Purpose
This review article explores the need for specialized pain care for children and adolescents and provides some historical context for our current knowledge base and clinical practice.
...Principal findings
Pediatric patients have specialized needs with respect to assessment and management of pain. Acute pain care is modified by developmental considerations in both these areas; chronic pain encompasses a wide range of complex developmental, social, and psychological factors requiring the skills of different health disciplines to provide the best care.
Conclusions
Awareness of children’s pain has increased dramatically over the past three decades, and Canadians have performed a leadership role in much of the research. Specific multidisciplinary teams are a more recent phenomenon, but they are shown to be more effective and probably more cost effective than traditional treatment models. Important gaps in availability of resources to manage these patients remain.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
BACKGROUNDKaposi sarcoma (KS) is among the most common childhood cancers in Eastern and Central Africa. Pediatric KS has a distinctive clinical presentation compared with adult KS, which includes a ...tendency for primary lymph node involvement, a considerable proportion of patients lacking cutaneous lesions, and a potential for fulminant disease. The molecular mechanisms or correlates for these disease features are unknown.METHODSThis was a cross-sectional study. All cases were confirmed by IHC for KS-associated herpesvirus (KSHV) LANA protein. Baseline blood samples were profiled for HIV and KSHV genome copy numbers by qPCR and secreted cytokines by ELISA. Biopsies were characterized for viral and human transcription, and KSHV genomes were determined when possible.RESULTSSeventy participants with pediatric KS were enrolled between June 2013 and August 2019 in Malawi and compared with adult patients with KS. They exhibited high KSHV genome copy numbers and IL-6/IL-10 levels. Four biopsies (16%) had a viral transcription pattern consistent with lytic viral replication.CONCLUSIONThe unique features of pediatric KS may contribute to the specific clinical manifestations and may direct future treatment options.FUNDINGUS National Institutes of Health U54-CA-254569, PO1-CA019014, U54-CA254564, RO1-CA23958.
Introduction. Parents of children living with type 1 diabetes (T1D) often report short and/or poor quality sleep. The development of closed-loop systems promises to transform the management of T1D. ...This study compared sleep quality and quantity in caregivers of children using a closed-loop system (CL) or sensor-augmented pump (SAP) therapy. Method. Data from sleep diaries, accelerometers, and questionnaires were provided by forty parents (classified as caregiver 1 (main analyses) or 2 (supplementary analyses) based on their contribution towards treatment management) of 21 very young children aged 1 to 7 years living with T1D (mean age: 4.7 (SD = 1.7)). Assessments were made at a single post-randomisation time point when the child was completing either the 16-week CL arm (n = 10) or the 16-week SAP arm (n = 11) of the main study. Results. Overall, there was a mixed pattern of results and group differences were not statistically significant at the p<0.05 level. However, when we consider the direction of results and results from caregiver 1, sleep diary data showed that parents of the CL (as compared to the SAP) group reported a shorter sleep duration but better sleep quality, fewer awakenings, and less wake after sleep onset (WASO). Actiwatch data showed that caregiver 1 of the CL (as compared to the SAP) group had a shorter sleep latency; greater sleep efficiency; and less wake after sleep onset. Results from the Pittsburgh Sleep Quality Index also showed better sleep quality for caregiver 1 of the CL group as compared to the SAP group. Conclusions. Results from this study suggest that sleep quality and quantity in parents of children using CL were not significantly different to those using SAP. Considering effect sizes and the direction of the non-significant results, CL treatment could be associated with better sleep quality in the primary caregiver. However, further research is needed to confirm these findings. This trial is registered with NCT05158816.
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Background: Patients with metastatic genitourinary malignancies with neuroendocrine have limited therapeutic options following platinum therapy. Given encouraging results in initial ...cohort analysis for small cell urinary tract carcinoma, a cohort of any genitourinary malignancy with neuroendocrine differentiation was added to a multicenter, single arm, multi-cohort phase II trial to evaluate the efficacy of N and I in this setting. (NCT 03333616) Methods: Eligible patients had metastatic or locally advanced genitourinary malignancy with neuroendocrine differentiation with an ECOG performance status of 0-2; they may have received any line of prior therapy excluding prior immunotherapy. Patients underwent baseline biopsy and received treatment with N 3 mg/kg and I 1 mg/kg intravenously every 3 weeks for 4 cycles with continued maintenance of N 480 mg IV every 4 weeks. Imaging was performed at 12 weeks and then every 8 weeks through month 6 and then every 12 weeks thereafter. The primary endpoint was investigator assessed objective response rate (ORR) by RECIST 1.1. Results: A total of 27 patients were enrolled between 06/27/2018 and 06/21/2021, 10 (37%) had urinary tract cancer and 17 (63%) had prostate cancer (19 in expansion cohort, 3 urinary tract and 5 prostate cancer from earlier cohorts). The majority (n=25, 93%) patients received prior systemic therapy. Nine (33%) patients received all 4 doses of N and I during the induction period. Nine (33%) patients (7 of whom received 4 cycles N+I) received N maintenance (median number of cycles 9 (range, 2-37)). Median follow-up was 6.8 (range, 0.9-37.3) months. Objective response was achieved in 8 (30%, 80% CI 18%-44%) patients (Table). Median duration of response was not reached with 4 patients maintaining response >9 months. Median progression-free survival time was 2.6 (95% CI 1.8-6.5) months At time of analysis, 13 (48%) death events were reported due to progressive disease, in which 3 were bladder and 10 were prostate cancer. 8 (30%) patients developed treatment-related grade 3 or higher toxicities; one grade 5 toxicity was deemed treatment-unrelated. Conclusions: In this study we demonstrate N+I resulted in objective responses in patients with genitourinary malignancy with neuroendocrine differentiation. ORR of 50% in small cell carcinoma is bladder cancer is noteworthy and will be evaluated further in ongoing expansion cohort of bladder or upper tract carcinoma with variant histology. Clinical trial information: NCT03333616. Table: see text
The underlying theme throughout this series of studies authored by the Multicenter anterior cruciate ligament (ACL) Revision Study consortium has been to determine the modifiable predictors or risk ...factors of long‐term outcomes of revision ACL reconstruction. The observational studies described and summarized in the manuscript are both clinically relevant and of great interest in finding out the long‐term consequences of the intervention and its relationship to the original injury. The successful completion of these studies has important implications for both therapy and future clinical trials. The identification of modifiable risk factors will play an important role in secondary prevention, while the identification of nonmodifiable risk factors will aid us in counseling our patients and making surgical decisions. Thus, we expect a profound clinical impact on patients' care. More importantly, this project represents an important step forward in bringing evidence to bear in clinical decision making in orthopedic surgery.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
Background
The precautionary allergen labelling (PAL) and Voluntary Incidental Trace Allergen Labelling (VITAL®) tools were designed by industry to assist consumers with selecting safe foods ...for consumption. However, a sizeable proportion of food products bear no label, and it is unclear whether these products are free from allergens and therefore safe to consume or have simply not undergone a risk assessment and therefore remain unlabelled for that reason.
Objective
To assess the prevalence of unlabelled products that have undergone a risk assessment process and to examine the factors influencing industry's uptake of the VITAL® process.
Methods
A web‐based questionnaire was distributed to Australasian food and grocery manufacturers.
Results
One hundred and thirty‐seven Australasian manufacturers were contacted, and 59 questionnaires were returned (response rate: 43%). The respondents represented 454 different manufacturing sites. Manufacturers reported that 23% (95% CI 19‐28) of products (n=102/434) that had been through the VITAL® risk assessment process had no PAL statement on the label. 34% (95% CI 30‐38), (n=204/600) of products that had undergone another (non‐VITAL®) risk assessment process had no PAL statement. In examining the factors that influenced industry's uptake of the VITAL® process, 25 manufacturers reported on factors that influenced the uptake of the VITAL® process, 76% (CI 95% 55‐91) reported that VITAL® was an effective tool because it was based on science; 52% (CI 95% 31‐72) reported that it was too time‐consuming and 36% (CI 95% 18‐57) identified a concern with it not being endorsed by the government.
Conclusion and Clinical Relevance
Currently, we estimate that at least 30% of products may have been through a risk assessment process and yet bear no PAL statement on the label. Permissive labelling could be incorporated onto these products if they have been assessed to be safe for consumption.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Several invasive mosquito species that are nuisances or of medical and veterinary importance have been introduced into the Southeastern region of the USA, posing a threat to other species and the ...local ecosystems and/or increasing the risk of pathogen transmission to people, livestock, and domestic pets. Prompt and effective monitoring and control of invasive species is essential to prevent them from spreading and causing harmful effects. However, the capacity for invasive mosquito species surveillance is highly variable among mosquito control programs in the Southeast, depending on a combination of factors such as regional geography and climate, access to resources, and the ability to interact with other programs. To facilitate the development of invasive mosquito surveillance in the region, we, the Mosquito BEACONS (Biodiversity Enhancement and Control of Non-native Species) working group, conducted a survey on the capacities of various public health agencies and pest control agencies engaged in mosquito surveillance and control in seven Southeastern states (Alabama, Florida, Georgia, Louisiana, Mississippi, North Carolina, and South Carolina). Ninety control programs completed the survey, representing an overall response rate of 25.8%. We report key findings from our survey, emphasizing the training and resource needs, and discuss their implications for future invasive mosquito surveillance and control capacity building. By increasing communication and collaboration opportunities (e.g., real-time sharing of collection records, coordinated multistate programs), the establishment of Mosquito BEACONS and the implementation of this survey can accelerate knowledge transfer and improve decision support capacity in response to or in preparation for invasive mosquito surveillance and can establish infrastructure that can be used to inform programs around the world.
The Multicenter Anterior Cruciate Ligament (ACL) Revision Study (MARS) group was formed to study a large cohort of revision ACL reconstruction patients. The purpose of this subset analysis study of ...the MARS database is to describe specific details of femoral tunnel malposition and subsequent management strategies that surgeons chose in the revision setting. The design of this study is a case series. The multicenter MARS database is compiled from a questionnaire regarding 460 ACL reconstruction revision cases returned by 87 surgeons. This subset analysis described technical aspects and operative findings in specifically those cases in which femoral tunnel malposition was cited as the cause of primary ACL reconstruction failure. Of the 460 revisions included for study, 276 (60%) cases cited a specific "technical cause of failure." Femoral tunnel malposition was cited in 219 (47.6%) of 460 cases. Femoral tunnel malposition was cited as the only cause of failure in 117 cases (25.4%). Surgeons judged the femoral tunnel too vertical in 42 cases (35.9%), too anterior in 35 cases (29.9%), and too vertical and anterior in 31 cases (26.5%). Revision reconstruction involved the drilling of an entirely new femoral tunnel in 91 cases (82.1%). For primary reconstruction, autograft tissue was used in 82 cases (70.1%). For revision reconstruction, autograft tissue was used in 61 cases (52.1%) and allograft tissue in 56 cases (47.9%). Femoral tunnel malposition in primary ACL reconstruction was the most commonly cited reason for graft failure in this cohort. Graft selection is widely variable among surgeons.
Abstract
Background: Neoadjuvant chemotherapy followed by radical cystectomy is the optimal treatment for patients with muscle invasive bladder cancer. Between 30 and 40% of patients receiving ...neoadjuvant chemotherapy will have pathological complete response at the time of radical cystectomy. Presence of somatic mutations in DNA damage repair genes correlate with chemoresponse, likely stemming from a loss-of-function in the ability to repair DNA damage brought on by cytotoxic chemotherapy. However, many chemoresponders have WT DNA repair status. As such, there is a keen interest to identify additional mechanisms associated with chemoresponse.
Results: A higher tumor mutation/neoantigen burden is associated with response to immune checkpoint blockade, so we sought to investigate a correlation between mutation burden and chemoresponse. We found that responders had a higher neoantigen burden and higher signature of tumor infiltrating CD8+ T cells (TILs). We interrogated a database of tumors that underwent clinical tumor sequencing (NextGen SEQ, Caris Life Sciences; 592 genes; n=897) and PD-L1 staining (Combined Positive Score CPS using 22C3 antibody) and found that mutation burden was directly proportional to CPS. In addition, we found that CPS was positively associated with KRAS and TP53 mutation, whereas it was negatively associated with FGFR3 activating alterations, MDM2 amplification and GATA3 amplification after correction for multiple comparisons. There was an overall increase in the proportional representation of TIL-derived T cell receptors (TCR) repertoire in the periphery after chemotherapy independent of responder status. This implies that the presence of immune response even in patients without pathologic response. Additionally, TIL-derived TCRs were also found in perivesical lymph nodes in both responders and non-responders, however, there was a distinct profile of activation/exhaustion associated with either patient group. Responders showed a unique CD69+/PD1−(activated/non-exhausted) population amongst the nodal CD8+ T cells suggesting that this population is required to achieve pathologic complete response.
Conclusions: These results further our understanding of immune responses to chemotherapy in bladder cancer and may enable the development of chemo-immunotherapy regimens to improve response rates to neoadjuvant chemotherapy.
Citation Format: Rashida Ginwala, Alexander Macfarlane, IV, David Liu, R K. Alpaugh, Joanne Xiu, Zoran Gatalica, W M. Korn, Eliezer M. Van Allen, Kerry S. Campbell, Alexander Kutikov, Elizabeth Plimack, Philip H. Abbosh. Immune correlates of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer abstract. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6624.
Complex regional pain syndromes (CRPS) and neuropathic pain are often poorly controlled by conventional pharmacologic interventions. We administered 8-methyl-N-vanillyl-noneamide (capsaicin) at doses ...of 5%-10% to individuals with such disorders in this trial. Previous limitations to trials with larger-dose, topical concentrations of capsaicin included intense burning sensations experienced after application. To enable patients to tolerate the high concentrations, we first performed regional anesthesia. All patients reported at least some relief. Of 10 patients, 9 obtained substantial analgesia that lasted 1-18 wk. At Week 1 after therapy, the mean verbal analog scale (VAS) scores decreased from 8.0 to 3.0. At Week 4 after therapy, mean VAS score was 4.5. Analgesia lasted from < 1 wk (1 patient) to more than 50 wk (1 patient). Patients received one to eight treatments. With one exception, patients receiving more than one treatment obtained additional relief with subsequent treatment. Pain responsive to opioids was the only side effect of treatment. Large-dose capsaicin administered with regional anesthesia may effectively minimize refractory CRPS and neuropathic pain. A double-blind, placebo-controlled study in patients with bilateral peripheral neuropathy using epidural anesthesia with and without large-dose topical capsaicin is in progress.
Sensory neuropathies are associated with many diseases. Pain from these disorders can produce greater disability than the primary disease processes themselves. Currently available therapies are limited. However, the intermittent application of large-dose topical capsaicin may provide significant pain relief, decrease chronic analgesic dependence, and decrease aggregate health care expenditures.
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