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This paper reports on the qualitative findings of the first phase of the INDEPENDENT Project, an EPSRC funded EQUAL 4 consortium project in the UK that aims to investigate enabling environments for people with dementia. The overall project focus is on wellbeing and quality of life for people in different types of housing, with particular focus on the possible roles technology can play in maintaining the person's independence as long as possible. Connection to nature, access to the outdoors, and participation in nature-based activities were among a wide range of enjoyable activities reported by study participants living in their own homes or in residential care. First, an overview of connection to nature for people with dementia and the importance of this connection within their home environments are given. Secondly, the research study is described and data from interviews with people with dementia and from focus groups with family and professional carers including access to, and preferences for nature are summarized. Multiple factors enabling or challenging a person's participation in nature-related activities included personal factors, formal support, social networks, as well as cultural and spiritual aspects. These factors are briefly described and compared. Lastly, factors of the built environment and differences between building types are presented and conclusions drawn. [ABSTRACT FROM AUTHOR]

Background: Chloroquine plus proguanil is widely used for malaria chemoprophylaxis despite low effectiveness in areas where multidrug-resistant malaria occurs. Studies have shown that atovaquone and proguanil hydrochloride is safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but little is known about non-immune travellers.Methods: In a double-blind equivalence trial, 1083 participants travelling to a malaria-endemic area were randomly assigned to two treatment groups: atovaquone-proguanil plus placebos for chloroquine and proguanil, or chloroquine, proguanil, and placebo for atovaquone-proguanil. Follow-up was by telephone 7 and 60 days after travel and at a clinic at 28 days. Serum samples were tested for antibodies to a malaria circumsporozoite protein. Blood and serum samples of participants with a potential malaria diagnosis were tested in a reference laboratory.Findings: 7 days after travel, at least one adverse event was reported by 311 (61%) of 511 participants who received atovaquone-proguanil and 329 (64%) of 511 who received chloroquine-proguanil. People receiving atovaquone-proguanil had a lower frequency of treatment-related gastrointestinal adverse events (59 [12%] vs 100 [20%], p=0.001), and of treatment-related adverse events of moderate or severe intensity (37 [7%] vs 56 [11%], p=0.05). There were fewer treatment-related adverse events that caused prophylaxis to be discontinued in the atovaquone-proguanil group than in the chloroquine-proguanil group (one [0.2%] vs ten [2%], p=0.015).Interpretation: Overall the two preparations were similarly tolerated. However, significantly fewer adverse gastrointestinal events were observed in the atovaquone-proguanil group in than in the chloroquine-proguanil group. [ABSTRACT FROM AUTHOR]

Aims: In vivo experiments were performed to establish and validate a rat model of urethral sphincter injury and to develop a method for leak point pressure (LPP) measurements performed repeatedly in the same animal., Methods: Twenty-four Sprague-Dawley female rats underwent bladder and epidural catheter implantation. Five days later, cystometry was performed using continuous infusion. Anesthesia with isoflurane, ketamine-xylazine (KX) or fentanyl-fluanisone-midazolam (FFM) was used. After three micturition cycles, intrathecal bupivacaine was administered leading to the suppression of reflex bladder contractions. LPP measurements were performed using vertical tilt. After the initial LPP measurement, animals underwent partial resection of the striated urethral sphincter. The effect was evaluated 6 weeks after surgery, by repeating the LPP measurement in the same animal., Results: Ten out of 19 animals showed full micturition cycles under isoflurane, and all 9 animals under KX anesthesia. No significant difference in micturition pressures (Mean ± SEM; 30.1 ± 2.3 vs. 26.8 ± 1.6 mmHg) and LPP (31.0 ± 2.4 vs. 28.0 ± 0.9 mmHg) was observed between isoflurane and KX groups, respectively. Reflex micturition was suppressed with FFM. Bupivacaine led to overflow incontinence in all cases. Sphincter injury caused fibrotic changes and a significant increase in LPP (26.4 ± 2.3 before vs. 46.9 ± 4.6 mmHg after injury, p  < 0.05)., Conclusions: KX anesthesia preserves bladder contractions. Intrathecal bupivacaine eliminates reflex micturition, allowing for repeated LPP measurements in the same animal. Resection of striated sphincter resulted in increased LPP 6 weeks post injury. The site of urethral sphincter resection healed with fibrosis.

Purpose: The authors discuss the evolution and application of 3 radiology teaching methods-a fundamentals-of-imaging course, a combined clinical-radiology case conference, and a radiology objective structured clinical examination-to medical education at the Brigham and Women's Hospital site of Harvard Medical School., Methods: The evolution of the medical student radiology teaching program from content needs assessment to blueprint creation, through implementation, is outlined., Results: The 3 components of the teaching program are described. The changes in format in response to feedback and challenges faced in deploying this new curriculum are detailed. Results from student surveys and the radiology objective structured clinical examination scores from recent years are also presented., Conclusions: As radiology assumes an increasingly central role in patient care and diagnosis, the need for effective integration of radiology teaching into medical education becomes more critical. The concepts presented here have been deemed to be successful by students and faculty members and may be applicable to other institutions., (Copyright © 2014 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: Since 2006 the Quality Outcomes Framework (QOF) has rewarded GPs for carrying out standardised assessments of the severity of symptoms of depression in newly diagnosed patients., Aim: To gain understanding of GPs' opinions and perceived impact on practice of the routine introduction of standardised questionnaire measures of severity of depression through the UK general practice contract QOF., Design of Study: Semi-structured qualitative interview study, with purposive sampling and constant comparative analysis., Setting: Thirty-four GPs from among 38 study general practices in three sites in England, UK: Southampton, Liverpool, and Norfolk., Method: GPs were interviewed at a time convenient to them by trained interviewers. Interviews were audiorecorded and transcribed verbatim in preparation for thematic analysis, to identify key views., Results: Analysis of the interviews suggested that the use of severity questionnaires posed an intrusion into the consultation. GPs discursively polarised two technologies: formal assessment versus personal enquiry, emphasising the need to ensure the scores are used sensitively and as an aid to clinical judgement rather than as a substitute. Importantly, these challenges implicitly served a function of preserving GPs' identities as professionals with expertise, constructed as integral to the process of diagnosis., Conclusion: GP accounts indicated concern about threats to patient care. Contention between using severity questionnaires and delivering individualised patient care is significantly motivated by GP concerns to preserve professional expertise and identity. It is important to learn from GP concerns to help establish how best to optimise the use of severity questionnaires in depression.

Background: Travellers increasingly require hepatitis A virus (HAV) vaccine for overseas travel to highly endemic areas. While the inactivated HAV vaccines currently in use are all highly immunogenic, studies have shown the aluminium-free, virosome-adjuvanted vaccine Epaxal to possess a superior local tolerability profile. The objective of this study was to analyse the pattern of local reactions caused by the aluminium-free Epaxal compared with an aluminium-adjuvanted HAV vaccine., Methods: Subjects recruited from travel health centres were randomised in a 4:1 ratio to receive a single dose of either Epaxal or Havrix vaccine. Vaccinees noted adverse reactions on a 7-day diary card that was returned by mail to the centre., Results: 529 adults (> or =16 years) were vaccinated, and 413 (78.1%) subjects returned diary cards, 338 (76.5%) in the Epaxal group and 75 (86.2%) in the Havrix group. Subjects reported fewer local adverse reactions for Epaxal (23.4% vs. 57.3%; p<0.0001). Injection site pain categorised as Grade 2 (painful on movement) or Grade 3 (spontaneously painful) (4.7% vs. 22.7%, p=0.0001) was less frequent in the Epaxal group and resolved more quickly (> or =3 days of pain, 8.6% vs. 22.7%, p=0.0001)., Conclusions: The lower reactogenicity of the virosome-adjuvanted vaccine is an important feature for travellers.

A prospective, randomised, observer-blind, comparative study was performed in healthy adults with a new hepatitis A/typhoid combined vaccine, Viatim, and the marketed Hepatyrix vaccine. Both vaccines induced high levels of protective antibodies, but typhoid responses were higher and hepatitis A responses more rapid with Viatim compared with Hepatyrix. Both vaccines were well tolerated, no serious adverse events (SAEs) occurred, but more Viatim vaccinees had more mild or moderate local reactions (82.7%) than Hepatyrix (53.1%, p < 0.001). In this direct comparison Viatim induced more local reactions, but elicited a more rapid and higher immune response to both antigens than Hepatyrix.

Concerns about the tolerability of mefloquine highlight the need for new drugs to prevent malaria. Atovaquone-proguanil (Malarone; GlaxoSmithKline) was safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but experience in nonimmune people is limited. In a randomized, double-blind study, nonimmune travelers received malaria prophylaxis with atovaquone-proguanil (493 subjects) or mefloquine (483 subjects). Information about adverse events (AEs) and potential episodes of malaria was obtained 7, 28, and 60 days after travel. AEs were reported by an equivalent proportion of subjects who had received atovaquone-proguanil or mefloquine (71.4% versus 67.3%; difference, 4.1%; 95% confidence interval, -1.71 to 9.9). Subjects who received atovaquone-proguanil had fewer treatment-related neuropsychiatric AEs (14% versus 29%; P=.001), fewer AEs of moderate or severe intensity (10% versus 19%; P=.001), and fewer AEs that caused prophylaxis to be discontinued (1.2% versus 5.0%; P=.001), compared with subjects who received melfoquine. No confirmed diagnoses of malaria occurred in either group. Atovaquone-proguanil was better tolerated than was mefloquine, and it was similarly effective for malaria prophylaxis in nonimmune travelers.

Background: Virtual colonoscopy is a new method of imaging the colon in which thin-section, helical computed tomography (CT) is used to generate high-resolution, two-dimensional axial images. Three-dimensional images of the colon simulating those obtained with conventional colonoscopy are then reconstructed off-line. We compared the performance of virtual and conventional colonoscopy for the detection of colorectal polyps., Methods: We prospectively studied 100 patients at high risk for colorectal neoplasia (60 men and 40 women; mean age, 62 years). We performed virtual colonoscopy immediately before conventional colonoscopy. We inserted a rectal tube and insufflated the colon with air to the maximal level that the patient could tolerate. We administered 1 mg of glucagon intravenously immediately before CT scanning to minimize the degree of smooth-muscle spasm and peristalsis and to reduce the patient's discomfort., Results: The entire colon was clearly seen by virtual colonoscopy in 87 patients and by conventional colonoscopy in 89. Fifty-one patients had normal findings on conventional colonoscopy. In the other 49, we identified a total of 115 polyps and 3 carcinomas. Virtual colonoscopy identified all 3 cancers, 20 of 22 polyps that were 10 mm or more in diameter (91 percent), 33 of 40 that were 6 to 9 mm (82 percent), and 29 of 53 that were 5 mm or smaller (55 percent). There were 19 false positive findings of polyps and no false positive findings of cancer. Of the 69 adenomatous polyps, 46 of the 51 that were 6 mm or more in diameter (90 percent) and 12 of the 18 that were 5 mm or smaller (67 percent) were correctly identified by virtual colonoscopy. Although discomfort was not specifically recorded, none of the patients requested that virtual colonoscopy be stopped because of discomfort or pain., Conclusions: In a group of patients at high risk for colorectal neoplasia, virtual and conventional colonoscopy had similar efficacy for the detection of polyps that were 6 mm or more in diameter.

Purpose: To evaluate the use of preoperative virtual colonoscopy to examine the proximal colon in patients with distal occlusive carcinomas, defined as cancers that cannot be traversed endoscopically., Materials and Methods: Twenty-nine patients with occlusive colorectal carcinomas underwent preoperative virtual colonoscopy with use of a standard protocol. Patients with acute bowel obstruction were excluded. Results of virtual colonoscopy were compared with the findings of preoperative colonoscopy, preoperative barium enema examination, intraoperative colon palpation, histopathologic outcome, and postoperative colonoscopy and barium enema examination, where possible., Results: Virtual colonoscopy helped identify all 29 occlusive carcinomas and demonstrated two cancers and 24 polyps in the proximal colon. Both synchronous cancers were confirmed intraoperatively and resected. Postoperative conventional colonoscopy in 12 patients confirmed 16 polyps identified at virtual colonoscopy and demonstrated two subcentimeter polyps missed at virtual colonoscopy. Postoperative barium enema examination was performed in two patients and helped confirm two polyps identified at virtual colonoscopy. Virtual colonoscopy successfully demonstrated the proximal colon in 26 of 29 patients examined compared with preoperative barium enema examination, which failed to adequately demonstrate the proximal colon in any patient examined., Conclusion: Virtual colonoscopy is a feasible and useful method for evaluating the entire colon before surgery in patients with occlusive carcinomas.

Background: Virtual colonoscopy is a potentially powerful tool for non-invasive colorectal evaluation. In vitro studies have established its accuracy in simulated polyp detection but little data exist regarding its use in clinical practice., Aims: To evaluate the ability of virtual colonoscopy to detect colorectal cancers and polyps in patients with endoscopically proven colorectal neoplasms and to correlate the findings of virtual colonoscopy with those of conventional colonoscopy, surgery, and histopathology., Patients: Thirty eight patients with endoscopic findings suggestive of colorectal carcinoma., Methods: Virtual colonoscopy was performed using thin section helical computed tomography (CT) of the abdomen and pelvis after rectal insufflation of room air. Commercially available software was used to generate endoscopic "fly through" examinations of the colon from the CT data. Results were correlated with the findings of conventional colonoscopy and with the surgical and histopathological outcome in each case., Results: Thirty eight pathologically proven colorectal cancers and 23 adenomatous polyps were present. On virtual colonoscopy, all cancers and all polyps measuring greater than 6 mm in size were identified; there were two false positive reports of polyps. On conventional colonoscopy, there was one false positive report of a malignant sigmoid stricture; four subcentimetre polyps were overlooked. Virtual colonoscopy enabled visualisation of the entire colon in 35 patients; conventional colonoscopy was incomplete in 14 patients. Virtual colonoscopy correctly localised all 38 cancers, compared with 32 using conventional colonoscopy., Conclusion: Virtual colonoscopy is a feasible method for evaluating the colon; it may have role in diagnosis of colorectal cancer and polyps.

Objective: The aim of this study was to compare the diagnostic accuracy of two-dimensional (2D) CT colonography and three-dimensional (3D) virtual colonoscopy with conventional colonoscopy in patients who have suspected colorectal neoplasms., Subjects and Methods: Twenty patients were studied (eight women and 12 men; mean age, 53 years; range, 42-85 years). All patients had findings on conventional colonoscopy suggestive of colorectal carcinoma and underwent colonic CT within 3 hr of endoscopy. Two-dimensional CT colonography and 3D virtual colonoscopy images were generated from the same data set that was obtained from thin-section helical CT of the abdomen and pelvis after rectal insufflation of room air. Three-dimensional virtual colonoscopy images were obtained by downloading CT data to a workstation equipped with commercially available software. Volume- and perspective-rendering techniques were used to achieve interactive, 3D virtual "fly-through" examinations of the colonic mucosa. The results of 2D CT colonography and 3D virtual colonoscopy were compared with the findings of conventional colonoscopy and correlated with surgical and pathologic outcome where possible., Results: Twenty masses (defined as intraluminal projections 2 cm or larger in diameter) and 15 polyps (defined as projections smaller than 2 cm in diameter) were identified in our study group. All masses and 14 of 15 polyps were successfully shown on 2D colonography. Three findings of polyps on 2D colonography were false-positive, and one was false-negative. Three-dimensional virtual colonoscopy revealed 19 of 20 masses and 13 of 15 polyps. On conventional colonoscopy, all 20 masses and 13 of 15 polyps were identified, with one false-positive finding of a malignant stricture in a normal colon. Complete examination of the colon was possible in 18 of 20 patients using the 2D technique and in 17 of 20 patients using 3D virtual colonoscopy, whereas conventional colonoscopy showed the entire colon in only 12 of 20 patients., Conclusion: Two-dimensional CT colonography and 3D virtual colonoscopy are complementary and effective techniques for examining the colon in patients with suspected colorectal carcinoma. CT techniques offer several advantages over conventional colonoscopy including the ability to detect abnormalities proximal to obstructing carcinomas, accurate localization of abnormalities within the colon, and good patient tolerance. These CT techniques may play an important role in future diagnosis of colorectal cancer and for screening patients at risk.

Objective: To compare the frequency of adverse events, particularly neuropsychiatric effects, from mefloquine and from chloroquine plus proguanil as used for malaria chemoprophylaxis., Design: Retrospective questionnaire to travellers taking either regimen between November 1993 and February 1995; telephone interview with those reporting pronounced side effects., Setting: Travellers from Britain who consulted an advisory helpline., Subjects: 1214 adults taking mefloquine and 1181 taking chloroquine plus proguanil., Main Outcome Measures: Reported presence of and degree of disability from 12 neuropsychiatric and other symptoms, as assessed by the subjects and by referees and on the basis of behaviour change., Results: There were equal rates of any side effects (40%) and of stopping or changing medication. Overall, neuropsychiatric adverse events were significantly more common in travellers taking mefloquine. In all, 333 neuropsychiatric adverse events were reported by 1214 travellers taking mefloquine, compared with 189 such events in 1181 travellers taking proguanil plus chloroquine (P < 0.001). In all, 0.7% of travellers taking mefloquine had disabling neuropsychiatric adverse effects, compared with 0.09% of those taking proguanil plus chloroquine (P = 0.021). Two travellers taking mefloquine (1 in 607) were admitted to hospital as a result of the adverse event, compared with 1 in 1181 travellers taking proguanil plus chloroquine., Conclusion: There is a significant excess of adverse neuropsychiatric events of intermediate degrees of severity associated with the use of mefloquine compared with proguanil plus chloroquine. This finding may also explain the discrepant findings between earlier studies and clinical experience.

Fatigue and recovery of mouse soleus and extensor digitorum longus muscles were investigated in standard saline and in saline containing the lactate + hydrogen ion transport blocker, alpha-cyano-4-hydroxycinnamic acid (cinnamate). The fatigue protocol was a series of brief isometric tetani which reduced isometric force by about 25%. Recovery was monitored by test tetani during recovery. Both muscles recovered completely in standard saline. Soleus muscle also recovered completely in the presence of cinnamate, whereas extensor digitorum longus hardly recovered at all. Force during fatigue and recovery can be described in a mathematical simulation in which force depends on intracellular inorganic phosphate and pH, and the only effect of cinnamate is to block lactate + hydrogen ion transport. The results of the simulation suggest that during the fatiguing series of tetani pH changes are small and have a negligible effect on force, but pH is a major determinant of the timecourse of recovery in extensor digitorum longus.

More controversial aspects of the administration of vaccines are discussed with particular emphasis on the uncertainties surrounding measurement and significance of immunological markers in predicting efficacy. New areas of vaccine development are highlighted, particularly the importance of greater understanding of the gut immune mechanisms which promise oral delivery routes for a variety of immunogens. Emphasis is laid on the requirement for expert administration of intradermal injection if protection is to be reliable. Several new vaccines have been introduced recently and relevant issues relating to typhoid, cholera and hepatitis A vaccines are discussed. New possibilities for immunisation against travellers diarrhoea are appraised. The required frequency of booster doses is discussed for several vaccines where it is found that long term protection has often not been well researched. This is nowhere better demonstrated than with hepatitis B. Finally less commonly used vaccines are discussed and the importance of assessing true risk before deciding on use is emphasized.

Bronchial secretions from 21 patients with moderate to severe chest infections were obtained by transtracheal aspiration. Six seriously ill patients showed greatly increased levels of amylase activity in the bronchial secretions compared with those found in the 15 less ill patients. This amylase was almost certainly derived from oropharyngeal contents and its presence suggests that aspiration may be more common in comatose and semi-comatose patients than is generally appreciated.

Mecillinam is a new antibiotic related to the penicillins but more active than ampicillin against salmonellae, including Salmonella typhi. Mecillinam must be administered parenterally, but the ester, pivmecillinam, is absorbed from the gut. Eight patients suffering from typhoid fever and one suffering from paratyphoid fever were treated with the antibiotic, and seven responded satisfactorily. One patient could not tolerate pivmecillinam because of vomiting but there were no other adverse reactions. Serum and bile levels of mecillinam were many times the minimum inhibitory concentrations for most salmonellae. The antibiotic is a promising addition to the agents available for treating typhoid.

In a case of gangrene, CT demonstrated a thin-walled appendix, dilated with gas. Such a presentation has not previously been described in the CT literature.

A case of histiocytic medullary reticulosis in a 45-year-old man is described. The presentation with a swinging pyrexia is typical. Associated features were very low levels of all immunoglobulins and proved disseminated intravascular coagulation. Heparin therapy was given and the difficulties of controlling such treatment are demonstrated. It is concluded that an increased awareness of the condition as a cause of pyrexia might lead to an improvement in prognosis.

In vitro studies carried out in this Department confirmed the high activity of mecillinam against Salmonella spp. As a result we set up a study to investigate the efficacy of mecillinam in patients suffering from enteric fever. To date 13 out of 15 patients with typhoid or paratyphoid fever have been successfully treated with this new amidinopenicillanic acid antibiotic.