Category: Nevin Manimala

Intern Med. 2023 Mar 31. doi: 10.2169/internalmedicine.1006-22. Online ahead of print.

ABSTRACT

Objective A T-SPOT.TB can yield indeterminate results under two test observation conditions: a high response to the nil in negative control wells (high nil-control) or a low response to the mitogen in positive control wells (low mitogen-control). The most strongly influential factors for these indeterminate results, however, have yet to be identified. Methods From June 1, 2015, to June 30, 2021, we conducted a 1:1 matched case-control, retrospective study. Patients Patients who underwent a T-SPOT.TB test at Chiba University Hospital. Results The study included 5,956 participants. Indeterminate results were found in 63 participants (1.1%), including high nil-control in 37 and low mitogen-control in 26. Human T-cell leukemia virus type 1 (HTLV-1) positivity was the only influencing factor associated with high nil-control (adjusted odds ratio=98.5, 95% confidence interval: 6.59-1480). Conclusion Regarding the indeterminate results, all HTLV-1 positive participants had a high nil response and no low mitogen response. It was suspected that abnormally produced interferon γ caused a nonspecific reaction to the negative control well, resulting in a high nil response. Low mitogen-control, conversely, did not appear to have any statistically significant influential factors.

PMID:37005270 | DOI:10.2169/internalmedicine.1006-22

Intern Med. 2023 Mar 31. doi: 10.2169/internalmedicine.1611-23. Online ahead of print.

ABSTRACT

Objective Pleural effusion (PE) is a common adverse event that occurs during dasatinib therapy for chronic myeloid leukemia (CML). However, the pathomechanism of PE and appropriate management of Asian patients with CML have not been elucidated. This study investigated the incidence rate, risk, and appropriate management of PE in Asian patients with CML treated with dasatinib. Methods We retrospectively collected data on patients in the chronic phase of CML who received first-line dasatinib therapy and were registered in the CML-Cooperative Study Group database. Patients We identified 44 cases of PE in a series of 89 patients and analyzed previously reported risk factors and effective management of PE. Results A univariate analysis revealed that age, diabetes mellitus, chronic renal failure, hypertension, the history of cardiovascular events, and dasatinib dose were significantly associated with PE. A multivariate analysis revealed that age ≥65 years old was the only independent risk factor for PE. Dasatinib dose reduction and switching to a tyrosine kinase inhibitor showed a statistically significant difference in effectively reducing PE volume compared to single diuretic use. Conclusion Although further studies are warranted, our observations showed that advanced age is a significant risk factor for PE, and tyrosine kinase inhibitor dose reduction or replacement of dasatinib may be an effective management strategy for PE in Asian CML patients who received first-line treatment with dasatinib in real-world clinical practice.

PMID:37005261 | DOI:10.2169/internalmedicine.1611-23

Yakugaku Zasshi. 2023;143(4):393-404. doi: 10.1248/yakushi.22-00151.

ABSTRACT

Community pharmacists in Japan participate in many important clinical cases involving drug therapies. This involvement should be researched and widely publicized to promote evidence-based medicine (EBM). However, the awareness level about the establishment of clinical evidence among community pharmacists remains unknown. Therefore, this large-scale questionnaire survey was conducted among members of the Okayama Pharmaceutical Association to clarify the awareness about the establishment of clinical evidence among community pharmacists to determine the major factors affecting their awareness. Questionnaires requiring open-ended responses were developed in Google Forms. Finally, 366 valid answers were obtained and statistically analyzed based on three aspects: academic conference presentation, research article publication, and research conduct. More than 50% of the participants agreed that they must engage in the establishment of clinical evidence. However, they were unwilling to engage in it by themselves. Additionally, the awareness about the establishment of clinical evidence among participants aged <40 years, who underwent a 6-year course, and with presentation experience was greater than that among participants aged ≥40 years, who underwent a 4-year course and without presentation experience. Thus, age, course duration, and presentation experience are important factors influencing awareness about the establishment of clinical evidence. Further, >70% of the participants did not have enough time to engage in the establishment of clinical evidence, suggesting that reducing workload and ensuring adequate time are necessary for such engagements. Our novel findings may increase the establishment of clinical evidence by community pharmacists, improve community pharmacists’ social standing, and promote EBM in Japan.

PMID:37005242 | DOI:10.1248/yakushi.22-00151

Yakugaku Zasshi. 2023;143(4):369-375. doi: 10.1248/yakushi.22-00219.

ABSTRACT

Today computational chemistry has become an established tool for medicinal chemists. However, softwares are becoming more sophisticated, and in order to master the tools, a wide range of fundamental competency such as thermodynamics, statistics, and physical chemistry are required in addition to chemical creativity. As a result, a software might be used as a black box. In this article, I would like to introduce what a simple computational conformation analysis can do and my experience of using it in actual wet research.

PMID:37005239 | DOI:10.1248/yakushi.22-00219

Infect Dis Health. 2023 Mar 31:S2468-0451(23)00013-5. doi: 10.1016/j.idh.2023.03.002. Online ahead of print.

ABSTRACT

BACKGROUND: The effectiveness of hand sanitizers marketed to the general population is essential for infection prevention and control. Main theme of the study was that whether the commercially available hand sanitizers meet the WHO recommended standards in terms of efficacy? Current study aims to investigate the efficacy of ten commercially available hand sanitizers.

METHODS: The methodology was based on European Standard EN-1500. Following the artificial contamination of hands, pre and post samples were obtained to determine the log reduction values for each sanitizer.

RESULTS: The results showed that out of ten only one sanitizer showed highest log reduction which was comparable to the reference product. Product B was most efficient in sanitization of hands with mean log reduction of 6.00 ± 0.15. The lowest sanitization efficacy was recorded for product F with mean log reduction of 2.40 ± 0.51, however the reference product 2-propanol result in mean log reduction of 6.0 ± 0.00. The products used in this study show a statistical significant results (p value: < 0.01).

CONCLUSION: It is concluded that only one product showed active sanitizer efficacy. This study provides an important insight for manufacturing company and authorizing authorities to assess the efficacy of hand sanitizer. Hand sanitization is one approach to stop the spread of diseases carried on by harmful bacteria inhabiting our hands. Apart from the manufacturing strategies, ensuring proper use and quantity of hand sanitizers is very important.

PMID:37005216 | DOI:10.1016/j.idh.2023.03.002

Eur Urol Oncol. 2023 Mar 31:S2588-9311(23)00068-8. doi: 10.1016/j.euo.2023.03.004. Online ahead of print.

ABSTRACT

BACKGROUND: Radiation therapy (RT) is an alternative to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC).

OBJECTIVE: To analyze predictors of complete response (CR) and survival after RT for MIBC.

DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter retrospective study of 864 patients with nonmetastatic MIBC who underwent curative-intent RT from 2002 to 2018.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Regression models were used to explore prognostic factors associated with CR, cancer-specific survival (CSS), and overall survival (OS).

RESULTS AND LIMITATIONS: The median patient age was 77 yr and median follow-up was 34 mo. Disease stage was cT2 in 675 patients (78%) and cN0 in 766 (89%). Neoadjuvant chemotherapy (NAC) was given to 147 patients (17%) and concurrent chemotherapy to 542 (63%). A CR was experienced by 592 patients (78%). cT3-4 stage (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.29-0.63; p < 0.001) and hydronephrosis (OR 0.50, 95% CI 034-0.74; p = 0.001) were significantly associated with lower CR. The 5-yr survival rates were 63% for CSS and 49% for OS. Higher cT stage (HR 1.93, 95% CI 1.46-2.56; p < 0.001), carcinoma in situ (HR 2.10, 95% CI 1.25-3.53; p = 0.005), hydronephrosis (HR 2.36, 95% CI 1.79-3.10; p < 0.001), NAC use (HR 0.66, 95% CI 0.46-0.95; p = 0.025), and whole-pelvis RT (HR 0.66, 95% CI 0.51-0.86; p = 0.002) were independently associated with CSS; advanced age (HR 1.03, 95% CI 1.01-1.05; p = 0.001), worse performance status (HR 1.73, 95% CI 1.34-2.22; p < 0.001), hydronephrosis (HR 1.50, 95% CI 1.17-1.91; p = 0.001), NAC use (HR 0.69, 95% CI 0.49-0.97; p = 0.033), whole-pelvis RT (HR 0.64, 95% CI 0.51-0.80; p < 0.001), and being surgically unfit (HR 1.42, 95% CI 1.12-1.80; p = 0.004) were associated with OS. The study is limited by the heterogeneity of different treatment protocols.

CONCLUSIONS: RT for MIBC yields a CR in most patients who elect for curative-intent bladder preservation. The benefit of NAC and whole-pelvis RT require prospective trial validation.

PATIENT SUMMARY: We investigated outcomes for patients with muscle-invasive bladder cancer treated with curative-intent radiation therapy as an alternative to surgical removal of the bladder. The benefit of chemotherapy before radiotherapy and whole-pelvis radiation (bladder plus the pelvis lymph nodes) needs further study.

PMID:37005214 | DOI:10.1016/j.euo.2023.03.004

Eur Urol Oncol. 2023 Mar 31:S2588-9311(23)00069-X. doi: 10.1016/j.euo.2023.02.014. Online ahead of print.

ABSTRACT

BACKGROUND: Family history (FH) of prostate cancer (PCa) is associated with an increased risk of PCa and adverse disease features. However, whether patients with localized PCa and FH could be considered for active surveillance (AS) remains controversial.

OBJECTIVE: To assess the association between FH and reclassification of AS candidates, and to define predictors of adverse outcomes in men with positive FH.

DESIGN, SETTING, AND PARTICIPANTS: Overall, 656 patients with grade group (GG) 1 PCa included in an AS protocol at a single institution were identified.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier analyses assessed the time to reclassification (GG ≥2 and GG ≥3 at follow-up biopsies) overall and according to FH status. Multivariable Cox regression tested the impact of FH on reclassification and identified the predictors among men with FH. Men treated with delayed radical prostatectomy (n = 197) or external-beam radiation therapy (n = 64) were identified, and the impact of FH on oncologic outcomes was assessed.

RESULTS AND LIMITATIONS: Overall, 119 men (18%) had FH. The median follow-up was 54 mo (interquartile range 29-84 mo), and 264 patients experienced reclassification. The 5-yr reclassification-free survival rate was 39% versus 57% for FH versus no FH (p = 0.006), and FH was associated with reclassification to GG ≥2 (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.19-2.15, p = 0.002). In men with FH, the strongest predictors of reclassification were prostate-specific antigen (PSA) density (PSAD), high-volume GG 1 (≥33% of cores involved or ≥50% of any core involved), and suspicious magnetic resonance imaging (MRI) of the prostate (HRs 2.87, 3.04, and 3.87, respectively; all p < 0.05). No association between FH, adverse pathologic features, and biochemical recurrence was observed (all p > 0.05).

CONCLUSIONS: Patients with FH on AS are at an increased risk of reclassification. Negative MRI, low disease volume, and low PSAD identify men with FH and a low risk of reclassification. Nonetheless, sample size and wide CIs entail caution in drawing conclusions based on these results.

PATIENT SUMMARY: We tested the impact of family history in men on active surveillance for localized prostate cancer. A significant risk of reclassification, but not adverse oncologic outcomes after deferred treatment, prompts the need for cautious discussion with these patients, without precluding initial expectant management.

PMID:37005213 | DOI:10.1016/j.euo.2023.02.014

Eur Urol Oncol. 2023 Mar 31:S2588-9311(23)00065-2. doi: 10.1016/j.euo.2023.03.003. Online ahead of print.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) are now a mainstay of metastatic renal cell carcinoma (RCC) management with five current Food and Drug Administration-approved regimens. However, data regarding nephrectomy outcomes following an ICI are limited.

OBJECTIVE: To evaluate the safety and outcomes of nephrectomy following an ICI.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was performed of patients with primary locally advanced or metastatic RCC undergoing nephrectomy following an ICI in five US academic centers between January 2011 and September 2021.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinical data, perioperative outcomes, and 90-d complications/readmissions were recorded and evaluated by univariate and logistic regression models. Recurrence-free and overall survival probabilities were estimated by the Kaplan-Meier method.

RESULTS AND LIMITATIONS: A total of 113 patients with a median (interquartile range) age of 63 (56-69) yr were included. The main ICI regimens were nivolumab ± ipilimumab (n = 85) and pembrolizumab ± axitinib (n = 24). Risk groups included 95% intermediate- and 5% poor-risk patients. Surgical procedures were 109 radical and four partial nephrectomies, including 60 open, 38 robotic, and 14 laparoscopic with five (10%) conversions. Two intraoperative complications were reported (bowel and pancreatic injury). The median operative time, estimated blood loss, and hospital stay were 3 h, 250 ml, and 3 d, respectively. A complete pathologic response (ypT0N0) was noted in six (5%) patients. The 90-d complication rate was 24%, with 12 (11%) patients requiring readmission. On a multivariable analysis, two or more risk factors (odds ratio [OR] 2.91, 95% confidence interval [CI]: 1.09, 7.42) and pathologic T stage ≥T3 (OR 4.21, 95% CI: 1.13-15.8) were independently associated with a higher 90-d complication rate. The 3-yr estimated overall survival and recurrence-free survival rates were 82% and 47%, respectively. Limitations include the retrospective nature and heterogeneous cohort in terms of clinicopathologic characteristics and ICI regimens received.

CONCLUSIONS: Nephrectomy following ICI therapy is feasible and a potential consolidative therapy option in select patients. Further research in the neoadjuvant setting is also warranted.

PATIENT SUMMARY: This study evaluates the outcomes of kidney surgery following immune checkpoint inhibitor therapy (mainly nivolumab and ipilimumab or pembrolizumab and axitinib) for patients with advanced kidney cancer. We utilized data from five academic centers across the USA and found that surgery in this setting did not have more complications or returns to the hospital than similar surgeries, indicating that it is a safe and feasible procedure at this time.

PMID:37005212 | DOI:10.1016/j.euo.2023.03.003

Int J Epidemiol. 2023 Apr 2:dyad035. doi: 10.1093/ije/dyad035. Online ahead of print.

NO ABSTRACT

PMID:37004248 | DOI:10.1093/ije/dyad035

J Gastrointestin Liver Dis. 2023 Apr 1;32(1):70-76. doi: 10.15403/jgld-4508.

ABSTRACT

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is often used in patients with cirrhosis to manage portal hypertension-related complications. Unfortunately, 35-50% of patients develop overt hepatic encephalopathy (HE) after TIPS. However, data on lactulose and rifaximin to prevent post-TIPS HE is limited. Therefore, we aimed to perform a network meta-analysis to investigate the efficacy of multiple pharmacological regimens in the prevention of post-TIPS HE.

METHODS: A comprehensive search strategy to identify reports of studies of rifaximin use on post-TIPS hepatic encephalopathy was constructed using truncated keywords, phrases, and subject headings developed in Embase. This strategy was translated to MEDLINE, Cochrane Central Register of Controlled Trials, and the Web of Science Core Collection, with all searches performed on 10 February 2022. No publication date or language limits were used.

RESULTS: The initial search identified 72 studies, and 56 studies were screened after removing duplicates. Five studies, two randomized controlled trials (RCTs) and three retrospective studies, met our inclusion criteria and were included in the final analysis. A total of 840 patients were included, with 65% male. Our meta- analysis did not find a statistically significant difference between lactulose vs placebo/no prophylaxis, nor rifaximin vs placebo/no prophylaxis, nor rifaximin plus lactulose vs placebo/no prophylaxis in the reduction of post-TIPS HE.

CONCLUSIONS: Rifaximin alone, lactulose alone, and rifaximin plus lactulose did not significantly reduce the development of post-TIPS HE. Based on the P-scores of the three treatment groups, the combination of rifaximin plus lactulose showed the most promising trend towards preventing post-TIPS HE. More studies, especially large RCTs, are warranted.

PMID:37004220 | DOI:10.15403/jgld-4508