Authors' reply: Comments regarding "Effects of therapeutic interventions on long COVID: a meta-analysis of randomized controlled trials".

This review assessed the effectiveness of interventions for improving outcomes among street‐connected children and young people, and for reducing some important health‐related risks; and to improve access to and integration into society, education, and employment opportunities. Eligible study designs compare outcomes from interventions for street‐connected children and young people aimed at reintegration, education, employment, improving health and/or harm reduction, and provision of shelter, versus a comparison group (e.g. shelter/drop‐in service as usual). The review identified 13 studies evaluating 19 interventions. All studies were conducted in the USA except one (South Korea). The outcome for integration was not measured in included studies. The same was the case for education and employment related outcomes – none of the included studies measured literacy, numeracy, or participation in education or skills‐based employment. Several studies measured health‐related outcomes. Five studies investigate the effect of interventions to encourage safe or reduced sexual activity (e.g. numbers of partners, frequency of sex, HIV knowledge, unprotected sex, condom use and rates of abstinence). The results are mixed, lacking enough evidence to support any of the interventions. Eight studies report outcomes of interventions promoting safe or reduced substance use. The outcomes used a variety of measures in different studies at various times making it difficult to get a clear overview. The overall effect was mixed; some studies report positive effect and the others reported negative or no effect. Three studies investigate the effect of family therapy on substance abuse and report improvements in some of the measures. Eight studies investigate the effect of therapeutic interventions to improve mental health (including self‐esteem and depression) in street‐connected kids. In general, there is no significant improvement in the intervention group compared to the control group. In some instances, both groups improved from the baseline. Finally, two studies investigate the effect of family‐based approaches on family functioning. No differences were found between intervention and control conditions on most of the outcome measures used. Plain language summary Lack of evidence on the effectiveness of interventions to reintegrate street‐connected children There are a range of interventions to improve the integration and well‐being of street‐connected children, yet no studies measure integration, education or employment outcomes. There appears to be no effect on and mixed evidence for mental health. There may be reductions in substance abuse. What is this review about? Millions of street‐connected children throughout the world are at risk of exploitation, violence, substance abuse, and health problems, and are not receiving skills‐based education. Interventions to promote access to education, healthy and settled lifestyles, and reduction of risks are intended to give this group a better chance in life and prevent marginalization from society. What is the aim of this review? This review assessed the effectiveness of interventions for improving outcomes among street‐connected children and young people, and for reducing some important health‐related risks; and to improve access to and integration into society, education, and employment opportunities. This review investigates the effects of interventions for street‐connected children to promote integration to the society, skills‐based education, prospects of employment and health risk reduction. What are the main findings of this review? What studies are included? Eligible study designs compare outcomes from interventions for street‐connected children and young people aimed at reintegration, education, employment, improving health and/or harm reduction, and provision of shelter, versus a comparison group (e.g. shelter/drop‐in service as usual). The review identified 13 studies evaluating 19 interventions. All studies were conducted in the USA except one (South Korea). The outcome for integration was not measured in included studies. The same was the case for education and employment related outcomes – none of the included studies measured literacy, numeracy, or participation in education or skills‐based employment. Several studies measured health‐related outcomes. Five studies investigate the effect of interventions to encourage safe or reduced sexual activity (e.g. numbers of partners, frequency of sex, HIV knowledge, unprotected sex, condom use and rates of abstinence). The results are mixed, lacking enough evidence to support any of the interventions. Eight studies report outcomes of interventions promoting safe or reduced substance use. The outcomes used a variety of measures in different studies at various times making it difficult to get a clear overview. The overall effect was mixed; some studies report positive effect and the others reported negative or no effect. Three studies investigate the effect of family therapy on substance abuse and report improvements in some of the measures. Eight studies investigate the effect of therapeutic interventions to improve mental health (including self‐esteem and depression) in street‐connected kids. In general, there is no significant improvement in the intervention group compared to the control group. In some instances, both groups improved from the baseline. Finally, two studies investigate the effect of family‐based approaches on family functioning. No differences were found between intervention and control conditions on most of the outcome measures used. What was the quality of the evidence? The quality of evidence was from low (i.e. for risk reduction in sexual activity and family therapy) to moderate (i.e. mental health improvement, harm reduction in substance abuse). What do the findings of this review mean? There is a dearth of evidence from controlled trials on interventions to improve integration of street‐connected children and young adults into society and providing skills‐based education. The evidence from health interventions aimed at engaging in safe sexual practices, and at improving mental health vary widely and are inconclusive as to their effectiveness. Some of the interventions aimed at reducing the risk of substance abuse may be effective. Further research in this area will be useful in understanding the effectiveness of these approaches and validating the effect of some of the interventions that are supported by moderate evidence. How up‐to‐date is this review? The review authors searched for relevant studies until April 2015. This Campbell review was published in 2016. Abstract Background Millions of street‐connected children and young people worldwide live or work in street environments. They are vulnerable to many risks, whether or not they remain connected to families of origin, and despite many strengths and resiliencies, they are excluded from mainstream social structures and opportunities. Objectives Primary research objectives To evaluate and summarise the effectiveness of interventions for street‐connected children and young people that aim to: promote inclusion and reintegration; increase literacy and numeracy; facilitate access to education and employment; promote mental health, including self esteem; reduce harms associated with early sexual activity and substance misuse. Secondary research objectives To explore whether effects of interventions differ within and between populations, and whether an equity gradient influences these effects, by extrapolating from all findings relevance for low‐ and middle‐income countries (LMICs) (Peters 2004). To describe other health, educational, psychosocial and behavioural effects, when appropriate outcomes are reported. To explore the influence of context in design, delivery and outcomes of interventions. To explore the relationship between numbers of components and duration and effects of interventions. To highlight implications of these findings for further research and research methods to improve evidence in relation to the primary research objective. To consider adverse or unintended outcomes. Search methods We searched the following bibliographic database

Vitiligo is the most common pigmentation disorder. It is an acquired, progressive disorder, presenting with white macules that can appear anywhere on the skin. Presently, there is no cure for vitiligo. Although there are therapies targeted at improving its appearance, their effectiveness is limited. Without satisfactory solution to vitiligo, patients are permanently disfigured for life. Quality of life of vitiligo patients has been commonly found to be moderately impaired. Patients are chronically embarrassed and depressed. Stigmatisation is also common and cause marginalization. Hence, while vitiligo is not "life-threatening", it can be "life-ruining". Because current treatments are unsatisfactory in repigmenting the skin, the question of continuing treatment must also consider the benefits to quality of life, and that is the purpose of this review. The overall objective of this systematic review was to examine the effectiveness of therapeutic interventions, in terms of quality of life for adult patients with vitiligo. Types of studies - The review considered quantitative papers, including randomised controlled trials and quasi-experimental studies.Types of participants - Adult patients who have vitiligo from 18 to 75 years-old.Types of interventions - This review considered studies of current therapeutic interventions for vitiligo, including oral, topical, combination, camouflage, cognitive-behavioural therapy and grafting.Types of measured outcomes - Quality of life outcomes as measured by validated tools. The search aimed to find published studies and papers, limited to English language reports. A three-step search strategy was utilised: An initial limited search of MEDLINE and CINAHL was undertaken, followed by an analysis of the text words contained in the title and abstract, and of the index terms used to describe the article. A second search using all identified keywords and index terms were then undertaken. Search strategies were developed using terms that were specific to the databases. Thirdly, the reference lists of all identified papers were searched for additional studies. The databases searched include: PubMed, CINAHL, Scopus, JSTOR, ScienceDirect,PsycARTICLES (Ovid) and PsycINFO (Ovid) DATA COLLECTION: Two reviewers critically appraised the methodological quality of research studies using a standardised critical appraisal tool from the Joanna-Briggs Institute. Data was extracted from nine papers for this review, however as the studies were heterogeneous in population, interventions and methodologies, it was not possible to conduct a meta-analysis to establish superiority of interventions in terms of improving quality of life. Hence, a narrative summary was presented to collate the results of the interventions where there were similar. All treatments were found to improve quality of life for vitiligo patients. Disease-altering interventions that were effective in repigmentation arrest of disease progression were also effective in improving quality of life. Lifestyle-altering interventions were found to be selectively effective for patients with more severe quality of life impairment and Subscale analysis showed particular effectiveness of interventions in improving the emotional dimension of quality of life. Current interventions for vitiligo are effective in bettering the quality of life either by improving physical appearance of the patient or by addressing the psychological distress directly. Less effectiveness was achieved for the functional and social dimensions, which are more dependent on social and cultural norms. This suggests that current interventions alone are inadequate to address the holistic quality of life challenges associated with vitiligo. IMPLICATIONS FOR RESEARCH.

Purpose: This systematic review investigated the effects of non-pharmacological interventions to improve the sleep of the Korean elderly at home and in facilities.Methods: A literature search was performed using electronic databases (RISS, KISS, KMbase, KoreaMed, DBpia) from 2010 to 2021. Participants’ characteristics, intervention characteristics, and measured sleep outcomes were systematically reviewed. A qualitative appraisal of studies was performed using the RoB 2.0 and ROBINS-I tools.Results: Of 954 publications identified, 23 met the inclusion criteria. Two studies were randomized controlled trials and 21 studies were quasi-experimental designs with a non-equivalent control group. The contents of 23 intervention studies that aimed to improve sleep included massage, auricular acupressure therapy, laughter therapy, heat therapy, exercise, and aromatherapy. The Korean Sleep Scale A was the most frequently used sleep instrument, in 18 studies. Most interventions were effective in improving sleep, but some inconsistent results were reported.Conclusion: Non-pharmacological interventions for the improvement of sleep in the elderly are useful as therapeutic interventions as part of nursing care, because they are simple and easy to apply. However, to draw clear conclusions about the effect of interventions, it will be necessary to gather results from intervention studies using rigorous methodologies in the future.

The Effectiveness of Therapeutic Play Intervention in Reducing Perioperative Anxiety, Negative Behaviors, and Postoperative Pain in Children Undergoing Elective Surgery: A Systematic Review

<h3>Objectives</h3> The animal model of silicosis of non-exposed tracheal instillation induced by SiO₂ in rats lung fibrosis were studied. To investigate: whether SiO₂ can induce fibrosis in lung tissue by induction of epithelial interstitial transformation (EMT); EMT in poly guanine nucleotide (PolyG) molecular biology mechanism of silicosis fibrosis reversal. the effects of PolyG preventive and therapeutic interventions on EMT in rats exposed to silica dust and the effect of intervention at different time points. <h3>Methods</h3> Ninety-six healthy male Sprague-Dawley (SD) rats weighing 180~220 g were randomly divided into normal saline group (n=32), silicosis model group (n=32), PolyG prevention group (n=16) and PolyG (28 days) treatment group (n=16). After the rats were anaesthetised with ether, the control group was injected with 1 ml normal saline by bronchial instillation. The rats in other groups were treated with non-exposed tracheal infusion of a one-time infusion of 50 ml/L silica suspension 1 ml. The rats in the PolyG preventive group were treated with PolyG 2.5 mg/kg body weight (the weight of each rat was determined 28 days after modelling) at the same time by tail vein injection. The rats in the PolyG treatment group were treated with intravenous injection of PolyG 2.5 mg/Kg body weight (by modelling 28 days after each rat weight to determine the appropriate dose). The rats in the polyG prevention group and the treatment group were sacrificed on the 28th day and the 56th day after the corresponding administration. Silicosis model group and saline control group also have 8 rats were sacrificed at the same time point.(Macrophage receptor with collagenous structure, MARCO), E-cadherin (E-cadherin) were detected by Western blotting. The macrophage receptor (MARCO) Cadherin, E-cadherin, α-smooth muscle actin (α-SMA), vimentin and type I and type III collagen; the right amount of lung tissue, The relative expression levels of E-cadherin, α-SMA, vimentin and type I and type III procollagen mRNA were detected by Real-time PCR. The right middle lobe tissue was fixed with 4% paraformaldehyde, paraffin section, the histopathological changes of lung tissue were observed by HE staining and Masson staining. Immunohistochemical staining was used to detect the localization and expression of E-cadherin, α-SMA and vimentin in lung tissue. <h3>Results</h3> Histopathological changes of lung tissue in different groups: The lung tissue structure of the rats in the control group was normal, and the infiltration of inflammatory cells was observed in the surrounding area, and the lung tissue structure of the control group did not change significantly over time; There were a large number of inflammatory cell infiltration in the lung tissue of the rats in the silicosis model, and the typical fibrous nodules were formed. The nodules were composed of macrophages and fibroblasts. Some areas of the alveolar structure still existed, showing different alveolar walls and small blood vessel wall thickening; with the dying time, the number of fibrous silicon nodules increased, some of the silicon nodules have a trend of integration and becoming bigger, in particular, is completely fibrous tissue, or even fibrotic changes; In PolyG prevention group and treatment group, the number of cell nodules or silicon nodules was lower than that of the model group; the degree of lesion in the rats was significantly lower than that in the control group. The results of immunohistochemistry showed that α-SMA and vimentin positive cells were significantly increased in the silicosis model group, and the number of E-cadherin positive cells was significantly decreased. After administration of PolyG, the number of E-cadherin-positive cells and the number of α-SMA and vimentin-positive cells were significantly increased. The expression of MARCO, E-cadherin, α-SMA and vimentin in the lung tissue of the control group were not significantly different (p&lt;0.05). There was no significant difference in the expression of MARCO and EMT-related proteins in rat lung tissue at different time points (p&lt;0.05). The levels of E-cadherin in the lung tissue of the silicosis model group were increased with the prolongation of observation time (p&lt;0.05). The expression levels of MARCO, α-SMA and vimentin protein in the lung tissue of the PolyG intervention group (prophylactic and therapeutic) were lower than those in the control group, but the E-cadherin was higher than that of the silicosis group model group (p&lt;0.05). The comparison of mRNA expression levels of E-cadherin, α-SMA and vimentin in lung tissue of different groups: the expression of E-cadherin, α-SMA and vimentin mRNA in lung tissue of all groups were the same as those of corresponding protein. The expression of collagen I and III in the lung tissue of different groups were significantly higher than those in the control group (p&lt;0.05). There was no significant difference in the expression of collagen I and III in rat lung tissue of control groups at different time points (p&lt;0.05). The expression level of collagen I and III in the lung tissue of silicosis model group increased with the prolongation of dying time (p&lt;0.05). The protein content of collagen I and III in PolyG intervention group was significantly higher than that in the control group (p&lt;0.05). The mRNA expression of type I and III procollagen were the same as that of I and III collagen. <h3>Conclusions</h3> The protein content and mRNA expression of E–cadherin were decreased, while α–SMA and vimentin in silicosis model group were increased, which indicated that there was epithelial–mesenchymal transition in the development of silicosis. After inhibition of MARCO combined with SiO₂, the protein content and mRNA expression of α–SMA and vimentin were significantly down–regulated, and the protein content and mRNA expression of E–cadherin were significantly up–regulated; I, III collagen content and I, III type procollagen mRNA expression levels were decreased and lung tissue pathological changes were reduced in vary degrees. PolyG intervention (prophylactic and therapeutic) can effectively inhibit the progression of EMT, and further delay the formation of pulmonary fibrosis, and the effect of early to give preventive intervention is better.

BackgroundPeriodontal disease is an inflammatory disease of the tissues supporting the teeth. Women who have periodontal disease while pregnant may be at risk of adverse pregnancy outcomes. Although the association between periodontal disease and adverse pregnancy outcomes has been addressed in a considerable number of systematic reviews and meta-analyses, there are important differences in the conclusions of these reviews. Systematic reviews assessing the effectivity of various therapeutic interventions to treat periodontal disease during pregnancy to try and reduce adverse pregnancy outcomes have also arrived at different conclusions. We aim to provide a systematic overview of systematic reviews comparing the frequency of adverse pregnancy outcomes between women with and without periodontal disease and/or evaluating the effect of preventive and therapeutic interventions for periodontal disease before or during pregnancy on adverse pregnancy outcomes.MethodsWe will include systematic reviews reporting on studies comparing adverse pregnancy outcomes: (i) between women with or without periodontal disease before (<6 months) or during pregnancy and/or (ii) according to preventive or therapeutic interventions for periodontal disease. Eligible interventions include (combinations of) the following: oral hygiene education, use of antibiotics, subgingival scaling, and root planing. For preventive and/or therapeutic reviews, the following comparisons will be considered: no intervention, a placebo intervention, or an alternative intervention. Our primary adverse pregnancy outcomes of interests are maternal mortality, preterm delivery, and perinatal mortality. Two reviewers will independently identify eligible published and unpublished systematic reviews from six electronic databases and using hand searching of reference lists and citations. Data items extracted from included systematic reviews are based on the Cochrane Effective Practice and Organization of Care checklist and the preferred reporting items for systematic review and meta-analysis (PRISMA) statement. In our narrative data synthesis, we will consider risk of bias of individual reviews, focusing mainly on the conclusions of the highest quality reviews using the assessment of multiple systematic reviews (AMSTAR) checklist. Disagreements during search, selection, data extraction, and risk of bias assessment will be resolved through discussion and/or consultation of a third reviewer.Systematic review registrationPROSPERO CRD42015030132Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-016-0195-7) contains supplementary material, which is available to authorized users.

Vascular and sympathetic abnormalities characterize chronic heart failure (CHF). Alterations include (1) a reduction in arterial distensibility, (2) endothelial dysfunction, (3) a decrease in arterial compliance and a parallel increase in arterial stiffness, and (4) sympathetic cardiovascular activation. Altogether, these alterations represent important targets in therapeutic interventions, because they display an independent negative impact on the disease prognosis, favouring disease progression and the development of cardiovascular complications with direct and indirect mechanisms. The present review will examine the effects of the different therapeutic interventions targeting the vascular/sympathetic alterations detected in CHF. Non-pharmacological, pharmacological and device-based treatments will be discussed in detail, highlighting the possible mechanisms responsible for the vascular/sympathetic effects of each intervention. Finally, the unmet goals in treatment in relation to endothelial and adrenergic targets will be also discussed.

acknowledges the increasing attention for economic evaluations and would like to stimulate researchers to submit original papers of economic evaluations of orthopedic devices/instruments and surgical interventions for spine problems, but also pharmaceutical and conservative interventions for back and neck pain. Because back and neck pain are among the most prevalent health problems and are associated with huge costs of health care utilization and productivity losses, economic evaluations in this field are direly needed to facilitate wellinformed clinical and policy decisions.

Therapeutic Risk Management Interventions: Feasibility and Effectiveness

Elderly subjects with mild memory impairment but not apparent dementia are the focus of early intervention trials. To examine the effects of structural psychosocial intervention for elderly subjects with very mild Alzheimer disease, i.e., Clinical Dementia Rating 0.5. The design is a prospective study. The experimental group (14 Clinical Dementia Rating 0.5 subjects) and the control group (11 Clinical Dementia Rating 0.5 subjects) were studied. Subjects with cerebrovascular disease as shown by magnetic resonance imaging were excluded. The experimental group participated in activities in a day-care-like setting once a week over a period of 6 months, whereas the control group did not. Each group was reevaluated after approximately 9 months. The effects of intervention were evaluated by cognitive tests, affective scales, a global clinical measure, an observation scale in the sessions, and a projective test. The experimental group showed a significant improvement on the word fluency test, whereas the control group showed a significant decline on the Mini-Mental State Examination, the digit span, and the Trail Making-A test. The experimental group revealed significantly higher levels on the Mini-Mental State Examination and the digit span compared with the control group after the 6-month intervention. A significant improvement was found for the global clinical measure, the observation scale, and the projective test in the experimental group after the intervention. After controlling the potential confounders (age, educational level, baseline cognitive, and affective status) in a multiple regression analysis, the same results were found. We considered that psychosocial intervention had beneficial effects for subjects with very mild Alzheimer disease.

SummaryBackgroundRepeat offending, also known as criminal recidivism, in people released from prison has remained high over many decades. To address this, psychological treatments have been increasingly used in criminal justice settings; however, there is little evidence about their effectiveness. We aimed to evaluate the effectiveness of interventions in prison to reduce recidivism after release.MethodsFor this systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, Embase, Global Health, MEDLINE, PsycINFO, and Google Scholar for articles published from database inception to Feb 17, 2021, without any language restrictions. We searched for randomised controlled trials (RCTs) that evaluated the effect of psychological interventions, delivered to adolescents and adults during incarceration, on recidivism outcomes after release. We excluded studies of solely pharmacological interventions and of participants in secure psychiatric hospitals or special residential units, or attending therapies mainly delivered outside of the prison setting. We extracted summary estimates from eligible RCTs. Data were extracted and appraised according to a prespecified protocol, with effect sizes converted to odds ratios. We used a standardised form to extract the effects of interventions on recidivism and estimated risk of bias for each RCT. Planned sensitivity analyses were done by removing studies with fewer than 50 participants. Our primary outcome was recidivism. Data from individual RCTs were combined in a random-effects meta-analysis as pooled odds ratios (ORs) and we explored sources of heterogeneity by comparing effect sizes by study size, control group, and intervention type. The protocol was pre-registered with PROSPERO, CRD42020167228.FindingsOf 6345 articles retrieved, 29 RCTs (9443 participants, 1104 [11·7%] females, 8111 [85·9%] males, and 228 [2·4%] unknown) met the inclusion criteria for the primary outcome. Mean ages were 31·4 years (SD 4·9, range 24·5–41·5) for adult participants and 17·5 years (SD 1·9; range 14·6–20·2) for adolescent participants. Race or ethnicity data were not sufficiently reported to be aggregated. If including all 29 RCTs, psychological interventions were associated with reduced reoffending outcomes (OR 0·72, 95% CI 0·56–0·92). However, after excluding smaller studies (<50 participants in the intervention group), there was no significant reduction in recidivism (OR 0.87, 95% CI 0·68–1·11). Based on two studies, therapeutic communities were associated with decreased rates of recidivism (OR 0·64, 95% CI 0·46–0·91). These risk estimates did not significantly differ by type of control group and other study characteristics.InterpretationWidely implemented psychological interventions for people in prison to reduce offending after release need improvement. Publication bias and small-study effects appear to have overestimated the reported modest effects of such interventions, which were no longer present when only larger studies were included in analyses. Findings suggest that therapeutic communities and interventions that ensure continuity of care in community settings should be prioritised for future research. Developing new treatments should focus on addressing modifiable risk factors for reoffending.FundingWellcome Trust, Fonds de recherche du Québec – Santé.

BackgroundPreterm infants are at greater risk for neurodevelopmental disabilities than full term infants. Interventions supporting parents to improve the quality of the infant’s environment should improve developmental outcomes for preterm infants. Many interventions that involve parents do not measure parental change, nor is it clear which intervention components are associated with improved parental outcomes. The aim of this review was to categorize the key components of early intervention programs and determine the direct effects of components on parents, as well as their preterm infants.MethodsMEDLINE, EMBASE, CINAHL, ERIC, and Cochrane Database of Systematic Reviews were searched between 1990 and December 2011. Eligible randomized controlled trials (RCTs) included an early intervention for preterm infants, involved parents, and had a community component. Of 2465 titles and abstracts identified, 254 full text articles were screened, and 18 met inclusion criteria. Eleven of these studies reported maternal outcomes of stress, anxiety, depressive symptoms, self-efficacy, and sensitivity/responsiveness in interactions with the infant. Meta-analyses using a random effects model were conducted with these 11 studies.ResultsInterventions employed multiple components categorized as (a) psychosocial support, (b) parent education, and/or (c) therapeutic developmental interventions targeting the infant. All interventions used some form of parenting education. The reporting quality of most trials was adequate, and the risk of bias was low based on the Cochrane Collaboration tool. Meta-analyses demonstrated limited effects of interventions on maternal stress (Z = 0.40, p = 0.69) and sensitivity/responsiveness (Z = 1.84, p = 0.07). There were positive pooled effects of interventions on maternal anxiety (Z = 2.54, p = 0.01), depressive symptoms (Z = 4.04, p <.0001), and self-efficacy (Z = 2.05, p = 0.04).ConclusionsPositive and clinically meaningful effects of early interventions were seen in some psychosocial aspects of mothers of preterm infants. This review was limited by the heterogeneity of outcome measures and inadequate reporting of statistics.Implications of key findingsInterventions for preterm infants and their mothers should consider including psychosocial support for mothers. If the intervention involves mothers, outcomes for both mothers and preterm infants should be measured to better understand the mechanisms for change.

“Living is easy with eyes closed …” on blinded RCTs and specific and non-specific effects of complex therapeutic interventions

Imagine a physician who wants to research options to help her patients lose weight. As a clinical researcher, she may first explore the efficacy of a medication. Not only is there an instrument that accurately collects patient weight but also the link between the intervention (medication) and the outcome (weight) has been established. Her study manipulates the behavior of the physician (what should be prescribed), and the intervention is administered to the patient, who in this case, is a relatively passive recipient.

The randomised controlled trial (RCT) is considered the 'gold standard' for establishing treatment efficacy or effectiveness of an intervention, but its data do not infer response in an individual patient. Individualised clinical care, a fundamental principle in complementary and alternative medicine (CAM), including homeopathy, seems well disposed in principle to being researched by single-patient (N-of-1) study design. Guidelines for reporting N-of-1 trials have recently been developed. To overview the current status in the literature of the N-of-1 method and its application in medicine, including CAM. To consider whether the N-of-1 trial design offers an opportunity for novel research in homeopathy. N-OF-1 TRIAL DESIGN: The N-of-1 trial applies the principles of the conventional crossover, blinded, RCT design. The treatment under study and the comparator are repeated in a randomised order, and with suitable washout time, over a defined period. N-of-1 design is constrained for use in chronic stable conditions, and for interventions that have quick onset and cessation of effect, with modest or negligible carryover. Outcome data can be aggregated and interpreted for the individual subject; they can also be pooled with data from several similar N-of-1 trials, enabling more generalisable conclusions. THE N-OF-1 TRIAL IN CAM: The typical individualisation of patient care can be accommodated in N-of-1 study design if the patient and the specific therapeutic intervention are selected within the constraints of the method. Application of the N-of-1 method in CAM has been advocated but has been mainly limited, in practice, to a small number of studies in herbal and traditional Chinese medicine. THE N-OF-1 TRIAL IN HOMEOPATHY: Individualised homeopathy can be accommodated for investigation within the same methodological constraints; less in-depth homeopathic approaches to prescribing are also amendable to investigation using the N-of-1 method. No such studies have been published. We identify three main targets in its ready applicability to homeopathy: (1) to optimise clinical care in an individual patient; (2) to investigate whether the outcomes of treatment using homeopathy differ from those of placebo; (3) to aggregate data from a series of N-of-1 trials to enable broader conclusions about a group of patients or intervention. The N-of-1 trial design offers important new investigative possibilities in homeopathy and should be explored as a means to optimise individualised health care or investigate effectiveness of the homeopathic intervention compared with placebo in individual subjects.