Raltegravir is the first integrase inhibitor to be ap- proved for the use in the treatment of HIV infection. Based on results of recent international trials, the US FDA has recently approved its use also for naïve pa- tients. Although not yet recommended by international guidelines, a great increase in the use of this com- pound as the first line treatment is certainly pre- dictable. In naïvepatients, raltegravir has demonstrated mid- and long-term efficacy in reducing HIV-RNA to < 50 copies, comparable to that of other recommend- ed first line agents [14, 15, 18]. In the short-term in ad- dition, raltegravir showed a faster viral decay compared to efavirenz. The reason and meaning of this is still to be definitely elucidated, although recently, mathemati- cal models confirmed how in general the later an in- hibitor acts in HIV life cycle, the more rapid the decay in viremia . Also, interesting models were devel- oped to study the specific contribution of an integrase inhibitor, suggesting a reduced second phase decline of HIV-RNA in patients treated with this compound . The authors suggested that this raltegravir effect might have an impact in reducing the time needed for clear- ance of infection. This hypothesis might have been far too optimistic given the subsequent demonstration of a third and fourth phase of viral decay after a long- term viral suppression, shown to be due to cells that had a half-life not different from infinite, mirroring long-lived chronically infected cells . Also some re- cent HAART intensification studies of patients sup- pressed for a long time, showed no additional viral de- cay when raltegravir was added to their regimen, rein- forcing the small role antiretrovirals have on latently
You are invited to take part in this study. The information in this document is meant to help you decide whether or not to take part. Please feel free to ask if you have any queries or concerns.We are conducting a study on:“SPECTRUM OF CUTANEOUS MANIFESTATIONS IN WILSON’S DISEASE-NAÏVEPATIENTS AND PATIENTS ON TREATMENT” among patients attending Rajiv Gandhi Government General Hospital, Chennai and for that your participation may be valuable to us.
decreased susceptibility to telaprevir [7,24] and all sequences from genotype 3 showed the D168Q mutation which is known to decrease the activity of non-covalent HCV NS3 protease inhibitors against genotype 3 (4, 14). Moreover, a higher number of polymorphic sites in HCV protease NS3/4A were observed in genotypes 1b and 4 compared with genotypes 1a, 2 and 3. Further studies are needed to better understand the potential implications on treatment of PI naïvepatients with re- sistance at baseline which could influence the treatment failure rate. On the other hand the clinical role of com- pensatory mutations impacting the viral fitness of PI re- sistant strains [25-27] requires additional investigation.
There are no published data from Ethiopia reporting on the prevalence of extrapyramidal symptoms or side effects; however, the incidence and prevalence of these symptoms are likely to be comparable to what has been reported in the broader literature. There are at least three outstanding issues that need addressing, which may be potentially relevant to our knowledge of extra- pyramidal symptoms: 1) The contribution of antipsy- chotics above and beyond the natural risk of movement disorders is unclear; 2) the prevalence of movement dis- orders in treatment-naïvepatients is not well docu- mented in low income settings; 3) it has not yet been established whether there are unique risk factors more relevant for low income settings, such as malnutrition, infection and trauma.
Sickle cell anemia is a genetic blood disorder that requires the patients to take a lifelong regimen of hydroxyurea drugs. Kenya, being a third world country, many of these patients are not able to afford to sustain their supply of the drug hence are off it most of the time. The primary aim of this study was to determine whether there were haematological differences between the sickle cell patients taking hydroxyurea and hydroxyurea naïvepatients. After obtaining consent and assent, a 2ml blood sample was collected from each study participant. A full blood count was run on the SYSMEX XT – 2000i and data entered into an Excel sheet. The parameters of interest were the hemoglobin, white blood cell count, and platelet count. A questionnaire was used to collect sociodemographic information and clinical history information. Ninety two sickle cell anemia patients participated in this study. Of these 46 were on hydroxyurea while the other 46 were off hydroxyurea. The mean Hb of those on hydroxyurea and those not on hydroxyurea was10.4 and 9.0 respectively (P value = 0.01). The mean WBC of those on hydroxyurea and those not on hydroxyurea was 11.0 and 14.7 respectively (P value =0.005). The mean Plt of those on hydroxyurea and those not on hydroxyurea was 384 and 485 respectively (P value= 0.01). A clinically significant difference between the Hb, WBC and platelet counts was noted between the 2 groups thus suggesting a positive impact of Hu on the haematological parameters of sickle cell patients. Studies such as this could help policy makers in devising strategies to make hydroxyurea more affordable to the Kenyan sickle cell population.
The selectin family has three molecules, designated as P, E, and L. vascular endothelial cells express E and P-selectin while L-selectin is expressed on leukocytes that are circulating. Platelets and endothelial cells upon activation express P-selectin (CD62p). Inactivated platelets store P-selectin in alpha granules and weibel-palade bodies. On activation of the endothelial cells by platelet activating molecules or surgical trauma, P- selectin is expressed on the surface membrane. It allows rolling and tethering of platelets and leucocytes on endothelial cells that is activated (Polgar et al., 2005). P- selectin has ligands in all leucocytes referred to as P-selectin glycoprotein ligand-1 (PSGL-1) which allows platelet-leukocyte interaction to the site of inflammation. Current clinical studies indicate plasma P-selectin could partly be used as a marker of platelet activation (Yeh et al., 2016). Eleveted levels of soluble P-selectin have also been shown to predict patients at greatest risk of adverse cardiovascular events (Schneida et al., 2009). Elevated levels of platelet P-selectin has been observed in HIV positive individuals (Mayne et al., 2012; Nkambule et al., 2015).
will provide more accurate detection of hippocampal morpho- logic changes in AD. Second, because we set the statistical signif- icance threshold as P ⬍ .001 for equivalence of the false discovery rate correction P ⬍ .05, we could not exclude the type II errors in the results. Indeed, we excluded the subfields with P values be- tween 0.05 and 0.001, such as the left hippocampal CA2–3 and CA4-DG, and the right hippocampal CA1. Hence, larger samples will be needed to investigate subtle differences in the hippocampal subfields between patients with AD and controls. Third, because the FreeSurfer analysis suite does not provide a bias-correction process in the hippocampal subfield segmentation, we could not conduct image correction of our subjects. Although we could not find any serious errors in the automated hippocampal subfield segmentation after thorough inspection of the image quality of our subjects, there would be somewhat serious problems in the feasibility of the method by Van Leemput et al 7 in patients with
23, 35]. Furthermore, over-night withdrawal of medica- tion had no effect on CPM responses in PD patients [22, 23]. However, this washout phase might have been too short to sufficiently eliminate the dopaminergic medica- tion. Although the plasma half-life period of dopamine agonists is relatively short (usually several hours)  and that of levodopa is generally estimated as 0.7 to 1.4 h , the latter can last up to 7.9 days . The residual dopaminergic concentration might therefore still have induced antinociceptive effects  and could have nor- malized a reduced CPM response in PD patients. A re- cent study in patients with restless leg syndrome suggested that antinociceptive/analgesic effects of dopa- mine are concentration-dependent . Low dopamin- ergic concentrations induced antinociceptive effects via dopaminergic D2 receptors, whereas higher levels had pro-nociceptive effects based on the activation of D1 re- ceptors [4, 40]. Dopamine could therefore either in- crease or decrease CPM responses in PD patients depending on its concentration and low concentra- tions might have led to decreased pain during the in- sufficient washout phase.
disorders in colorectal cancer patients. In a study of 157 adults with colon or rectal cancer, sleep problems were reported by 35% of patients, and higher levels of sleep problems predicted for more fatigue, together with more depression and poorer performance status 5 . In another small study involving 21 patients with colorectal cancer undergoing adjuvant chemotherapy, clinically significant sleep disturbance was observed 6 . Berger et al. also noted substantial evidence of circadian disruption in that sample, suggesting that patients diagnosed with these types of cancer experience lack of distinction between nighttime and daytime in their activities 6 . This phenomenon was previously described in patients with advanced cancers where substantial amount of time spent asleep during the day and awake during the night effectively blurs the line between day and nighttime 7-9 . The observed association between altered rest-activity rhythm and subjectively-reported sleep problems in two independent cohorts of patients with metastatic colorectal cancer 10, 11 further supported the hypothesis that disruption of circadian rhythms in cancer patients plays a role in the occurrence of sleep problems. .
Results: There were no significant differences in baseline characteristics between antidepressant- naïve and antidepressant-treated patients. In antidepressant-treated patients, the mean DAI-10 total score was significantly lower and awareness of side effects was significantly higher than in antidepressant-naïvepatients who have never taken antidepressants, nor been referred to psychiatry services (according to pharmacist interviews and medical records). On the first day of self-management of drug intake, the DAI-10 total score in patients with melancholic and bipolar depression was significantly lower than that in patients with nonmelancholic depres- sion. On the day of discharge, there was a significant improvement of DAI-10 total score in all antidepressant-treated patients, and the DAI-10 total score in patients with melancholic depression was significantly lower than that in patients with nonmelancholic depression. The limitation of the study was the small sample size and the fact that we followed only acute phase inpatients. However, the findings seem particularly robust in view of this.
Similar to the findings with Certad et al., we have not seen gender difference in the prevalence of Cryptosporidium spp infection . In addition, the role of CD4 cell counts seems to be insignificant on the prevalence of Cryptosporidium spp infection in this report. However, the effect of CD4 cells count on the prevalence of Cryptosporidium spp infection has been well documented and is biologically well explained [14,17-19]. In this study CD4 counts were not measured at the time of the stool specimen collection; instead, we have taken the most recent CD4 counts that were documented in the HIV care clinic of the hospital. In fact it might have happened that the CD4 counts of patients may in reality be higher (for patients who started treatment) or lower (for HAART naïvepatients) than the collected data by the time of stool sample collection. The median recent CD4 counts among patients infected with Cryptosporidium spp was 166.0 (IQR 80.8, 266.0) where as it was 192.0 (IQR 112.8, 280.0) among uninfected patients.
HIV-infection in men is more prevalent among the age 45-54 years HAART naïve men and 15-24 years HIV patients on HAART (Table 3). There was significant decrease in testosterone among HIV infected men on HAART (3.40±0.70) and HAART naïvepatients (3.43±0.59) compared with negative control (10.34±0.56) (p < 0.05, Table 4). There was significant increase in estrogen, follicle stimulating hormone and luteinizing hormones compared with the negative control (p < 0.05,
therapeutic drug levels were monitored, and ADAs were measured by using conventional and bridging enzyme-linked immunosorbent assay (ELISA) methods. This study showed that CT-P13 induces and maintains high clinical remission and response rates in both CD and UC patients up to week 30, while early response and remission rates were significantly different between patients previously exposed to the IFX as compared with the naïvepatients. This was associated with significantly higher baseline ADA positivity in both CD and UC patients previously exposed to the originator drug. In conclusion, this study showed that patients with previ- ous IFX exposure had a tendency toward lower early mean trough levels of the drug, decreased response rates, and more frequent allergic reactions.
In two phase 3 studies, a larger number of treat- ment-naïve (sPRINt-2; n= 1097) and treatment-ex- perienced (REsPoND-2; n= 403; partial non-respon- ders and relapsers only) patients with HCv genotype 1 infection were enrolled to receive a 4-week lead-in with PEG-IFN alfa-2b/RBv alone, followed by either 44 weeks of triple combination therapy or a response- guided schedule with the possibility of stopping ther- apy at week 28 or week 36 of overall treatment dura- tion (based on eRvR, defined as HCv RNa negative at week 8 and week 24), respectively [32, 33]. among treatment-naïvepatients, 66% in the 48-week treat- ment group and 63% in the response-guided therapy group achieved svR compared to 38% in the control group. In treatment-experienced patients, 66% in the 48-week treatment group and 59% in the response- guided therapy group achieved svR compared to 21% in the control group. overall, 44% of patients in the sPRINt-2 response-guided treatment arm and 46% of patients in the REsPoND-2 response-guided treatment arm were eligible to undergo shortened treatment durations, based on eRvR results. treatment discontinuations due to adverse events oc-
Outcomes data were extracted for both treatment-naïvepatients (generally defined as patients with no exposure to peginterferon alpha plus ribavirin) and treatment- experienced patients (generally defined as patients with prior exposure to peginterferon alpha plus ribavirin), and the subgroups of patients with compensated cirrhosis, prior relapse (generally defined as patients who had a full decrease in hepatitis C viral load after peginterferon alpha plus ribavirin treatment, but a subsequent reoccurrence of the virus during the 24-week follow-up period after the end of treatment), and prior nonresponse (generally defined as patients who did not achieve a decrease in hepatitis C viral load during peginterferon alpha plus ribavirin treatment or a partial decrease in hepatitis C viral load during peginterferon alpha plus ribavirin treatment). Data was also abstracted for commonly reported adverse events: anemia (generally defined as hemoglobin less than 100 g/L), neutropenia (generally defined as absolute neutrophil count less than 0.75 10 9 /L), rash (any, as reported by site investigators), and
Patients and methods: This is a randomized Phase II study comparing toxicity profile and survival in 41 chemotherapy-naïvepatients with stage IIIB or IV non-squamous NSCLC, with an ECOG performance status of 0 to 2. The epidermal growth factor receptor (EGFR) mutation detection was performed prior to treatment of all patients. Patients in the first group received: bevacizumab 7.5 mg/m 2 on Day 1 and Day 15; carboplatin area under the curve-5 on Day 1; and
Results: Primary mutations associated with resistance to INI were not detected in patients not previously treated with this class of drug. However, some secondary mutations which have been shown to contribute to INI resistance were found. Only limited differences in codon usage distribution between patient groups were found. HIV-2 strains from INI naïvepatients showed the presence of both primary and secondary resistance mutations. Conclusion: Exposure to antivirals other than INI does not seem to significantly influence the emergence of mutations implicated in INI resistance. HIV-2 strain might have reduced susceptibility to INI.
PRESTO study (Parkinson’s Rasagiline: Efficacy and Safety in the Treatment of “Off ”) was a randomized, placebo-controlled, double-blind trial of subjects with advanced PD with motor fluctuations. The efficacy, toler- ability and safety of rasagiline as adjunctive therapy were determined in 472 PD patients at sites in the US and Canada. Eligible patients had to have a Hoehn and Yahr score of less than 5 in the “off ” state, experience at least 2½ hours in the “off “ state daily, and be maintained on an optimal and stable dose of levodopa therapy for at least 2 weeks prior to screen- ing visit. Subjects were randomized to receive rasagiline 0.5 mg/day, rasagiline 1 mg/day, or matching placebo. The primary measure of efficacy was change from baseline in mean total daily “off ” time; secondary endpoints included changes from baseline in the UPDRS-ADL subscale during “off ” periods, changes in UPDRS-motor subscale during
chronic pain is epidemic in the US, and many cLBP and other chronic pain patients are not highly passionate advocates for better pain control. This is in part the nature of the disorder: with the passage of time, chronic pain causes individuals to withdraw from society, to retreat from activities, and to cope with life rather than engage. Opioids are effective pain relievers, and many patients benefit from their appropriate use. However, opioids carry with them a well-recognized abuse liability, and for this reason, many clinicians hesitate to prescribe them except for patients with the most severe forms of chronic noncancer pain. Indeed, there are respected experts who challenge the use of opioids in the setting of chronic nonmalignant pain altogether. 58,59 Recent guidelines