An Exploratory Study of Suboxone (Buprenorphine/ Naloxone) Film Splitting: Cutting Methods, Content Uniformity, and Stability

Suboxone films are U.S. Food and Drug Administration approved to treat opioid dependence. While the package insert states that films should not be cut, physicians often prescribe film fractions for treatment and tapering. There is no data to support this practice, and this study was initiated to evaluate cutting methods, content uniformity, and stability of split films. Suboxone 8-mg buprenorphine/2-mg naloxone films were split using four methods: 1) ruler/razor cut, 2) scissor cut, 3) fold/rip, and 4) fold/scissor cut. United States Pharmacopeia Chapter \u3c905\u3e was used to evaluate the weight variation and content uniformity of split films. The stability of split films stored in polybags was evaluated over 7 days. A stability-indicating high-performance liquid chromatography method was used for content uniformity and stability evaluation. The weight variation results were acceptable for the half films from all four cutting methods, but this was not true for the quarter films. The method of ruler/razor cut was determined most favorable and used for the content uniformity test. Based on the high-performance liquid chromatography results, the half films from the ruler/razor cut method met the passing criteria of United States Pharmacopeia Chapter \u3c905\u3e with acceptance values of 9.8 to 10.4 for buprenorphine and 8.4 to 11.5 for naloxone (≤15 is considered passing). The stability results indicated that both actives retained \u3e97.7% of initial strength. Four cutting methods were found to be acceptable for splitting Suboxone films into half but not quarter fractions. The half films from the ruler/razor cut method also passed United States Pharmacopeia Chapter \u3c905\u3e content uniformity test. Both actives remained stable for 7 days when the half films were stored in polybags at room temperature

Communication transforms the impact of the COVID-19 pandemic on children with cancer and their families

Pediatric cancer; Psychosocial studies; Quality of lifeCàncer pediàtric; Estudis psicosocials; Qualitat de vidaCáncer pediátrico; Estudios psicosociales; Calidad de vidaBackground The COVID-19 pandemic altered healthcare systems globally, causing delays in care delivery and increased anxiety among patients and families. This study examined how hospital stakeholders and clinicians perceived the global impact of the COVID-19 pandemic on children with cancer and their families. Methods This secondary analysis examined data from a qualitative study consisting of 19 focus groups conducted in 8 languages throughout 16 countries. A codebook was developed with novel codes derived inductively from transcript review. In-depth analysis focused on the impact of the COVID-19 pandemic on children with cancer and their families. Results Eight themes describing the impact of the pandemic on patients and their families were identified and classified into three domains: contributing factors (COVID-19 Policies, Cancer Treatment Modifications, COVID-19 Symptoms, Beliefs), patient-related impacts (Quality of Care, Psychosocial impacts, Treatment Reluctance), and the central transformer (Communication). Participants described the ability of communication to transform the effect of contributing factors on patient-related impacts. The valence of impacts depended on the quality and quantity of communication among clinicians and between clinicians and patients and families. Conclusions Communication served as the central factor impacting whether the COVID-19 pandemic positively or negatively affected children with cancer and families. These findings emphasize the key role communication plays in delivering patient-centered care and can guide future development of communication-centered interventions globally.Funding support to St. Jude Children's Research Hospital provided by the Cancer Center Support (CORE) grant (CA21765) and the American Lebanese-Syrian Associated Charities (ALSAC)

Distinct immune signatures in directly treated and distant tumors result from TLR adjuvants and focal ablation.

Both adjuvants and focal ablation can alter the local innate immune system and trigger a highly effective systemic response. Our goal is to determine the impact of these treatments on directly treated and distant disease and the mechanisms for the enhanced response obtained by combinatorial treatments. Methods: We combined RNA-sequencing, flow cytometry and TCR-sequencing to dissect the impact of immunotherapy and of immunotherapy combined with ablation on local and systemic immune components. Results: With administration of a toll-like receptor agonist agonist (CpG) alone or CpG combined with same-site ablation, we found dramatic differences between the local and distant tumor environments, where the directly treated tumors were skewed to high expression of F4/80, Cd11b and Tnf and the distant tumors to enhanced Cd11c, Cd3 and Ifng. When ablation was added to immunotherapy, 100% (n=20/20) of directly treated tumors and 90% (n=18/20) of distant tumors were responsive. Comparing the combined ablation-immunotherapy treatment to immunotherapy alone, we find three major mechanistic differences. First, while ablation alone enhanced intratumoral antigen cross-presentation (up to ~8% of CD45+ cells), systemic cross-presentation of tumor antigen remained low. Combining same-site ablation with CpG amplified cross-presentation in the draining lymph node (~16% of CD45+ cells) compared to the ablation-only (~0.1% of CD45+ cells) and immunotherapy-only cohorts (~10% of CD45+ cells). Macrophages and DCs process and present this antigen to CD8+ T-cells, increasing the number of unique T-cell receptor rearrangements in distant tumors. Second, type I interferon (IFN) release from tumor cells increased with the ablation-immunotherapy treatment as compared with ablation or immunotherapy alone. Type I IFN release is synergistic with toll-like receptor activation in enhancing cytokine and chemokine expression. Expression of genes associated with T-cell activation and stimulation (Eomes, Prf1 and Icos) was 27, 56 and 89-fold higher with ablation-immunotherapy treatment as compared to the no-treatment controls (and 12, 32 and 60-fold higher for immunotherapy-only treatment as compared to the no-treatment controls). Third, we found that the ablation-immunotherapy treatment polarized macrophages and dendritic cells towards a CD169 subset systemically, where CD169+ macrophages are an IFN-enhanced subpopulation associated with dead-cell antigen presentation. Conclusion: While the local and distant responses are distinct, CpG combined with ablative focal therapy drives a highly effective systemic immune response

The Cosmic Near Infrared Background II: Fluctuations

The Near Infrared Background (NIRB) is one of a few methods that can be used to observe the redshifted light from early stars at a redshift of six and above. Fluctuations of the NIRB can provide information on the first structures, such as halos and their surrounding ionized regions in the IGM. We combine, for the first time, N-body simulations, radiative transfer code, and analytic calculations of luminosity of early structures to predict the angular power spectrum (C_l) of fluctuations in the NIRB. We study the effects of various assumptions about the stellar mass, the initial mass spectrum of stars, metallicity, the star formation efficiency (f_*), the escape fraction of ionizing photons (f_esc), and the star formation timescale (t_SF), on the amplitude as well as the shape of C_l. The power spectrum of NIRB fluctuations is maximized when f_* is the largest (as C_l ~ (f_*)^2) and f_esc is the smallest. A significant uncertainty in the predicted amplitude of C_l exists due to our lack of knowledge of t_SF of these galaxies, which is equivalent to our lack of knowledge of the mass-to-light ratio. We do not see a turnover in the NIRB angular power spectrum of the halo contribution and explain this as the effect of high levels of non-linear bias. This is partly due to our choice of the minimum mass of halos contributing to NIRB, and a smaller minimum mass, which has a smaller non-linear bias, may still exhibit a turn over. Therefore, both the amplitude and shape of the NIRB power spectrum provide important information regarding the nature of sources contributing to the cosmic reionization. The angular power spectrum of the IGM, in most cases, is much smaller than the halo angular power spectrum. In addition, low levels of the observed mean background intensity tend to rule out high values of f_* > 0.2.Comment: 54 pages, 22 figures, Accepted for publication in ApJ. v2: Comments and references added, along with new figures and a section on fractional anisotrop

AMI observations of Lynds Dark Nebulae: further evidence for anomalous cm-wave emission

Observations at 14.2 to 17.9 GHz made with the AMI Small Array towards fourteen Lynds Dark Nebulae with a resolution of 2' are reported. These sources are selected from the SCUBA observations of Visser et al. (2001) as small angular diameter clouds well matched to the synthesized beam of the AMI Small Array. Comparison of the AMI observations with radio observations at lower frequencies with matched uv-plane coverage is made, in order to search for any anomalous excess emission which can be attributed to spinning dust. Possible emission from spinning dust is identified as a source within a 2' radius of the Scuba position of the Lynds dark nebula, exhibiting an excess with respect to lower frequency radio emission. We find five sources which show a possible spinning dust component in their spectra. These sources have rising spectral indices in the frequency range 14.2--17.9 GHz. Of these five one has already been reported, L1111, we report one new definite detection, L675, and three new probable detections (L944, L1103 and L1246). The relative certainty of these detections is assessed on the basis of three criteria: the extent of the emission, the coincidence of the emission with the Scuba position and the likelihood of alternative explanations for the excess. Extended microwave emission makes the likelihood of the anomalous emission arising as a consequence of a radio counterpart to a protostar or a proto-planetary disk unlikely. We use a 2' radius in order to be consistent with the IRAS identifications of dark nebulae (Parker 1988), and our third criterion is used in the case of L1103 where a high flux density at 850 microns relative to the FIR data suggests a more complicated emission spectrum.Comment: submitted MNRA