Post-treatment Adverse Events Research Articles

Topical Riboflavin versus 5-Aminolevulinic Acid Photodynamic Therapy for the Treatment of Mild to Moderate Acne: A Split-face Randomized Study.

ALA-PDT has been widely used in mild to moderate acne vulgaris worldwide. However, very few studies used riboflavin-PDT to treat acne vulgaris. To investigate the efficacy and adverse events of riboflavin-PDT to treat mild to moderate facial acne, and compare it with ALA-PDT on a non-inferiority basis. 33 eligible patients were enrolled, and 30 patients completed follow-up. Either side of the face was assigned randomly to riboflavin or ALA blue-light-PDT. Patients received 3 sessions of PDT in 1-week intervals and were followed up at weeks 4, 6, and 10. Both ALA and riboflavin-PDT significantly reduced non-inflammatory and inflammatory lesions at weeks 4, 6, and 10 compared to baseline (P all <0.001). For the primary outcome, the difference in the improvement rate of total lesions between the Ribo and ALA side was 2.6% (-4.3%, 12.5%; p=0.71), which didn't reach the inferiority margin. Patients described greater in-treatment pain and burning sensation (P<0.001), more prominent post-treatment erythema (P=0.003), hyperpigmentation (P<0.001), and desquamation (P=0.006) on the ALA side than on riboflavin side. The efficacy of riboflavin-PDT was comparable to that of blue-light ALA-PDT in treating mild to moderate acne vulgaris. Riboflavin-PDT had fewer in-treatment and post-treatment adverse events than ALA-PDT.

Clinical characteristics and prognostic analysis of prolonged cytopenia after CAR-T cell therapy in LBCL patients

Objective: To investigate the clinical features and prognosis of prolonged cytopenia (PC) in patients with large B-cell lymphoma (LBCL) undergoing anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy. Methods: A retrospective case series study was conducted on LBCL patients who received CAR-T cell therapy with a survival time of over one month at the Hematology Department of Peking Union Medical College Hospital from March 2019 to December 2023. Statistical analyses were performed on hematologic changes at 1, 3, 6, and 12 months post-CAR-T infusion, as well as on the progression-free survival (PFS) and post-treatment adverse events, including infections. Patients were categorized into the PC and non-PC groups based on the occurrence of cytopenia at 90 days post-infusion. Differences between groups were compared, and univariate logistic regression analysis was used to identify risk factors. Results: The median age of 27 LBCL patients receiving CAR-T cell therapy was 58 years (range 27-69 years), with 18 males. Among the 27 LBCL patients who received CAR-T cell therapy, PC was observed in 19 patients (70.4%), with instances of neutropenia (48.1%, 13 cases), anemia (37.0%, 10 cases), and thrombocytopenia (22.2%, 6 cases). Univariate logistic regression analysis revealed that prior chemotherapy sensitivity (OR=18.00, 95%CI 1.56-207.45, P=0.020) and bone marrow suppression (OR=18.00, 95%CI 1.38-235.69, P=0.028) were associated with PC. The median follow-up time was 13.5 months. The PC group exhibited a higher risk of infection within 3 months (9/19 vs. 1/8) and a shorter mean PFS (19.3 months vs. 24.4 months), although the difference was not statistically significant (both P>0.05). Conclusions: PC is common following CAR-T cell therapy and is associated with an increased risk of infection and poorer prognosis. Prior treatment sensitivity and bone marrow suppression may serve as indicators of PC.

A Prospective, Randomized, Double-Blind, Split-Face, Comparative Study to Evaluate the Efficacy and Safety of DKL23 and Juvéderm Volift for Correcting Moderate-to-Severe Nasolabial Folds.

Hyaluronic acid dermal fillers are used for multiple indications, including wrinkle correction and restoration of volume/fullness. The aim of this study was to compare the efficacy and safety of 2 hyaluronic acid products for correcting moderate to severe nasolabial folds (NLFs). A prospective, randomized, double-blind, split-face study was undertaken. The subjects' left and right NLFs were randomly allocated for treatment with DKL23 or Juvéderm Volift. Follow-up was conducted at 1, 3, 6, and 9 months. The changes from baseline on the Wrinkle Severity Rating Scale and the Global Aesthetics Improvement Scale were evaluated. Posttreatment adverse events (AEs) were recorded. Forty-eight women (median age, 57.0 years) with Type I to VI skin were enrolled. Both treatments showed statistically significant improvement (P < .0001) in NLFs according to the Wrinkle Severity Rating Scale score from baseline to each of the time points assessed. The improvement in NLFs was maintained until the end of the study (9 months). Furthermore, the change from baseline to each of the time points assessed was similar between DKL23 and Juvéderm Volift. Investigator- and subject-rated Global Aesthetics Improvement Scale scores showed similar rates of improvement (indicated by the sum of responses of improved, much improved, or very much improved) between the 2 products. The AEs reported in the study were in line with previous and expected experience after injection of hyaluronic acid dermal fillers. The types of AEs, their rates, intensity, and duration were comparable between the 2 products. DKL23 improved NLF severity from baseline and for up to 9 months, and the results were comparable to the improvement shown by Juvéderm Volift. Treatment was safe and well tolerated.

Effect of tirofiban combined with endovascular treatment on hemorrhagic transformation and neurological function in patients with ischemic stroke.

To evaluate the effect of Tirofiban combined with endovascular treatment on hemorrhagic transformation (HT) and neurological function in patients with ischemic stroke. A retrospective analysis was performed on 94 patients with ischemic stroke treated at Xi'an International Medical Center Hospital from January 2020 to January 2023. Among them, 45 patients underwent endovascular treatment only and served as the control group. Another 49 patients received Tirofiban in addition to endovascular treatment and they formed the study group. The pre-treatment and 14-day post-treatment NIHSS scores were compared between the two groups. The 24-hour HT rate and the incidence of post-treatment adverse events were also compared between the two groups. Multivariate Cox regression analysis was used to identify factors influencing patient prognosis. The NIHSS scores in the study group were significantly lower than those in the control group 14 days after treatment (P<0.05). There was no statistically significant difference in the 24-hour HT rate between the two groups (P>0.05). In addition, there were no significant differences in the incidence of adverse events between the two groups (P>0.05). Multivariate Cox regression analysis showed that treatment regimen, age, and time from onset to admission were independent factors affecting 90-day prognosis (P<0.01). A prognostic model based on β-coefficients was constructed: Cox risk = 2.729 * treatment regimen + 2.881 * age + 2.795 * time from onset to admission. The Cox risk was significantly lower in the good prognosis group compared to the poor prognosis group (P<0.0001), with an area under the curve of 0.925 in predicting patient prognosis. Tirofiban combined with endovascular treatment can improve quality of life, neurological function, and short-term prognosis in patients with ischemic stroke without increasing the incidence of adverse effects and HT.

Efficacy and safety of magnetic resonance-guided focused ultrasound for the treatment of osteoid osteoma: A systematic review and meta-analysis

ObjectiveMagnetic resonance-guided focused ultrasound (MRgFUS) is a novel noninvasive interventional technique for osteoid osteoma (OO). The purpose of this study was to evaluate the efficacy and safety of MRgFUS in the treatment of OO through a systematic review and meta-analysis of pain scores and post-treatment adverse events before and after MRgFUS treatment. Materials and MethodsA comprehensive literature search of PubMed, Embase, Web of science, and Cochrane Library databases was conducted to screen the study literature based on inclusion and exclusion criteria to extract and analyze pre- and post-treatment pain score data, success rates (complete pain relief with no recurrence until the last follow-up), recurrence rates, secondary intervention rates, and complications to evaluate the efficacy and/or safety of MRgFUS for OO. ResultsA total of 113 studies published between 2012 and 2022were collected, resulting in a total sample size of 353 patients. The majority of the studies were prospective and had a follow-up period of 4 weeks or more, and overall, the quality of evidence ranged from low to high. Pain scores at 1 week and 1 month after the merger were 0.62 (9.5% CI:0.28–0.96) and 0.37 (9.5% CI:0.07–0.68), respectively. The success rate of the combination was 92.8% (95% CI: 89.8%-95.7%), the incidence of minor complications (thermal injury at the ablation site) was 0.85%, and no major complications were recorded in any of the included literature. ConclusionMRgFUS is an effective procedure that is able to treat pain for patients with OO with satisfying efficacy and safety.PROSPERO: No.CRD42023415573.

Yttrium-90 Radiation Segmentectomy of Hepatocellular Carcinoma: A Comparative Study of the Effectiveness, Safety, and Dosimetry of Glass-Based versus Resin-Based Microspheres

PurposeTo evaluate the differences in safety, effectiveness, and dosimetry between glass-based and resin-based ablative yttrium-90 (90Y) transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC). Materials and MethodsUsing the modified Response Evaluation Criteria in Solid Tumors and Common Terminology Criteria for Adverse Events, both tumor response and adverse events (AEs) were assessed at 3 months after 90Y-TARE. Post procedure 90Y-bremsstrahlung single-photon emission computed tomography/computed tomography voxel-based dosimetry analysis was used to create tumor dose (TD) and normal tissue dose (NTD) volume histograms, and to calculate tumor particle loading and specific activity. The TD and NTD receiver operating characteristic curves evaluated the dose threshold able to predict objective (partial or complete) and complete tumor responses in addition to any-grade and grade ≥3 AE incidences. The chi-square test and Student t-test were used to assess variable differences where appropriate. ResultsBetween 2019 and 2020, 81 patients with HCC (20 in the resin-based cohort and 61 in the glass-based cohort) underwent ablative 90Y-TARE. The resin-based cohort had more males (89% vs 65%, P = .03), lower tumor-to-normal ratio (1.81 ± 0.39 vs 2.22 ± 0.94, P = .03), higher tumor particle loading (40,172 particles/mL ± 28,039 vs 17,081 particles/mL ± 12,555, P = .0001), lower specific activity (158 Bq/particle ± 3 vs 1,058 Bq/particle ± 331, P = .001), and lower mean TD (308 Gy ± 210 vs 794 Gy ± 523, P = .0002) than the glass-based cohort. No significant differences in baseline characteristics or posttreatment AEs were noted. The overall objective and complete response rates were 85% (95% resin-based vs 82% glass-based; P = .1) and 65% (95% resin-based vs 56% glass-based; P = .003), respectively. The mean TD thresholds able to predict the objective and complete responses were 176 Gy and 247 Gy for resin-based radioembolization and 290 Gy and 481 Gy for glass-based radioembolization, respectively. A maximum NTD of 999 Gy predicted any-grade AEs in glass-based ablative 90Y-TARE. ConclusionsCompared with glass-based ablative 90Y-TARE, resin-based ablative 90Y-TARE can offer comparable safety and effectiveness profiles for patients with HCC. The impact of the significantly different tumor particle loading, particle specific activities, and delivered TDs on tumor response outcomes merits further investigation.

Transepithelial Corneal Cross-linking with Supplemental Oxygen in Keratoconus Treatment - Corneal Stromal Demarcation Line and Safety

Purpose: To evaluate the corneal stromal demarcation line and safety of transepithelial corneal cross-linking (CXL) with supplemental oxygen in progressive keratoconus treatment. Methods: This is a retrospective review of 25 patients with progressive keratoconus who underwent epithelial-on CXL with supplemental oxygen from December 2019 to February 2022. Outcomes measured include corneal stromal demarcation line depth, volume of cornea treated, endothelial cell count, best-corrected visual acuity, keratometric parameters and post-treatment adverse events. Results: 25 eyes of 25 patients were included and mean age was 28.3 years. Mean follow-up period was 11.5 ± 1.39 months. Pre-operatively, mean ± standard deviation (SD) of K1, K2, Kmax and minimal corneal thickness were 45.9D ± 3.79D, 50.2D ± 4.83D, 57.5D ± 6.98D and 482.3um ± 36.8um respectively. There is no significant difference between pre and post-treatment corneal topographic parameters. There was improvement in BCVA post-treatment. The mean post-treatment corneal stromal demarcation line depth was 367.3 ± 89.8um. The volume of treated cornea including the central corneal epithelial thickness was 73.3 ± 4.39%. There was no reduction in endothelial cell count (ECC) post-procedure (pre-treatment mean ECC±SD: 2695.4 ± 224.5 cells/mm2, post-treatment ECC 2730.1 ± 252.0 cells/mm2, p-value = 0.33). Post-treatment corneal haze was mild and seen in 8 patients postoperatively. One patient developed a non-visual axis involving stromal infiltrate that resolved with topical broad-spectrum anti-microbials. Conclusion: Trans-epithelial CXL with supplemental oxygen for keratoconus treatment achieved comparable corneal stromal demarcation line depth comparable to that of conventional epithelial-off corneal cross-linking and had a similar safety profile.

Real-world data comparing third and subsequent line regimens for treatment of metastatic triple-negative breast cancer in the United States.

e18765 Background: Eribulin is a commonly prescribed regimen for metastatic triple negative breast cancer (mTNBC) patients pre-treated with one or more chemotherapy regimens, although no clear survival benefit has been shown when compared to treatment of physician's choice (TPC) [1]. Here, using real-world oncology data we compare the impact of treatment with Eribulin vs. other common chemotherapies as third and subsequent lines of therapy on overall survival and post-treatment hospitalizations. Methods: We performed a retrospective cohort study of third and subsequent lines (3L+) treatment of patients with mTNBC between 1/2016 and 6/2021 using administrative claims data from the Anthem Cancer Care Quality Program. Real-world overall survival (rwOS) was defined as time from diagnosis to death. Real-world overall survival (rwOS) was defined as time from diagnosis to death. A Cox model with inverse probability of treatment weighting was used to adjust for age, ECOG, socioeconomic status, comorbidity, and liver and bone metastatic sites. Median rwOS was estimated using the weighted Kaplan-Meier method. Adjusted hazard ratios (aHR) were estimated using weighted Cox proportional hazards models. Results: We identified 210 (52%) individuals with mTNBC who received Eribulin (E) for 3L+, compared to 189 patients treated with other chemotherapies (O), which include carboplatin+gemcitabine, nab-paclitaxel, vinorelbine, paclitaxel, carboplatin and nab-paclitaxel+atezolizumab, ordered by frequency. We found no significant difference in any of the demographic and clinical features tested between the groups (Table). Median rwOS in the E group was 6.4 months, compared to 7.6 months in the O group (p-value = 0.4). In adjusted survival analyses to known confounders, E showed no significant difference in mortality (aHR: 1.09, 95% Confidence Interval [CI]: 0.87-1.37, p-value = 0.46). Furthermore, we found no significant difference in hospitalizations following the treatment between the E to the O group (36% vs. 39%, p-value = 0.6), length of stay (7 vs. 8 days, p-value = 0.8) and classes of associated severe adverse events. Conclusions: Our analysis of real-world oncology data aligns with National Institute for Health and Care Excellence (NICE) recent recommendation in showing no survival benefit or reduction in post-treatment adverse events when treating with Eribulin at 3L+ in metastatic TNBC patients.[Table: see text]

Real-world data comparing atezolizumab plus taxane therapy versus taxane alone as first-line treatment of metastatic triple-negative breast cancer patients in the United States.

e18767 Background: A recent clinical trial (Impassion131) showed that addition of atezolizumab to paclitaxel does not provide survival benefit for first-line (1L) treatment of metastatic triple-negative breast cancer (mTNBC) patients. The study was in contradiction to a previous study (Impassion130) that did show benefit using atezolizumab plus nab-paclitaxel. Using real-world data, we evaluated the impact on overall survival and post-treatment hospitalizations of 1L Atezolizumab + Taxane (Nab-Paclitaxel) (A+T) vs. Taxane agents alone (Paclitaxel or Nab-Paclitaxel) (T) in individuals with mTNBC. Methods: We performed a retrospective cohort study of 1L mTNBC patients between 1/2016 and 6/2021, utilizing administrative claims data from the Anthem Cancer Care Quality Program. Real-world overall survival (rwOS) was defined as time from diagnosis to death. Cox model with inverse probability of treatment weighting was used to adjust for age, ECOG, Socioeconomic deprivation index (SDI), comorbidity, and liver and bone metastatic sites. Median rwOS was estimated using the weighted Kaplan-Meier method. Adjusted hazard ratios (aHR) were estimated using weighted Cox proportional hazards models. We do not adjust for PD-L1 levels shown to have association with improved OS regardless of treatment, therefore, unlikely to confound our results. Results: The A+T combination therapy became a preferred 1L type of treatment for mTNBC patients since its introduction in 2019. We identified 155 (55%) individuals with 1L mTNBC who received A+T and compared this cohort to 128 (45%) individuals who received T alone. The A+T group were younger and had lower proportion of bone metastatic sites (Table). Percentage of patients with previous chemotherapy in the last year was similar between the groups (p = 0.9). Median rwOS was 13.6 and 17.5 months, in A+T and T group, respectively (p = 0.2). In adjusted survival analysis, the addition of atezolizumab showed insignificant increase in the risk of mortality (aHR: 1.09 (0.74-1.61), p = 0.66). Our post-treatment analysis did not identify statistically significant differences between the groups, in terms of post-treatment hospitalizations, adverse events classes, or length of stay of hospitalized patients. Conclusions: Our retrospective cohort study demonstrated that the addition of atezolizumab to 1L treatment, was not associated with survival benefit or reduce post-treatment adverse events in mTNBC patients.[Table: see text]

Clinical Efficacy and Safety of Non-Cross-Linked Hyaluronic Acid Combined with L-carnosine for Horizontal Neck Wrinkles Treatment

Background Horizontal neck wrinkle formation is gaining more attention among cosmetic practitioners and clients. To date, hyaluronic acid products are one of the most common treatment options for this aesthetic concern. However, different therapeutic strategies should be given to solve the problem due to multiple etiological reasons. Given that oxidative damage plays a critical role in neck wrinkle formation, anti-oxidative compounds are now considered by physicians when making a treatment plan. Aims To evaluate the efficacy and safety of a non-cross-linked hyaluronic acid filler in combination with L-carnosine in treating horizontal neck wrinkles. Methods Thirteen patients with a Wrinkle Assessment Scale (WAS) of 2–5 for horizontal neck wrinkles were treated with L-carnosine-containing non-cross-linked hyaluronic acid. Participants were followed-up for 3 months after treatment. The post-treated WAS scores evaluated by physicians were collected when patient satisfaction was surveyed. Any post-treatment adverse events were recorded. Results With a single injection of the above filler, the physician-evaluated WAS scores improved by at least one score at one month and the improvement kept consistent as far as three months after injection. According to the last follow-up visit, 11/13 patients were satisfied with the treatment effect of their neck wrinkle. Moreover, adverse events were rare after filler injection, except for local complications that were considered common reactions to the filler injection procedure. Conclusion The non-cross-linked hyaluronic acid filler containing L-carnosine is safe and effective for treating horizontal neck wrinkles.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Efficacy and safety of magnetic resonance-guided focused ultrasound for the treatment of painful bone metastases: a systematic review and meta-analysis

ObjectiveTo report the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) in the treatment of painful bone metastases through a systematic review and meta-analysis of pain scores before and after MRgFUS treatment and post-treatment adverse events.Materials and methodsA comprehensive literature search of PubMed and Embase databases was performed for studies evaluating the efficacy and/or safety of MRgFUS. The mean difference of pain scores (10-point visual analogue scale or numerical rating scale) between baseline and 1-month/3-month pain scores was collected and analyzed in a pooled meta-analysis. Post-treatment adverse events based on the Common Terminology Criteria for Adverse Events (CTCAE) grading were recorded and the pooled prevalence was calculated.ResultsA total of 33 studies published between 2007 and 2019 were collected, resulting in a total sample size of 1082 patients. The majority of the studies were prospective with a reported follow-up period of 3 months. The pooled proportion of patients that achieved pain relief from MRgFUS (complete response or partial response [≥ 2-point improvement of pain score]) was 79% (95% CI 73–83%). The pooled 1-month and 3-month mean difference in pain score were − 3.8 (95% CI − 4.3; − 3.3) and − 4.4 (95% CI − 5.0; − 3.7), respectively. The overall rate of high-grade (CTCAE grade 3 or higher) and low-grade (CTCAE grade 2 or lower) MRgFUS-related adverse events were 0.9% and 5.9%, respectively.ConclusionMRgFUS is an effective procedure that is able to provide significant pain palliation for patients with symptomatic bone metastases with a favorable safety profile.

Sa1312 CLINICAL OUTCOME OF PERORAL ENDOSCOPIC MYOTOMY IN ADVANCED ACHALASIA TREATMENT STRATIFIED BY MORPHOLOGICAL SUBTYPES

Peroral endoscopic myotomy (POEM) has been first-line treatment of achalasia. However, the efficacy and safety of POEM on advanced achalasia remains to be clarified. Our purpose was to evaluate the feasibility and clinical outcome of POEM for advanced AC with various esophageal morphological changes. From June 2015 to March 2019, a total of 50 patients were enrolled with advance achalasia (megaesophagus type in 23 patients, sigmoid type in 19 patients and both type in 8 patients). Primary endpoint was symptomatic relief during follow-up, defined as an Eckardt score ≤3. Secondary endpoints were intra-procedural details such as operation time, length of myotomy, post-treatment adverse events, hospital stay, as well as delayed AE, named gastroesophageal reflux disease (GERD). All patients successfully received endoscopic myotomy, with a mean procedure time of 38.5±26.3 (range, 10.7-162.6) min. In 10 patients (20%) adverse events were encountered, including mild (n=8) and moderate (n=6) without conversion to surgery and ICU admission. During a mean follow-up of 23.8 months, despite 41 (89.1%) patients achieved treatment success with a decrease in mean Eckardt score from 7.2 to 1.7 (P=6.7×10-9), only 4 (57.1%) patients in subgroup 3 (dilation and sigmoid esophagus) obtained clinical success. Symptomatic reflux occurred in 13 patients (13/46, 28.3%), and all reflux symptoms were easily controlled by intermittent oral medication with PPIs. In advanced achalasia patients with various esophageal morphological changes, POEM was a technically feasible, safe and effective option. POEM appears to be less effective in patients with significant dilated and distorted esophagus, which should be paid more attention in future managements.

Limited Efficacy of Thrombolytics for Pump Thrombosis in Durable Left Ventricular Assist Devices

This study reports a single-center experience with thrombolytics for left ventricular assist device (LVAD) pump thrombosis. Adults undergoing continuous-flow LVAD implantation between 2004 and 2018 at a single center were reviewed and those with pump thrombosis were identified. Primary outcomes included 1-year survival and success rates of thrombolytic therapy. Secondary outcomes included posttreatment adverse events, freedom from major bleeding at 1 year, and freedom from stroke at 1-year follow-up. A total of 341 patients underwent LVAD implantation and 10.8% (n= 37) developed pump thrombosis. Of those 37, 26 received initial thrombolytic therapy (70.2%), 5 underwent direct pump exchange (13.5%), and 6 received only intravenous heparin owing to presentation with acute stroke or severe multiorgan failure (16.2%). Successful treatment was achieved in 11.5% of patients receiving thrombolytics (n= 3). Early adverse events after thrombolytic therapy included major bleeding in 11.5% (n= 3) and new stroke in 7.7% (n= 2). Most patients undergoing thrombolytic therapy underwent subsequent device exchange (69.2%; n= 18). Overall survival in patients with pump thrombosis after treatment was 96.8% at 30 days, 78.9% at 90 days, and 63.1% at 1 year. Freedom from major bleeding and stroke at 1 year was 74.2% and 87.2%, respectively. In this single-center experience of thrombolytics for pump thrombosis in LVAD patients, there was limited efficacy; most patients required subsequent pump exchange. Combined with the risk for major bleeding or stroke with thrombolysis, this underscores the importance of further refining patient selection for direct pump exchange in those presenting with pump thrombosis.

Outpatient Yttrium-90 microsphere radioembolization: assessment of radiation safety and quantification of post-treatment adverse events causing hospitalization.

Quantification of post-interventional adverse events of outpatient SIRT leading to hospitalization and quantification of radiation exposure. In this single-center, retrospective cohort study, we reviewed 212 patients treated with SIRT (90Y-microspheres) for primary and secondary liver malignancies. We searched for adverse events (AEs) and serious adverse events (SAEs), defined as AE's causing hospitalization. Additionally, radiation exposure was measured in 36 patients. Seven patients had an SAE (3.3%), four patients had AE without readmission/hospitalization (1.9%) and 201 patients had no complications (94.8%). The mean ambient dose rate at 1m distance from the source after administration of 90Y-microspheres was 1.88µSv/h ± 0.74 (± SD) with a range from 4.3 to 0.2µSv/h. Outpatient radioembolization with 90Y-microspheres is safe and requires hospitalization only in a very small number of patients. The mean dose rate was low and met the national conditions for outpatient treatment (< 5µSv/h).

Infection-associated Immune Perturbations Resolve 1 Year Following Treatment for Loa loa.

We have previously demonstrated that eosinophil-associated processes underlie some of the differences in clinical presentation among patients with Loa loa infection prior to therapy and that some posttreatment adverse events appear to be dependent on eosinophil activation. We first conducted a retrospective review of 204 patients (70 microfilaria [MF] positive/134 negative) with Loa loa both before and following definitive therapy. We then measured filarial-specific antibodies, eosinophil- and Th2-associated cytokines, and eosinophil granule proteins in their banked serum prior to and at 1 year following definitive treatment. We also evaluated the influence of pretreatment corticosteroids and/or apheresis in altering the efficacy of treatment. Patients without circulating microfilariae (MF negative) not only had a higher likelihood of peripheral eosinophilia and increased antifilarial antibody levels but also had significantly increased concentrations of granulocyte-macrophage colony-stimulating factor, interleukin (IL) 5, and IL-4 compared with MF-positive patients. However, these differences had all resolved by 1 year after treatment, when all parameters approached the levels seen in uninfected individuals. Neither pretreatment with corticosteroids nor apheresis reduced the efficacy of the diethylcarbamazine used to treat these subjects. Our results highlight that, by 1 year following treatment, infection-associated immunologic abnormalities had resolved in nearly all patients treated for loiasis, and pretreatment corticosteroids had no influence on the resolution of the immunologic perturbations nor on the efficacy of diethylcarbamazine as a curative agent in loiasis. NCT00001230.

An Observational Study of Follow Up of MDR Tuberculosis Patients after Successful Completion of Category 4 Treatment under RNTCP (PMDT) in Allahabad District

Introduction: Drug-resistant TB is a persistent threat, with 490 000 million cases of multidrug-resistant TB emerging in 2016.The countries with the largest numbers of MDR/RR-TB cases were China, India and the Russian Federation. Given the prolonged nature of MDR-TB, one might expect higher rates of chronic disability among cured patients with MDR-TB. To explore these questions, we conducted an observational study focusing on: clinical, bacteriological, biochemical and various health parameter status of successfully treated MDR-TB patients.&#x0D; Methods: Subjects enrolled in study as per inclusion and exclusion criteria were assessed by recording of demographic data and were subjected to a predetermined set of questions for determining the history of previous anti tubercular treatment and exposure to various type of risk factor for development of MDR TB. Physical parameters of health were determined and recorded.&#x0D; Results: Total of 84 patients were enrolled in our study (57-males, 27 females).69 subjects (46-males, 23-Females) were found apparently healthy. 25 subjects migrated outside.6 patients (male-6, Female-2) died.7 patients were diagnosed as XDR-TB (5-Males,2-Females).34 subjects (18- males, 16-females) (44.73%) were very under weight. Total 13 (Males-12, Females-1) out of 76 subjects (17.10%) were under weight. Mid arm circumference (MAC) of 35 out of 76(21- males, 18-females) subjects (46.05%) was below 5th percentile. Majority of subjects showed moderate &amp; severe obstruction in PEFR.&#x0D; Conclusion: This study shows that the community based standardized treatment regimen is effective as only one of the patients was bacteriologically positive on follow up. However, significant numbers of treated MDR-TB patients suffer from clinical, nutritional and functional post-treatment adverse events leading to some morbidity.

Post-interventional adverse event risk by vascular access site among patients with acute coronary syndrome in Japan: observational analysis with a national registry J-PCI database.

This study evaluated whether radial access intervention had a lower risk of post-treatment adverse events in acute coronary syndrome (ACS) even in Japan where the use of a strong antithrombotic regimen was not approved. We retrospectively analyzed a large nation-wide registry in Japan to compare the incidence of post-treatment adverse events according to the types of vessel access (trans-radial; TRI vs. trans-femoral; TFI) among ACS cases (n = 76,835; 43,288 TRI group and 33,547 TFI group). Primary outcome was a composite of in-hospital death, myocardial infarction associated with percutaneous coronary intervention, bleeding complication requiring transfusion, and stent thrombosis during in-hospital stay. Propensity score matching (PS) and instrumental variable (IV) analyses were used to account for treatment selection. The incidence of post-treatment adverse events was lower in the TRI group by 0.95% compared to the TFI group with PS (p < 0.001) and by 0.34% with IV (p = 0.127). A significantly lower risk for access site bleeding was observed by 0.34% with PS (p < 0.001) and by 0.53% with IV (p < 0.001). Radial access was related to a significantly lower risk for access site bleeding compared with femoral access, even without strong antithrombotic drugs for ACS in Japan, and may also relate to lower risk for a wider set of post-treatment adverse events.

Adverse events following single dose treatment of lymphatic filariasis: Observations from a review of the literature.

BackgroundWHO’s Global Programme to Eliminate Lymphatic Filariasis (LF) uses mass drug administration (MDA) of anthelmintic medications to interrupt LF transmission in endemic areas. Recently, a single dose combination of ivermectin (IVM), diethylcarbamazine (DEC), and albendazole (ALB) was shown to be markedly more effective than the standard two-drug regimens (DEC or IVM, plus ALB) for achieving long-term clearance of microfilaremia.Objective and methodsTo provide context for the results of a large-scale, international safety trial of MDA using triple drug therapy, we searched Ovid Medline for studies published from 1985–2017 that reported adverse events (AEs) following treatment of LF with IVM, DEC, ALB, or any combination of these medications. Studies that reported AE rates by treatment group were included.FindingsWe reviewed 162 published manuscripts, 55 of which met inclusion criteria. Among these, 34 were clinic or hospital-based clinical trials, and 21 were community-based studies. Reported AE rates varied widely. The median AE rate following DEC or IVM treatment was greater than 60% among microfilaremic participants and less than 10% in persons without microfilaremia. The most common AEs reported were fever, headache, myalgia or arthralgia, fatigue, and malaise.InterpretationMild to moderate systemic AEs related to death of microfilariae are common following LF treatment. Post-treatment AEs are transient and rarely severe or serious. Comparison of AE rates from different community studies is difficult due to inconsistent AE reporting, varied infection rates, and varied intensity of follow-up. A more uniform approach for assessing and reporting AEs in LF community treatment studies would be helpful.

A Test-and-Not-Treat Strategy for Onchocerciasis in Loa loa–Endemic Areas

BackgroundImplementation of an ivermectin-based community treatment strategy for the elimination of onchocerciasis or lymphatic filariasis has been delayed in Central Africa because of the occurrence of serious adverse events, including death, in persons with high levels of circulating Loa loa microfilariae. The LoaScope, a field-friendly diagnostic tool to quantify L. loa microfilariae in peripheral blood, enables rapid, point-of-care identification of persons at risk for serious adverse events.MethodsA test-and-not-treat strategy was used in the approach to ivermectin treatment in the Okola health district in Cameroon, where the distribution of ivermectin was halted in 1999 after the occurrence of fatal events related to L. loa infection. The LoaScope was used to identify persons with an L. loa microfilarial density greater than 20,000 microfilariae per milliliter of blood, who were considered to be at risk for serious adverse events, and exclude them from ivermectin distribution. Active surveillance for posttreatment adverse events was performed daily for 6 days.ResultsFrom August through October 2015, a total of 16,259 of 22,842 persons 5 years of age or older (71.2% of the target population) were tested for L. loa microfilaremia. Among the participants who underwent testing, a total of 15,522 (95.5%) received ivermectin, 340 (2.1%) were excluded from ivermectin distribution because of an L. loa microfilarial density above the risk threshold, and 397 (2.4%) were excluded because of pregnancy or illness. No serious adverse events were observed. Nonserious adverse events were recorded in 934 participants, most of whom (67.5%) had no detectable L. loa microfilariae.ConclusionsThe LoaScope-based test-and-not-treat strategy enabled the reimplementation of community-wide ivermectin distribution in a heretofore “off limits” health district in Cameroon and is a potentially practical approach to larger-scale ivermectin treatment for lymphatic filariasis and onchocerciasis in areas where L. loa infection is endemic. (Funded by the Bill and Melinda Gates Foundation and others.)

Repurposed automated handheld counter as a point-of-care tool to identify individuals 'at risk' of serious post-ivermectin encephalopathy.

IntroductionAdministration of ivermectin (IVM) as part of mass drug administration (MDA) campaigns for onchocerciasis and/or lymphatic filariasis (LF) has been suspended in areas co-endemic for Loa loa due to severe post-treatment adverse events (SAEs) associated with high-burden of infection (>30,000 mf/ml). One simple approach for preventing SAEs is to identify and exclude individuals at risk from MDA. Here, we describe a repurposed hand-held automated cell counter (Scepter 2.0; HHAC) as a rapid, point-of-care method for quantifying microfilariae (mf) in the blood of infected individuals.Methodology/Principal FindingsThe quantification of microfilarial levels in blood of naturally infected humans, experimentally infected baboons, or mf-spiked human blood was tested using a microfluidic-based automated counter and compared to traditional calibrated thick-smears. We demonstrate that mf can be quantified in 20 µl of whole blood following lysis with 10% saponin within a minute of obtaining blood. There was a highly significant concordance between the counts obtained by the HHAC and those by microscopy for mf densities of >5,000 (p<0.0001, rc = 0.97) or >30,000 per ml (p<0.0001, rc = 0.90). Preliminary proof of concept field studies in Cameroon with 20 µl of blood from L. loa infected humans (n = 22) and baboons (n = 4) also demonstrated a significantly high concordance (p<0.0001, rc = 0.89) with calibrated thick blood smears counts.Conclusions/SignificanceA repurposed HHAC is a portable, sensitive, rapid, point-of-care and quantitative tool to identify individuals with high levels of L. loa mf that put them at risk for SAEs following MDA. In addition, it provides ease of data storage and accessibility.