Head Games: A Systematic Review and Meta-analysis Examining Concussion and Head Impact Incidence Rates, Modifiable Risk Factors, and Prevention Strategies in Youth Tackle Football.

OBJECTIVES: The aims were to (1) examine the rates and mechanisms of concussion and head impact in youth football (high school level or younger); (2) identify modifiable risk factors for concussion and head impact; and (3) evaluate the effectiveness of prevention strategies in tackle football at any level. METHODS: Nine databases (CINAHL Plus with Full Text; Cochrane Central Register of Controlled Trials; EMBASE; ERIC; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; ProQuest Dissertations & Theses Global Database; PsycINFO; Scopus; and SPORTDiscus with Full Text) were searched using the search strategy focusing on four main concepts: concussion/head impact, tackle football, modifiable risk factors, and primary prevention. Two reviewers completed title, abstract, and full-text screening as well as risk of bias assessment (using the Downs and Black checklist), with a third author available to resolve any disagreements. MAIN RESULTS: After removing duplicates, 1911 articles were returned. Fifty-eight articles were included in the review and 20 in the meta-analysis. The overall combined rates of concussion (including game and practice-related concussion) based on the meta-analysis were 0.78 concussions/1000 athlete exposures [95% confidence interval (CI) 0.67-0.89] for high school football (ages 13-19) and 1.15 concussions/1000 athlete exposures (95% CI 0.89-1.41) for minor football players (ages 5-15). There is evidence that contact training and practice contact restrictions have reduced the rate of head impacts and concussion. Heads Up Football (an intervention focused on coach education and contact training) has been shown to reduce the rate of concussion by 32% and head impacts by 38% amongst high school football players. Limiting contact practices in high schools to 2 days per week reduced practice head impacts per player-season by 42%, and limiting full contact in practice to 75 min per week in the second week of the season and 60 min in week 3 and beyond resulted in a 54% decrease in the practice-related concussion rate (p = 0.003). CONCLUSIONS: This review identified a critical need for interventions to address the high rates of concussion and head impact in youth football. To date, contact training and contact restrictions have the strongest evidence supporting their effectiveness at reducing these rates. Future research should use consistent concussion definitions and validated injury surveillance systems, and ensure complete reporting of participant characteristics and sampling details. Prospero ID CRD42020193775.

Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study.

BACKGROUND: Many patients with aggressive B-cell lymphomas and high clinical risk score still die of lymphoma after conventional R-CHOP chemoimmunotherapy. We hypothesized that intensified chemoimmunotherapy including systemic central nervous system (CNS) prophylaxis improves outcome and reduces the incidence of CNS-related events. PATIENTS AND METHODS: Inclusion criteria were age 18-65 years, primary diffuse large B-cell lymphoma or grade III follicular lymphoma without clinical signs of CNS disease and negative cerebrospinal fluid cytology, age-adjusted International Prognostic Index 2-3 and WHO performance score 0-3. Treatment consisted of six courses of R-CHOEP-14 followed by a course of high-dose cytarabine and a course of high-dose methotrexate. Primary end point was failure-free survival (FFS) at 3 years. RESULTS: A total of 156 eligible patients with a median age of 54 years (range 20-64) were included. Three toxic deaths were observed. Three-year overall survival (OS) and FFS rates (median observation time 52 months for survivors) were 81% and 65%, respectively. Seven patients experienced CNS relapse, all within 6 months. CONCLUSIONS: The results are promising with favorable 3-year OS and FFS rates, a low toxic death rate and a lower than expected number of CNS events. CNS progression might be further reduced by earlier CNS prophylaxis. CinicalTrials.gov. identifier NCT01502982.

Ultra-short course sirolimus contributes to effective GVHD prophylaxis after reduced-intensity allogeneic hematopoietic cell transplantation.

Reduced-intensity conditioning (RIC) allo-SCT is a potentially curative treatment approach for patients with relapsed Hodgkin's or non-Hodgkin's lymphoma. In the present study, 37 patients underwent RIC allo-SCT after induction treatment with EPOCH-F(R) using a novel form of dual-agent immunosuppression for GVHD prophylaxis with CsA and sirolimus. With a median follow-up of 28 months among survivors, the probability for OS at 3 and 5 years was 56%. Treatment-related mortality was 16% at day +100 and 30% after 1 year of transplant. Acute GVHD grades II-IV developed in 38% of patients, suggesting that the regimen consisting of CsA and an ultra-short course of sirolimus is effective in the prevention of acute GVHD.

Two escalated followed by six standard BEACOPP in advanced-stage high-risk classical Hodgkin lymphoma: high cure rates but increased risk of aseptic osteonecrosis.

BACKGROUND: From 1999, Norwegian guidelines recommend two escalated (esc) BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone) followed by six standard (s) BEACOPP for patients with advanced-stage classical Hodgkin lymphoma (HL) with an international prognostic score (IPS) ≥ 4. We evaluated retrospectively the experience with this recommendation at the Norwegian Radium Hospital, also including all IPS 3 patients treated with the same regimen. PATIENTS AND METHODS: Forty-seven patients were treated between June 1999 and December 2008. IPS was 3 in 10 patients and ≥ 4 in 37. RESULTS: Thirty-five patients received eight cycles of BEACOPP, 12 patients received one to six cycles only, mainly due to toxicity. Sixty percent of patients had dose reductions. With median follow-up of survivors of 89 months, 5-year progression-free and overall survival are 84% [95% confidence interval (CI) 73% to 95%] and 91% (95% CI 82% to 100%), respectively. Toxicity was considerable with grade 3 or more infections/febrile neutropenia in 66% of patients, including one death and three cases of Pneumocystis jiroveci pneumonia. Of note, 10 patients (21%) experienced symptomatic aseptic osteonecrosis, of whom 3 have had hip replacement surgery after treatment. CONCLUSION: Two escBEACOPP plus six sBEACOPP is efficacious in advanced-stage high-risk HL. We document a high incidence of aseptic bone necrosis, possibly related to prednisolone.

Clinical evidence of a graft-versus-lymphoma effect against relapsed diffuse large B-cell lymphoma after allogeneic hematopoietic stem-cell transplantation.

BACKGROUND: A graft-versus-lymphoma effect against diffuse large B-cell lymphoma (DLBCL) is inferred by sustained relapse-free survival after allogeneic stem-cell transplantation; however, there are limited data on a direct graft-versus-lymphoma effect against DLBCL following immunotherapeutic intervention by either withdrawal of immunosuppression or donor lymphocyte infusion (DLI). MATERIALS AND METHODS: An analysis was carried out to determine whether a direct graft-versus-lymphoma effect exists against DLBCL. The analysis was restricted to patients with DLBCL, who were either not in complete remission at day +100 after allogeneic stem-cell transplantation or subsequently relapsed beyond this time point. RESULTS: Fifteen patients were identified as either not in complete remission (n = 13) at their day +100 evaluation or subsequently relapsed (n = 2) and were assessed for subsequent responses after withdrawal of immunosuppression or DLI. Eleven patients were treated with either withdrawal of immunosuppression (n = 10) or a DLI (n = 1) alone; four patients received chemotherapy with DLI to reduce tumor bulk. Nine (60%) patients subsequently responded (complete = 8, partial = 1). Six responses occurred after withdrawal of immunosuppression alone. Six patients are alive (range 42-83+ months) in complete remission without further treatment. CONCLUSION: The demonstration of sustained complete remission following immunotherapeutic intervention provides direct evidence of a graft-versus-lymphoma effect against DLBCL.

Standard CHOP-21 as first line therapy for elderly patients with Hodgkin's lymphoma.

There is no consensus on the optimal chemotherapy regimen for Hodgkin's lymphoma patients > or = 60 years. We present our institution's results of 5 years, using CHOP-21 as standard for this patient group. Twenty-nine patients with a median age of 71 years (range, 60 - 91) were included in this cohort. Fifty-five percent had known co-morbidities. Stage I/IIA patients (38%) were treated with 2 - 4 cycles of CHOP followed by radiotherapy. Stage IIB - IV patients (62%) received 6 - 8 cycles of CHOP and for the majority (13/18 pts) no radiotherapy. Two treatment-related deaths occurred. Febrile neutropenia was the most common toxicity (31%). The complete response rate after CHOP +/- radiotherapy was 93%. With a median follow-up of 41 months, five patients have relapsed and four have died from Hodgkin's lymphoma. So far, no relapses have occurred after 2 years from the end of therapy. Overall survival and progression-free survival at 3 years were 79% and 76%, respectively. We conclude that CHOP-21 is a well-tolerated and effective treatment for elderly patients with Hodgkin's lymphoma.

Knowledge of and attitudes toward complementary and alternative therapies; a national multicentre study of oncology professionals in Norway.

This study reports on oncology professionals' knowledge and attitude toward complementary and alternative medicines (CAM), classified according to their primary application as complementary or alternative methods. In June 2002, we conducted a national, multicentre survey of 828 Norwegian oncologists, nurses, clerks and therapeutic radiographers. A response rate of 61% was achieved. Only a few physicians (4%) described their reactions to alternative medicine as positive compared with nurses (33%), therapeutic radiographers (32%) and clerks (55%) (P<0.0001). Females showed a more positive view than males (33% versus 14%, P<0.0001). More participants expressed a positive attitude to complementary versus alternative medicines. Most respondents regarded healing by hand or prayer, homeopathy, and Iscador (mistletoe) as alternative therapies. In contrast, most respondents classified acupuncture, meditation, reflexology, music/art-therapy, aromatherapy and massage as complementary therapies. This survey demonstrates major differences, by gender as well as oncology health profession in views about and the classification of various CAM methods.

Use of complementary and alternative therapies: a national multicentre study of oncology health professionals in Norway.

GOALS OF WORK: It is well documented that an increasing proportion of cancer patients today use complementary and alternative medicine, mostly alongside conventional therapies. This study investigates the use of complementary and alternative medicine among oncology health workers and the reported effects. PATIENTS AND METHODS: In June 2002, we conducted a national multicentre survey including 828 Norwegian oncologists, nurses, clerks and therapeutic radiographers. The response rate was 61.5%. MAIN RESULTS: We found that females were more often users of both complementary and alternative methods than males (39% versus 15% and 47% versus 17%) and that few oncologists had tried such treatments compared to nurses, therapeutic radiographers and clerks (20/12% versus 50/40%, 41/33%,and 31/50%). Interestingly, the majority of those who had tried unconventional methods reported some or very good effects. Acupuncture, homeopathy, aromatherapy and massage were the most popular therapies. Sub-group analyses including only oncologists showed that female physicians were more often users of both complementary and alternative methods compared to males (33% versus 12%, 25% versus 3%). Moreover, participants below the age of 35 years and Christians more often reported use. CONCLUSIONS: This survey demonstrates that significant proportion of oncology health workers in Norway have used non-proven therapies and that most have had a positive experience. Differences in use is highly dependent on gender, profession, age and religion.

Humoral immunity to viral and bacterial antigens in lymphoma patients 4-10 years after high-dose therapy with ABMT. Serological responses to revaccinations according to EBMT guidelines.

The aim of this study was to investigate the late effects of ABMT on the immune system with regard to protective humoral immunity against common antigens and responses to recall antigens (vaccines). The vaccines were given according to EBMT guidelines from 1995. The protocol included 35 patients with malignant lymphoma in CR 4-10 years after ABMT, and 35 controls. The results show that prior to ABMT the proportion of patients with protective immunity against poliomyelitis, tetanus and diphtheria was similar to that of controls. At study entry 4-10 years after ABMT, the proportion of patients with protective immunity against poliomyelitis and diphtheria was reduced, while all patients maintained protection against tetanus. A significant decrease in geometric mean antibody concentrations or titres was observed against all three antigens during this period. Serum levels of antibodies against different pneumococcal serotypes were lower in the patients than in the controls prior to vaccination. The responses to pneumococcal vaccination, which is considered to be a T cell-independent vaccine, were studied. Unlike controls, a minority of patients achieved protective levels of antibodies after a single vaccination. Despite persistent levels of protective antibodies in many patients post ABMT, secondary booster responses after one vaccination with T cell-dependent vaccines (tetanus, diphtheria and polio) were absent. In conclusion, this study shows that post ABMT, a full re-vaccination program was necessary to mount responses comparable to those observed after a single vaccination in controls.

Radioimmunotherapy with iodine-131 tositumomab in patients with low-grade non-Hodgkin's B-cell lymphoma does not induce loss of acquired humoral immunity against common antigens.

Thirty-one previously untreated patients with follicular low-grade B-cell non-Hodgkin's lymphoma expressing the CD20 antigen were treated with iodine-131 tositumomab therapy between 1996 and 1998. The therapy led to a temporary depletion of peripheral blood B-lymphocytes. Recovery of B-cells occurred in most cases by 3 to 6 months and in all patients by 12 months posttherapy. A temporary decline in T-cell subpopulations, but no reduction in serum immunoglobulin levels, could be observed. ELISA techniques were used to detect specific antibodies against rubella, mumps, varicella zoster, measles, and tetanus. Almost all patients remained seropositive against the different antigens during the 1- to 2-year follow-up. No significant reduction in antibody concentrations to tetanus or measles could be detected. The data show that acquired humoral immunity against common antigens appears to be preserved despite a temporary loss of B-lymphocytes.

High level of fatigue in lymphoma patients treated with high dose therapy.

With the success of high dose therapy supported by autologous bone marrow transplantation (ABMT) for malignant lymphomas, medical late-effects and secondary effects on subjective health, like fatigue, are of concern. Fatigue is poorly understood and correlates have been barely addressed. Health-related quality of life (HRQL), fatigue, and correlates to fatigue, including endocrinological status and serum levels of interleukin-6, tumor necrosis factor, and soluble tumor necrosis factor receptors, were investigated in a cross-sectional study of 33 lymphoma patients (median age 39 years) 4-10 years after ABMT. The survivors were compared to general population norms. Fatigue was highly prevalent, and females reported significantly more fatigue and impaired HRQL compared to males and the normal population. Gonadal dysfunction was found in the majority of the patients, but no statistically significant endocrinological or immunological associations with fatigue could be demonstrated. The high level of fatigue among female long-term survivors after ABMT may be related to the gonadal dysfunction, but further studies of possible mechanisms behind fatigue are necessary.

The South Asian cataract management study: complications, vision outcomes, and corneal endothelial cell loss in a randomized multicenter clinical trial comparing intracapsular cataract extraction with and without anterior chamber intraocular lens implantation.

OBJECTIVE: To determine clinical outcomes of primary intracapsular cataract surgery with and without implantation of anterior chamber lenses. DESIGN: A multicenter randomized clinical trial. PARTICIPANTS: One thousand two hundred twenty-nine male and female patients 40-75 years of age with senile cataract. METHODS: Study patients were recruited from screening eye camps and outpatient clinics. Randomization to the two treatment groups was performed after screening for predetermined inclusion and exclusion criteria. Demographics, visual acuity, intraocular pressures, and corneal endothelial cell data were recorded before surgery and at 6 weeks, 12 months, and 24 months after surgery. Monitoring of the study was secured by a standardized image documentation procedure on all patients using the IMAGEnet digital imaging system. Analysis of corneal endothelial cell images was performed with the Cell Soft software (Topcon Corporation, Japan). MAIN OUTCOME MEASURES: Visual acuity and central corneal endothelial cell loss. RESULTS: The patients were randomized to intraocular lens (IOL; n = 616) and no IOL (n = 613) implantation. Surgical complications were reported in 177 (14.4%) patients (IOL = 14.8%; no IOL = 14.0%). The most frequent complication observed was vitreous loss which occurred in 10.3% of eyes (IOL = 11.2%; no IOL = 9.5%). At the final examination (2 years after surgery), 88% of the operated eyes had a best corrected vision of 6/18 or better (IOL = 88.8%; no IOL = 86.6%). Analysis of corneal endothelial cell data showed a small but significantly greater cell loss 6 weeks after surgery in eyes with IOL compared with those without IOL, but no overall difference was found between the treatment groups in the long term follow-up. CONCLUSIONS: The findings indicate that there is a rationale for the use of anterior chamber intraocular lenses in primary intracapsular cataract surgery.

Persistent changes in the immune system 4-10 years after ABMT.

The aim of the present study was to investigate whether the early changes in the immune system observed after ABMT would persist over years. Eighty-five patients with malignant lymphoma were treated with ABMT in Norway from 1987 until 1993. Of the 46 patients in CR by 1997, 36 were enrolled in our study. Median time from ABMT was 5 years (4-10 years). Immunophenotyping showed an increase in the median number of B cells (0.35 x 109/l in patients vs 0.28 x 109/l in controls), and a decrease in T cells (1.08 vs 1.35 x 109/l). Furthermore, a lower median count of CD4+ T cells (0.54 x 109/l in patients vs0.87 x 109/l in controls) resulted in reduced CD4/CD8 ratios (0.8 in patients vs 1.6 in controls). The subgroup of CD4+ T cells expressing the 'naive' phenotype CD45RA was 19.5% in patients vs 38% in controls. In contrast, the fraction expressing the 'memory' phenotype CD45RO was higher in the ABMT group (76% vs 54%). When stimulated, larger fractions of CD3+CD4+ cells in patients produced IFN-gamma (32% vs 16%) or IL-4 (7% vs 1%) compared to controls; thus a differentiation into the functionally separate subgroups Th1 and Th2, with a dominant Th2 response. Our data further suggest that the decrease in CD4+ T cell counts and the imbalance between CD45RA+ and CD45RO+ subsets persists 4-10 years after ABMT.

Opinions on and use of alternative medicine among physicians, nurses and clerks in northern Norway.

In February 1997 a questionnaire on alternative medicine was distributed to 172 physicians, 374 nurses and 96 clerks, all employed in hospitals in the northern part of Norway. A response rate of 57% was achieved. The aim of the study was to compare different health professions regarding views on and use of alternative medicine. Among all respondents 56% described themselves as having a positive attitude towards alternative medicine (16% of the physicians, 71% of the nurses and 72% of the clerks). Twelve percent of physicians, 32% of nurses and 46% of clerks had been using alternative medicine. Female physicians and female nurses showed a more positive attitude and were more frequent users of alternative medicine than their male counterparts. Physicians had confidence in acupuncture, herbs and diets, mainly as treatment of muscle-skeletal disorders, and migraine. Nurses and clerks on the other hand tended to believe in various alternative methods against a broad range of disorders. Female physicians and nurses emphasised the importance of more information, knowledge and openness towards alternative treatments more than their male counterparts. They also believed that traditional medicine could benefit from adopting principles from alternative medicine.

The applicability of the flow cytometric sperm chromatin structure assay in epidemiological studies. Asclepios.

The impact of demographic, lifestyle, and seminal factors on the sperm chromatin structure assay (SCSA) parameters was evaluated in a population of 277 healthy Danish men. This cohort was established within the framework of a European Concerted Action on occupational hazards to male reproductive capability in order to examine the possible reproductive effects of exposure to styrene or pesticides. The SCSA measures the susceptibility of sperm DNA to in-situ acid-induced denaturation, by multiparameter flow cytometric analysis after staining with the DNA-specific fluorescent dye acridine orange. The green versus red bivariate cytogram patterns were quite variable among donors, showing a wide heterogeneity of sperm DNA denaturability. Nevertheless, in those cases where we had the possibility to measure two semen samples from the same donor, the cytogram pattern remained stable over time (0.64 < r < 0.78). Analysis of variance demonstrated that the SCSA results can be influenced by the age of the donor (P < 0.0001), smoking habits (P < 0.05), the presence of leukocytes and immature germ forms in the ejaculate (P < 0.0001), and the duration of sexual abstinence (P < 0.0001). Furthermore, the relationship between the SCSA data and sperm concentration, morphology, and vitality was weak (-0.22 < r < -0.46). Therefore, the SCSA provides independent and complementary measurements of semen quality and is thus a useful tool for epidemiological studies, but the effects of some confounders should be accounted for in the survey design and analysis.

[Decentralized high-dose cytostatic treatment with autologous stem cell support]. / Regionalisert høydose cellegiftbehandling med autolog stamcellestøtte.

In the past high-dose chemotherapy with autologous stem cell support in the treatment of certain types of cancer, was centralized to two hospitals in Norway. Almost three years ago it was decided that the treatment should be offered by all five university hospitals. In the northernmost university hospital of Norway, Tromsø, peripheral stem cells were harvested from 29 patients after successful mobilization with chemotherapy and granulocyte colony-stimulating factor (G-CSF). After high-dose chemotherapy, more than 2 x 10(6) CD34-positive stem cells/kg were transplanted in 24 patients and a sign of reconstitution of bone marrow function was achieved with mean time for neutrophils > 0.5x10(9)/l, 9.8 days and for platelets > 20x10(9)/l, 10.8 days. No treatment-related deaths have occurred. Transplantation of selected CD34-positive stem cells has been performed in one patient. Recovery was comparable to the recovery of patients who had undergone transplantation with unselected products. This indicates that even small centres performing as few as ten procedures per year may offer high-dose chemotherapy with autologous stem cell support safely and successfully.

Risk perception related to depletion of the ozone layer and UV-B radiation in the arctic.

Increase in UV-B radiation, due to stratospheric ozone depletion, is an environmental threat to arctic ecosystems and the health of their inhabitants. The aims of this longitudinal study are to provide basic population risk perception data related to UV-B and ozone depletion, and to compare the UV-B risk perception over time and with risk perception related to other objects and occurrences. A survey questionnaire, calling for a total of 118 judgments, measures risk perception, worries, and anticipated consequences. In the 1996 study, 143 persons completed the questionnaire, 34 of whom belong to the indigenous Sami population. Risk perception and the possibility of protecting oneself against 13 risks were measured on 7-point scales. The mean risk rating for depletion of the ozone layer and UV-B radiation was moderate to high. The possibility of protection was rated relatively low. Women, the youngest, and respondents in the North were most worried and perceived the highest risks. The Sami respondents are less worried and perceive a lower risk, a realistic short-term evaluation due to their protection by pigment in the skin and their clothing habits.

Sequence-selective interaction between mercury(II) ions and the DNA dodecamer [d(GCCGATATCGGC)]2 studied by 1H NMR spectroscopy.

The palindromic dodecamer [d(GCCGATATCGGC)]2 has been titrated by Hg(ClO4)2 in order to study sequence dependent HgII ion interactions. The titration pattern as monitored by 1D and 2D 1H NMR is consistent with a transition to a new conformer of the dodecamer induced by HgII ions. At intermediate stages of the titration, the proton signals from the new conformer coexist with those of the original one, indicating slow exchange between the two forms on the NMR timescale. The data clearly show that there is no major alteration in the secondary structure, e.g. B-->Z-form or duplex-->hairpin transition. The intra- and inter-residue sequential walk is completed except for a break between T6 and A7. At a concentration level r = [HgII]/[nucleobase] < 0.20 all four central imino signals are present. This definitely excludes thymine N3 as a possible mercuration site. In the imino region of the spectra HgII ions induce a large upfield shift of the thymine imino resonance T8-N3H, while the other thymine resonance T6-N3H is unperturbed. The guanine imino signal G4-N1H shows a large downfield ring current shift caused by major conformational changes in the duplex. The complete titration experiment indicates that mercury, initially, binds selectively to the A5'-T8 base pair. A tentative model is proposed where mercury is cross-linking the two strands via thymine T8-O4 and the deprotonated amino group of the complementary adenine base A5'.