Post-treatment Observation Research Articles

Arterial spin labeling detects trapped labeled spins in flow-diverted aneurysms and it reflects intra-aneurysmal flow stasis.

This study evaluated arterial spin labeling (ASL) imaging findings in flow-diverted aneurysms (FD-ANs). Twenty-one patients with internal carotid artery aneurysms treated with flow-diverter stent (FDS) were included. Time-of-flight magnetic resonance angiography (TOF-MRA) and ASL were performed before and after follow-up digital subtraction angiography (DSA) on the day, 6 months, and/or 1 year after treatment. Two radiologists rated the clarity of the depiction of FD-ANs for MRA on a 3-point scale and the ASL signal intensity of the aneurysm as negative or positive. A neurosurgeon assessed DSA findings using the O'Kelly-Marotta (OKM) grading scale, categorizing them into filling and stasis grades. The 23 examinations were classified according to the OKM grading scale, and the proportion of ASL-positive cases and the proportion of cases with MRA scores of 1-2 (detectable) were calculated for each grade. The relationship between the OKM grading scale and ASL positivity or MRA detectable was examined using Fisher's exact test. Of seven examinations where the statis grade was 1 or 2, no examinations showed ASL positivity. However, among the 16 examinations in which the stasis grade was 3, 9 examinations showed ASL positivity. A significant association was observed between stasis grade and ASL positivity (p = 0.035). In contrast, no significant relationship was observed between the OKM grading scale and the MRA 3-point scale. High-signal ASL in FD-ANs could reflect stasis within the aneurysm; therefore, noninvasive ASL can indicate reduction in intra-aneurysmal blood flow after treatment and reperfusion during posttreatment observation.

Azacitidine and cytarabine induce sustained lymphopenia with abnormal differentiation of common lymphoid progenitors and prolonged suppression of Dnmt3a and Dnmt3b expression in mice.

Myelosuppression is a major side effect of chemotherapy. Although decreased blood cells are restored with the recovery of bone marrow cells, insufficient recovery of decreased lymphocytes was observed in mice given azacitidine (AZA), a DNA methyltransferase (DNMT) inhibitor, even following the restoration of bone marrow cells. To understand the mechanisms behind this sustained lymphopenia, we examined AZA's impact on the hematopoietic progenitor cells and the expression of Dnmts and differentiation-related genes. An antimetabolite of cytidine analog, cytarabine (Ara-C), was used as a reference compound. Decreases in almost all blood parameters and common lymphoid progenitors (CLPs) and the downregulation of Dnmts and differentiation-related genes in Lineage-Sca-1+c-kit+ (LSK) cells were observed in mice administered AZA or Ara-C for 7 d. In the posttreatment observation, all parameters, except for lymphocytes and monocytes, exhibited recovery within 3 wk after the final dosing in both treated groups. However, no recovery from the decreases in lymphocytes, especially B cells, and monocytes occurred even after 5 wk. The number of CLPs was elevated after 3 wk. There was a tendency toward recovery from the decreased expression of Dnmt1 and differentiation-related genes, but the expression levels of Dnmt3a and Dnmt3b did not fully recover even 5 wk after the final dosing. Taken together, the findings revealed that the mechanism of sustained lymphopenia observed in mice treated with AZA or Ara-C is associated, at least in part, with the abnormal differentiation of CLPs into B cells accompanied by the prolonged suppression of Dnmt3a and Dnmt3b expression on LSK cells.

Efficacy and Safety of Valbenazine in Elderly and Nonelderly Japanese Patients With Tardive Dyskinesia: A Post Hoc Analysis of the J-KINECT Study.

The efficacy and safety of valbenazine, a selective vesicular monoamine transporter 2 inhibitor, has been confirmed for treatment of tardive dyskinesia (TD) in patients aged ≥65 years in non-Asian clinical trials; however, data are lacking in elderly Asian patients. This post hoc analysis of J-KINECT aimed to evaluate the efficacy and safety of valbenazine in elderly Japanese patients with TD. J-KINECT was a randomized, double-blind, placebo-controlled study with a 6-week double-blind, placebo-controlled period; 42-week double-blind, valbenazine extension period; and 4-week posttreatment observation period. Outcomes were summarized by age (≥65 years [elderly] and <65 [nonelderly]) and treatment group. The safety analysis set included 100 and 153 patients aged ≥65 and <65 years, respectively (intention-to-treat set: 98 and 151 patients, respectively). In the elderly group, the difference versus placebo in least-squares mean change from baseline in the Abnormal Involuntary Movement Scale total score at week 6 was -3.1 (95% confidence interval: -4.5, -1.7) and -5.5 (-7.0, -3.9) with valbenazine 40 and 80 mg, respectively; in the nonelderly group, respective differences were -1.5 (-2.6, -0.4) and -2.5 (-3.6, -1.3). Both age groups showed improvement in Clinical Global Impression of Change-Tardive Dyskinesia scores with valbenazine. The incidence of treatment-emergent adverse events (TEAEs) leading to treatment discontinuation was higher in the elderly versus nonelderly group. There was no trend toward higher incidences of TEAEs or related TEAEs in the elderly group. The findings suggest that valbenazine may be used effectively and safely as a treatment for TD, even in elderly patients.

Impact of YouTube-based Learning on Early Childhood Education

The development of spiritual intelligence in five to six year old children warrants effective stimulation. Various tools are used in kindergartens for this purpose, yet there remains a scope for improvement. Consequently, this study advocates the use of Youtube as a medium for enhancing spiritual intelligence in children. Preliminary observations at the Asyiyah Bustanul Atfhal Dolago Kindergarten indicate a lack in spiritual understanding among children, from recognizing divinity in creation to showing respect to others as an expression of gratitude to God, and a basic understanding of hijaiyyah letters. Therefore, parents and teachers are encouraged to utilize Youtube to stimulate spiritual intelligence in these children, especially amidst the Covid-19 circumstances. This research employs an experimental design, conducted in three stages: preparatory, implementation, and final stages. The techniques for data collection include the use of observation sheets, with descriptive and inferential data analysis. The evaluation factors include understanding the pillars of faith and Islam, recognition of hijaiyyah letters, and knowing the two sentences of shahada. The findings suggest that the use of Youtube Audio Visual media successfully boosts spiritual intelligence in children aged five to six, as indicated by improved post-treatment observation results. Keywords: spiritual intelligence, Youtube, early childhood

THE OUTCOME OF ANTIBIOTICS VS OPEN APPENDECTOMY FOR ACUTE NON-PERFORATED APPENDICITIS

Acute appendicitis is a common surgical emergency. While appendectomy has been the conventional treatment for this condition, recent advancements in antibiotic therapy have led to exploring the use of antibiotics as a non-surgical alternative for treating non-complicated acute appendicitis. Objective: The objective of the present study was to compare the outcomes of administering antibiotics and performing emergency appendicectomy in a cohort of individuals diagnosed with non-perforated acute appendicitis based on CT evaluation. Methods: After the ethical approval from the institutional review board, this randomised control trial was conducted at Combined Military Hospital Jhelum from July 2022 to December 2023. The patients were randomly assigned, using a closed envelope method, to either have open appendectomy (Group A, n=60) or receive antibiotic therapy (Group B, n=60) with intravenous ertapenem. Open appendectomy was conducted utilising the McBurney technique. The patient’s outcomes were assessed during their hospitalization period, specifically on days 0, 1, and 2, and by telephone interviews one week and two months following the intervention. Pain scores were collected at two specific time points, one week and two months after randomisation, utilising a visual analogue scale (VAS). Results: No significant differences were observed in the baseline characteristics in both groups. Mean± S.D of the pain experience of the study participants in both groups was 4.16±1.04 and 3.68±1.02 (days) (P value=0.008). Mean± S.D of the hospital stay of the study participants in both groups was 3.13±0.87 and 3.16±0.83 (days) (P value=0.843). A significant difference in the VAS score was observed (p &lt;0.0001) in the participants of both groups at discharge and after a one-week follow-up period. Conclusion: The findings of the study indicate that a significant proportion of individuals who received antibiotic therapy for non-perforated acute appendicitis did not necessitate the surgical procedure of appendectomy within the two-month post-treatment observation period.

In-feed Praziquantel treatment ofgrass carp (Ctenopharyngodon idella) infected with eye flukes.

Praziquantel (PZQ) isadrug effective against several parasitic diseases offish caused byPlatyhelminthes. The study assesses the efficacy ofselected in-feed PZQ doses ineliminating metacercariae Diplostomum pseudospathaceum ingrass carp. The fish were infected with D.pseudospathaceum inlaboratory conditions and subsequently treated with PZQ atdaily doses of30 (PZQ1), 50 (PZQ2), and 100 (PZQ3) mg/kgbwfor seven days. The treatment trial was followed bya23-day observation period during which the fish were parasitologically examined ondays0, 2, 8 and 23. Smaller fish were infected with asignificantly higher (P < 0.05) number ofmetacercariae than bigger fish among three weight groups asfollows: upto7 g > 7 to12 g > 12 g. The in-feed PZQ atdoses of30, 50 and 100mg/kgbwfor seven days was 47%, 84% and 88% effective against metacercariae D.pseudospathaceum, respectively. Asignificant decrease (P < 0.01) inmoving and anincrease (P < 0.01) intheimmotile metacercariae inthe eye's lens were recorded inall the trial groups oneach sampling day. Anincreasing proportion ofmotile metacercariae inthe post-treatment observation period was seen inPZQ2 and PZQ3, indicating adecreasing trend inthe actual efficacy inanenvironment with noreinfection possibility.

Frequency of complications of transurethral pneumatic lithotripsy in pediatric bladder stone disease.

Background: Despite advancements, underdeveloped countries continue to face the burden of widespread illness causing pain, often attributed to factors like low nutrition and recurring infections, particularly vitamin A deficiency.&#x0D; Methodology: This descriptive study employed a non probability convenient sampling technique and was conducted at the Urology Department of Lady Reading Hospital, Peshawar. The investigation spanned six months from January 25, 2019, to June 25, 2019. The study encompas sed a cohort of 369 patients, each subjected to comprehensive urine tests and detailed history and physical examinations. Procedures were performed under general anesthesia, utilizing Pediatric URS and pneumatic intracorporeal lithotripsy with Swiss lithoc last for bladder stone treatment. A 48 hour post treatment observation period assessed common intraoperative and postoperative consequences of transurethral pneumatic lithotripsy, including hematuria, bladder perforation, acute urine retention, and fever.&#x0D; Results: Among the participants, 32% were female, and 68% were male. Notably, 5% experienced bladder perforation, 7% had hematuria, 4% exhibited acute urinary retention, and 7% presented with fever.&#x0D; Conclusion: This study highlights complications of transurethral pneumatic lithotripsy in pediatric bladder stone disease, including bladder perforation, hematuria, acute urinary retention, and fever, providing crucial insights for clinical decisions.

Ceftobiprole Medocaril Is an Effective Post-Exposure Treatment in the Fischer 344 Rat Model of Pneumonic Tularemia.

Francisella tularensis subspecies tularensis is a category-A biothreat agent that can cause lethal tularemia. Ceftobiprole medocaril is being explored as a medical countermeasure for the treatment of pneumonic tularemia. The efficacy of ceftobiprole medocaril against inhalational tularemia was evaluated in the Fischer 344 rat model of infection. The dose was expected to be effective against F. tularensis isolates with ceftobiprole minimum inhibitory concentrations ≤0.5 µg/mL. Animals treated with ceftobiprole medocaril exhibited a 92% survival rate 31 days post-challenge, identical to the survival of levofloxacin-treated rats. By comparison, rats receiving placebo experienced 100% mortality. Terminally collected blood, liver, lung, and spleen samples confirmed disseminated F. tularensis infections in most animals that died prior to completing treatments (placebo animals and a rat treated with ceftobiprole medocaril), although levels of bacteria detected in the placebo samples were significantly elevated compared to the ceftobiprole-medocaril-treated group geometric mean. Furthermore, no evidence of infection was detected in any rat that completed ceftobiprole medocaril or levofloxacin treatment and survived to the end of the post-treatment observation period. Overall, survival rates, body weights, and bacterial burdens consistently demonstrated that treatment with ceftobiprole medocaril is efficacious against otherwise fatal cases of pneumonic tularemia in the rat model.

Time and productivity loss associated with immunotherapy infusions for the treatment of melanoma in the United States: a survey of health care professionals and patients

IntroductionA new dosing schedule for the oncology immunotherapy pembrolizumab, every 6 weeks (Q6W), has been approved by the U.S. FDA, reducing the frequency of visits to infusion centers. We quantified the time spent by oncologists, nurses, patients, and caregivers per melanoma-related immunotherapy infusion visit to evaluate its potential impact.MethodsSurveys were self-completed by 100 oncologists, 101 oncology nurses, and 100 patients with melanoma across the U.S. to quantify the time spent per infusion visit with pembrolizumab (Q3W or Q6W), nivolumab (Q2W or Q4W), or nivolumab+ipilimumab (nivolumab in combination: Q3W; nivolumab maintenance: Q2W or Q4W). Time measures included traveling, waiting, consultation, infusion, post-treatment observation, and caregiving. Respondents were also surveyed regarding the impact of the COVID-19 pandemic on infusion treatments.ResultsResponses deemed valid were provided by 89 oncologists, 93 nurses, and 100 patients. For each new [returning] patient treated with pembrolizumab, nivolumab or nivolumab+ipilimumab, oncologists reported to spend an average of 90 [64], 87 [60] and 101 [69] minutes per infusion visit (p-value for between-group difference = 0.300 [0.627]). For first [subsequent] treatment cycles, nurses reported spending 160 [145] average minutes per visit for nivolumab+ipilimumab, versus roughly 120 [110] for the single agents (p-value for between-group difference = 0.018 [0.022]). Patients reported to spend an average of 263, 382, and 224 minutes per visit at the center for pembrolizumab (N = 47), nivolumab (n = 34), and nivolumab+ipilimumab (n = 15) respectively (p-value for between-group difference = 0.0002). Patients also reported that their unpaid (N = 20) and paid caregivers (N = 41) spent with them an average of 966 and 333 minutes, respectively, from the day before to the day after the infusion visit.ConclusionLess frequent immunotherapy infusion visits may result in substantial time savings for oncologists, nurses, patients, and caregivers.

Nonacog Alfa for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Patients with Moderately Severe or Severe Hemophilia B in India

PurposeHemophilia B is an X-linked congenital bleeding disorder caused by a deficiency of coagulation factor IX (FIX) clotting activity. This study evaluated safety and efficacy of nonacog alfa, a recombinant human blood coagulation FIX replacement product, in males aged 12–65 years with hemophilia B (FIX activity ≤ 2%) with or without inhibitors in India.MethodsIn this multicenter, open-label, post-approval phase 4 study, participants were treated for up to 8 weeks, with up to a 4-week screening period and a subsequent post-treatment 28-day safety observation period. Intravenous nonacog alfa 40 IU/kg (range 13–78 IU/kg) was administered at intervals of 3–4 days, in accordance with the approved local product document.ResultsA total of 25 participants were enrolled and completed the study. No participants developed FIX inhibitors during the study, experienced treatment-related adverse events (AEs) or serious AEs, or developed a thrombotic event and/or hypersensitivity reaction. No participants experienced bleeding events requiring on-demand treatment with nonacog alfa. Seventeen bleeding episodes (16 spontaneous and 1 traumatic) were reported in 10 participants; all occurred post treatment, with the exception of a minor gum-bleeding event, and were managed without treatment. The mean (SD) annualized total factor consumption (TFC) per patient was 224,582 (75,527) IU; the mean (SD) annualized TFC by weight per patient was 3639 (573) IU/kg.ConclusionNonacog alfa was safe and effective for the prevention of hemorrhagic episodes in Indian males with congenital, severe hemophilia B. No participants developed FIX inhibitors, and no new safety signals were reported.

Short-term efficacy and long-term survival of nasopharyngeal carcinoma patients with radiographically visible residual disease following observation or additional intervention: A real-world study in China.

To explore the short- and long-term outcomes in patients with nasopharyngeal carcinoma (NPC) with magnetic resonance imaging (MRI)-detected residual disease at 3 months post-treatment who received intervention either promptly (0 month) or following observation (after an additional 3 months). A total of 272 patients with residual disease at 3 months post-treatment (observation [observation for additional 3 months]: 122, intervention [prompt intervention]: 150) were analyzed. Univariate and multivariate analyses were performed to examine the survival. Adverse events were analyzed in all patients. Patients in the observation group had a lower 3-year overall survival (77.1% vs. 85.2%), progression-free survival (10.2% vs. 18.1%), and locoregional relapse-free survival (10.2% vs. 20.6%) (all p< .05), but not distant metastasis-free survival (83.8% vs. 78.4%, p= .189), whereas patients in the intervention group achieved higher complete remission (CR) rates (43.3% vs. 21.2%, p= .003). Patients who achieved CR after prompt intervention had a better survival rate than those who achieved observation-CR or non-CR (p< .001). Multivariate analyses revealed that a wait-and-see policy was an independent prognostic factor for impaired survival (p< .001). No significant differences of acute or late toxicities were observed between the two groups. Patients with NPC with MRI-detected residual disease 3 months post-radiotherapy should be encouraged to undergo prompt intervention rather than adopting a passive wait-and-see policy.

RF06 | PSAT171 Impact of GH Administration on Skeletal Endpoints in Adults with Overweight/Obesity

Abstract Background Obesity is associated with relative growth hormone (GH) deficiency and increased fracture risk. We hypothesized that GH administration would improve bone endpoints in individuals with overweight/obesity. Methods 77 adults ages 18-65 years, BMI ≥25 kg/m2, and BMD T- or Z-score ≤ -1.0 were randomized in a double-blind protocol to daily subcutaneous GH or placebo for 18 months, targeting IGF-1 in the upper quartile of the age-appropriate normal range. There was a post-treatment observation period from 18-24 months. DXA and high-resolution peripheral quantitative CT were performed at baseline, 18 months and 24 months. Volumetric quantitative CT was performed at baseline and 18 months. Results are reported as mean ±SD or mean (95% confidence interval). Results There were no pretreatment differences between the GH (n=39) and placebo groups (n=38), including mean age (48±12y), BMI (33.1±5.7kg/m2) and BMD at any site. Forty-nine subjects (47% female) completed 18 months. P1NP, osteocalcin and CTX increased (p&amp;lt;0.005) and visceral adipose tissue decreased (p=0.04) at 18 months in the GH vs placebo group. Hip and radius aBMD, spine and tibial vBMD, tibial cortical thickness, and radial and tibial failure load decreased at 18 months in the GH vs placebo group (p&amp;lt;0.05). During the post-treatment observation period (18 to 24 months), total radius aBMD and tibia cortical thickness increased in the GH vs placebo group (p&amp;lt;0.05); there was also a trend toward an increase in total hip aBMD in the GH vs placebo group (p=0.06). At 24 months, none of the differences between the GH and placebo groups remained significant. There was a higher incidence of numbness and tingling (33% vs 8%, p=0.01) and joint pain or stiffness (33% vs 5%, p=0.003) in the GH vs placebo group. There were no other differences in adverse events between groups. Conclusions We demonstrated that GH administration for 18 months to individuals with overweight/obesity and low BMD decreased some measures of BMD, bone microarchitecture, and bone strength compared with placebo. None of these differences remained significant after 6 months off therapy. A longer duration of treatment, or a longer duration of observation post-treatment, may be necessary to see the expected biphasic decline and then increase in BMD reflecting an expanding remodeling space followed by mineralization that has previously been seen with GH administration in other populations, including individuals with and without GH deficiency. Although future investigation of the effects of GH on bone is required to assess the true long-term impact on skeletal integrity as well as fracture reduction, our study suggests that GH administration for 18 months to adults with overweight/obesity does not improve BMD, bone microarchitecture, or bone strength. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:12 p.m. - 1:17 p.m.

Is there an association between left atrial outpouching structures and recurrence of atrial fibrillation after catheter ablation?

ObjectiveThe aim of this study was to investigate the impact of left atrial diverticula (LADs), left sided septal pouches (LSSPs) and middle right pulmonary veins (MRPVs) on recurrent atrial fibrillation (rAF) in patients undergoing laser pulmonary vein isolation procedure (PVI).Material and methodsThis retrospective study enrolled 139 patients with pre-procedural multiple detector computed tomography (MDCT) imaging and 12 months follow-up examination. LADs, LSSPs and MRPV were identified by two radiologists on a dedicated workstation using multiplanar reconstructions and volume rendering technique. Univariate and bivariate regression analyses with patient demographics and cardiovascular risk factors as covariates were performed to reveal independent factors associated with rAF.ResultsLADs were recorded in 41 patients (29%), LSSPs in 20 (14%) and MRPVs in 15 (11%). The right anterosuperior wall of the left atrium was the most prevalent location of LADs (68%). rAF occured in 20 patients, thereof, 15 exhibited an outpouching structure of the left atrium (LAD: 9, LSSP: 2 and MRPV: 3). Presence of an LAD (HR: 2.7, 95%CI: 1.0–8.4, p = 0.04) and permanent AF (HR: 4.8, 95%CI: 1.5–16.3, p = 0.01) were independently associated with rAF.ConclusionsLAD, LSSP and MRPV were common findings on pre-procedural cardiac computed tomography. LADs were revealed as potential independent risk factor of rAF, which might be considered for treatment planning and post-treatment observation.

Impact of GH administration on skeletal endpoints in adults with overweight/obesity.

Overweight/obesity is associated with relative growth hormone (GH) deficiency and increased fracture risk. We hypothesized that GH administration would improve bone endpoints in individuals with overweight/obesity. An 18-month, randomized, double-blind, placebo-controlled study of GH, followed by 6-month observation. In this study, 77 adults (53% men), aged 18-65 years, BMI ≥ 25 kg/m2, and BMD T- or Z-score ≤ -1.0 were randomized to daily subcutaneous GH or placebo, targeting IGF1 in the upper quartile of the age-appropriate normal range. Forty-nine completed 18 months. DXA, volumetric quantitative CT, and high-resolution peripheral quantitative CT were performed. Pre-treatment mean age (48 ± 12 years), BMI (33.1 ± 5.7 kg/m2), and BMD were similar between groups. P1NP, osteocalcin, and CTX increased (P < 0.005) and visceral adipose tissue decreased (P = 0.04) at 18 months in the GH vs placebo group. Hip and radius aBMD, spine and tibial vBMD, tibial cortical thickness, and radial and tibial failure load decreased in the GH vs placebo group (P < 0.05). Between 18 and 24 months (post-treatment observation period), radius aBMD and tibia cortical thickness increased in the GH vs placebo group. At 24 months, there were no differences between the GH and placebo groups in bone density, structure, or strength compared to baseline. GH administration for 18 months increased bone turnover in adults with overweight/obesity. It also decreased some measures of BMD, bone microarchitecture, and bone strength, which all returned to pre-treatment levels 6 months post-therapy. Whether GH administration increases BMD with longer treatment duration, or after mineralization of an expanded remodeling space post-treatment, requires further investigation.

Efficacy of New Generation Insecticides in Comparison with Biopesticides and their Economics against Chickpea Pod Borer (Helicoverpa armigera Hub.)

Background: Chickpea (Cicer arietinum L.) is one of the most important pulses. Helicoverpa armigera [Hubner] is the most devastating chickpea pest responsible for substantial yield loss. Chickpea crop is damaged by a large number of insect species, both under field conditions and in storage. Productivity losses by gram pod borer range from 20 to 90 per cent depending upon the severity of insect attack. Among the biotic factors responsible for low yield the, damage due to insect pests is the major limiting factor. Keeping the above facts in view, the present investigation was planned and carried out to establish a new generation molecules are comparatively safer to natural enemies, honeybees and other pollinators than old generation molecules play an important role in reducing the pest populations. Methods: Field experiment was during Rabi season 2018-19 on chickpea in district Rewa. The field was prepared following the recommended package of practices. The incidence of H. armigera was observed from five randomly selected plants from four middle rows of each plot at weekly interval. The spray of insecticides was applied as soon as the pest incidence is noted. The first spray was done at 50% flowering stage of the crop and repeated after 15 days. Pre-treatment observation on pest population was undertaken one day before the application of the first spray by direct counting of H. armigera larvae per five randomly pre-selected plants in each plot. Similar procedure was followed for post-treatment observation which was recorded at 1, 3, 7, 10, 15 days after both the spray operations. Result: The experiment was laid out in randomized block design with 09 treatments (Chlorantraniliprole 18.5 SC @ 37 g a.i./ha, Fipronil 5% SC @ 50 g a.i./ha, Indoxacarb 15.8 EC @ 79 g a.i./ha, Spinosad 45 SC @ 90 g a.i./ha, Novaluron 10 EC @ 100 g a.i./ha, Emamectine benzoate 5 SG @ 10 g a.i./ha, Neem oil 0.15% , Bt.K. 3.5% and untreated check. First spray of insecticides over all mean analysis indicated that all the insecticidal treatments were significantly effective in reducing the larval population of Helicoverpa armigera Hub. as compared to untreated plots (1.56 larvae/plant) in the first and second spray (0.92 larva/plant) of insecticides over all mean larval population Indoxacarb 15.8 EC @ 79 g a.i./ha was effective in controlling the incidence of gram pod borer due to the first spray (0.59 larva/plant) and also the second spray (0.27 larva/plant) among all treatments. Resulting in the seed yield 1989.00 kg/ha with the highest cost: benefit ratio of 1:12.3, which was followed by the treatment of Emamectin benzoate 5 SG @ 10 g a.i./ha with cost benefit ratio of 1:10.83.

Methenamine hippurate compared with antibiotic prophylaxis to prevent recurrent urinary tract infections in women: the ALTAR non-inferiority RCT.

Daily, low-dose antibiotic prophylaxis is the current standard care for women with recurrent urinary tract infection. Emerging antimicrobial resistance is a global health concern, prompting research interest in non-antibiotic agents such as methenamine hippurate, but comparative data on their efficacy and safety are lacking. To assess the clinical effectiveness and cost-effectiveness of methenamine hippurate (Hiprex®; Mylan NV, Canonsburg, PA, USA) compared with current standard care (antibiotic prophylaxis) for recurrent urinary tract infection prevention in adult women. Multicentre, pragmatic, open-label, randomised, non-inferiority trial of 12 months' treatment with the allocated intervention, including an early, embedded qualitative study and a 6-month post-treatment observation phase. The predefined non-inferiority margin was one urinary tract infection per person-year. Eight UK NHS secondary care sites. A total of 240 adult women with recurrent urinary tract infection requiring preventative treatment participated in the trial. A central randomisation system allocated participants 1 : 1 to the experimental (methenamine hippurate: 1 g twice daily) or control (once-daily low-dose antibiotics: 50/100 mg of nitrofurantoin, 100 mg of trimethoprim or 250 mg of cefalexin) arm. Crossover between treatment arms was permitted. The primary clinical outcome was incidence of symptomatic antibiotic-treated urinary tract infection during the 12-month treatment period. Cost-effectiveness was assessed by incremental cost per quality-adjusted life-year gained, extrapolated over the patient's expected lifetime using a Markov cohort model. Secondary outcomes included post-treatment urinary tract infections, total antibiotic use, microbiologically proven urinary tract infections, antimicrobial resistance, bacteriuria, hospitalisations and treatment satisfaction. Primary modified intention-to-treat analysis comprised 205 (85%) randomised participants [102/120 (85%) participants in the antibiotics arm and 103/120 (86%) participants in the methenamine hippurate arm] with at least 6 months' data available. During treatment, the incidence rate of symptomatic, antibiotic-treated urinary tract infections decreased substantially in both arms to 1.38 episodes per person-year (95% confidence interval 1.05 to 1.72 episodes per person-year) for methenamine hippurate and 0.89 episodes per person year (95% confidence interval 0.65 to 1.12 episodes per person-year) for antibiotics (absolute difference 0.49; 90% confidence interval 0.15 to 0.84). This absolute difference did not exceed the predefined, strict, non-inferiority limit of one urinary tract infection per person-year. On average, methenamine hippurate was less costly and more effective than antibiotics in terms of quality-adjusted life-years gained; however, this finding was not consistent over the longer term. The urinary tract infection incidence rate 6 months after treatment completion was 1.72 episodes per year in the methenamine hippurate arm and 1.19 in the antibiotics arm. During treatment, 52% of urine samples taken during symptomatic urinary tract infections were microbiologically confirmed and higher proportions of participants taking daily antibiotics (46/64; 72%) demonstrated antibiotic resistance in Escherichia coli cultured from perineal swabs than participants in the methenamine hippurate arm (39/70; 56%) (p-value = 0.05). Urine cultures revealed that during treatment higher proportions of participants and samples from the antibiotic arm grew E. coli resistant to trimethoprim/co-trimoxazole and cephalosporins, respectively. Conversely, post treatment, higher proportions of participants in the methenamine hippurate arm (9/45; 20%) demonstrated multidrug resistance in E. coli isolated from perineal swabs than participants in the antibiotic arm (2/39; 5%) (p = 0.06). All other secondary outcomes and adverse events were similar in both arms. This trial could not define whether or not one particular antibiotic was more beneficial, and progressive data loss hampered economic evaluation. This large, randomised, pragmatic trial in a routine NHS setting has clearly shown that methenamine hippurate is not inferior to current standard care (daily low-dose antibiotics) in preventing recurrent urinary tract infections in women. The results suggest that antimicrobial resistance is proportionally higher in women taking prophylactic antibiotics. Future research should include evaluation of other non-antibiotic preventative treatments in well-defined homogeneous patient groups, preferably with the comparator of daily antibiotics. This trial is registered as ISRCTN70219762 and EudraCT 2015-003487-36. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 23. See the NIHR Journals Library website for further project information.

The Effects of the Uncontrolled Use of Biomodulina T on the Severity of Severe Acute Respiratory Syndrome-Coronavirus 2 Infection in Older Cuban Adults: An Open Label Evaluation

BackgroundThe ongoing coronavirus disease 2019 (COVID-19) pandemic is a worldwide public health threat. Millions of people are at risk and older adults are more susceptible to developing the most serious manifestations of the disease, in part because of the effects of ageing on the immune system. Biomodulina T is an injectable immune modulator that has been licensed for use in Cuba for many years.ObjectiveAn open-label, uncontrolled trial was conducted to investigate whether or not it might be useful to prevent or modulate the serious effects of severe acute respiratory syndrome coronavirus 2 infections in older Cuban adults before the availability of vaccinations.MethodsFrom April 12 to August 31, 2021, 1239 adults aged 60 years and older, unvaccinated against COVID-19 were recruited from the José Luis Dubrocq polyclinics, to receive Biomodulina T, 1 intramuscular 3 mL dose weekly for 6 weeks. Each person was visited at home weekly to be administered Biomodulina T. Once daily patients were seen by a medical student to collect information on any possible adverse events related to the medication as well as any symptoms of COVID-19. The possible usefulness of the intervention and its potential adverse events were assessed based on the number of older adults who became infected with COVID-19, and the severity of any symptoms reported or noted both during the 6-week treatment period and during an additional 6-week posttreatment observation period.ResultsSixteen patients were diagnosed with symptomatic COVID-19 during the intervention using a specific reverse transcription polymerase chain reaction test. One patient died because of COVID-19. The most common preexisting diagnoses in treated patients included high blood pressure in 64.8%, diabetes mellitus in 19.85%, and ischemic cardiopathy in 13.88%. Biomodulina T was well tolerated. Only infrequent, mild, transient, and self-limited adverse events were identified. Both the incidence of COVID-19 infections and the overall mortality rate were lower in the treated patients than what was observed in the untreated general population of this Cuban province during the same time period.ConclusionsAlthough further, confirmatory, double-blind, controlled clinical trials are needed, Biomodulina T injections were well tolerated, and the results of this open, uncontrolled study suggest that it may have been useful to decrease the incidence and severity of symptomatic COVID-19 infection in these older Cuban adults. (Curr Ther Res Clin Exp. 2022; 82:XXX–XXX) © 2022 Elsevier HS Journals, Inc

Laparoscopic and imaging findings of growing teratoma syndrome

Growing teratoma syndrome (GTS) occurs during post-treatment observation of ovarian malignant germ cell tumors. The characteristic features of this syndrome are normal tumor marker levels and evident tumoral mass or implants on imaging studies. We report a case of GTS in a 22-year-old woman with a malignant germ cell tumor. After staging surgery and chemotherapy, computed tomography showed peritoneal implants. Laparoscopy was planned to exclude malignant recurrence. During laparoscopy, smooth and pink-colored lesions were seen at the lateral pelvic wall. Histopathologic evaluation reported mature teratoma tissue with extensive mature glial components. GTS is not a malignant condition and the benefit of radical surgical intervention in cases without mass-related complication is not proven. GTS should be kept in mind after primary treatment of ovarian immature teratoma.

Safety Monitoring of Gene Therapy for Spinal Muscular Atrophy with Onasemnogene Abeparvovec -A Single Centre Experience.

Background:Recently gene therapy with onasemnogene abeparvovec has been approved for the treatment of spinal muscular atrophy (SMA). As the experience from clinical trials is limited, there are still uncertainties for which patient population the treatment can be considered safe and effective.Methods:We report our experience with eight consecutive patients with SMA who were treated with the standard dose of onasemnogene abeparvovec (1.1×1014 vg/kg) at the University Hospital Bonn, Germany. All patients received prophylactic immunosuppression with 1 mg/kg/d prednisolone for four weeks starting on the day before gene therapy.Results:We treated eight patients (4 male, 4 female, age range 10–37 months) with a body weight between 7.1 and 11.9 kg. All patients had 2 or 3 copies of the SMN2-gene and were previously treated with nusinersen. Following treatment with onasemnogene abeparvovec all patients showed a temporary increase of the body temperature and an increase of transaminase levels. In all but one patient it was necessary to increase or prolong the standard steroid dose to control the immune response. In one severe case, liver damage was associated with impaired liver function. This patient received a steroid pulse therapy for five days. Blood counts revealed asymptomatic thrombocytopenia (<150×109/L) in 6/8 patients and a significant increase of monocytes following gene therapy. Liver values and blood counts returned to almost normal levels during the post-treatment observation period. Troponin I increased above normal limit in 4/8 patients but was not associated with any abnormalities on cardiac evaluation.Conclusions:In a broader spectrum of patients, treatment with onasemnogene abeparvovec was associated with a higher rate of adverse events. In our cases it was possible to control the immune response by close monitoring and adaptation of the immunosuppressive regimen. Further research is needed to better understand the immune response following gene therapy and ideally to identify patients at risk for a more severe reaction.

Maintenance acne therapy: prophylactic efficacy of fixed combination of adapalene and benzoyl peroxide

Acne is a chronic disease and even reliable therapies do not completely ensure absence of relapses. Acne relapses have a negative psychological impact on patients, as they feel unable to control the disease and achieve complete and long-lasting recovery. Supportive therapy is necessary to prolong the remission of acne achieved with initial successful treatment and to minimize the risk of relapse. According to the literature sources, the most justified as a maintenance therapy is the use of topical retinoids, which have been shown to be effective in the prevention of exacerbations of acne. In the present study 54 patients were involved who after the active therapy used a fixed combination of adapalene 0.1% / BPO 2.5% as maintenance treatment. Only 1 patient (2.9%) with moderate acne and 2 patients (5.8%) with severe acne had a relapse within 6 months of maintenance therapy. The absence of adverse events during the course of treatment was recorded, as well as high adherence of patients to the treatment. During the period of post-treatment observation (6 months after maintenance therapy), among the patients without exacerbations during maintenance therapy, a relapse occurred in 2 (7.1%) patients of group 1 (n = 28) and 2 (8.7%) patients of group 2 (n = 23). The obtained data indicates that maintenance therapy with Effezel® gel can extend the achieved effectiveness of the treatment and prevent the development of relapses.