples from 31 patients were resistant to LPV/r, only for 14 it was the only reason for stopping the treatment. Technical reasons include refrigeration problems, inability to increase volume of syrup, travel, unavailability for follow-up, <i>etc.</i> (B). Side effects reported by physicians.</p><p>Abbreviations: CNS –Central Nervous System; ND – no data; PMTCT – treatment during pregnancy only, to Prevent Mother to Child Transmission.</p