Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047).

BACKGROUND: The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. PATIENTS AND METHODS: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ('Adjuvant-RT') or an observation policy with salvage RT for PSA failure ('Salvage-RT') defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. RESULTS: Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). CONCLUSION: Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy. TRIAL IDENTIFICATION: RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047.

Emerging responses to the COVID-19 crisis from family farming and the agroecology movement in Latin America - A rediscovery of food, farmers and collective action.

CONTEXT: In Latin America, the so-called informal sector associated with family farming and the agroecology movements were instrumental at coping with and adapting to the COVID-19 challenges. OBJECTIVE: To assess the nature and extent of the early initiatives (first three months) deployed by this informal sector to cope with and adapt to the impacts of the COVID-19 pandemic on food production and consumption in several countries of the region. METHODS: We used key used informant consultation (n = 168), an online survey (n = 125) and the detailed characterisation of regional case studies (n = 4). Textual data was analysed and categorised using Reinert's method, combined with similarity analysis. RESULTS AND CONCLUSIONS: 65% of the initiatives were 'local' in terms of geographic reach, 30% of them started within the first month after the pandemic and most of them were urban or urban-rural, whereas only 29% of them were exclusively rural. The analysis of the textual information captured through the survey revealed four major types of initiatives that were deployed or adapted in response to COVID-19:1.Direct producer-to-consumer food sales, generally existing before the COVID-19 crisis but adapted/strengthened to cope with it;2.Short value chains that linked rural and urban organisations and individuals supported by national or local governments, readapted through new health and safety protocols;3.Newly developed support and training programs on sustainable food production for self-consumption or local commerce, in rural, urban or peri-urban settings;4.Food assistance and aid initiatives focusing on vulnerable populations, relying on solidarity networks associated with the agroecological movement. SIGNIFICANCE: The pandemic highlighted the key role played by local food systems and value chains and the need to strengthening them through public policies, as a way to build food resilience in times of crisis.

Local bone loss in patients with anti-citrullinated peptide antibody and arthralgia, evaluated with high-resolution peripheral quantitative computed tomography.

OBJECTIVE: To investigate bone changes in the metacarpophalangeal (MCP) joints of anti-citrullinated peptide antibody (ACPA)-positive patients with arthralgia, but not arthritis, compared to healthy controls. METHOD: Using a cross-sectional study design, patients were recruited from hospitals and private care rheumatologists, and controls from a test subject website. All subjects underwent medical history interview, clinical examination, and biochemical screening including ACPA. Patients with positive ACPA, arthralgia, and no rheumatic disease were included. Controls without a history or signs of rheumatological disease or positive ACPA were included. A 2.7-cm-long region around the second and third MCP joints was evaluated using high-resolution peripheral quantitative computed tomography with a voxel size of 82 µm. RESULTS: Twenty-nine ACPA-positive patients and 29 healthy controls were evaluated. Trabecular volumetric bone mineral density and bone volume fraction did not differ between the groups. In addition, the cortical bone was not affected in patients, as we found no difference in average cortical thickness and cortical bone area between the groups. In contrast, the trabeculae were significantly (p < 0.05) thinner in both second and third MCP heads compared with controls, whereas trabecular number and trabecular separation did not differ between the groups. No erosions were demonstrated and the number of non-specific breaks did not differ between the groups. CONCLUSION: Trabecular bone changes were observed in ACPA-positive patients with arthralgia compared with healthy controls. The results may reflect inflammatory up-regulated trabecular bone resorption leading to early bone loss before the onset of clinical arthritis.

Effect of pre-operative methylprednisolone on orthostatic hypotension during early mobilization after total hip arthroplasty.

BACKGROUND: Orthostatic hypotension (OH) and intolerance (OI) are common after total hip arthroplasty (THA) and may delay early mobilization. The pathology of OH and OI includes a dysregulated post-operative vasopressor response, by a hitherto unknown mechanism. We hypothesized that OI could be related to the inflammatory stress response which is inhibited by steroid administration. Consequently, this study evaluated the effect of a pre-operative high-dose methylprednisolone on OH and OI early after THA. METHODS: Randomized, double-blind, placebo-controlled study in 59 patients undergoing elective unilateral THA with spinal anesthesia and a standardized multimodal analgesic regime. Patients were allocated (1 : 1) to pre-operative intravenous (IV) methylprednisolone (MP) 125 mg or isotonic saline (C). OH, OI and cardiovascular responses to sitting and standing were evaluated using a standardized mobilization protocol pre-operatively, 6, and 24 h after surgery. Systolic and diastolic arterial pressure and heart rate were measured non-invasively (Nexfin® ). The systemic inflammation was monitored by the C-reactive protein (CRP) response. RESULTS: At 6 h post-operatively, 11 (38%) versus 11 (37%) patients had OH in group MP and group C, respectively (RR 1.02 (0.60 to 1.75; P = 1.00)), whereas OI was present in 9 (31%) versus 13 (43%) patients (RR 0.76 (0.42 to 1.36; P = 0.42)), respectively. At 24 h post-operatively, the prevalence of OH and OI did not differ between groups, though CRP levels were significantly reduced in group MP (P < 0.001). CONCLUSION: Pre-operative administration of 125 mg methylprednisolone IV did not reduce OH or OI compared with placebo despite a reduced inflammatory response.

Salmon gill poxvirus disease in Atlantic salmon fry as recognized by improved immunohistochemistry also demonstrates infected cells in non-respiratory epithelial cells.

Gill diseases cause serious losses in farming of Atlantic salmon and the number of agents involved increases. Salmon gill poxvirus (SGPV) and the gill disease in causes where SGPV apparently was the only disease-causing agent were initially characterized. Recently, it was further shown that SGPV can be a common denominator in widely different multifactorial gill diseases. Here, we present the challenge of diagnosing gill disease with SGPV in salmon fry of 0,3-5 grams. Apoptosis of gill lamellar epithelial cells and hemophagocytosis was also observed in fry similar to findings in smolts and grow-out fish. Using our newly developed immunohistochemistry method, we further demonstrate that some of the apoptotic epithelial cells covering the oral cavity were positive for SGPV. Thus, SGPV is not restricted to respiratory epithelium alone and may infect the fish at very early life stages. Furthermore, as the cases examined here are from Norway, Faroe Island and Scotland, we show that SGPV is more widespread than previously reported.

Recall intervals and time used for examination and prevention by dentists in child dental care in Denmark, Iceland, Norway and Sweden in 1996 and 2014.

OBJECTIVE: The purpose of the present study was to explore intervals between regular dental examination and the time dentists spent for examination and preventive dental care of children in 1996 and 2014. PARTICIPANTS AND METHODS: In Denmark, Norway and Sweden, random samples of dentists working with children were included, while in Iceland all dentists were mailed questionnaires. Complete information was provided by 1082 of 1834 dentists (64%) in 1996 and 1366 of 2334 dentists (59%) in 2014. Results were assessed using chi-square and analysis of variance with post-hoc tests. RESULTS: Some trends were consistent in all countries, but considerable differences in routines between the countries persisted during the period. The most used and maximum planned recall intervals were on average 14.8 (sd 4.8) and 18.5 (sd 4.6) months in 2014, respectively 3.1 and 3.5 months longer than in 1996 (p⟨0.05). In 2014 dentists used ample time delivering preventive care to children. Dentists reported spending significantly more time providing preventive care for caries risk children than for other children both in 1996 and 2014. Concurrent with extended intervals, dentists reported spending longer performing routine examinations in three of the four countries in 2014 than in 1996. CONCLUSIONS: This study of trends in dental care delivered by dentists during recent decades showed moves towards extended recall intervals and preventive care individualized according to caries risk. In addition, extending intervals could necessitate more time for a routine dental examination.

Benefit and harm of pregabalin in acute pain treatment: a systematic review with meta-analyses and trial sequential analyses.

Pregabalin has demonstrated anti-hyperalgesic properties and was introduced into acute pain treatment in 2001. Our aim was to evaluate the beneficial and harmful effects of pregabalin in postoperative pain management. We included randomized clinical trials investigating perioperative pregabalin treatment in adult surgical patients. The review followed Cochrane methodology, including Grading of Recommendations Assessment, Development, and Evaluation (GRADE), and used trial sequential analyses (TSAs). The primary outcomes were 24 h morphine i.v. consumption and the incidence of serious adverse events (SAEs) defined by International Conference of Harmonisation Good Clinical Practice guidelines. Conclusions were based primarily on trials with low risk of bias. Ninety-seven randomized clinical trials with 7201 patients were included. The 24 h morphine i.v. consumption was reported in 11 trials with overall low risk of bias, finding a reduction of 5.8 mg (3.2, 8.5; TSA adjusted confidence interval: 3.2, 8.5). Incidence of SAEs was reported in 21 trials, with 55 SAEs reported in 12 of these trials, and 22 SAEs reported in 10 trials with overall low risk of bias. In trials with overall low risk of bias, Peto's odds ratio was 2.9 (1.2, 6.8; TSA adjusted confidence interval: 0.1, 97.1). Based on trials with low risk of bias, pregabalin may have a minimal opioid-sparing effect, but the risk of SAEs seems increased. However, the GRADE-rated evaluations showed only moderate to very low quality of evidence. Consequently, a routine use of pregabalin for postoperative pain treatment cannot be recommended.

Delirium after fast-track hip and knee arthroplasty - a cohort study of 6331 elderly patients.

BACKGROUND: Postoperative delirium (PD) is a well-known complication among elderly surgical patients and associated with increased morbidity, mortality and length of stay (LOS). In elective orthopedic surgery, including hip and knee arthroplasty (THA/TKA), most studies report incidences between 5% and 10%. The multimodal optimization of perioperative care (fast-track) aims to enhance recovery and reduce morbidity and LOS, but limited data are available on the effect on PD. Consequently, the study investigated signs of PD associated with LOS > 4 days. METHODS: Prospective risk assessment study with retrospective analysis of discharge notes or medical records of signs of PD in 6331 elective primary unilateral THA and TKA patients ≥ 70 years, and LOS > 4 days. Preoperative patient characteristics collected from eight high volume centers with similar standardized fast-track protocols from January 2010 to November 2013. RESULTS: We identified 43 (0.7%) cases of PD symptoms mentioned as a reason for LOS > 4 days among the 789 patients with LOS > 4 days (12.5% of all THA and TKA). PD patients had a mean age of 80.7 [[95% CI] 79.3-82.1] years, being 4.0 [[95% CI] 2.5-5.5] years older compared to patients without PD (P < 0.001). LOS was median 10 [[Q2-Q3] 7-14] days in the PD group vs. 3 [2-3] days in the non-PD group (P < 0.001), without differences in gender or site of arthroplasty (P = 0.139 and 0.499, respectively). CONCLUSION: Postoperative delirium symptoms contributing to LOS > 4 days in fast-track THA and TKA are rare in elderly patients.

Prevalence and severity of hip and groin pain in sub-elite male football: a cross-sectional cohort study of 695 players.

The purpose of this study was twofold: (a) to investigate the prevalence of hip and groin pain in sub-elite male adult football in Denmark and (b) to explore the association between prevalence and duration of hip and groin pain in the previous season with the Copenhagen Hip and Groin Outcome Score (HAGOS) in the beginning of the new season. In total 695 respondents from 40 teams (Division 1-4) were included. Players completed in the beginning of the new season (July-Sept 2011) a self-reported paper questionnaire on hip and/or groin pain during the previous season and HAGOS. In total 49% (95% CI: 45-52%) reported hip and/or groin pain during the previous season. Of these, 31% (95% CI: 26-36%) reported pain for >6 weeks. Players with the longest duration of pain during the previous season had the lowest HAGOS scores, when assessed at the beginning of the new season, P < 0.001. This study documents that half of sub-elite male adult football players report pain in the hip and/or groin during a football season. The football players with the longest duration of pain in previous season displayed the lowest HAGOS scores in the beginning of the new season.

Gabapentin for post-operative pain management - a systematic review with meta-analyses and trial sequential analyses.

BACKGROUND: Perioperative pain treatment often consist of combinations of non-opioid and opioid analgesics, 'multimodal analgesia', in which gabapentin is currently used. The aim was to document beneficial and harmful effects of perioperative gabapentin treatment. METHODS: Randomized clinical trials comparing gabapentin vs. placebo or active placebo in adult surgical patients receiving gabapentin perioperatively were included. This review was conducted using Cochrane standards, trial sequential analysis (TSA), and Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The primary outcomes were 24-h opioid consumption and incidence of serious adverse events (SAE). RESULTS: One hundred and thirty-two trials with 9498 patients were included. Thirteen trials with low risk of bias reported a reduction in 24-h opioid consumption of 3.1 mg [0.5, 5.6] [corrected]. In the analysis of gabapentin as add-on analgesic to another non-opioid analgesic regimen found a mean reduction in 24-h morphine consumption of 1.2 mg [-0.3, 2.6; TSA-adjusted CI: -0.3, 2.6] in trials with low risk of bias. [corrected]. Nine trials with low risk of bias reported a risk ratio of SAEs of 1.61 [0.91; 2.86; TSA-adjusted CI: 0.57, 4.57]. CONCLUSION: Based on GRADE assessment of the primary outcomes in trials with low risk of bias, the results are low or very low quality of evidence due to imprecision, inconsistency, and in some outcomes indirectness. Firm evidence for use of gabapentin is lacking as clinically relevant beneficial effect of gabapentin may be absent and harm is imminent, especially when added to multimodal analgesia.

Clinical and morphological aspects of adenocarcinomas of the intestinal type in the inner nose: a retrospective multicenter analysis.

Clinical and histological parameters from 117 patients with wood dust-related sinonasal adenocarcinomas of intestinal type (ITAC) were analyzed and correlated with a follow-up period of 5 years at least. The rate of survival for 5 years was 53.1 % and for 10 years 30.2 %. Only 33 patients were free of disease. 74.2 % of patients with recurrences died in relation to ITAC. As expected, tumors of T4-category had the worst prognosis. The mucus content of a tumor was the most important histological parameter. Endonasal methods of surgery had no more positive survival rates after 5 years. An effect of radiotherapy has to be in discussion. The high incidence of tumor recurrences requires control examinations consistently.

Metastatic behaviour of sinonasal adenocarcinomas of the intestinal type (ITAC).

The relative frequency of regional lymphogenic versus distant hematogenic metastases was evaluated in 369 patients with sinonasal adenocarcinoma of the intestinal type (ITAC). We assessed the results of neck dissections for a limited number of patients undergoing this surgical intervention. 117 ITAC patients were followed up for at least 5 years. Neck dissections were performed in 18 cases (15 primary and 3 secondary operations), 4 of which revealed carcinoma-positive lymph nodes. Metastases in lymph nodes were also diagnosed clinically in three other patients adding up to a total of seven individuals (6 % of 117) with lymphogenic metastases. In comparison, distant hematogenic metastases were identified in 15.4 % of these 117 patients. In the second group of 252 patients, the occurrence of distant hematogenic metastases and colorectal adenocarcinomas was registered but no formal follow-up procedure was applied. 50 neck dissections were performed in this group, 46 of which exhibited no histological evidence for metastases in lymph nodes, while in 1 case they were carcinoma-positive. Three additional cases showed clinical signs of metastases in regional lymph nodes. Taken together, our observations indicate that regional lymphogenic metastases are rather rare (about 2 %) in patients with sinonasal adenocarcinoma of the intestinal type. Therefore, the surgery of neck dissection appears not advised as routine intervention in these cases. ITAC patients show a normal prevalence of colorectal adenocarcinomas.

Fluoride and Oral Health.

The discovery during the first half of the 20th century of the link between natural fluoride, adjusted fluoride levels in drinking water and reduced dental caries prevalence proved to be a stimulus for worldwide on-going research into the role of fluoride in improving oral health. Epidemiological studies of fluoridation programmes have confirmed their safety and their effectiveness in controlling dental caries. Major advances in our knowledge of how fluoride impacts the caries process have led to the development, assessment of effectiveness and promotion of other fluoride vehicles including salt, milk, tablets, toothpaste, gels and varnishes. In 1993, the World Health Organization convened an Expert Committee to provide authoritative information on the role of fluorides in the promotion of oral health throughout the world (WHO TRS 846, 1994). This present publication is a revision of the original 1994 document, again using the expertise of researchers from the extensive fields of knowledge required to successfully implement complex interventions such as the use of fluorides to improve dental and oral health. Financial support for research into the development of these new fluoride strategies has come from many sources including government health departments as well as international and national grant agencies. In addition, the unique role which industry has played in the development, formulation, assessment of effectiveness and promotion of the various fluoride vehicles and strategies is noteworthy. This updated version of 'Fluoride and Oral Health' has adopted an evidence-based approach to its commentary on the different fluoride vehicles and strategies and also to its recommendations. In this regard, full account is taken of the many recent systematic reviews published in peer reviewed literature.

Concept for power scaling second harmonic generation using a cascade of nonlinear crystals.

Within the field of high-power second harmonic generation (SHG), power scaling is often hindered by adverse crystal effects such as thermal dephasing arising from the second harmonic (SH) light, which imposes limits on the power that can be generated in many crystals. Here we demonstrate a concept for efficient power scaling of single-pass SHG beyond such limits using a cascade of nonlinear crystals, in which the first crystal is chosen for high nonlinear efficiency and the subsequent crystal(s) are chosen for power handling ability. Using this highly efficient single-pass concept, we generate 3.7 W of continuous-wave diffraction-limited (M(2)=1.25) light at 532 nm from 9.5 W of non-diffraction-limited (M(2)=7.7) light from a tapered laser diode, while avoiding significant thermal effects. Besides constituting the highest SH power yet achieved using a laser diode, this demonstrates that the concept successfully combines the high efficiency of the first stage with the good power handling properties of the subsequent stages. The concept is generally applicable and can be expanded with more stages to obtain even higher efficiency, and extends also to other combinations of nonlinear media suitable for other wavelengths.

Transversus abdominis plane (TAP) block after robot-assisted laparoscopic hysterectomy: a randomised clinical trial.

BACKGROUND: Transversus abdominis plane (TAP) block is widely used as a part of pain management after various abdominal surgeries. We evaluated the effect of TAP block as an add-on to the routine analgesic regimen in patients undergoing robot-assisted laparoscopic hysterectomy. METHODS: In a prospective blinded study, 70 patients scheduled for elective robot-assisted laparoscopic hysterectomy were randomised to receive either TAP block (ropivacaine 0.5%, 20 ml on each side) or sham block (isotonic saline 0.9%, 20 ml on each side). All patients had patient-controlled analgesia (PCA) with morphine on top of paracetamol and ibuprofen or diclofenac. For the first 24 post-operative hours, we monitored PCA morphine consumption and pain scores with visual analogue scale (VAS) at rest and while coughing. Post-operative nausea and number of vomits (PONV) were recorded. RESULTS: Sixty-five patients completed the study, 34 receiving TAP block with ropivacaine and 31 receiving sham block with isotonic saline. We found no differences in median (interquartile range) morphine consumption the first 24 h between the TAP block group [17.5 mg (6.9-36.0 mg)] and the placebo group [17.5 mg (2.9-38.0 mg)] (95% confidence interval 10.0-22.6 mg, P = 0.648). No differences were found for VAS scores between the two groups, calculated as area under the curve/1-24 h, neither at rest (P = 0.112) nor while coughing (P = 0.345), or for PONV between groups. CONCLUSIONS: In our study, the TAP block combined with paracetamol and Nonsteroidal anti-inflammatory drugs (NSAID) treatment, had no effect on morphine consumption, VAS pain scores, or frequency of nausea and vomiting after robot-assisted laparoscopic hysterectomy compared with paracetamol and NSAID alone.

Long-term evaluation of the clinical effectiveness of community milk fluoridation in Bulgaria.

OBJECTIVE: To determine the clinical effectiveness of a community milk fluoridation programme. BASIC RESEARCH DESIGN: Parallel arm 5-year cohort study, with final cross-sectional comparisons between groups. PARTICIPANTS: 3-year-olds in 8 Bulgarian cities/towns entered the cohort study with random samples (n = 1,782) recruited at baseline in 2004. After 5 years in 2009 sub-samples (about 30%) of these now aged 8 were randomly selected in intervention sites for follow-up examination (n = 454); 276 controls were examined at the age 8 years. For cross-sectional comparisons, in 2004, 284 3-year-olds from control cities were baseline examined for caries, then 276 children at the age 8 years in 2009. INTERVENTIONS: In six intervention communities: 1,498 examined children received 0.5 mg F in 100 or 200 ml school milk or yogurt provided each school day; a further 180 received non-fluoridated milk. In two control communities, fluoride was not added to 284 children's school milk. MAIN OUTCOME MEASURES: Dental caries experience of primary, and permanent teeth. RESULTS: For primary teeth, caries increments were 46% (p < 0.001) and 30% (p < 0.01) lower in the fluoridated milk groups compared with non-fluoridated milk groups in the intervention and control communities, respectively. For permanent teeth those reductions were 61% and 53% (p < 0.001). The cross-sectional comparisons of 8-year-olds showed significant changes in dental caries experience over time; in children consuming fluoridated milk the level of dmfs fell by 43% (2004 and 2009) against 11% in the control group. Among children consuming fluoridated milk the DMFS fell 68% against rising 3% in the controls. CONCLUSIONS: Fluoridated milk delivered daily in schools in Bulgaria resulted in substantially lower caries development compared with children in schools receiving milk without added fluoride. The nation-wide experiences from milk fluoridation indicate that such a public health scheme can be effective to the global fight against dental caries of children.

School-based intervention for improving the oral health of children in southern Thailand.

OBJECTIVE: A two-year study assessed the benefit of an enhanced oral health promotion program combined with a closely supervised tooth brushing program in schools, using toothpaste containing 1,450 ppm F- and 1.5% arginine, on oral health and dental caries. METHODS: 15 southern Thailand schools and 3,706 pre-school children were recruited: 8 schools with 1,766 children as controls; 7 schools with 1,940 children in the intervention groups. Of the intervention schools five were classified as cooperative school and two as non-cooperative schools, based on the criteria of 80% participation in the prescribed tooth brushing activities. RESULTS: The DMFT and DMFS increments ("enamel and dentine") were 1.19 and 1.91 for the control group and 1.04 and 1.59 for the intervention groups. These represent 12.6% and 16.8% reductions in caries respectively. The DMFT and DMFS increments ("dentine threshold") were 0.26 and 0.44 for the control group and 0.19 and 0.29 for the intervention group, representing 26.9%, and 34.1% reductions in caries incidence respectively. For the more cooperative schools the benefits were greater: up to a 40.9% reduction in caries for DMFS ("dentine threshold"). At the 24 month examination there were significant improvements in dental plaque scores with greater improvements seen in the intervention group, greater still in the cooperative schools. CONCLUSIONS: This study documents the positive effect from use of fluoridated toothpaste (1,450 ppm F- and 1.5% arginine) administered by schoolteachers and undertaken via an enhanced school oral health program. Optimising oral health interventions for young children in Thai schools may have a significant impact on caries incidence resulting in reductions of up to 34% reductions in caries for all schools included in the study and up to 41% for the most cooperative.

The impact of involved node, involved field and mantle field radiotherapy on estimated radiation doses and risk of late effects for pediatric patients with Hodgkin lymphoma.

BACKGROUND: The use of radiotherapy (RT) is debated for pediatric patients with Hodgkin lymphoma (HL) due to the late effects of treatment. Radiation doses to the thyroid, heart, lungs, and breasts are compared with the extensive mantle field (MF), Involved Field RT(IFRT), Modified IFRT (mIFRT), and Involved Node RT (INRT) and the risk of radiation-induced cardiovascular disease, secondary cancers, and the corresponding Life Years Lost (LYL) is estimated with each technique. PROCEDURE: INRT, mIFRT, IFRT, and MF plans (20 and 30 Gy) were simulated for 10 supradiaphragmatic, clinical stage I­II classical HL patients <18 years old, total of 4 x 2 plans for each patient. The lifetime excess risks of cardiac morbidity, cardiac mortality, lung, breast, and thyroid cancer with each technique were estimated. The estimated excess risks attributable to RT were based on HL series with long-term follow-up, treating death from other causes as competing risks. The corresponding LYL were derived from the estimated excess risks. Statistical analyses were performed with repeated measures ANOVA. RESULTS: Both a reduction in field size and in prescribed radiation dose significantly lowered the estimated dose to the heart, lungs, breasts, and thyroid compared to past,extended fields, even for patients with mediastinal disease. This translated into a significantly reduced estimated risk of cardiovascular disease, secondary cancers, and LYL. CONCLUSIONS: Involved Node Radiotherapy should be considered for pediatric patients with Hodgkin lymphoma since it is estimated to substantially lower the risk of severe long-term complications.

Treatment with docetaxel and cisplatin in advanced adrenocortical carcinoma, a phase II study.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare disease with a poor response to chemotherapy. Cisplatin is the most widely investigated drug in the treatment of ACC and in vitro studies have indicated activity of taxanes. The objectives of this study were to evaluate the efficacy and toxicity of cisplatin combined with docetaxel as first-line treatment of advanced ACC. METHODS: Patients with advanced ACC were included in this phase II trial investigating the response to a combination of cisplatin (50 mg m(-2)) and docetaxel (60 mg m(-2)) administered with a 3-week interval. RESULTS: Nineteen patients were included in this study. The response rate was 21% (95% CI: 3-39%). No patients obtained a complete response, 32% had stable disease, and 37% progressed while on treatment. The median progression-free survival (PFS) was 3 months (95% CI: 0.7-5.3 months) and 1 year PFS was 21% (95% CI: 3-39%). Median survival was 12.5 months (95% CI: 6-19 months). The predominant grade 3/4 toxicity was neutropenia (35%); febrile neutropenia occurred in 5% of cycles. CONCLUSION: This study could not demonstrate that the combination of cisplatin and docetaxel has higher efficacy than other regimens reported in previous studies.

Estimated risk of cardiovascular disease and secondary cancers with modern highly conformal radiotherapy for early-stage mediastinal Hodgkin lymphoma.

BACKGROUND: Hodgkin lymphoma (HL) survivors have an increased morbidity and mortality from secondary cancers and cardiovascular disease (CD). We evaluate doses with involved node radiotherapy (INRT) delivered as 3D conformal radiotherapy (3D CRT), volumetric modulated arc therapy (VMAT), or proton therapy (PT), compared with the extensive Mantle Field (MF). PATIENTS AND METHODS: For 27 patients with early-stage, mediastinal HL, treated with chemotherapy and INRT delivered as 3D CRT (30 Gy), we simulated an MF (36 Gy), INRT-VMAT and INRT-PT (30 Gy). Dose to the heart, lungs, and breasts, estimated risks of CD, lung (LC) and breast cancer (BC), and corresponding life years lost (LYL) were compared. RESULTS: 3D CRT, VMAT or PT significantly lower the dose to the heart, lungs and breasts and provide lower risk estimates compared with MF, but with substantial patient variability. The risk of CD is not significantly different for 3D CRT versus VMAT. The risk of LC and BC is highest with VMAT. For LYL, PT is the superior modern technique. CONCLUSIONS: In early-stage, mediastinal HL modern radiotherapy provides superior results compared with MF. However, there is no single best radiotherapy technique for HL-the decision should be made at the individual patient level.