No 'Christmas holiday effect' in Australia for cardiovascular and stroke mortality.

OBJECTIVES: Cardiovascular events and mortality have shown a higher incidence within the Christmas holiday period in previous studies and in the northern and southern hemisphere. Our study aimed to assess changes in cardiovascular and stroke mortality variation around the Christmas period in Australia. STUDY DESIGN: The study design is a population-based case-control study. METHODS: Daily mortality data attributed to stroke and cardiovascular was compiled from Australia between 1989 and 2015, amounting to approximately 700,000 and 250,000 deaths, respectively. A locally weighted polynomial regression line was used to estimate expected mortality rates during that period and compared with actual results. RESULTS: There was a non-significant increase of 1.08% (P = 0.35) and 0.20% (P = 0.87) for coronary heart disease and stroke mortality, respectively, in the Christmas holiday period. CONCLUSIONS: There is no evidence of an increase in cardiovascular and stroke mortality in the Christmas holiday period in Australia.

Adductor canal versus femoral triangle anatomical locations for continuous catheter analgesia after total knee arthroplasty: a multicentre randomised controlled study.

BACKGROUND: Adductor canal (AC) catheters are being used to provide continuous postoperative analgesia after total knee arthroplasty (TKA) surgery. There are anatomical arguments that most AC catheters are being inserted into the femoral triangle (FT) compartment of the thigh rather than the AC compartment. The clinical relevance of this is unknown with respect to motor weakness, quality of analgesia, and opioid consumption. We hypothesised that AC catheters provide superior functional mobilisation on postoperative Day 1 after TKA as measured using the Timed Up and Go (TUG) test. METHODS: In this multinational, multicentre, double-blinded RCT, catheters were inserted under ultrasound guidance into the anatomical AC and FT compartments. The standardised protocol included spinal anaesthesia without intrathecal morphine, fixed catheter infusion rates, and oral analgesia. RESULTS: Of 151 subjects recruited, 75 were in the AC group and 76 in the FT group. There was no statistically significant difference in TUG on postoperative Day 1 between AC (38 [29-55] s) and FT subjects (44 [32-64] s) (median [inter-quartile range]); P=0.11). There was no difference in TUG Day 2, AC (38 [27-53] s) vs FT (42 [31-59] s); P=0.66. There were no statistically significant differences for secondary endpoints of pain level, effectiveness of pain relief, interference of functional activities and interpersonal relationships by pain, and opioid consumption between groups. CONCLUSIONS: There were no differences in immediate postoperative functional mobility, analgesia, and opioid consumption provided by catheters inserted into the AC vs FT locations for TKA surgery. CLINICAL TRIAL REGISTRATION: ANZCTR12617001421325.

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.

Community-oriented administration of fluoride for the prevention of dental caries: a summary of the current situation in Asia.

Dental caries is the most prevalent chronic disease affecting human populations around the world. It is recognized that fluoride plays a significant role in dental caries reduction. Meanwhile, several low- and middle-income countries of Asia have not yet implemented systematic fluoride programs; contributing factors relate to misconceptions about the mechanisms of fluoride, low priority given to oral health in national health policy and strategic plans, and lack of interest among public health administrators. A workshop on the effective use of fluoride in Asia took place in Phang-Nga, Thailand, in 2011. A series of country presentations addressed some of the topics mentioned above; in addition, speakers from countries of the region provided examples of successful fluoride interventions and discussed program limitations, barriers encountered, and solutions, as well as possibilities for expanding coverage. Participants acknowledged that automatic fluoridation through water, salt, and milk is the most effective and equitable strategy for the prevention of dental caries. Concerns were expressed that government-subsidized community fluoride prevention programs may face privatization. In addition, the use of affordable fluoride-containing toothpastes should be encouraged. The workshop identified: strengths and weaknesses of ongoing community-based fluoride programs, as well as the interest of countries in a particular method; the requirement for World Health Organization (WHO) technical assistance on various aspects, including fluoridation process, feasibility studies, and implementation of effective epidemiological surveillance of the program; exchange of information; and the need for inter-country collaboration. It was acknowledged that program process and evaluation at the local and country levels need further dissemination. The meeting was co-sponsored by the World Health Organization, the International Association for Dental Research, and the World Dental Federation.

Development of a web-based application to improve data collection of antimicrobial utilization in the public health care system in South Africa.

OBJECTIVE: Determining antimicrobial utilization patterns in hospitals can be a challenge given personnel and resource constraints with paper-based systems. A web-based application (APP) was developed in South Africa to address this, building on a recent point prevalence survey (PPS) using a paper-based system. Consequently, there was a need to test and evaluate the ease of use of a newly developed app and potential time saving versus paper-based methods for PPS. The findings can be used to further refine the APP. METHODS: The developed app was tested in a large academic public hospital in a PPS in South Africa. During data collection, the app was evaluated for functionality on 35 variables and subsequently refined. After data collection, the app was evaluated in terms of its time-saving potential and ease of use. RESULTS: 181 patient's files were surveyed across 13 wards in the hospital, with the antimicrobial usage findings similar to the previous paper-based study in the same hospital. The median age for males was 45.5 years and 42 years for females. Overall 80 out of 181 (44%) patients received antibiotics. Whilst 38% (12 out of 31) of patients in the adult surgical ward received antimicrobials, the prevalence was the highest (78%) in the pediatric medical wards. All the data collectors were confident in using the app after training and found the tool is not complex at all to use. In addition, the time taken to plan for the study and to collect data was considerably reduced. Reduced time spent in data collection and analysis is important for timely instigation of quality improvement programs in resource limited settings. CONCLUSIONS: All data collectors would recommend the app for future PPSs. Several concerns with data entry were identified, which have now been addressed. The app development has been successful and is now being deployed across South Africa as part of a national PPS as well as wider.

Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function.

Schizophrenia is a severe psychiatric disorder with a world-wide prevalence of 1%. The pathophysiology of the illness is not understood, but is thought to have a strong genetic component with some environmental influences on aetiology. To gain further insight into disease mechanism, we used microarray technology to determine the expression of over 30 000 mRNA transcripts in post-mortem tissue from a brain region associated with the pathophysiology of the disease (Brodmann area 10: anterior prefrontal cortex) in 28 schizophrenic and 23 control patients. We then compared our study (Charing Cross Hospital prospective collection) with that of an independent prefrontal cortex dataset from the Harvard Brain Bank. We report the first direct comparison between two independent studies. A total of 51 gene expression changes have been identified that are common between the schizophrenia cohorts, and 49 show the same direction of disease-associated regulation. In particular, changes were observed in gene sets associated with synaptic vesicle recycling, transmitter release and cytoskeletal dynamics. This strongly suggests multiple, small but synergistic changes in gene expression that affect nerve terminal function.

Students' clinical experience on outreach placements.

UNLABELLED: Primary care outreach placements increasingly feature in UK undergraduate dental curricula. The profile of clinical work undertaken on placement may differ from traditional hospital-based programmes and between outreach settings. An appreciation of any differences could inform curriculum development. OBJECTIVE: To compare the profiles of clinical work experienced on a traditional hospital-based programme and outreach placements in different settings. SETTING: One dental hospital and eight existing primary care block placements in England. SUBJECTS AND METHODS: Subjects were four cohorts of senior dental students in one UK dental school. Departmental records provided data on students' clinical experience in different settings and their achievement of placement learning objectives. Descriptive statistics for groups were compared. MAIN OUTCOME MEASURES: (1) Counts of patients encountered and of clinical procedures completed in the following categories: simple plastic restorations, endodontics, cast restorations, dentures, extractions and children's dentistry. (2) Student perceptions of placement learning reported via Likert scales. RESULTS: Outreach students encountered twice as many patients and typically completed about three times as much clinical work as students in the hospital, e.g. 44 cf 16 simple plastic restorations, seven cf two endodontic procedures. There were variations in profiles by setting. For example, amalgam being more likely to be used on outreach especially in the General Dental Service; more children's dentistry in community services and more extractions in Dental Access Centres. Students reported learning outcomes generally being achieved (average 94%) although with some variation by setting. CONCLUSION: Dental outreach training greatly increases the quantity of students' clinical experience in everyday dentistry compared to a hospital-based programme. Placements also increase awareness of service delivery and develop clinical skills. There are appreciable variations between outreach settings possibly reflecting their purposes. Multiple contrasting outreach placements for each student might increase the uniformity of learning experiences.

Evaluation of a mobile phone-based, advanced symptom management system (ASyMS) in the management of chemotherapy-related toxicity.

OBJECTIVES: To evaluate the impact of a mobile phone-based, remote monitoring, advanced symptom management system (ASyMS) on the incidence, severity and distress of six chemotherapy-related symptoms (nausea, vomiting, fatigue, mucositis, hand-foot syndrome and diarrhoea) in patients with lung, breast or colorectal cancer. DESIGN: A two group (intervention and control) by five time points (baseline, pre-cycle 2, pre-cycle 3, pre-cycle 4 and pre-cycle 5) randomised controlled trial. SETTING: Seven clinical sites in the UK; five specialist cancer centres and two local district hospitals. PARTICIPANTS: One hundred and twelve people with breast, lung or colorectal cancer receiving outpatient chemotherapy. INTERVENTIONS: A mobile phone-based, remote monitoring, advanced symptom management system (ASyMS). MAIN OUTCOME MEASURES: Chemotherapy-related morbidity of six common chemotherapy-related symptoms (nausea, vomiting, fatigue, mucositis, hand-foot syndrome and diarrhoea). RESULTS: There were significantly higher reports of fatigue in the control group compared to the intervention group (odds ratio = 2.29, 95%CI = 1.04 to 5.05, P = 0.040) and reports of hand-foot syndrome were on average lower in the control group (odds ratio control/intervention = 0.39, 95%CI = 0.17 to 0.92, P = 0.031). CONCLUSION: The study demonstrates that ASyMS can support the management of symptoms in patients with lung, breast and colorectal cancer receiving chemotherapy.

RCT of the effects of block absence for outreach placements on dental students' finals grades.

UNLABELLED: Undergraduate dental curricula are being supplemented with primary care placements requiring periods away from the dental school. These absences may impact negatively on students' other studies. OBJECTIVE: To compare the effect of outreach placement and traditional hospital-based training alone on students' final examination scores. Existing primary care placements in northern England about one year from students' qualification. SUBJECTS AND METHODS: Analysis of secondary outcomes in a randomised controlled trial with students' final examination marks being compared on qualification. To reduce Type I error only 4 of 24 available scores were considered and multiple testing correction applied. Five-week block outreach placements for 25 of 49 students. Honours awarded and examination scores for children's dentistry, overall clinical work and theory. RESULTS: Groups' final exam scores were similar: children's dentistry - outreach 64.9 (SD 2.1), hospital-based 65.0 (3.0); overall clinical work 58.3 (3.4) cf 60.7 (4.8) and theory 54.6 (3.5) cf 56.5 (4.0). The numbers of students awarded honours (outreach 1, hospital 4) showed no significant difference (Fisher's exact text P = 0.19). CONCLUSION: Dental outreach training involving several weeks' absence from the school had no negative impact on students' finals scores.

Extended duration regional analgesia for total knee arthroplasty: a randomised controlled trial comparing five days to three days of continuous adductor canal ropivacaine infusion.

There is a growing body of evidence in favour of continuous adductor canal block (CACB) for total knee arthroplasty. However, there are no studies describing the optimal duration of the infusion. At our institution the usual practice was to stop the infusion on day three. Our hypothesis was that extending the infusion to five days would improve analgesia and quality of recovery. A prospective, non-blinded, randomised trial was undertaken. Patients received a continuous infusion of 0.2% ropivacaine via an adductor canal catheter for either three or five days. Primary outcome was pain while walking during the 24-hour period up to day five (numeric rating scale from 0 to 10). The minimum clinically important difference was set at 1.5 on the numeric rating scale. Secondary outcome measures included quality of recovery, mobility, pain while walking on postoperative day six, Oxford Knee Scores, and complications. Eighty-six patients were recruited with 43 randomised to each group. Seventy-eight were analysed. Median pain scores reported on day five were significantly better in the intervention group (1 versus 3, P=0.003). Furthermore, quality of recovery (QOR-15) scores were significantly better in the intervention group (133.6 versus 123.4, P=0.017). No statistically significant difference between groups was identified for other secondary outcome measures. CACB prolonged to five days provides superior analgesia and a higher quality of recovery on postoperative days four and five compared to a three-day infusion. This benefit did not extend beyond the period of infusion.

A randomised controlled trial of the effect of outreach placement on treatment planning by dental students.

UNLABELLED: Undergraduate dental students' curricula are being supplemented with primary care placements. OBJECTIVE: To compare the effect of outreach placement and traditional hospital-based training alone on students' treatment planning ability. DESIGN: Randomised controlled trial.Setting Four existing primary care placements in England during 2004. SUBJECTS AND METHODS: At follow-up the fourth-year students took a history from a standard 'patient' then recorded a treatment plan. Interview skill was scored. The history and plan were assessed by clinicians blind to the intervention. INTERVENTION: Five-week block outreach placements for 25 of 49 students. MAIN OUTCOME MEASURES: Interviewing skill, quality of dental and social histories, the appropriateness of planned treatments and the consideration of wider issues. RESULTS: The two groups were similar in the scores for interviewing and taking a dental history. The outreach group scored higher for capturing a social history (outreach mean 4.4, SD = 2.1, n = 22 and hospital 2.8, SD = 1.9, n = 23; p = 0.01) and for developing an appropriate treatment plan (5.6 [SD = 2.1] and 3.9 [SD = 2.3]; p = 0.01). There were no differences in scores relating to the wider issues. CONCLUSION: Dental outreach training was significantly more effective than traditional training alone in improving students' ability to capture relevant points of social history from a patient and to consider them when planning treatment.

Critique of the review of 'Water fluoridation for the prevention of dental caries' published by the Cochrane Collaboration in 2015.

The Cochrane Review on water fluoridation for the prevention of dental caries was published in 2015 and attracted considerable interest and comment, especially in countries with extensive water fluoridation programmes. The Review had two objectives: (i) to evaluate the effects of water fluoridation (artificial or natural) on the prevention of dental caries, and (ii) to evaluate the effects of water fluoridation (artificial or natural) on dental fluorosis. The authors concluded, inter alia, that there was very little contemporary evidence, meeting the Review's inclusion criteria, that evaluated the effectiveness of water fluoridation for the prevention of dental caries. The purpose of this critique is to examine the conduct of the above Review, and to put it into context in the wider body of evidence regarding the effectiveness of water fluoridation. While the overall conclusion that water fluoridation is effective in caries prevention agrees with previous reviews, many important public health questions could not be answered by the Review because of the restrictive criteria used to judge adequacy of study design and risk of bias. The potential benefits of using wider criteria in order to achieve a fuller understanding of the effectiveness of water fluoridation are discussed.

Biosynthesis of 3'-deoxyadenosine by Cordyceps militaris. Mechanism of reduction.

The biosynthesis of 3'-deoxyadenosine (cordycepin) by Cordyceps militaris has been investigated using [U-14C]adenosine and [3-3H]ribose. Crystallization of the resulting radioactive 3'-deoxyadenosine to a constant specific activity showed incorporation of both labeled compounds. A control showed that the 3H:14C ratio of the AMP isolated from the RNA was the same as the 3H:14C ratio in the 3'-deoxyadenosine. The 14C ratio in the adenine: ribose of the [U-14C]adenosine added to the 3'-deoxyadenosine producing cultures of C. militaris and of the isolated 3'-deoxyadenosine was the same, e.g. 50:50. These data provide strong evidence that adenosine in converted to 3'-deoxyadenosine without hydrolysis of the N-riboside bond. Degradation of the 3-deoxyribose from 3'-deoxyadenosine showed that the 3H was retained on carbon-3. These results suggest that the formation of 3'-deoxyadenosine may proceed by a reductive mechanism similar to that for the formation of 2'-deoxynucleotides.

Partial versus full hospitalization for adults in psychiatric distress: a systematic review of the published literature (1957-1997).

OBJECTIVE: The authors reviewed published research that compared partial and full hospitalization as alternative programs for the care of mentally ill adults, with the goal of both systematizing the knowledge base and providing directions for future research. METHOD: Studies published since 1950 were obtained through manual and electronic searches. Results were stratified by outcome domain, type of measure used to report between-group differences (global, partial, or rate-based), and time of assessment. Effect sizes were computed and combined within a random-effects framework. RESULTS: Eighteen investigations published between 1957 and 1997 were systematically reviewed. Over half of eligible patients were excluded a priori; diagnostic severity of enrollees varied widely. On measures of psychopathology, social functioning, family burden, and service utilization, the authors found no evidence of differential outcome in the selected patient population admitted to the studies reviewed. Rates of satisfaction with services suggested an advantage for partial hospitalization within 1 year of discharge, with the gap being largest at 7-12 months. CONCLUSIONS: Although partial hospitalization is not an option for all patients requiring intensive services, outcomes of partial hospitalization patients in these studies were no different from those of inpatients. Further, patients and families were more satisfied with partial hospitalization in the short term. Weaknesses of the studies limited the scope of our inquiry and the generalizability of findings. Positive findings require replication under the present circumstances of mental health care, and more research is needed to identify predictors of differential outcome and successful partial hospitalization. A clearer definition of partial hospitalization will help consolidate its role in the continuum of mental health services.

Relationship between lifetime occupation and parietal flow: implications for a reserve against Alzheimer's disease pathology.

We previously reported an inverse relation between parietal cerebral blood flow and years of education in Alzheimer's disease (AD) patients matched for clinical severity. This suggested that the clinical manifestation of advancing AD pathology is delayed in patients with higher educational attainment. Other aspects of life experience may also provide a reserve against the clinical expression of AD. To test this hypothesis, we classified the primary life-time occupations of 51 AD patients using the Dictionary of Occupational Titles, published by the US Department of Labor, and derived six factor scores describing intellectual, interpersonal, and physical job demands. Regional cerebral blood flow was measured using the xenon-133 inhalation method. After controlling for age, clinical dementia severity, and education, there was less relative perfusion in the parietal region in subjects whose occupations were associated with higher interpersonal skills and physical demands factor scores. We conclude that independent of education, aspects of occupational experience may provide a reserve that delays the clinical manifestation of AD.

Identification of differentially expressed genes in coronary atherosclerotic plaques from patients with stable or unstable angina by cDNA array analysis.

The composition of atherosclerotic plaques is a crucial factor in determining rupture, thrombosis and clinical events. In this study, we analyzed gene expression in coronary plaques from patients with stable or unstable angina using gene arrays. Total RNA was extracted from eight plaques collected by therapeutic directional coronary atherectomy. cDNA probes, generated by amplification, were hybridized to nylon arrays containing 482 genes. Here we report the results for the inflammation, adhesion and hemostasis subsets. Many genes not previously associated with atherosclerosis, such as the lymphocyte adhesion molecule MadCAM, were expressed in the plaques. anova analysis showed higher tissue factor (TF) expression in unstable angina samples. Five genes were expressed at lower levels in unstable angina samples: anticoagulant protein S, cyclooxygenase (COX)-1, interleukin (IL)-7 and chemokines monocyte chemotactic protein (MCP)-1 and -2. Gene arrays provide a new approach to study plaque composition and identify candidate markers of plaque instability.