Objective : To measure the change in cardiovascular risk factors achievable in families over one year by a cardiovascular screening and lifestyle intervention in general practice. Design : Randomised controlled trial in 26 general practices in 13 towns in Britain. Subjects : 12472 men aged 40-59 and their partners (7460 men and 5012 women) identified by household. Intervention : Nurse led programme using a family centred approach with follow up according to degree of risk. Main outcome measures : After one year the pairs of practices were compared for differences in (a) total coronary (Dundee) risk score and (b) cigarette smoking, weight, blood pressure, and random blood cholesterol and glucose concentrations. Results : In men the overall reduction in coronary risk score was 16% (95% confidence interval 11% to 21%) in the intervention practices at one year. This was partitioned between systolic pressure (7%), smoking (5%), and cholesterol concentration (4%). The reduction for women was similar. For both sexes reported cigarette smoking at one year was lower by about 4%, systolic pressure by 7 mm Hg, diastolic pressure by 3 mm Hg, weight by 1 kg, and cholesterol concentration by 0.1 mmol/l, but there was no shift in glucose concentration. Weight, blood pressure, and cholesterol concentration showed the greatest difference at the top of the distribution. If maintained long term the differences in risk factors achieved would mean only a 12% reduction in risk of coronary events. Conclusions : As most general practices are not using such an intensive programme the changes in coronary risk factors achieved by the voluntary health promotion package for primary care are likely to be even smaller. The government's screening policy cannot be justified by these results.
A recurrence of cancer is a traumatic and stressful experience, and a number of approaches have been proposed to manage or treat the associated psychological distress. Meditative techniques such as mindfulness may be able to improve an individual’s ability to cope with stressful life events such as cancer diagnosis or treatment. This single-arm mixed-methods study primarily aimed to determine the feasibility of using a mindfulness-based intervention in managing psychosocial distress in recurrent ovarian cancer. Twenty-eight participants took part in a mindfulness-based program, involving six group sessions, each lasting 1.5 hours and delivered at weekly intervals. The study found that the mindfulness-based intervention was acceptable to women with recurrent ovarian cancer and feasible to deliver within a standard cancer care pathway in a UK hospital setting. The results suggested a positive impact on symptoms of depression and anxiety, but further study is needed to explore the effectiveness of the intervention.
The pathology of tuberculosis in humans starts with an initial Ghon focus in the lungs followed by transmission of bacilli though the blood and lymph to other regions in the lungs and to other organs. While these bacilli usually lie latent without causing further disease, some 10% start foci of adult type disease usually starting in the sub-apical regions of the lungs. Bacilli multiply, killing tissue by caseation and then forming colonies within the caseum. Cavities form connecting to the air in whose walls vigorous bacillary multiplication occurs. The history of the development of anti-tuberculosis chemotherapy is described, starting with the use of multi-drug regimens to prevent the emergence of drug resistance and continuing with the shortening of the treatment period to 6 months by the incorporation in the regimens of rifampicin and pyrazinamide, which are the two drug responsible for bactericidal activity during treatment. Prospects for further shortening of treatment rest with the introduction of higher dosage with rifamycins and with new anti-tuberculosis drugs. These new drugs include the 8 methoxyfluoroquinolones moxifloxacin and gatifloxacin which inhibit topoisomerases and protein formation, the diarylquinoline TM-207 which inhibits the mycobacterial ATP synthase and thus energy formation, the nitroimidazopyran PA-824 and the closely related OPC-676832 which are pro-drugs with uncertain modes of action and the pyrrole SQ-109, a cell wall inhibitor. Anti-tuberculosis drugs have widely variable pharmacokinetic characteristics but as they work efficiently together, it is unnecessary to match these when giving drug combinations. The effects of drug-drug interactions are usually small though the interactions with anti-retroviral drugs can pose problems. Dose sizes have usually been chosen to minimize side effects while retaining activity and thus tend to have low therapeutic margins, the exception being the margin of about 20 for isoniazid. The role of high plasma binding, important in limiting the efficacy of rifamycins, is uncertain for the newer drugs. Post antibiotic effects are vital to the prevention of drug resistance and need exploration for new drugs. The main aims of current drug development are (1) to shorten treatment, and (2) to make it more convenient, by for instance using widely intermittent regimens. The current techniques for measuring efficacy during drug development start with in vitro models, including the Hu/Coates models, which should contain bacterial populations resembling the bacterial persisters in lesions that are responsible for the long duration of treatment. The next stage is the mouse model of the chemotherapy of established tuberculosis, which has proved remarkably useful in assessing the value of the different drugs. The main problem in clinical assessment arises from the use of relapse after treatment as the main end-point, and the consequent need for very large numbers of patients required to provide measurable relapse rates in final phase III licensing studies....
The intensive follow up of non-attenders resulted in real intervention opportunities in only a small number. Since the effect of any intervention in a population is reduced by non-attendance audit of preventive medical programmes aimed at the population should allow for the effect of non-attenders on the overall results.
Tuberculosis (TB) remains a leading cause of infectious death worldwide, and poverty is a major driver. Clinically, TB presents as “latent” TB and active TB disease, and the treatment for each is different. TB drugs can display “early bactericidal activity (EBA)” and / or “sterilizing activity” (clearing persisters). Isoniazid is excellent at the former, and rifampin is excellent at the latter. Pyrazinamide and ethambutol complete the first‐line regimen for drug‐susceptible TB, each playing a specific role. Drug‐resistant TB is an increasing concern, being met, in part, with repurposed drugs (including moxifloxacin, levofloxacin, linezolid, clofazimine, and beta‐lactams) and new drugs (including bedaquiline, pretomanid, and delamanid). One challenge is to select drugs without overlapping adverse drug reaction profiles. QTc interval prolongation is one such concern, but to date, it has been manageable. Drug penetration into organism sanctuaries, such as the central nervous system, bone, and pulmonary TB cavities remain important challenges. The pharmacodynamics of most TB drugs can be described by the area under the curve (AUC) divided by the minimal inhibitory concentration (MIC). The hollow fiber infection model (HFIM) and various animal models (especially mouse and macaque) allow for sophisticated pharmacokinetic/pharmacodynamic experiments. These experiments may hasten the selection of the most potent, shortest possible regimens to treat even extremely drug resistant TB. These findings can be translated to humans by optimizing drug exposure in each patient, using therapeutic drug monitoring and dose individualization.
ObjectivesTo design and test the delivery of an intervention targeting the non-motor symptoms of dystonia and pilot key health and well-being questionnaires in this population.DesignA proof-of-concept study to test the delivery, acceptability, relevance, structure and content for a 3-day group residential programme for the management of dystonia.SettingParticipants were recruited from a single botulinum toxin clinic. The intervention was delivered in the community.Participants14 participants consented to take part (2 withdrew prior to the starting of intervention). The average age was 60 years (range 44–77), 8 of whom were female. After drop-out, 9 participants completed the 3-day programme.InterventionA 3-day group residential programme.Primary and secondary outcome measuresProcess evaluation and interviews were carried out before and after the intervention to explore participant's views and expectations, as well as experiences of the intervention. Select questionnaires were completed at baseline, 1-month and 3-month follow-up.ResultsAlthough participants were not sure what to expect from the programme, they found it informative and for many this together with being in a group with other people with dystonia legitimised their condition. Mindfulness was accepted and adopted as a coping strategy. This was reflected in the 1-month follow-up.ConclusionsWe successfully delivered a 3-day residential programme to help those living with dystonia manage their condition. Further improvements are suggested. The quantitative outcome measures were acceptable to this group of patients with dystonia.
BackgroundPrimary dystonia is a chronic neurological movement disorder that causes abnormal muscle movements. Pain and emotional distress may accompany these physical symptoms. Behavioural interventions are used to help people with long term conditions improve their quality of life. Little is known about behavioural interventions applied to Dystonia. We report a systematic review of studies reporting current evidence of behavioural interventions for people with primary dystonia.MethodsWe did systematic searches of Medline, PsycINFO, AHMED and CINAHL. We assessed the methodological quality of included studies using a risk of bias tool. Any disagreements were resolved by liaising with an independent rater. Physiological outcomes such as dystonia severity and psychological outcomes such as sleep and depression were selected on the basis that primary dystonia causes motor and non-motor symptoms. No time limit was placed on the searches. A narrative synthesis of the results is presented.ResultsOf 1798 titles and abstracts screened, 14 full articles were retrieved and inclusion and exclusion criteria applied. Of these a final nine were eligible for the review (N = 73). Only two were Randomised Controlled Trials (RCTs). Using the Movement Disorders Society (MDS) dystonia classification, that was published after this work started, all of the included studies were of idiopathic adult onset focal dystonia without associated features. These included: blepharospasm (eye dystonia) (N = 1), cervical dystonia (neck dystonia) (N = 2), writer’s cramp (hand dystonia) (N = 3) and the yips (N = 3). No studies reported on dystonia that affects two or more body regions. Studies reported good adherence and response rates to treatment. Physiological and psychological improvements were noted in all studies at weekly, monthly and yearly follow-ups. Caution should be taken when interpreting the results because of the scarcity of RCTs identified, use of small sample sizes, and inappropriate statistical methods.ConclusionWe identified few studies; mainly of poor methodological quality that all studied a focal dystonia. It is not possible to draw firm conclusions. Nevertheless, the data suggests that a combined behavioural therapy approach including relaxation practice for people with idiopathic adult onset focal dystonia merits further investigation.
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