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IntroductionPrior studies have evaluated the level of evidence behind treatment options listed in the National Comprehensive Cancer Network (NCCN) guidelines, but no study has categorized the life cycle of regimens listed in the NCCN guidelines. We longitudinally assessed the life cycle for each regimen for newly diagnosed multiple myeloma. We track the date of first clinical data, the date of regimen addition to NCCN guidelines, the date phase 3 data (if performed) were reported, and the results of phase 3 trials.MethodsWe systematically examined NCCN guidelines from January 2000 to April 2021. The primary objective of our study was to assess the life cycle of each drug/regimen listed on the NCCN guidelines. We systematically examined the following aspects for each regimen: (1) the inception of prospective clinical data, (2) its inclusion in the NCCN guidelines, (3) the completion of a randomized trial (if done), (4) the presence of an overall survival benefit in such trials, and (5) the removal of a regimen from NCCN guidelines (if done) and its corresponding timeline.ResultsTwenty-one regimens were added across 50 NCCN guideline document iterations during a 22-year period. The median time from when clinical data were first presented to when a regimen was first listed in the guidelines was 15 months. Phase 3 studies were conducted for 17 regimens (80%), with a surrogate endpoint (response rate or progression-free survival) as endpoint for all trials, other than one. The median time from a regimen being included in the NCCN guideline to its phase 3 data publication was 43 months. The primary endpoint was met for 13 trials (81%). No regimen was removed for a phase 3 endpoint not being met. Six regimens (38%) showed overall survival benefit. Five (23%) regimens were removed from NCCN guidelines, with none being due to failure in phase 3 testing.ConclusionMyeloma NCCN guidelines remain relevant and current, adding new regimens with promising early-phase data, and removing regimens that become obsolete over time. However, this process is inconsistent and may benefit from standardization.

The objective of the research was to evaluate the utilization of starch acetate nanoparticles (SANPs) as drug delivery carriers for antitubercular drugs (Isoniazid, Rifampicin, and Pyrazinamide). The SANPs were synthesized employing ultrasonic-assisted double emulsification solvent evaporation method, permitting effective drug encapsulation. Chemical modification of native starch strengthened its hydrophobicity, as indicated by lower crystallinity in XRD analysis. The TGA validated the thermal stability of SANPs. Morphological investigation indicated a beehive-like structure with constant porosity changed to evenly dispersed spherical nanoparticles when Starch acetate is converted into SANPs. Dynamic light scattering measured the particle sizes of SANPs to be 161 nm. Drug encapsulation brought up the SANPs particle size to 249 nm. Isoniazid, Rifampicin, and Pyrazinamide exhibited 72 %, 83 %, and 75 % encapsulation efficiency at a 2:1 polymer-drug ratio, respectively. In phosphate-buffered saline (pH 7.4), drug release behavior exhibited 55 %, 30 %, and 45 % release of isoniazid, rifampicin, and pyrazinamide over 24 hours. The Korsmeyer-Peppas model demonstrated non-Fickian diffusion for all drug-encapsulated SANPs. Thus, these results contribute to the development of biopolymer-based drug delivery systems for sustainable release of antitubercular drugs.

Breast cancer is the biggest cause of death among women worldwide. Natural chemicals from medicinal plants offer promise for cancer therapy. This research screens 29 Dryopteris species plant-derived chemicals, mostly phloroglucinols, for breast cancer therapy potential. First, we used Gaussian09 and DFT/B3LYP/6-311+G(d, p) calculations to evaluate compound stability and reactivity. We conducted molecular docking experiments to identify drugs with high binding affinity for the PI3Kα protein’s active pocket. DJ1–DJ22 were found to be the most effective PI3Kα inhibitors, with energies ranging from −8.0 to −9.2 kJ/mol. From in silico pharmacokinetic and bioactivity screening, DJ3, DJ7, and DJ18 were identified as promising PI3Kα inhibitors. PI3Kα backbone stability was tested in a water model using molecular dynamics simulations employing DJ3, DJ7, DJ18, and Trastuzumab as a pharmacological reference. Synthesis of target-hit DJ3, DJ7, and DJ18 derivatives may lead to breast cancer drug-like molecules for related cancers. The work uses in silico methods to find natural phloroglucinols for breast cancer therapy, enabling new chemotherapeutic drugs.

This Viewpoint discusses the limitations that observational studies have in drawing causal inferences.

IntroductionOncology media websites such as Oncology Live (OncLive) and Targeted Oncology (TargetedOnc) play an important role in the dissemination of oncology news to patients and clinicians; however, the quality of the content on these websites has not been assessed. Our study aimed to analyze content from these websites and assess financial conflicts of interest (FCOI) amongst speakers interviewed on these websites.MethodsArticles published on OncLive and TargetedOnc during October 2021, were prospectively captured and analyzed. The primary outcome of our study was the quality of oncology news reporting in OncLive and TargetedOnc. We assessed the FCOI amongst speakers using data from Open Payments.ResultsWe examined 196 articles (OncLive 108, TargetedOnc 88). Limitations of cited research were reported in 7% (7/105) of OncLive and zero TargetedOnc articles. Benefit and risks in absolute numbers were reported in 28% (28/99) of OncLive and 16% (7/45) of TargetedOnc articles. Independent experts were quoted in 47% (51/108) and 51% (44/86) of the OncLive and TargetedOnc articles, respectively (Table 3). Pharmaceutical executives were quoted in 18% (20/108) and 11% (10/88) of OncLive and TargetedOnc articles, respectively. No FCOI disclosures were listed or reported for any articles. The mean general payment received from industry by United States physicians was $63,861 in 2019 and $39,639 in 2020.ConclusionOur study demonstrates low quality and potentially biased reporting of oncology news on OncLive and TargetedOnc. Careful safeguards, oversight and reporting of relevant FCOI are needed to maintain the quality and transparency of content being provided.

ABSTRACT: Objective: To evaluate the impact of vitamin D supplementation on fasting blood sugar & HbA1c in Type-2 diabetes mellitus patients. Methodology: This was an analytical case control study and was carried out by the Pharmacology Department at the Basic Medical Sciences Institute (BMSI, JPMC) with the collaboration of Diabetic OPD, JPMC, Karachi for the duration of 6 months. In this study 80 patients were selected by non-probability purposive sampling method and open EPI 3.01 version was used to estimate the sample size. Results: The study revealed that pre and post plasma vitamin D proportions in the intervention group were significant (P

Use of surrogate end-points such as progression-free survival (PFS) and other time-to-event (TTE) end-points is common in multiple myeloma (MM) clinical trials. This systematic review characterises all published randomised controlled trials (RCTs) in MM using PFS or other TTE end-points between 2005 and 2019 and assesses strength of surrogacy of PFS for overall survival (OS). The association between OS hazard ratios (HRs) and PFS HRs was evaluated with linear regression, and the coefficient of determination with Pearson's correlation. We identified 88 RCTs of which 67 (76%) used PFS as the primary/co-primary end-point. One trial indicated whether progression was biochemical or clinical. Of the variance in OS, 39% was due to variance in PFS. Correlation between PFS and OS was weak (0.62, 95% confidence interval [CI] 0.38-0.78). In newly diagnosed MM, 43% of the variance in OS was due to changes in PFS. The correlation between PFS and OS was weak (0.65, 95% CI 0.30-0.84). In relapsed/refractory MM, 58% of the variance in OS was due to changes in PFS. Correlation between PFS and OS was medium (0.76, 95% CI 0.42-0.91). We demonstrate that PFS and progression characteristics are characterised poorly in MM trials and that PFS is a poor surrogate for OS in MM.

Use of surrogate end-points such as progression-free survival (PFS) and other time-to-event (TTE) end-points is common in multiple myeloma (MM) clinical trials. This systematic review characterises all published randomised controlled trials (RCTs) in MM using PFS or other TTE end-points between 2005 and 2019 and assesses strength of surrogacy of PFS for overall survival (OS). The association between OS hazard ratios (HRs) and PFS HRs was evaluated with linear regression, and the coefficient of determination with Pearson's correlation. We identified 88 RCTs of which 67 (76%) used PFS as the primary/co-primary end-point. One trial indicated whether progression was biochemical or clinical. Of the variance in OS, 39% was due to variance in PFS. Correlation between PFS and OS was weak (0.62, 95% confidence interval [CI] 0.38-0.78). In newly diagnosed MM, 43% of the variance in OS was due to changes in PFS. The correlation between PFS and OS was weak (0.65, 95% CI 0.30-0.84). In relapsed/refractory MM, 58% of the variance in OS was due to changes in PFS. Correlation between PFS and OS was medium (0.76, 95% CI 0.42-0.91). We demonstrate that PFS and progression characteristics are characterised poorly in MM trials and that PFS is a poor surrogate for OS in MM.

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In the backdrop of persistent haze occurrences affecting Southeast Asia and Pakistan's environmental landscape, this study delves into an in-depth analysis of atmospheric Particulate Matter (PM2.5) during intense haze episodes prevalent in Lahore throughout October, November, and December 2019. Employing advanced analytical techniques encompassing Scanning Electron Microscopy (SEM) coupled with Energy-Dispersive Spectroscopy (EDX), X-ray Diffraction (XRD), and Raman Spectroscopy (RS), this investigation meticulously scrutinized PM2.5 samples. The findings showcased substantial variability in PM2.5 concentrations, peaking notably in December within the range of 43.2–301 μgm−3, averaging 168 ± 88.3 μgm−3, whereas lower concentrations ranging from 30.9 to 268 μgm−3, with an average of 106 ± 66.1 μgm−3, were observed in October. These concentrations displayed correlations with meteorological parameters, demonstrating a direct association with relative humidity and varying relationships with temperature and wind speed. The maximal PM2.5 concentrations aligned with lower temperatures (19.1 °C), while higher temperatures (26.1 °C) coincided with the lowest concentrations, illustrating distinct relationships with relative humidity percentages and wind speeds. Advanced spectroscopic analyses (RS and XRD) confirmed the presence of various minerals and elements within PM2.5 samples, encompassing calcite, calcium aluminosilicate, hematite, barite, quartz, gypsum, organic carbon, and nineteen elements identified by EDX. Morphological evaluations unveiled diverse particle shapes, from round, pointed, and irregular to rod-like, and agglomerate structures. SEM investigations delineated distinctive groups of anthropogenic and geogenic particles, emphasizing emission sources such as automobile emissions, crop residue burning, biomass burning, construction activities, soil dust, and industrial emissions. This comprehensive study lays the groundwork for source apportionment, vital for understanding consequential impacts on climate, visibility, and human health, fostering future investigations in this domain.