Categories
Nevin Manimala Statistics

Efficacy and Safety of Letrozole in the Management of Constitutional Delay in Growth and Puberty: A Systematic Review and Meta-analysis

J Clin Res Pediatr Endocrinol. 2021 Sep 3. doi: 10.4274/jcrpe.galenos.2021.2021.0169. Online ahead of print.

ABSTRACT

BACKGROUND: No meta-analysis is available which has analysed role of letrozole in constitutional delay in growth and puberty (CDGP).

METHODS: Electronic databases were searched for RCTs involving children with CDGP receiving letrozole. Primary outcome were changes in predicted adult height (PAH) and pubertal progression. Secondary outcomes were alterations in bone age, hormonal markers of puberty, bone mineral density and side-effects.

RESULTS: One hundred-thirty articles were reviewed, from which 7 RCTs which fulfilled all criteria were analysed. Letrozole was superior to placebo [mean difference (MD) 4.63cm (95% CI: 3.90 – 5.36); P<0.01; I2=0%] but not testosterone [MD 2.21cm (95% CI: -1.71 – 6.16); P=0.27; I2=98%] with regards to improvement in PAH after 12-months use. Letrozole was superior to both placebo [MD 4.80ml (95% CI: 0.57 – 9.03); P=0.03] and testosterone [MD 3.36ml (95% CI: 0.58 – 6.75); P=0.02; I2=0%] with regards to improvement in testicular volume after 12-months use. Letrozole was superior to testosterone [MD -0.84 years (95% CI: 2.83 – 8.18); P=0.06; I2=0%] with regards to slowing in bone age progression after 12-months use, which approached statistical significance. Serum LH, FSH, testosterone and inhibin-B were significantly higher after 6-months letrozole use compared to active as well as passive controls. No increased occurrence of adverse events, spinal deformities were noted with letrozole.

CONCLUSION: Letrozole is safe and effective for improving height and pubertal outcomes in CDGP, and is better than testosterone with regards to improvement in testicular volume and delaying bone-age progression.

PMID:34477355 | DOI:10.4274/jcrpe.galenos.2021.2021.0169

Categories
Nevin Manimala Statistics

Reply to Dr. Lai regarding Allopurinol Hypersensitivity Syndrome in patients of Asian ancestry

Arthritis Care Res (Hoboken). 2021 Sep 3. doi: 10.1002/acr.24777. Online ahead of print.

ABSTRACT

We thank Dr Lai for their interest in our study (1). While we did not show a statistically significant link between the use of allopurinol and mortality in people with gout, we agree that Allopurinol Hypersensitivity Syndrome (AHS) is the most serious side-effect of allopurinol, particularly in populations with South East Asian ancestry, leading to the recommendation to screen people of South East Asian descent for the HLA-B*5801 allele prior to starting treatment with allopurinol (2,3).

PMID:34477323 | DOI:10.1002/acr.24777

Categories
Nevin Manimala Statistics

Detection rate of 18F-Choline positron emission tomography/computed tomography in patients with non-metastatic hormone sensitive and castrate resistant prostate cancer

Q J Nucl Med Mol Imaging. 2021 Sep 3. doi: 10.23736/S1824-4785.21.03366-5. Online ahead of print.

ABSTRACT

AIM: To assess the detection rate of 18F-choline PET/CT in non-metastatic hormone-sensitive prostate cancer (hsPCa) and non-metastatic castrate resistant prostate cancer (CRPCa), based on the criteria proposed in the phase III SPARTAN trial and with high Gleason Score (GS).

METHODS: Between October 2008 and September 2019, data from a retrospective multicenter study (n=4 centers), involving patients undergoing 18F-choline PET/CT scans for a biochemical recurrence of PCa, were collected. The following inclusion criteria were used: 1) histologically proven PCa, 2) a non-metastatic disease in accordance with conventional imaging findings; 3) a PSA doubling time (PSAdt) <10 months, 4) a GS > 8 and 5) no pelvic node > 2 cm. The group of hsPCa and CRPCa patients, were compared by using a non-parametric statistical analysis. Moreover, a logistic regression analysis and ROC curves were used.

RESULTS: 140 patients were included. Of these, 82 patients were affected by hsPCa, and 58 had a CRPCa. Overall, 18F-Choline PET/CT was positive in 99/140 (70.7%). It was positive in 55/82 (67.1%) hsPCa patients and in 44/58 (75.9%) CRPCa subjects, respectively. The site of recurrence at 18F-Choline PET/CT were: 16 (27.6%) and 20 (24.4%) in prostatic bed, 25 (43.1%) and 24 (29.3%) in loco-regional lymph nodes and in 27 (46.6%) and 28 (34.1%) in distant organs, respectively for CRPCa and hsPCa patients. The optimal cut-off values for PSA at the time of PET/CT for the prediction or recurrence were 0.5 vs. 2.5 ng/mL for all site of recurrence (AUC: 0.70 vs. 0.72), 0.48 vs. 3.4 ng/mL for prostatic bed (AUC: 0.60 vs. 0.59), 0.5 vs. 1.5 for loco-regional lymph nodes (AUC: 0.62 vs. 0.57) and 2.2 vs. 2.8 ng/mL for distant metastasis (AUC: 0.74 vs. 0.71), respectively in CRPCa and hsPCa (all p=NS). Sensitivities and specificities of 18F-Choline PET/CT for the identification of recurrence disease in all patient population, in hsPCa and CRPCa were 83.7% and 87.5%, 78.9% and 88.9%, 91.4% and 85.7%, respectively.

CONCLUSIONS: the rate of positive 18F-Choline PET/CT is similar in patients with a hsPCa and CRPCa, in case of low PSAdt and high GS. Therefore, non-metastatic PCa patients should be assessed by molecular imaging, in order to adapt the most appropriate therapeutic approach.

PMID:34477346 | DOI:10.23736/S1824-4785.21.03366-5

Categories
Nevin Manimala Statistics

Disparities in cancer prevalence, incidence, and mortality for incarcerated and formerly incarcerated patients: A scoping review

Cancer Med. 2021 Sep 3. doi: 10.1002/cam4.4251. Online ahead of print.

ABSTRACT

BACKGROUND: Racial and ethnic minority status, structural racism, low educational attainment, and poverty are consistently associated with cancer disparities and with higher rates of incarceration. The objective of this scoping review is to conduct a qualitative synthesis of the literature on cancer prevalence, incidence, mortality, and disparities in these outcomes for incarcerated and formerly incarcerated patients, as this literature is fragmented and heterogenous.

METHODS: This scoping review included Bureau of Justice Statistics reports and searched PubMed in May 2021 for all English language studies published between 1990 and 30 April 2021, that reported on cancer prevalence, incidence, or mortality for incarcerated or formerly incarcerated individuals in the United States.

RESULTS: Twenty studies were selected. Data on cancer prevalence and incidence were scarce but suggested that incarcerated and formerly incarcerated patients have a similar overall risk of cancer diagnosis as the general population, but elevated risk of certain cancers such as cervical, lung, colorectal, and hepatocellular carcinoma for which effective prevention and screening interventions exist. Cancer mortality data in state and local jails as well as prisons were robust and suggests that both incarcerated and formerly incarcerated patients have higher cancer mortality than the general population.

CONCLUSIONS: Incarcerated and formerly incarcerated patients likely have a higher risk of dying from cancer than the general population, but important gaps in our knowledge about the extent and drivers of disparities for this population remain. Additional research is needed to guide interventions to reduce cancer disparities for patients experiencing incarceration.

PMID:34477309 | DOI:10.1002/cam4.4251

Categories
Nevin Manimala Statistics

Expression of telomerase reverse transcriptase in peripheral T-cell lymphoma

Cancer Med. 2021 Sep 3. doi: 10.1002/cam4.4200. Online ahead of print.

ABSTRACT

Telomere length is maintained by the activation of telomerase, which causes continuous cell division and proliferation in many carcinomas. A catalytic reverse transcriptase protein (TERT) encoded by the TERT gene plays a critical role in the activation of telomerase. We performed a molecular and pathological analysis of the TERT against three different peripheral T-cell lymphoma (PTCL) subtypes: PTCL, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and adult T-cell leukemia/lymphoma (ATLL). Immunohistochemical analysis demonstrated TERT expression in 31% of AITL, 11% of PTCL-NOS, and 5% of ATLL. Among them, AITL frequently showed high TERT expression with statistical significance. TERT promoter mutation analysis and genomic copy number evaluation were performed. TERT promoter mutation was observed in two cases of PTCL-NOS (2/40) and not in other PTCLs. Genome copy number amplification was detected in 33% of PTCL-NOS, 33% of AITL, and 50% of ATLL cases. We evaluated the relationship between the analyzed TERT genomic abnormalities and protein expression; however, no apparent relationship was observed. Furthermore, immunostaining showed TERT expression in the PTCL cytoplasm, suggesting the existence of mechanisms other than the maintenance of telomere length. Statistical analysis of the effect of TERT expression on the prognosis in PTCL cases revealed that TERT expression tended to have a poor prognosis in PTCL-NOS. Since TERT expression was not an independent factor in multivariate analysis, further research will be needed to clarify the poor prognosis of PTCL-NOS in TERT expression.

PMID:34477310 | DOI:10.1002/cam4.4200

Categories
Nevin Manimala Statistics

Autologous blood pleurodesis for the treatment of postoperative air leaks. A systematic review and meta-analysis

Thorac Cancer. 2021 Sep 3. doi: 10.1111/1759-7714.14138. Online ahead of print.

ABSTRACT

BACKGROUND: Postoperative air leaks are a common complication after lung surgery. They are associated with prolonged hospital stay, increased postoperative pain and treatment costs. The treatment of prolonged air leaks remains controversial. Several treatments have been proposed including different types of sealants, chemical pleurodesis, or early surgical intervention. The aim of this review was to analyze the impact of autologous blood pleurodesis in a systematic way.

METHODS: A systematic review of the literature was conducted until July 2020. Studies with more than five adult patients undergoing lung resections were included. Studies in patients receiving blood pleurodesis for pneumothorax were excluded. The search strategy included proper combinations of the MeSH terms “air leak”, “blood transfusion” and “lung surgery”.

RESULTS: Ten studies with a total of 198 patients were included in the analysis. The pooled success rate for sealing the air leak within 48 h of the blood pleurodesis was 83.7% (95% CI: 75.7; 90.3). The pooled incidence of the post-interventional empyema was 1.5%, with a pooled incidence of post-interventional fever of 8.6%.

CONCLUSIONS: Current evidence supports the idea that autologous blood pleurodesis leads to a faster healing of postoperative air leaks than conservative treatment. The complication rate is very low. Formal recommendations on how to perform the procedure are not possible with the current evidence. A randomized controlled trial in the modern era is necessary to confirm the benefits.

PMID:34477307 | DOI:10.1111/1759-7714.14138

Categories
Nevin Manimala Statistics

Peracetic Acid-Ethanol Processed Human Tendon Allograft: A Morphological, Biochemical, and Biomechanical Study In Vitro

Orthop Surg. 2021 Sep 3. doi: 10.1111/os.13030. Online ahead of print.

ABSTRACT

OBJECTIVE: To clarify the morphological, biochemical, and biomechanical effects of peracetic acid-ethanol sterilization processing to human hamstring tendon allografts for different time periods.

METHODS: Thirty-two fresh-frozen human hamstring tendon allografts obtained from an allograft supplier were prepared and incubated in peracetic acid-ethanol solution (PES) containing 1% v/v peracetic acid and 24% v/v ethanol. Specimens were randomly classified into four groups according to the PES processing time (untreated as the control group, 30 min as the PES30 group, 120 min as the PES120 group, and 240 min as the PES240group). Light microscopy with hematoxylin-eosin and toluidine blue were performed, along with transmission electron microscopy (TEM) to measure the collagen fibril diameters and their distributions, from which the collagen fibril index (CFI) and mass average diameter (MAD) were calculated. The thermal stability and collagen denaturation were analyzed by differential scanning calorimetry (DSC) and collagen denaturation test by α-chymotrypsin. Cyclic loading and failure testing were applied on five tendons from each group, from which the cyclic creep strain, elastic modulus, maximum stress, maximum strain, and strain energy density were calculated.

RESULTS: Tendons in the control, PES30, PES120 groups showed similar regularly aligned collagen fibers in light microscopy images, while the images from the PES240 group revealed relatively disordered and heterogeneous collagen bundles with larger interfiber spaces. TEM analysis showed that the mean diameter (F = 3.09, P = 0.04) was lower in the PES120 group (87.15 ± 4.76 nm) than it was in the control group (99.39 ± 9.19 nm) but not statistically (P = 0.05). Moreover, the CFI value in the PES30 group (65.37 ± 4.14%) was the lowest among groups (all P ≤ 0.01), while no variance existed in density and MAD among groups (F = 2.09, P = 0.13, and F = 0.27, P = 0.85, respectively). The onset temperature (H = 8.74, P = 0.03) and peak temperature (H = 9.97, P = 0.02) were decreased in the PES30 group compared to the control group (P = 0.02 and P = 0.01, respectively), but there were no differences in enthalpy of denaturation among groups (F = 2.20, P = 0.17). The collagen denaturation test revealed lower hydroxyproline concentrations in PES-treated specimens with no statistical differences among groups (H = 8.86, P = 0.07). The maximum stress showed variance (F = 10.52, P < 0.01) that it was higher in PES30 group (68.29 ± 10.86 MPa) compared to the PES120 and the PES240 group, while it was lower in the PES120 group (19.40 ± 4.94 MPa) compared to the control and the PES30 group (all P < 0.05). The strain energy density (F = 7.34, P < 0.01) was over 4 times higher in the PES30 group (7.39 ± 2.51 MPa) than it was in the PES120 group (1.56 ± 0.64 MPa, P < 0.01).

CONCLUSION: PES treatment for 30 min has no adverse effect on the properties of human hamstring tendon allografts, longer processing time could not promise better properties preservation.

PMID:34477308 | DOI:10.1111/os.13030

Categories
Nevin Manimala Statistics

Effects of Levodopa Therapy on Cerebral Arteries and Perfusion in Parkinson’s Disease Patients

J Magn Reson Imaging. 2021 Sep 3. doi: 10.1002/jmri.27903. Online ahead of print.

ABSTRACT

BACKGROUND: Levodopa is the most-commonly used therapy for Parkinson’s Disease (PD). Imaging findings show increased cerebral blood flow (CBF) response to levodopa, but the artery morphological change is less studied.

PURPOSE: To investigate the effect of levodopa on cerebral arteries and CBF.

STUDY TYPE: Prospective.

POPULATION: 57 PD patients (56 ± 10 years, 26 males) and 17 age-matched healthy controls (AMC, 57 ± 9 years, 9 males) were scanned at baseline (OFF). Patients were rescanned 50 minutes after taking levodopa (ON).

FIELD STRENGTH AND SEQUENCE: 3 T; Simultaneous noncontrast angiography intraplaque imaging (SNAP) based on turbo field echo; Pseudo-continuous arterial spin labeling (PCASL) based on echo-planner imaging.

ASSESSMENT: The Unified Parkinson’s Disease Rating Scale (UPDRS-III) was used to assess the disease severity. Length and radius of arteries were measured from SNAP images. CBF was calculated from PCASL images globally and regionally.

STATISTICAL TESTS: Mann Whitney U tests were conducted in comparing PD vs. AMC. Wilcoxon matched-pairs signed rank tests were used in comparing OFF vs. ON, and the more-affected vs. the less-affected hemisphere in PD. Linear regressions were performed to test the correlations of neuroimaging findings with behavioral changes. Significance threshold was P < 0.05 with Bonferroni correction.

RESULTS: PD patients were identified with significantly lower CBF (PD OFF Mean = 40.15 ± 5.99, AMC Mean = 43.48 ± 6.21 mL/100 g/min) and shortened total artery length (PD OFF Mean = 5851.07 ± 1393.45, AMC Mean = 7479.16 ± 1335.93 mm). Levodopa elevated CBF of PD brains (PD ON Mean = 41.48 ± 6.32 mL/100 g/min) and expanded radius of proximal arteries. Artery radius change significantly correlated with CBF change in corresponding territories (r = 0.559 for Internal Carotid Arteries, r = 0.448 for Basilar Artery, and r = 0.464 for Middle Cerebral Artery M1). Global CBF significantly related to UPDRS-III (r = -0.391) post-levodopa.

DATA CONCLUSION: Levodopa can increase CBF by dilating proximal arteries.

LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 4.

PMID:34477268 | DOI:10.1002/jmri.27903

Categories
Nevin Manimala Statistics

Impact of missing outcome data in meta-analyses of lifestyle interventions during pregnancy to reduce postpartum weight retention: An overview of systematic reviews with meta-analyses and additional sensitivity analyses

Obes Rev. 2021 Sep 3:e13318. doi: 10.1111/obr.13318. Online ahead of print.

ABSTRACT

High risk of bias associated with missing outcome data (MOD) in meta-analyses (MAs) of the effects of lifestyle interventions during pregnancy on postpartum weight retention (PPWR) casts doubt on whether such interventions can be relied upon as truly effective. This systematic overview of three MAs (19 RCTs), each with high MOD rates in the subset of RCTs included, examined how MOD were addressed in the estimation of summary intervention effects. All MAs reported beneficial and statistically significant intervention effects estimated based on complete case analyses, deemed valid if MOD was missing at random (MAR). Therefore, we conducted sensitivity analyses using pattern mixture models and informative missingness parameters (describing how the outcome in the missing participants may be related to the outcome in the completers), to ascertain the robustness of the estimates to reasonable deviations from the MAR assumption. In plausible scenarios where the response in intervention group participants with versus without MOD was worse (by just 0.5 kg), effect estimates were attenuated in all MAs and no longer statistically significant in two MAs. Statistical significance was retained when all 19 RCTs identified across MAs were examined together in a broader meta-analysis: -0.63 kg (95%CI -0.17, -0.08), but the clinical relevancy of effects of this magnitude remains unclear.

PMID:34477276 | DOI:10.1111/obr.13318

Categories
Nevin Manimala Statistics

Actor-Network Analysis of Community-Based Organisations in Health Pandemics: Evidence from Covid-19 Response in Freetown, Sierra Leone

Disasters. 2021 Sep 3. doi: 10.1111/disa.12508. Online ahead of print.

ABSTRACT

Freetown is confronted with health-related risks that are compounded by rapid unplanned urbanisation and weak capacities of local government institutions. Addressing such community health risks implies a shared responsibility between government and non-state actors. In low-income communities, the role of Community-Based Organisations (CBOs) in combatting health disasters is well-recognized. Yet, empirical evidence about how CBOs have drawn on their networks and coordinated community-level strategies in responding to the Covid-19 pandemic is scant. Based on a qualitative study in two informal settlements in Freetown, this paper draws on actor-network theory to understand how CBOs problematize Covid-19 as a health risk, interact with other actors and the tensions that arise within these actor networks. The study findings show that community vulnerabilities and past experiences with health disasters such as Ebola informed CBOs’ perception of Covid-19 as communal emergency. In response, CBOs coordinated sensitization and mobilization programs by relying on a network of internal and external actors to support Covid-19 risk reduction strategies. Nonetheless, misunderstandings among actors caused tensions in the actor- network. The study suggests that creating new channels for knowledge exchange and building on CBO capacity can help strengthen actor networks in communities and combat current and future health disasters. This article is protected by copyright. All rights reserved.

PMID:34477244 | DOI:10.1111/disa.12508