Nevin Manimala

Adv Sci (Weinh). 2022 Jul 10:e2201621. doi: 10.1002/advs.202201621. Online ahead of print.

ABSTRACT

Cognitive decline is amongst one of the most commonly reported complaints during normal aging. Despite evidence that age and cognition are linked with similar neural correlates, no previous studies have directly ascertained how these two constructs overlap in the brain in terms of neuroimaging-based prediction. Based on a long lifespan healthy cohort (CamCAN, aged 19-89 years, n = 567), it is shown that both cognitive function (domains spanning executive function, emotion processing, motor function, and memory) and human age can be reliably predicted from unique patterns of functional connectivity, with models generalizable in two external datasets (n = 533 and n = 453). Results show that cognitive decline and normal aging both manifest decrease within-network connections (especially default mode and ventral attention networks) and increase between-network connections (somatomotor network). Whereas dorsal attention network is an exception, which is highly predictive on cognitive ability but is weakly correlated with aging. Further, the positively weighted connections in predicting fluid intelligence significantly mediate its association with age. Together, these findings offer insights into why normal aging is often associated with cognitive decline in terms of brain network organization, indicating a process of neural dedifferentiation and compensational theory, and providing potential connectivity markers for hinting at multiple cognitive deficits.

PMID:35811304 | DOI:10.1002/advs.202201621

Eur Urol Oncol. 2022 Jul 7:S2588-9311(22)00092-X. doi: 10.1016/j.euo.2022.06.003. Online ahead of print.

ABSTRACT

CONTEXT: Randomized controlled trials (RCTs) have shown that addition of docetaxel or androgen receptor axis-targeted therapy (ARAT) to androgen deprivation therapy (ADT) or addition of ARAT to ADT and docetaxel improves overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC). However, it is unknown whether docetaxel, when given as part of triplet therapy, has an independent OS benefit.

OBJECTIVE: To compare the efficacy of ADT plus ARAT with the triplet of ADT, ARAT, and docetaxel through a network meta-analysis (NMA) of RCTs in mHSPC.

EVIDENCE ACQUISITION: Bibliographic databases and conference proceedings were searched in March 2022 for RCTs that evaluated the addition of docetaxel, ARAT, or both to ADT in mHSPC. The primary endpoint was OS. Standard random-effect NMA and Bayesian analyses were performed to compare ADT plus ARAT with triplet therapy.

EVIDENCE SYNTHESIS: Eleven RCTs (n = 11 546) were eligible. Compared with ADT plus ARAT, the triplet had a nonsignificant OS benefit (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.68-1.16), while ADT plus docetaxel (HR 1.16 [0.94-1.43]) and ADT alone (HR 1.46 [1.30-1.64]) had an increased risk of death. By P-score ordering, the triplet was the most effective treatment strategy (P score = 0.936) followed by ADT plus ARAT (P score = 0.704). The triplet had a 77% likelihood of being the best treatment strategy compared with a 23% likelihood for ADT plus ARAT.

CONCLUSIONS: The triplet of ADT, ARAT, and docetaxel was the highest ranked treatment strategy, but it did not confer a statistically significant OS benefit over ADT plus ARAT. This NMA provides the highest-level comparative evidence for these treatment approaches in the initial management of mHSPC.

PATIENT SUMMARY: We synthesized the available evidence from clinical trials conducted in newly diagnosed metastatic prostate cancer to compare the survival of patients receiving triplet therapy (androgen receptor axis-targeted therapy [ARAT], androgen deprivation therapy [ADT], and docetaxel) with those receiving only ARAT and ADT. We conclude that the triplet is a somewhat more effective treatment approach.

PMID:35811293 | DOI:10.1016/j.euo.2022.06.003

Eur Urol Focus. 2022 Jul 7:S2405-4569(22)00135-3. doi: 10.1016/j.euf.2022.06.008. Online ahead of print.

ABSTRACT

BACKGROUND: European guidelines recommend that well-informed men at elevated risk of having prostate cancer (PCa) should be offered prostate-specific antigen (PSA) testing with risk-stratified follow-up. The Swedish National Board of Health and Welfare recommends against screening for PCa but supports regional implementation of organised prostate cancer testing (OPT).

OBJECTIVE: To report the process for designing and implementing OPT programmes.

DESIGN, SETTING, AND PARTICIPANTS: Population-based OPT programmes in two Swedish regions, designed to include men aged between 50 and 74 yr, launched in September 2020 for 50-yr-old men.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The number of men invited, the participation rate, and the numbers of magnetic resonance imaging (MRI) scans, urological visits, and biopsies from September 2020 to June 2021 were recorded.

RESULTS AND LIMITATIONS: Two Swedish regions co-designed an OPT programme with a risk-stratified diagnostic algorithm based on prostate-specific antigen (PSA), PSA density, MRI findings, and age. An automated administrative system was developed on a nationwide web-based platform. Invitation letters and test results are automatically generated and sent out by post. Men with PSA ≥3ng/ml, a suspicious MRI lesion, and/or PSA density ≥0.15 ng/ml/cm³ are referred for a prostate biopsy. Test results are registered for quality control and research. By June 2021, a total of 16 515 men were invited, of whom 6309 (38%) participated; 147 had an MRI scan and 39 underwent prostate biopsy. The OPT framework, algorithm, and diagnostic pathways have been working well.

CONCLUSIONS: We designed and implemented a framework for OPT with a high grade of automation. The framework and organisational experiences may be of value for others who plan a programme for early detection of PCa.

PATIENT SUMMARY: We describe the implementation of an organised testing programme for early detection of prostate cancer in two Swedish regions. This model is the first of its kind and may serve as a template for similar programmes.

PMID:35811285 | DOI:10.1016/j.euf.2022.06.008

J Am Pharm Assoc (2003). 2022 Jun 16:S1544-3191(22)00217-5. doi: 10.1016/j.japh.2022.06.004. Online ahead of print.

ABSTRACT

BACKGROUND: Urgent care medicine is a rapidly growing health care sector where patients are commonly treated for acute infectious diseases-related conditions. However, there are few antimicrobial stewardship interventions described in these settings.

OBJECTIVE: The objective of this study is to determine whether implementing outpatient antimicrobial stewardship guidelines would improve antibiotic prescribing for acute upper respiratory tract infections (ARTIs), skin and soft tissue infections (SSTI), and urinary tract infections (UTI) at a single urgent care site.

METHODS: This was a pre-post interventional study comparing antibiotic prescribing patterns for ARTI, SSTI, and UTI at a single urgent care site in the preintervention group (November 2019 to January 2020) with the postintervention group (November 2020 to January 2021) after implementation of outpatient stewardship guidelines. A second urgent care site that did not receive any interventions served as a control. The outpatient stewardship guidelines were implemented in October 2020 via didactic provider education and pocket guide distribution. The primary end point was the rate of total guideline-concordant antibiotic prescribing. Secondary end points included the rates of guideline concordance of each component of the prescription, including antibiotic selection, duration, dose, therapy indication, and patient safety outcomes.

RESULTS: The primary outcome of total guideline-concordant antibiotic prescribing significantly improved after implementation of outpatient antimicrobial stewardship guidelines at the study site (50% vs. 70%, P < 0.001), which was also reflected when comparing postintervention study site with postperiod control site (70% vs. 48%, P < 0.001). There was a statistically significant improvement in guideline-concordant duration of antibiotic therapy (43% vs. 61%, P = 0.001), driven by a reduction in antibiotic duration for UTI (7 [interquartile range (IQR) 5-7] vs. 5 [IQR 5-7] days, P = 0.007), which was also observed when comparing the postintervention study site with the postperiod control site (61% vs. 48%, P = 0.02). Patient safety outcomes were similar between groups.

CONCLUSION: An antimicrobial stewardship intervention comprising institutional outpatient guideline implementation and provider education significantly improved total guideline-concordant antibiotic prescribing by 20% for ARTI, UTI, and SSTI in an urgent care site.

PMID:35811280 | DOI:10.1016/j.japh.2022.06.004

J Cardiovasc Comput Tomogr. 2022 Jun 30:S1934-5925(22)00100-9. doi: 10.1016/j.jcct.2022.06.002. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the diagnostic performance of coronary CT angiography (CTA)-based quantitative flow ratio (QFR), namely CT-QFR, and compare it with invasive coronary angiography (ICA)-based Murray law QFR (μQFR), using fractional flow reserve (FFR) as the reference standard.

METHODS: Patients who underwent coronary CTA, ICA and pressure wire-based FFR assessment within two months were retrospectively analyzed. CT-QFR and μQFR were computed in blinded fashion and compared with FFR, all applying the same cut-off value of ≤0.80 to identify hemodynamically significant stenosis.

RESULTS: Paired comparison between CT-QFR and μQFR was performed in 191 vessels from 167 patients. Average FFR was 0.81 ​± ​0.10 and 42.4% vessels had an FFR ≤0.80. CT-QFR had a slightly lower correlation with FFR compared with μQFR, although statistically non-significant (r ​= ​0.87 versus 0.90, p ​= ​0.110). The vessel-level diagnostic performance of CT-QFR was slightly lower but without statistical significance than μQFR (AUC ​= ​0.94 versus 0.97, difference: -0.03 [95%CI: -0.00-0.06], p ​= ​0.095), and substantially higher than diameter stenosis by CTA (AUC difference: 0.17 [95%CI: -0.10-0.23], p ​< ​0.001). The patient-level diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio for CT-QFR to identify FFR value ​≤ ​0.80 was 88%, 90%, 86%, 86%, 91%, 6.59 and 0.12, respectively. The diagnostic accuracy of CT-QFR was 84% in extensively calcified lesions, while in vessels with no or less calcification, CT-QFR showed a comparable diagnostic accuracy with μQFR (91% versus 92%, p ​= ​0.595). Intra- and inter-observer variability in CT-QFR analysis was -0.00 ​± ​0.04 and 0.00 ​± ​0.04, respectively.

CONCLUSIONS: Performance in diagnosis of hemodynamically significant coronary stenosis by CT-QFR was slightly lower but without statistical significance than μQFR, and substantially higher than CTA-derived diameter stenosis. Extensively calcified lesions reduced the diagnostic accuracy of CT-QFR.

PMID:35811245 | DOI:10.1016/j.jcct.2022.06.002

Ultrasound Med Biol. 2022 Jul 7:S0301-5629(22)00411-2. doi: 10.1016/j.ultrasmedbio.2022.05.022. Online ahead of print.

ABSTRACT

In this study, we compared multiple quantitative ultrasound metrics for the purpose of differentiating muscle in 20 healthy, 10 dystrophic and 10 obese mice. High-frequency ultrasound scans were acquired on dystrophic (D2-mdx), obese (db/db) and control mouse hindlimbs. A total of 248 image features were extracted from each scan, using brightness-mode statistics, Canny edge detection metrics, Haralick features, envelope statistics and radiofrequency statistics. Naïve Bayes and other classifiers were trained on single and pairs of features. The a parameter from the Homodyned K distribution at 40 MHz achieved the best univariate classification (accuracy = 85.3%). Maximum classification accuracy of 97.7% was achieved using a logistic regression classifier on the feature pair of a² (K distribution) at 30 MHz and brightness-mode variance at 40MHz. Dystrophic and obese mice have muscle with distinct acoustic properties and can be classified to a high level of accuracy using a combination of multiple features.

PMID:35811236 | DOI:10.1016/j.ultrasmedbio.2022.05.022

Urol Oncol. 2022 Jul 7:S1078-1439(22)00192-2. doi: 10.1016/j.urolonc.2022.05.023. Online ahead of print.

ABSTRACT

PURPOSE: Because the optimal number of cycles of neoadjuvant gemcitabine and cisplatin chemotherapy (GC) is unclear, we aimed to compare disease response and survival outcomes of patients receiving either 3 or 4 cycles of neoadjuvant GC for muscle-invasive bladder cancer (MIBC).

METHODS: A total of 166 patients who were treated with neoadjuvant GC and radical cystectomy for clinical stage T2-4N0M0 were identified. Response and effectiveness of different cycle counts were assessed using downstaging (complete pathologic and partial pathologic response), cancer-specific survival (CSS), and overall survival (OS). Response and survival outcomes were examined with adjusted logistic regression and Cox regression models. Statistical significance was defined as P < 0.05.

RESULTS: Of 166 patients who received neoadjuvant GC, 107 (64.5%) received 3 cycles and 59 (35.5%) received 4 cycles. Age, insurance, comorbidity, tumor histology (pure urothelial carcinoma, urothelial with divergent differentiation, variant histology), and tumor stage were similar between the 2 treatment groups. Rates of complete response or any downstaging were similar between groups (21.5% and 40.2% in the 3-cycle group and 20.3% and 44.1% in the 4-cycle group, respectively). While disease response was similar (OR 1.03, 95% CI 0.43-2.45), both cancer-specific survival (HR 1.69, 95% CI 0.87-3.26) and overall survival (HR:1.88, 95% CI:1.02-3.48) were more favorable among patients managed with 4 cycles of neoadjuvant chemotherapy compared to those who received 3 cycles in adjusted models.

CONCLUSIONS: Our analysis demonstrated that survival outcomes tended to be better among patients who received 4 cycle of neoadjuvant GC compared to those treated with 3 cycles. Although potential benefits of omission of fourth cycle may include expedited time to surgery, reduced chemotherapy-associated toxicity, and lower treatment costs, continuation of treatment with a fourth cycle of neoadjuvant GC chemotherapy may benefit patients with muscle-invasive bladder cancer and further improve disease outcomes.

PMID:35811208 | DOI:10.1016/j.urolonc.2022.05.023

An Bras Dermatol. 2022 Jul 7:S0365-0596(22)00111-8. doi: 10.1016/j.abd.2021.09.011. Online ahead of print.

ABSTRACT

BACKGROUND: Erythema Nodosum (EN) is the most common skin manifestation in sarcoidosis and has often been associated with a good prognosis.

OBJECTIVES: To compare the clinical characteristics and treatment-related features in patients with sarcoidosis according to whether or not EN was seen as a presenting symptom at the time of diagnosis.

METHODS: A 20-year single-center retrospective study was performed. The following two groups were identified: one group with EN as one of the presenting symptoms at the time of diagnosis of sarcoidosis (EN group) and a second group without EN as a presenting symptom at diagnosis (non-EN group). The clinical characteristics and treatment modalities were collected from the medical records.

RESULTS: A total of 122 patients (31 in the EN group, 91 in the non-EN group) were included. Radiological stages of pulmonary disease were significantly lower in the EN group. Articular involvement was more common in the EN group (p = 0.001), whereas other systemic organ involvements (p = 0.025), especially neurological involvement (p = 0.036), were significantly more common in the non-EN group. In the EN group, a higher percentage of patients were managed without systemic therapy (71.0% vs. 54.9%) and spontaneous remission was more frequent (25.0% vs. 14.1%), however, this wasn’t statistically significant.

STUDY LIMITATIONS: Retrospective design.

CONCLUSIONS: The lower radiological stage of pulmonary sarcoidosis and lower frequency of systemic organ involvement in patients with EN augment the prognostic value of EN highlighted in the literature. However, this study couldn’t confirm that the patients with EN would need less systemic therapy in the course of their disease.

PMID:35811196 | DOI:10.1016/j.abd.2021.09.011

J Hand Ther. 2022 Jul 7:S0894-1130(22)00040-0. doi: 10.1016/j.jht.2022.03.009. Online ahead of print.

ABSTRACT

STUDY DESIGN: Randomized, interventional trial with 1 year follow-up.

INTRODUCTION: Though recommended, evidence is lacking to support specific exercises to stabilize and strengthen the first carpometacarpal (CMC) joint for cases of osteoarthritis (OA).

PURPOSE OF THE STUDY: To determine in a naturalistic setting, whether standard treatment plus a home exercise program (ST+HEP) is more effective than standard treatment (ST) alone in improving Quick Disabilities of Arm, Shoulder and Hand (qDASH) scores, and secondarily, in other patient-centered (pain, function) and clinical outcomes (range of motion, strength).

METHODS: A total of 190 patients from a hand therapy practice in northwestern PA were enrolled by informed consent and randomized into ST or ST+HEP groups. Average age was 60 years, most were female (78%) with sedentary occupations most common (36%). ST group received orthotic interventions, modalities, joint protection education and adaptive equipment recommendations, while the ST+HEP group received a home exercise program in addition to ST for 6-12 months. Follow-up occurred at 3, 6, and 12 months. Outcomes included grip strength, pinch strength, range of motion (ROM), qDASH, Patient Specific Functional Scale (PSFS) and pain ratings. At the 6 month mark, all subjects could change groups if desired. Efficacy data analysis included both parametric and non-parametric tests. The threshold for statistical significance was 0.05 and adjusted for multiple comparisons.

RESULTS: Repeated measures ANOVA failed to show a statistically significant difference in strength and ROM assessments between treatment groups over the 12 month follow-up (P ≥ .398). Differences between groups did not exceed 13%. Both the ST and ST+HEP groups evidenced improvement over time in most patient-focused assessments (P ≤ .011), including improvements exceeding reported clinically important differences in pain with activity and PSFS scores. Scores for these measures were similar at each follow-up period (P ≥ .080) in each group. The presence of CTS exerted no effect on outcomes; longer treatment time was weakly related to poorer qDASH and PSFS scores initially. Of those enrolled, 48% of subjects completed the study.

CONCLUSIONS: The addition of a high-frequency home exercise program did not improve clinical or patient-centered outcomes more so than standard care in our sample however, study limitations are numerous. Both groups had decreased pain with activity and improved PSFS scores, meeting the established minimally clinically important difference (MCID) of each at 6 and 12 months. Adherence with the home program was poor and/or unknown.

PMID:35811182 | DOI:10.1016/j.jht.2022.03.009

Eur J Surg Oncol. 2022 Jun 25:S0748-7983(22)00536-4. doi: 10.1016/j.ejso.2022.06.031. Online ahead of print.

ABSTRACT

The prognostic role of perineural invasion (PNI) in vulvar squamous cell carcinoma (VSCC) has not been fully established since few studies on this topic are currently available in the literature. In the present study, we conducted a systematic review and metanalysis of literature data in order to determine if PNI could be an independent prognostic predictor of patient’s survival in VSCC. Four electronic databases (PubMed, ISI Web of Science, Scopus and Google Scholar) were searched from their inception to December 2021 for all studies assessing the prognostic value of PNI in VSCC. Multivariate hazard ratios (HRs) for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were pooled. Six studies with 1048 patients were included. PNI was significantly associated with decreased OS (HR = 2.687; p < 0.001), DSS (HR = 2.375; p = 0.014) and PFS (HR = 1.757; p = 0.001), with no statistical heterogeneity among studies and no significant risk of bias across studies. The present meta-analysis highlights that PNI is independently associated with unfavorable prognosis in patients with VSCC. Therefore, PNI should be included in the pathological report of VSCC and considered in combination with other risk factors as a possible criteria for prognostic assessment adjuvant treatment planning inclusion.

PMID:35811178 | DOI:10.1016/j.ejso.2022.06.031