Summary Background Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is used to treat patients with non-Hodgkin lymphoma. Interval decrease from 3 weeks of treatment (CHOP-21) to 2 ...weeks (CHOP-14), and addition of rituximab to CHOP-21 (R-CHOP-21) has been shown to improve outcome in elderly patients with diffuse large B-cell lymphoma (DLBCL). This randomised trial assessed whether six or eight cycles of R-CHOP-14 can improve outcome of these patients compared with six or eight cycles of CHOP-14. Methods 1222 elderly patients (aged 61–80 years) were randomly assigned to six or eight cycles of CHOP-14 with or without rituximab. Radiotherapy was planned to sites of initial bulky disease with or without extranodal involvement. The primary endpoint was event-free survival; secondary endpoints were response, progression during treatment, progression-free survival, overall survival, and frequency of toxic effects. Analyses were done by intention to treat. The trial is registered on National Cancer Institute website, number NCT00052936 and as EU-20243. Findings 3-year event-free survival was 47·2% after six cycles of CHOP-14 (95% CI 41·2–53·3), 53·0% (47·0–59·1) after eight cycles of CHOP-14, 66·5% (60·9–72·0) after six cycles of R-CHOP-14, and 63·1% (57·4–68·8) after eight cycles of R-CHOP-14. Compared with six cycles of CHOP-14, the improvement in 3-year event-free survival was 5·8% (−2·8–14·4) for eight cycles of CHOP-14, 19·3% (11·1–27·5) for six cycles of R-CHOP-14, and 15·9% (7·6–24·2) for eight cycles of R-CHOP-14. 3-year overall survival was 67·7% (62·0–73·5) for six cycles of CHOP-14, 66·0% (60·1–71·9) for eight cycles of CHOP-14, 78·1% (73·2–83·0) for six cycles of R-CHOP-14, and 72·5% (67·1–77·9) for eight cycles of R-CHOP-14. Compared with treatment with six cycles of CHOP-14, overall survival improved by −1·7% (−10·0–6·6) after eight cycles of CHOP-14, 10·4% (2·8–18·0) after six cycles of R-CHOP-14, and 4·8% (−3·1–12·7) after eight cycles of R-CHOP-14. In a multivariate analysis that used six cycles of CHOP-14 without rituximab as the reference, and adjusting for known prognostic factors, all three intensified regimens improved 3-year event-free survival (eight cycles of CHOP-14: RR relative risk 0·76 0·60–0·95, p=0·0172; six cycles of R-CHOP-14: RR 0·51 0·40–0·65, p<0·0001; eight cycles of R-CHOP-14: RR 0·54 0·43–0·69, p<0·0001). Progression-free survival improved after six cycles of R-CHOP-14 (RR 0·50 0·38–0·67, p<0·0001), and eight cycles of R-CHOP-14 (RR 0·59 0·45–0·77, p=0·0001). Overall survival improved only after six cycles of R-CHOP-14 (RR 0·63 0·46–0·85, p=0·0031). In patients with a partial response after four cycles of chemotherapy, eight cycles were not better than six cycles. Interpretation Six cycles of R-CHOP-14 significantly improved event-free, progression-free, and overall survival over six cycles of CHOP-14 treatment. Response-adapted addition of chemotherapy beyond six cycles, though widely practiced, is not justified. Of the four regimens assessed in this study, six cycles of R-CHOP-14 is the preferred treatment for elderly patients, with which other approaches should be compared.
Summary Background High-dose therapy (HDT) followed by transplantation of autologous haemopoietic stem cells is frequently done as part of first-line therapy in young patients with high-risk ...aggressive B-cell lymphoma. We investigated whether HDT with cytotoxic agents identical to those used for conventional therapy followed by autologous stem-cell transplantation (ASCT) improved survival outcome compared with conventional chemotherapy when rituximab was added to both modalities. Methods We did an open-label, randomised trial comparing conventional chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone) and rituximab (R-CHOEP-14) with dose-escalated sequential HDT and rituximab (R-MegaCHOEP) followed by repetitive ASCT in high-risk (age-adjusted International Prognostic Index IPI 2 or 3) patients aged 18–60 years with aggressive B-cell lymphoma. Eligible patients received radiotherapy for bulky, extranodal disease, or both. Randomisation (1:1) used the Pocock minimisation algorithm; patients were stratified by age-adjusted IPI factors, bulky disease, and centre. The primary endpoint was event-free survival. All analyses were done on the intention-to-treat population. This trial is registered with ClinicalTrials.gov , number NCT00129090. Findings 136 patients were randomly assigned to R-CHOEP-14 and 139 to R-MegaCHOEP. 130 patients in the R-CHOEP-14 group and 132 in the R-MegaCHOEP group were included in the intention-to-treat population. After a median of 42 months (IQR 29–59), 3-year event-free survival was 69·5% (95% CI 61·3–77·7) in the R-CHOEP-14 group and 61·4% (52·8–70·0) in the R-MegaCHOEP group (p=0·14; hazard ratio 1·3, 95% CI 0·9–2·0). All 128 evaluable patients treated with R-MegaCHOEP had grade 4 leucopenia, as did 48 (58·5%) of 82 patients with documented blood counts in the R-CHOEP-14 group. All 128 evaluable patients in the R-MegaCHOEP group had grade 3–4 thrombocytopenia, as did 26 (33·8%) of 77 patients in the R-CHOEP-14 group with documented blood counts. The most important non-haematological grade 3 or 4 adverse event was infection, which occurred in 96 (75·0%) of 128 patients treated with R-MegaCHOEP and in 40 (31·3%) of 128 patients treated with R-CHOEP-14. Interpretation In young patients with high-risk aggressive B-cell lymphoma, R-MegaCHOEP was not superior to conventional R-CHOEP therapy and was associated with significantly more toxic effects. R-CHOEP-14 with or without radiotherapy remains a treatment option for these patients, with encouraging efficacy. Funding Deutsche Krebshilfe.
...although packaging often reports that cannabinoid compounds JWH and HU are not present in the herbal mixtures, it would be interesting to elicit whether these SC compounds actually exist.
Background Significant confusion exists about management of blunt carotid injuries (BCI). Currently, three common treatments are being used without significant longterm followup data to demonstrate ...efficacy. Although heparin has been shown to reduce in-hospital stroke rates, antiplatelet therapy (aspirin and clopidogrel) has emerged as an alternate therapy without proved efficacy; carotid stenting has also been implemented for pseudoaneurysms (13% BCI), but its utility has recently been challenged. This is the first study to assess longterm efficacy of various therapeutic approaches. Study Design Consecutive patients treated and followed at a single regional trauma center over 10 years (1996 to 2005) were reviewed. Outcomes evaluated included cerebral infarction, functional status, and angiographic evolution. Results One hundred ten patients (11/year) were diagnosed with 133 injuries (23 bilateral). Overall mortality was 26%, with 6% directly attributable to BCI. Angiographic followup was available on 67 injuries (in 50 patients) at a mean of 6 months (range 0.25 to 67 months); 75% remained the same or improved. Clinical followup was available in 55 of 81 patients (68%) who survived to discharge (mean, 34.4 months range 1 to 109 months). Of surviving patients receiving antithrombotic therapy, 44% were treated with antiplatelet therapy, 49% with anticoagulation, and 7% with both. No patients experienced cerebral infarction after discharge, and there was no difference in functional outcomes based on the therapy received. Twenty-two endovascular stents were placed (18 for pseudoaneurysms, 4 for extensive dissection). Mean followup on these patients was 29.7 months (range 3 to 94 months). No patients receiving stents experienced periprocedural complications, and one patient with an associated brain injury had a cerebral infarction. Conclusions Longterm followup of BCI demonstrates that antithrombotic therapy prevents cerebral infarction; antiplatelet therapy and anticoagulation are equally effective; and carotid stents appear to be safe and effective for lesions that develop pseudoaneurysms or extensive dissections.
Acute infections with Mycoplasma pneumoniae (Mp) have been associated with worsening asthma in children. Mp can be present in the respiratory tract for extended periods; it is unknown whether the ...long-term persistence of Mp in the respiratory tract affects long-term asthma control.
To determine the effect of Mp on asthma control.
We enrolled 31 pediatric subjects 3 to 10 years of age with persistent asthma who completed up to 8 visits over a 24-month period. We detected Mp by antigen capture and polymerase chain reaction. Primary outcome measurements included symptom scores, quality of life, medication scores, oral corticosteroid use, health care usage, school absences, and exhaled breath condensate pH.
Low levels of Mp community-acquired respiratory distress syndrome toxin were detected in 20 subjects (64.5%) at enrollment. Subjects with Mp positivity at a given visit had a .579 probability of remaining Mp positive at the subsequent visit, whereas those with Mp negativity had a .348 probability of becoming Mp positive at the following visit. The incidence of Mp overall was higher in the spring and summer months. Overall, we found no significant relation between the detection of Mp and worse outcome measurements at the same visit or at subsequent visits.
The long-term persistence of Mp in the respiratory tract is common in children with asthma. However, the detection of Mp was not associated significantly with worse asthma symptoms, quality of life, health care usage, school absences, or exhaled breath condensate pH in this pediatric asthma cohort.
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•Tribe Toxotrypanini is non-monophyletic and Hexachaeta is not related to Anastrepha.•Genera Anastrepha and Toxotrypana should be considered synonyms.•Anastrepha, including ...Toxotrypana, is well-supported by molecular evidence.•Present results support most of the studied Anastrepha species groups.
Current hypotheses of relationship among the species of the fruit fly genera Anastrepha and Toxotrypana are tested using sequence data from six DNA regions: the mitochondrial regions 16S, CAD, and COI, and the nuclear regions EF1a, PER, and PGD. DNA sequences were obtained from 146 species of Anastrepha, representing 19 of the 21 species groups as well as five of the six clades of the robusta group, and four species of Toxotrypana in addition to species of Hexachaeta, Pseudophorellia, Alujamyia, and 13 other tephritid genera used as outgroups. The results indicate that Hexachaeta is more closely related to the Molynocoelia group than to Toxotrypana and Anastrepha, and it is removed from the tribe Toxotrypanini. The group Anastrepha+Toxotrypana and the genus Toxotrypana are strongly supported as monophyletic, consistent with previous studies, but Toxotrypana arises within Anastrepha, confirming that Anastrepha as currently defined is paraphyletic. The placement of Toxotrypana within Anastrepha is clearly defined for the first time with high support, as the sister group to the cryptostrepha clade of the robusta group of Anastrepha. Within Anastrepha, the daciformis, dentata, leptozona, raveni, and striata species groups are highly supported clades. The serpentina group is recognized with lower support, and the fraterculus and pseudoparallela groups are supported with minor alterations. The robusta group is resolved as polyphyletic, but four of the six species clades within it are recovered monophyletic (one clade is not represented and another is represented by one species). The punctata and panamensis groups are resolved together in a clade. At least some species of the mucronota group are related, however this group requires further study. The benjamini, grandis, and spatulata groups appear to be polyphyletic. Relationships among the species groups are generally poorly resolved, with the following exceptions: (1) the lineage including Toxotrypana, the cryptostrepha clade, and the tripunctata group; (2) the sister group relationship of the daciformis+dentata groups; (3) a clade comprising the punctata and panamensis groups; and (4) the large clade comprising the pseudoparallela+spatulata+ramosa+grandis+serpentina+striata+fraterculus groups.
Lower respiratory tract infections (LRTI) are a leading cause of critical illness and mortality in mechanically ventilated children; however, the pathogenic microbes frequently remain unknown. We ...combined traditional diagnostics with metagenomic next generation sequencing (mNGS) to evaluate the cause of LRTI in critically ill children.
We conducted a prospective, multicentre cohort study of critically ill children aged 31 days to 17 years with respiratory failure requiring mechanical ventilation (>72 h) in the USA. By combining bacterial culture and upper respiratory viral PCR testing with mNGS of tracheal aspirate collected from all patients within 24 h of intubation, we determined the prevalence, age distribution, and seasonal variation of viral and bacterial respiratory pathogens detected by either method in children with or without LRTI.
Between Feb 26, 2015, and Dec 31, 2017, of the 514 enrolled patients, 397 were eligible and included in the study (276 children with LRTI and 121 with no evidence of LRTI). A presumptive microbiological cause was identified in 255 (92%) children with LRTI, with respiratory syncytial virus (127 46%), Haemophilus influenzae (70 25%), and Moraxella catarrhalis (65 24%) being most prevalent. mNGS identified uncommon pathogens including Ureaplasma parvum and Bocavirus. Co-detection of viral and bacterial pathogens occurred in 144 (52%) patients. Incidental carriage of potentially pathogenic microbes occurred in 82 (68%) children without LRTI, with rhinovirus (30 25%) being most prevalent. Respiratory syncytial virus (p<0·0001), H influenzae (p=0·0006), and M catarrhalis (p=0·0002) were most common in children younger than 5 years. Viral and bacterial LRTI occurred predominantly during winter months.
These findings demonstrate that respiratory syncytial virus, H influenzae, and M catarrhalis contribute disproportionately to severe paediatric LRTI, co-infections are common, and incidental carriage of potentially pathogenic microbes occurs frequently. Further, we provide a framework for future epidemiological and emerging pathogen surveillance studies, highlighting the potential for metagenomics to enhance clinical diagnosis.
US National Institutes of Health and CZ Biohub
This study assessed individual and organizational context (work environment) factors that influence use of best practices by care aides (nursing assistants) in nursing homes. Little scientific ...attention has been focused on understanding best practice use in nursing homes and almost none on care aides.
A total of 1262 care aides in 25 nursing homes in the 3 Canadian prairie provinces. Care aides are unregulated workers who provide 80% of direct care to residents in Canadian nursing homes.
We used hierarchical linear modeling to (1) assess the amount of variance in use of best practices, as reported by care aides, that could be attributed to individual or organizational factors, and (2) identify predictors of best practices use by care aides.
At the individual level, statistically significant predictors of instrumental use of best practices included sex, age, shift worked, job efficacy, and belief suspension. At the unit level, significant predictors were social capital, organizational slack (staffing and time), number of informal interactions, and unit type. At the facility level, ownership model and province were significant. Significant predictors of conceptual use of best practices at the individual level included English as a first language, job efficacy, belief suspension, intent to use research, adequate knowledge, and number of information sources used. At the unit level, significant predictors were evaluation (feedback mechanisms), structural resources, and organizational slack (time). At the facility level, province was significant. The R2 was 18.3% for instrumental use of best practices and 43.4% for conceptual use. Unit level factors added a substantial amount of explained variance whereas facility level factors added relatively little explained variance.
Our study suggests that context plays an important role in care aides' use of best practices in nursing homes. Individual characteristics played a more prominent role than contextual factors in predicting conceptual use of best practices.
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