Post-treatment Week Research Articles

Treatment of comorbid sleep disorders and posttraumatic stress disorder in active duty military: Design and methodology of a randomized clinical trial

Many individuals with posttraumatic stress disorder (PTSD) also suffer from insomnia and nightmares, which may be symptoms of PTSD or constitute partially independent comorbid disorders. Sleep disturbances are resistant to current treatments for PTSD, and those suffering from PTSD, insomnia, and nightmares have worse PTSD treatment outcomes. In addition, insomnia and nightmares are risk factors for depression, substance abuse, anxiety, and suicide. Cognitive-Behavioral Therapy for Insomnia and Nightmares (CBT-I&N) and Cognitive Processing Therapy (CPT) for PTSD are first line treatments of these conditions. CPT does not typically address insomnia or nightmares, and CBT-I&N does not typically address other symptoms of PTSD. There are limited scientific data on how best to provide these therapies to individuals suffering with all three disorders. This project aims to inform the most effective way to treat individuals suffering from PTSD, insomnia, and nightmares, potentially changing the standard of care. U.S. military personnel and recently discharged Veterans who served in support of combat operations following 9/11 aged 18–65 with PTSD, insomnia, and nightmares (N = 222) will be randomly assigned to one of the following 18-session individual treatment conditions delivered over 12-weeks: (1) 6 sessions of CBT-I&N followed by 12 sessions of CPT; (2) 12 sessions of CPT followed by 6 sessions of CBT-I&N; or (3) 12 sessions of CPT followed by an additional 6 sessions of CPT. All participants will be assessed at baseline, during treatment, and at 1-week, 1-month, 3-months, and 6-months posttreatment. The primary outcome will be PTSD symptom severity.

Safety and Efficacy of Direct Acting Antivirals (Sofosbuvir & Daclatasvir) in treatment of Chronic HCV in HIV-HCV Co-Infected Egyptian Patients

Background: Liver-related mortality is considered the most common cause of death in HIV/HCV-co infected individuals. Accordingly, treatment of HCV infection in HIV/HCV-co infected individuals is a priority to manage such major health burden. Objectives: To evaluate the safety and efficacy of treatment of chronic HCV by DDAs in HCV-HIV co-infected Egyptian patients. Patients and methods: It is an observational study that included 22 patients; only 18 HCVHIV co-infected patients completed the study [14 males (77.8 %) and 4 females (22.8 %)]. Their ages ranged from 21 to 46 years with a mean age of 32.89 years. Half of them married and 72% of them working. 61% of them are smokers and IV addicts. Patients were divided into two groups according to HIV PCR. Group I included 12 Patients with HIV PCR > 50 copies/mm and group II that included 6 patients with HIV PCR < 50 copies mm. Results: The rates of a sustained virologic response (SVR) at post-treatment week 12 (SVR 12) were high [17/18 (94.4%)]. The most common adverse events were fatigue (66.7%), headache (50%) and there was a high safety profile on using direct-acting antivirals (DAAs) and no patient discontinued treatment because of adverse events. No serious adverse events or mortality was reported. In addition, AST & ALT were significantly decreased at end of treatment and 12 weeks after treatment. Otherwise there were no significant changes in both hematological and chemistry labs. Conclusions: Daclatasvir plus sofosbuvir for 12 weeks resulted in a high rate of sustained virologic response in patients co infected with HIV and HCV with high safety profile after treatment completion.

A robust and reproducible connectome fingerprint of ketamine is highly associated with the connectomic signature of antidepressants.

Over the past decade, various N-methyl-D-aspartate modulators have failed in clinical trials, underscoring the challenges of developing novel rapid-acting antidepressants based solely on the receptor or regional targets of ketamine. Thus, identifying the effect of ketamine on the brain circuitry and networks is becoming increasingly critical. In this longitudinal functional magnetic resonance imaging study of data from 265 participants, we used a validated predictive model approach that allows the full assessment of brain functional connectivity, without the need for seed selection or connectivity summaries. First, we identified a connectome fingerprint (CFP) in healthy participants (Cohort A, n = 25) during intravenous infusion of a subanesthetic dose of ketamine, compared to normal saline. We then demonstrated the robustness and reproducibility of the discovered ketamine CFP in two separate healthy samples (Cohort B, n = 22; Cohort C, n = 18). Finally, we investigated the ketamine CFP connectivity at 1-week post treatment in major depressive disorder patients randomized to 8 weeks of sertraline or placebo (Cohort D, n = 200). We found a significant, robust, and reproducible ketamine CFP, consistent with reduced connectivity within the primary cortices and within the executive network, but increased connectivity between the executive network and the rest of the brain. Compared to placebo, the ketamine CFP connectivity changes at 1 week predicted response to sertraline at 8 weeks. In each of Cohorts A-C, ketamine significantly increased connectivity in a previously identified antidepressant CFP. Investigating the brain connectivity networks, we successfully identified a robust and reproducible ketamine biomarker that is related to the mechanisms of antidepressants.

Efficacy and safety of glecaprevir/pibrentasvir in treatment-naïve adults with chronic hepatitis C virus genotypes 1–6 in Brazil

Introduction and objectivesGlecaprevir/pibrentasvir is a highly effective and well tolerated treatment for hepatitis C infection. Brazilian patients were not included in the original development studies for glecaprevir/pibrentasvir. This study aimed to assess safety and efficacy of glecaprevir/pibrentasvir in treatment-naïve Brazilian adults without cirrhosis or with compensated cirrhosis. Patients and methodsEXPEDITION-3 was a Phase 3, open-label, multicenter study in treatment-naïve Brazilian adults with hepatitis C infection genotype 1–6. Patients without cirrhosis (F2 or F3) or with compensated cirrhosis (F4) received 8 or 12 weeks of glecaprevir/pibrentasvir, respectively. The primary efficacy endpoint was the rate of sustained virologic response at post-treatment Week 12. Secondary endpoints were on-treatment virologic failure and relapse rates. Baseline polymorphisms were assessed in NS3 and NS5A. Adverse events and laboratory abnormalities were monitored. Results100 patients were enrolled, 75 received 8 weeks of treatment and 25 received 12 weeks; all patients completed treatment. Overall sustained virologic response at post-treatment Week 12 rate was high (98.0%; 98/100; 95% confidence interval: 93.0–99.4) and remained high regardless of baseline viral or host factors, including demographics, hepatitis C virus RNA levels, polymorphisms in NS3 and/or NS5A, genotype, and relevant comorbidities. 55% of patients reported ≥1 adverse event, the most common being headache (18.0%). Four patients reported serious adverse events; none were considered drug related or led to study drug discontinuation. No hepatic decompensations were observed. ConclusionsGlecaprevir/pibrentasvir was effective and well tolerated in treatment-naïve Brazilian patients with hepatitis C infection without cirrhosis and with compensated cirrhosis. Trial RegistrationClinicalTrials.gov NCT03219216.

Post-treatment neutrophil-to-lymphocyte ratio (NLR) predicts response to anti-PD-1/PD-L1 antibody in SCLC patients at early phase.

Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) have been identified as predictors of treatment response in a variety of cancers. We conducted a retrospective analysis to investigate the usefulness of NLR, PLR and SII at baseline and at 6weeks post-treatment as predictors of response to anti-PD-1/PD-L1 antibody treatment in small cell lung cancer (SCLC). Data of 41 SCLC patients receiving immunotherapy as second- or later-line treatment were analyzed. The overall median progression-free survival (PFS) was 5.1months (95% CI 3.2-6.2). The median PFS was significantly longer in patients with NLR < 5 than in patients with NLR ≥ 5 at 6weeks post treatment (HR = 0.29, 95%CI 0.09-0.96, P = 0.04). However, median PFS was comparable between patients with NLR < 5 and patients with NLR ≥ 5 at baseline (HR = 0.75, 95% CI 0.24-2.26, P = 0.56). The median PFS was similar between patients with PLR < 169 and those with PLR ≥ 169 at baseline (HR = 0.67, 95% CI 0.25-1.80, P = 0.43) and at 6weeks post treatment (HR = 0.69, 95% CI 0.25-1.86, P = 0.46). No statistically different PFS was found between patients with SII < 730 and those with SII ≥ 730 at baseline (HR = 0.70, 95% CI 0.26-1.89, P = 0.48) and at 6weeks post treatment (HR = 0.38, 95% CI 0.013-1.09, P = 0.07). In conclusion, NLR at 6weeks after start of treatment appears to be a biomarker of response in the early phase in SCLC patients treated with anti-PD-1/PD-L1 antibodies as second- or later-line treatment.

105. VITALS ARE VITAL

Background In our pediatric clinic, there were repeated cases of ill patients failing to receive care in a timely fashion. Our clinic is the continuity site for our pediatric residency program, and a site for family med interns and med students. Using a fishbone diagram, residents and nurses outlined problems and areas for improvement. One major area identified was accuracy/completeness of vital signs. Chart review pre-intervention showed that 0% of patients had a full set of vitals for acute and well visits. Vital signs are essential, giving providers objective data to help determine the level of acuity. Insufficient/inaccurate vital signs can lead to poor patient care. An intervention was designed to address this problem. Aim Statement To increase the percentage of patients in our clinic with a full set of vitals during well and acute visits from 0% to 80% over a 2-month time period. Interventions Pre-intervention, nurses were using a card that indicated which vitals to check for each visit type. No visit types included a full set of vitals. A new evidence-based protocol for vital signs was created. We identified a nurse leader who was key for execution. A fact sheet was created to explain the updated expectations. The new protocol was introduced at a meeting with the nurses. A vital signs manual, with instructions for proper techniques, normal ranges by age and references used, was provided. The new protocol stated: a full set of vitals (Wt/Ht/Temp/BP/HR/RR) should be taken for all well and acute visits, with BP excluded for patients less than 3 years with a few exceptions. A month later, a 2nd meeting was held to reestablish the expectations and discuss problems nurses had identified, e.g. the need for more equipment. This project received exemption from our local IRB. Measures Charts for all acute and well visits were reviewed from 3 one-week time periods to determine the percentage of patients with a full set of vitals: pre-intervention, 1-week post-intervention, and 7 weeks post-intervention. Results There was an increase from 0% to a median of 52% and 44% for well and acute visits, respectively, over 2 months (see run charts). Conclusions and Next Steps This protocol can easily be applied in any outpatient clinic setting. We will explore further interventions, such as using the EMR to prompt nurses and posting signs. Additionally, we will begin skills sessions led by nurses to further ensure consistency/accuracy of vital signs.

Systematic review with meta-analysis: the efficacy and safety of direct-acting antivirals in children and adolescents with chronic hepatitis C virus infection.

The effect of direct-acting anti-virals (DAAs) in children and adolescents with chronic hepatitis C virus (HCV) infection is difficult to determine, since few, aged between 3 and 18years, have been enrolled in clinical trials, and some data come from observational studies. To summarise the evidence on efficacy and safety of DAAs in children and adolescents with chronic HCV infection. We performed a systematic review and meta-analysis of prospective studies on the efficacy and safety of DAAs in subjects <18years of age. We considered the sustained virological response at post-treatment week 12 as efficacy outcome and adverse events as safety outcome. We considered intervention effect for each study arm by calculating the proportion of sustained virologic response at post-treatment week 12 in subjects receiving all doses of treatment and proportion of adverse events in subjects receiving at least one dose of treatment. Pooled proportions were calculated using the Freeman-Tukey double arcsine transformation. Random effects model was used for all analyses. Among 39 included studies (1796 subjects), the pooled proportion among those receiving all doses of treatment and reaching sustained virologic response at post-treatment week 12 was 100% (95% confidence interval: 100-100). Considering subjects receiving at least one dose of treatment, lowest estimates were reported among children with cirrhosis (83%). Headache and fatigue were the most common adverse events. Serious adverse events were uncommon. Children and adolescents with chronic HCV infection can be safely treated with DAAs with similar efficacy as reported in adults.

Comparing the Safety and Effectiveness of Radiofrequency Thermocoagulation on Genicular Nerve, Intraarticular Pulsed Radiofrequency with Steroid Injection in the Pain Management of Knee Osteoarthritis

Background: Knee osteoarthritis (KOA) is characterized by the clinical symptoms of chronic knee pain and knee dysfunction, leading to disability and influencing the quality of life in severe cases. Radiofrequency treatment is a new method to reduce KOA-related pain and partially improve knee joint dysfunction without adverse effect. Objective: The present study aimed to assess the treatment efficacy of radiofrequency thermocoagulation on the genicular nerve (RFTGN) and intraarticular pulsed radiofrequency (IAPRF) for KOA. Study Design: Retrospective comparative study design. Setting: This study took place at Shengjing Hospital of China Medical University. Method: KOA patients were randomly assigned to the RFTGN, IAPRF, and intraarticular steroid injection (IAS) groups. All procedures were performed under the guidance of computed tomography (CT). The observation indicators of this study were the numeric rating scale (NRS), Oxford knee scale (OKS), and perceived global effect (GPE). The time points for the assessment were 1-week, 1-month, 3-months, and 6-months after the treatment. Results: The postoperative NRS scores in the 3 groups decreased significantly at all the observation time points as compared to the pretreatment scores (P &lt; 0.05). For the patients in the IAS group, the analgesic effect was in a rebound trend, which was the best at 1-week posttreatment, and was close to the preoperative level at 6-months posttreatment. The short-term (1 week or 1 month) analgesic effect of the RFTGN group was better than that of the IAPRF group, and was similar in the long-term (3 or 6 months). The long-term analgesic effect of RFTGN and IAPRF groups was better than that of IAS group. The results of the OKS score were similar to the NRS score. The RFTGN group showed markedly improved knee function in the long-term than the IAPRF and IAS groups. The short-term treatment satisfaction was similar in each group, and some differences were detected between the groups with respect to long-term treatment satisfaction. Limitation: This study was a single-center retrospective study with a relatively small sample cohort and short follow-up period Conclusion: Both RFTGN and IAPRF could alleviate the knee joint pain and improve the knee joint dysfunction; however, the treatment efficacy of RFTGN was better than that of IAPRF. Key words: radiofrequency thermocoagulation, genicular nerve, pulsed radiofrequency, knee osteoarthritis, knee pain, intraarticular, steroid

Ten‐year follow‐up of a randomized controlled clinical trial in chronic hepatitis delta

Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis. PEG-interferon alpha-2a (PEG-IFNα-2a) is the only effective treatment but its long-term clinical impact is unclear. The aim of this study was to investigate the long-term outcome after 48weeks of pegylated interferon alpha-2a therapy. We performed a retrospective follow-up study of the Hep-Net-International-Delta-Hepatitis-Intervention-Study 1 (HIDIT-I trial). Patients had received 48weeks of treatment with either PEG-IFNα-2a plus adefovir dipivoxil (ADV) (Group I), PEG-IFNα-2a alone (Group II) or adefovir dipivoxil alone (Group III). Liver-related complications were defined as liver-related death, liver transplantation, liver cancer and hepatic decompensation defined as development of Child-Pugh scores B or C or an increase in Model for End-stage Liver Disease (MELD) scores of five or more points in relation to baseline values. Patients were considered for further analysis when they were retreated with PEG-IFNα-2a. Follow-up data (at least 1 visit beyond post-treatment week 24) were available for 60 patients [Group I, (n=19), Group II (n=20), Group III (n=21)]. Mean time of follow-up was 8.9 (1.6 - 13.4) years. 19 patients were retreated with IFN-based therapy: 42% (n=8) in PEG-IFNα-2a arms and 58% (n=11) in the adefovir only arm. Clinical complications on long-term follow-up occurred in 17 patients and were associated with nonresponse to therapy and baseline cirrhosis. The annual event-free survival rate in patients with cirrhosis vs noncirrhotic patients at year 5 and 10 was 70% vs 91% and 35% vs 76%. Long-term follow-up of a large randomized clinical trial suggests that off-treatment HDV RNA response to PEG-IFNα-2a treatment leads to improved clinical long-term outcome.

Safety, Pharmacokinetics, and Efficacy of Efinaconazole 10% Topical Solution for Onychomycosis Treatment in Pediatric Patients

Background: Pediatric onychomycosis management is challenging as there are limited treatment options. The objective of this study was to evaluate efinaconazole 10% topical solution in children with onychomycosis. Methods: This phase 4, multicenter, open-label study (NCT02812771) evaluated safety, pharmacokinetics (PK), and efficacy of efinaconazole 10% topical solution in pediatric participants (6-16 years). Efinaconazole was administered once daily for 48 weeks, with a 4-week posttreatment follow up. Participants had culture-positive, mild-to-severe distal lateral subungual onychomycosis affecting at least 20% of at least 1 great toenail. The PK subset included participants 12-16 years with moderate-to-severe onychomycosis affecting at least 50% of each great toenail and onychomycosis in at least 4 additional toenails. Results: Of 62 enrolled participants, 60 were included in the safety population and 17 in the PK population. Efinaconazole 10% topical solution was well tolerated. The concentration-time profiles for efinaconazole and its major metabolite were relatively stable, with only minor fluctuations during the 24-hour dosing interval. Systemic exposure to efinaconazole was low. By week 52, 65.0% of participants achieved mycologic cure, with a 36.7% mycologic cure rate observed as early as week 12. A total of 40.0% of participants achieved complete cure, 50.0% achieved clinical efficacy, and 88.3% achieved fungal cure by week 52. Conclusion: Efinaconazole was safe and efficacious in pediatric participants with mild-to-severe onychomycosis, with improved mycologic cure and complete cure rates compared with adults from two 52-week studies. J Drugs Dermatol. 2020;19(9):867-872. doi:10.36849/JDD.2020.5401

Clinical periodontal, bacterial, and immunological outcomes of antimicrobial photodynamic therapy in orthodontic treatment-induced gingival enlargement.

The aim of the present clinical trial is to evaluate the clinical, bacterial, and immunological outcomes of photodynamic therapy (PDT) in adolescent patients with orthodontic treatment-induced gingival enlargement (OTGE). A total of 26 adolescent patients, 16 girls and 10 boys, of mean age 16.8 years, undergoing fixed orthodontic treatment for at least 6 months (mean duration in months, 8.3 ± 1.9) and presenting with GE were included in the clinical trial. All patients undergoing fixed orthodontic treatment with clinical diagnosis of OTGE were divided into two groups: Patients receiving full-mouth periodontal debridement (FMPD) 'Group-FMPD' and 'Group-PDT' included participants receiving methylene blue-assisted PDT in the selected area along with FMPD. Clinical periodontal assessments included the evaluation of plaque scores (PS), bleeding on probing (BOP), probing depth (PD) and hyperplastic index (HI). The total bacterial counts of Porphyromonas gingivalis (P. gingivalis), Treponema denticola (T. denticola), and Tannerella forsythia (T. forsythia) were estimated and expressed as log CFU/mL of each bacteria. Cytokines including interleukin (IL)-1β and IL-6 were analyzed using enzyme-linked immunosorbent assay (ELISA) kit. The mean percentage of PS and BOP statistically significantly reduced with both FMPD and PDT from baseline to 4 weeks (p < 0.05). Although mean PD significantly reduced in both the groups at all time points, there was significantly higher reduction with PDT as compared to FMPD at 2 weeks post treatment (p < 0.05). Inter-group comparison showed PDT demonstrated significantly higher HI at 2- and 4-weeks post treatment (p < 0.05). The mean log CFU/mL of P. gingivalis and T. forsythia showed statistically significantly higher reduction with PDT than FMPD (p < 0.05) at both 2-and 4-weeks follow-up. T. denticola reported significantly reduced levels at 2 weeks follow-up period only with PDT (p < 0.05). No statistically significant difference appeared when both treatment modalities were compared with one another (p > 0.05). Four weeks after periodontal treatment, IL-6 significantly reduced with PDT compared to FMPD (p < 0.05). PDT assisted in reducing bacterial counts and improving hyperplastic index in OTGE.

The Efficacy of Generic Daclatasvir-Sofosbuvir as Pan-Genotypic Regiment for Hepatitis C Virus (HCV) Infected Patients in Bandung Indonesia

Background: Direct-acting antivirals (DAAs) have altered the prognosis of hepatitis C virus (HCV) disease but its access is limited by socioeconomic factors. Generic DAAs with lower prices were available in Indonesia in 2016. The aim of this study was to determine the efficacy of generic daclatasvir-sofosbuvir.Method: We performed an observational study from January to December 2016 in a tertiary care center in Bandung, Indonesia. Data were obtained from medical registry. All study subjects received oral daclatasvir (60 mg, once daily) and sofosbuvir (400 mg, once daily) for 12 weeks for noncirrhotic chronic HCV patients and 24 weeks for cirrhotic chronic HCV patients. The main endpoint criterion was sustained virologic response at post-treatment week 12 (SVR12).Results: We enrolled 32 subjects (20 noncirrhotic, 12 cirrhotic). All noncirrhotic subjects (eighteen were previously untreated patients) and cirrhotic subjects (all were previously untreated patients) achieved SVR12 of 100%. These high rates of SVR12 were observed in all patients with HCV infection regardless of the genotype. ALT normalization was achieved in all patients 12 weeks after therapy. The most common adverse events were fatigue and nausea.Conclusion: Once-daily oral generic daclatasvir-sofosbuvir showed good efficacy and safety. Furthermore, it yielded a high rate of SVR among patients infected with HCV of all genotypes.

Cure or curd: Modification of lipid profiles and cardio-cerebrovascular events after hepatitis C virus eradication.

Hepatitis C virus (HCV) eradication deteriorates lipid profiles. Although HCV eradication may reduce the risk of vascular events as a whole, whether deteriorated lipid profiles increases the risk of cardio-cerebral disease in certain patients is elusive. Serial lipid profiles were measured before, during, at and 3 months after the end of direct-acting antivirals (DAAs) therapy, and annually thereafter in chronic hepatitis C patients who achieved a sustained virological response (SVR, undetectable HCV RNA at posttreatment week 12). The primary end-point was the occurrence of the events. A total of 617 patients were included, with a mean follow-up period of 26.8 months (range: 1-65 months). The total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels increased significantly from treatment week 4 to 2 years after treatment. Logistic regression analysis revealed that the factors independently associated with a significant cholesterol increase included age (odds ratio [OR]/95% confidence intervals [CIs]:1.02/1.006-1.039, P = .007) and smoking (OR/CI:3.21/1.14-9.02, P = .027). Five patients developed cardio-cerebral diseases during 1376 person-years follow-up period. Compared to patients without vascular events, a significantly higher proportion of those with vascular events experienced an LDL-C surge >40% (80% vs 19.9%, P = .001). Cox-regression analysis revealed that an LDL-C surge >40% was the only factor predictive of vascular events (HR/CI: 15.44/1.73-138.20, P = .014). Dyslipidemia occurred after HCV eradication, and it was associated with the risk of cardio-cerebrovascular diseases. Attention should also be paid to the extrahepatic consequence beyond liver-related complications in the post-SVR era.

Eight Weeks of Treatment With Glecaprevir/Pibrentasvir Is Safe and Efficacious in an Integrated Analysis of Treatment-Naïve Patients With Hepatitis C Virus Infection

The direct-acting antiviral combination glecaprevir/pibrentasvir has been approved by the Food and Drug Administration for 8 weeks of treatment in treatment-naïve patients with hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. We performed an integrated analysis of data from trials to evaluate the overall efficacy and safety of 8 weeks of glecaprevir/pibrentasvir in treatment-naïve patients without cirrhosis or with compensated cirrhosis. We pooled data from 8 phase 2 or phase 3 trials of treatment-naïve patients with HCV genotype 1 to 6 infections, without cirrhosis or with compensated cirrhosis, who received 8 weeks of glecaprevir/pibrentasvir. Of 1248 patients, 343 (27%) had cirrhosis. Most patients were white (80%) and had HCV genotype 1 infection (47%) or genotype 3 infection (22%); the median age was 54 years. Overall rates of sustained virologic response at post-treatment week 12 were 97.6% (1218 of 1248) in the intention to treat (ITT) and 99.3% (1218 of 1226) in the modified ITT populations. When we excluded patients with genotype 3 infections with compensated cirrhosis (consistent with the European label), rates of sustained virologic response at post-treatment week 12 were 97.6% in the ITT and 99.4% in the modified ITT populations. Eight virologic failures (7 in patients without cirrhosis and 1 in a patient with cirrhosis) occurred in the ITT population. Virologic failure was not associated with markers of advanced liver disease or populations of interest (current alcohol use, opioid substitution therapy, history of injection-drug use, and severe renal impairment). Treatment-emergent adverse events (AEs) occurred in 58% of patients. The most frequent AEs (>10%) were headache (12%) and fatigue (12%). Serious AEs and AEs that led to glecaprevir/pibrentasvir discontinuation were reported in 2% and less than 1% of patients, respectively. In a pooled analysis of data from 8 trials, we found that 8 weeks of treatment with glecaprevir/pibrentasvir is efficacious and well tolerated in treatment-naïve patients with HCV genotype 1 to 6 infections, with or without cirrhosis.

Adverse To Converse

Toe Pain--- Cross-Country HISTORY: A 12 year-old female cross country runner presented to the pediatric sports medicine clinic with 3 months of right second toe pain. Initially, the pain started after stubbing her toe. She developed a constant dull ache that was present at rest and worsened with prolonged walking and during cross country. She noted that her symptoms gradually worsened with time, and she was having no improvement with rest, icing and anti-inflammatories. PHYSICAL EXAMINATION: Overlying skin with no rashes or lesions. Tenderness along the plantar surface of her right second metatarsophalangeal (MTP) joint. ROM was limited in both passive and active flexion and extension of the affected joint. Sensation was intact, and strength with flexion and extension of the toe was normal, however there was significant pain with testing. MT squeeze test was negative. Varus and valgus stress to MTP joint elicited no laxity, and “drawer test” of MTP joint showed mild instability. DIFFERENTIAL DIAGNOSIS: 1. Sprain of plantar plate 2. Metatarsal fracture/stress fracture 3. Osteochondrosis of the metatarsal head 4. Metatarsalgia 5. Lisfranc injury 6. Intermetatarsal neuroma TEST RESULTS: X-ray R foot: --- Flattening of the second metatarsal head. MRI R foot without contrast: --- Flattening/collapse of the 2nd metatarsal head/distal epiphysis with prominent marrow edema of the 2nd metatarsal head and neck. Mild MTP joint space narrowing. FINAL/WORKING DIAGNOSIS: Osteochondrosis of the metatarsal head (Freiberg Disease) - Stage 4 TREATMENT AND OUTCOMES: 1. Placed in short leg walking boot with protected weight-bearing, ice 1-2 times daily, Foot/Ankle Surgery consultation with discussion of conservative care vs surgical (chondral drilling and/or chondroplasty). Patient opted for conservative care. 2. At 4-week follow-up, patient’s pain significantly reduced. Continued walking boot additional 4 weeks with transition into stiff-soled shoe. 3. At 8-weeks post treatment, follow-up MRI showed no progression of disease. Clinically with almost complete resolution of pain. 4. By 10 weeks, transitioned into a custom foot orthotic with added support to float 2nd MTP joint. Restrictions included low impact sports only with plan for repeat MRI at 6 months.

Efficacy of Electroacupuncture on Treating Depression-Related Insomnia: A Randomized Controlled Trial.

ObjectiveTo evaluate the efficacy of electroacupuncture (EA) on treating insomnia in patients with depression.Patients and MethodsIn a patient-assessor-blind, randomized and sham controlled trial, 90 depression patients with insomnia were assigned into three different groups, receiving EA in the treatment group, superficial acupuncture at sham points in the control group A, or Streitberger non-insertion sham acupuncture in the control group B. Treatment was applied 3 times weekly for 8 consecutive weeks. The primary outcome was measured using the Pittsburgh Sleep Quality Index (PSQI). Secondary outcomes were sleep parameters including sleep efficiency (SE), total sleep time (TST) and numbers of sleep awakenings (SA) recorded in the actigraphy, as well as applying the Hamilton Rating Scale for Depression (HAMD-17), Self-Rating Depression Scale (SDS) and Hamilton Rating Scale for Anxiety (HAMA). Assessments were performed at the baseline (week 0), week 4, week 8, and week 12. Linear mixed-effects models were used for analyses and all statistical tests were two-sided.ResultsPatients in the EA group had more significant improvement in PSQI scores than those in the control groups over time (respectively p<0.001 and p=0.04 for treatment and time interaction). At 8-week posttreatment, the EA group reported a reduction of −6.64 points in PSQI scores compared with −2.23 points in the control group A (95% CI= −5.74 to −2.39) and −2.94 points in the control group B (95% CI= −5.73 to −2.47). Compared with the two control groups, significant between-group differences were seen in SE (both p<0.01) and TST (both p<0.01) at week 8; similar results can be found in HAMD-17, SDS, and HAMA scores as well. However, there were no between-group differences in SA (respectively p=0.24 and p=0.08) after 8-weeks of treatment.ConclusionElectroacupuncture may improve the sleep quality of patients with depression.Trial RegistrationChinese Clinical Trial Registry (ChiCTR); URL: http://www.chictr.org.cn/showproj.aspx?proj=12327; Trial ID: ChiCTR-IIR-16008058.

Danoprevir for the Treatment of Hepatitis C Virus Infection: Design, Development, and Place in Therapy.

On June 8, 2018, an NS3/4A protease inhibitor called danoprevir was approved in China to treat the infections of HCV genotype (GT) 1b – the most common HCV genotype worldwide. Based on phase 2 and 3 clinical trials, the 12-week regimen of ritonavir-boosted danoprevir (danoprevir/r) plus peginterferon alpha-2a and ribavirin offered 97.1% (200/206) of sustained virologic response at post-treatment week 12 (SVR12) in treatment-naïve non-cirrhotic patients infected with HCV genotype 1b. Adverse events such as anemia, fatigue, fever, and headache were associated with the inclusion of peginterferon alpha-2a and ribavirin in the danoprevir-based regimen. Moreover, drug resistance to danoprevir could be traced to amino acid substitutions (Q80K/R, R155K, D168A/E/H/N/T/V) near the drug-binding pocket of HCV NS3 protease. Despite its approval, the clinical use of danoprevir is currently limited to its combination with peginterferon alpha-2a and ribavirin, thereby driving its development towards interferon-free, ribavirin-free regimens with improved tolerability and adherence. In the foreseeable future, pan-genotypic direct-acting antivirals with better clinical efficacy and less adverse events will be available to treat HCV infections worldwide.

Neu-horizons: neuroprotection and therapeutic use of riluzole for the prevention of oxaliplatin-induced neuropathy-a randomised controlled trial.

Peripheral neuropathy is a commonly reported adverse effect of oxaliplatin treatment, representing a significant limitation which may require discontinuation of effective therapy. The present study investigated the neuroprotective potential of riluzole in patients undergoing oxaliplatin treatment in a randomised-controlled trial comparing riluzole and placebo-control. Fifty-two patients (17 females, 58.1 ± 12.7years) receiving oxaliplatin treatment were randomised into either a treatment (50mg riluzole) or lactose placebo group. The primary outcome measure was the total neuropathy score-reduced (TNSr). Secondary outcome measures include nerve excitability measures, 9-hole pegboard and FACT-GOG NTX questionnaire. Patients were assessed at baseline, pre-cycle 10 or 12, 4-week and 12-week post-treatment. Both the treatment and placebo groups developed objective and patient reported evidence of neurotoxicity over the course of oxaliplatin treatment, although there were no significant differences across any parameters between the two groups. However, across follow-up assessments, the treatment group experienced greater neuropathy, represented by a higher TNSr score at 4-week post-chemotherapy of 8.3 ± 2.7 compared with 4.6 ± 3.6 (p = 0.032) which was sustained at 12-week post-treatment (p = 0.089). Similarly, patients in the treatment group reported worse symptoms with a FACT-GOG NTX score of 37.4 ± 10.2 compared with 43.3 ± 7.4 (p = 0.02) in the placebo group at 4-week post-treatment. This study is the first to provide an objective clinical investigation of riluzole in oxaliplatin-induced peripheral neuropathy employing both functional and neurophysiological measures. Although the recruitment target was not reached, the results do not show any benefit of riluzole in minimising neuropathy and may suggest that riluzole worsens neuropathy associated with oxaliplatin treatment.

Sofosbuvir and Daclatasvir Bypassing Genotypic Investigation of Chronic Hepatitis C Infection: A Real-Life Experience at Tertiary care center in North Indian Population Sofosbuvir and Daclatasvir Bypassing Genotypic Investigation

Background and Aims: The goal of Hepatitis C Virus infection treatment is to remove the virus, to avoid advancement of Hepatitis C Virus (HCV) infection and progression of related disease such as liver cirrhosis and hepatocellular carcinoma and to achieve End of Treatment Response (ETR) with 12-week therapy and Sustained Virological Response (SVR) at post-treatment week 12 (SVR-12), which is defined as undetectable HCV RNA at 12 weeks post ETR. In the Compassionate Use Program (CUP) in Europe, Sofosbuvir (SOF) and Daclatasvir (DCV) were used in all genotypes and achieved SVR-12. Aims: Our aim is to compare the efficacy and effectiveness of Sofosbuvir and Daclatasvir in the treatment of HCV infection in the patients who could not afford for the investigating of HCVGenotype and to those in whom genotyping was done. Methods: Group 1 includes ten patients, given Sofosbuvir and Daclatasvir without genotype and group 2 includes nine patients, given Sofosbuvir and Daclatasvir with genotype. The patient group selection was done using a randomized table generated by using excel. All the patients in the groups completed the twelve weeks treatment with twelve weeks and twenty-four weeks of follow up. All the nineteen patients were given Sofosbuvir and Daclatasvir for twelve weeks and the endpoint of therapy was marked by undetectable HCV-RNA in blood by ETR-12 (end of treatment response), Sustained Virological Response at post-treatment week 12 (SVR-12) and Sustained Virological Response at post-treatment week 24 (SVR- 24). Results: Quantitative HCV-RNA (IU/ml) by RT-PCR was undetectable in all the patients in both groups at the end of treatment (ETR-12) and SVR-12- and SVR-24-weeks follow-up after completion of treatment i.e. Sofosbuvir and Daclatasvir has 100% ETR-12, SVR-12 and SVR-24 in both the groups. Conclusion: If patients do not investigate for genotype and use the Sofosbuvir and Daclatasvir in HCV infected patients, there is no effect on outcome ETR. This will reduce the risk of late stage complications such as liver cirrhosis and hepatocellular carcinoma and will also leads to the economic benefits such as no extra burden on patients.

Changes of inflammatory cytokines/chemokines during ravidasvir plus ritonavir-boosted danoprevir and ribavirin therapy for patients with genotype 1b hepatitis C infection.

This study investigated the safety and efficacy of ravidasvir (RDV) plus ritonavir-boosted danoprevir (DNVr) and ribavirin (RBV) regimens for treatment-naïve non-cirrhotic patients with hepatitis C virus (HCV) genotype 1b in mainland China. We also gained insight into HCV-host interactions during anti-HCV treatment. 16patients with HCV and 10 healthy people enrolled the study. Threeof 16 patients received 12-weeks' placebo treatment first and served as the placebo controls. All (n = 16) patients received 12-weeks' RDV plus DNVr and RBV treatment. The adverse effects (AEs), viral loads, alanine transaminase,and aspartate aminotransferasewere recorded during study. We also performed multianalyte profiling of 48 cytokines/chemokines in 16 patients with HCV and 10 normal controls. Seventy-five percent patients treated with RDV plus DNVr and RBV experienced AEs. No death, treatment-related serious AEs or AEs leading to discontinuation were reported. The serum HCV-RNA levels remained extremely high in 3placebo controls after treated with placebo. After RDV plus DNVr and RBV treatment, all patients achieved sustained virologic response (SVR) at posttreatment week 12, but 1patient experienced viral relapse at SVR 24. The cytokine/chemokine expression pattern was markedly altered in patients with HCV as compared withhealthy controls. The interferon-inducible protein-10 (IP-10) decreased after anti-HCV treatment, and dramatically increased in one patient with viral relapse. The regimen of RDV and DNVr plus RBV represents a highly safe and effective treatment option for HCV patients in mainland China. The IP-10 has the potential to be an indicator of innate immune viral recognition.