An analysis of quality of life and functional outcomes as reported in randomized trials for red cell transfusions.

BACKGROUND: Meta-analyses of randomized controlled trials (RCTs) evaluating thresholds for red blood cell (RBC) transfusion typically focus on mortality; however, other outcomes are highly relevant. The aim of this study is to summarize the effects of different transfusion thresholds on the outcomes of quality of life (QoL) and function. STUDY DESIGN: We extracted data from RCTs identified in a recently published Cochrane systematic review. Primary analysis was descriptive. RESULTS: A total of 23 RCTs with 13,743 adult participants were included. Fifteen RCTs included patients in the postoperative period, of which 9 RCTs were conducted in hip (n = 3024) and 6 (n = 8672) in cardiac surgeries; 5 RCTs (n = 489) were in patients with hematological malignancies; 2 in the setting of bleeding (gastrointestinal bleed [n = 936] and postpartum [n = 521]); and one RCT (n = 936) included critically ill patients. QoL and function were reported using a variety of questionnaires and tools. The timing of assessments varied between trials. No clear clinical differences in QoL outcomes were identified in comparisons between restrictive and liberal transfusion thresholds. DISCUSSION: There is no evidence that a liberal transfusion strategy improves QoL and functional outcomes. However, the substantial limitations of many included studies indicate the need for further well-designed and adequately powered trials.

Glucocorticoid with cyclophosphamide for oral paraquat poisoning.

BACKGROUND: This an update of a Cochrane Review. Paraquat is a widely used herbicide, but is also a lethal poison. In some low- and middle-income countries (LMICs) paraquat is commonly available and inexpensive, making poisoning prevention difficult. Most of the people poisoned by paraquat have taken it as a means of self-poisoning. Standard treatment for paraquat poisoning prevents further absorption and reduces the load of paraquat in the blood through haemoperfusion or haemodialysis. The effectiveness of standard treatments is extremely limited. The immune system plays an important role in exacerbating paraquat-induced lung fibrosis. Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination has been developed and studied as an intervention for paraquat poisoning. OBJECTIVES: To assess the effects of glucocorticoid with cyclophosphamide for moderate to severe oral paraquat poisoning. SEARCH METHODS: The most recent searches were run in September 2020. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Injuries Trials Register), Ovid MEDLINE(R), Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid OLDMEDLINE, Embase Classic + Embase (Ovid), ISI WOS (SCI-EXPANDED, SSCI, CPCI-S, and CPSI-SSH), and trials registries. We also searched the following three resources: China National Knowledge Infrastructure database (CNKI ); Wanfang Data (); and VIP () on 12 November 2020. We examined the reference lists of included studies and review papers. SELECTION CRITERIA: We included randomised controlled trials (RCTs). For this update, in accordance with Cochrane Injuries' Group policy (2015), we included only prospectively registered RCTs for trials published after 2010. We included trials which assessed the effects of glucocorticoid with cyclophosphamide delivered in combination. Eligible comparators were standard care (with or without a placebo), or any other therapy in addition to standard care. Outcomes of interest included mortality and infections. DATA COLLECTION AND ANALYSIS: We calculated the mortality risk ratio (RR) and 95% confidence interval (CI). Where possible, we summarised data for all-cause mortality at relevant time periods (from hospital discharge to three months after discharge) in meta-analysis, using a fixed-effect model. We conducted sensitivity analyses based on factors including whether participants were assessed at baseline for plasma paraquat levels. We also reported data on infections within one week after initiation of treatment. MAIN RESULTS: We included four trials with a total of 463 participants. The included studies were conducted in Taiwan (Republic of China), Iran, and Sri Lanka. Most participants were male. The mean age of participants was 28 years. We judged two of the four included studies, including the largest and most recently conducted study (n = 299), to be at low risk of bias for key domains including sequence generation. We assessed one study to be at high risk of selection bias and another at unclear risk, since allocation concealment was either not mentioned in the trial report or explicitly not undertaken. We assessed three of the four studies to be at unclear risk of selective reporting, as no protocols could be identified. An important source of heterogeneity amongst the included studies was the method of assessment of participants' baseline severity using analysis of plasma levels (two studies employed this method, whilst the other two did not). No studies assessed the outcome of mortality at 30 days following ingestion of paraquat. Low-certainty evidence from two studies indicates that glucocorticoids with cyclophosphamide in addition to standard care may slightly reduce the risk of death in hospital compared to standard care alone ((RR 0.82, 95% CI 0.68 to 0.99; participants = 322); results come from sensitivity analysis excluding studies not assessing plasma at baseline). However, we have limited confidence in this finding as heterogeneity was high (I2 = 77%) and studies varied in terms of size and comparators. A single large study provided data showing that there may be little or no effect of treatment at three months post discharge from hospital (RR 0.98, 95% CI 0.85 to 1.13; 1 study, 293 participants; low-certainty evidence); however, analysis of long-term results amongst participants whose injuries arose from self-poisoning must be interpreted with caution. We remain uncertain of the effect of glucocorticoids with cyclophosphamide on infection within one week after initiation of the treatment; this outcome was assessed by two small studies only (31 participants, very low-certainty evidence) that considered leukopenia as a proxy or risk factor for infection. Neither study reported infections in any participants. AUTHORS' CONCLUSIONS: Low-certainly evidence suggests that glucocorticoids with cyclophosphamide in addition to standard care may slightly reduce mortality in hospitalised people with oral paraquat poisoning. However, we have limited confidence in this finding because of substantial heterogeneity and concerns about imprecision. Glucocorticoids with cyclophosphamide in addition to standard care may have little or no effect on mortality at three months after hospital discharge. We are uncertain whether glucocorticoid with cyclophosphamide puts patients at an increased risk of infection due to the limited evidence available for this outcome. Future research should be prospectively registered and CONSORT-compliant. Investigators should attempt to ensure an adequate sample size, screen participants for inclusion rigorously, and seek long-term follow-up of participants. Investigators may wish to research the effects of glucocorticoid in combination with other treatments.

Transfusion thresholds for guiding red blood cell transfusion.

BACKGROUND: The optimal haemoglobin threshold for use of red blood cell (RBC) transfusions in anaemic patients remains an active field of research. Blood is a scarce resource, and in some countries, transfusions are less safe than in others because of inadequate testing for viral pathogens. If a liberal transfusion policy does not improve clinical outcomes, or if it is equivalent, then adopting a more restrictive approach could be recognised as the standard of care.  OBJECTIVES: The aim of this review update was to compare 30-day mortality and other clinical outcomes for participants randomised to restrictive versus liberal red blood cell (RBC) transfusion thresholds (triggers) for all clinical conditions. The restrictive transfusion threshold uses a lower haemoglobin concentration as a threshold for transfusion (most commonly, 7.0 g/dL to 8.0 g/dL), and the liberal transfusion threshold uses a higher haemoglobin concentration as a threshold for transfusion (most commonly, 9.0 g/dL to 10.0 g/dL). SEARCH METHODS: We identified trials through updated searches: CENTRAL (2020, Issue 11), MEDLINE (1946 to November 2020), Embase (1974 to November 2020), Transfusion Evidence Library (1950 to November 2020), Web of Science Conference Proceedings Citation Index (1990 to November 2020), and trial registries (November 2020). We  checked the reference lists of other published reviews and relevant papers to identify additional trials. We were aware of one trial identified in earlier searching that was in the process of being published (in February 2021), and we were able to include it before this review was finalised. SELECTION CRITERIA: We included randomised trials of surgical or medical participants that recruited adults or children, or both. We excluded studies that focused on neonates. Eligible trials assigned intervention groups on the basis of different transfusion schedules or thresholds or 'triggers'. These thresholds would be defined by a haemoglobin (Hb) or haematocrit (Hct) concentration below which an RBC transfusion would be administered; the haemoglobin concentration remains the most commonly applied marker of the need for RBC transfusion in clinical practice. We included trials in which investigators had allocated participants to higher thresholds or more liberal transfusion strategies compared to more restrictive ones, which might include no transfusion. As in previous versions of this review, we did not exclude unregistered trials published after 2010 (as per the policy of the Cochrane Injuries Group, 2015), however, we did conduct analyses to consider the differential impact of results of trials for which prospective registration could not be confirmed.   DATA COLLECTION AND ANALYSIS: We identified trials for inclusion and extracted data using Cochrane methods. We pooled risk ratios of clinical outcomes across trials using a random-effects model. Two review authors independently extracted data and assessed risk of bias. We conducted predefined analyses by clinical subgroups. We defined participants randomly allocated to the lower transfusion threshold as being in the 'restrictive transfusion' group and those randomly allocated to the higher transfusion threshold as being in the 'liberal transfusion' group. MAIN RESULTS: A total of 48 trials, involving data from 21,433 participants (at baseline), across a range of clinical contexts (e.g. orthopaedic, cardiac, or vascular surgery; critical care; acute blood loss (including gastrointestinal bleeding); acute coronary syndrome; cancer; leukaemia; haematological malignancies), met the eligibility criteria. The haemoglobin concentration used to define the restrictive transfusion group in most trials (36) was between 7.0 g/dL and 8.0 g/dL.  Most trials included only adults; three trials focused on children. The included studies were generally at low risk of bias for key domains including allocation concealment and incomplete outcome data. Restrictive transfusion strategies reduced the risk of receiving at least one RBC transfusion by 41% across a broad range of clinical contexts (risk ratio (RR) 0.59, 95% confidence interval (CI) 0.53 to 0.66; 42 studies, 20,057 participants; high-quality evidence), with a large amount of heterogeneity between trials (I² = 96%). Overall, restrictive transfusion strategies did not increase or decrease the risk of 30-day mortality compared with liberal transfusion strategies (RR 0.99, 95% CI 0.86 to 1.15; 31 studies, 16,729 participants; I² = 30%; moderate-quality evidence) or any of the other outcomes assessed (i.e. cardiac events (low-quality evidence), myocardial infarction, stroke, thromboembolism (all high-quality evidence)). High-quality evidence shows that the liberal transfusion threshold did not affect the risk of infection (pneumonia, wound infection, or bacteraemia). Transfusion-specific reactions are uncommon and were inconsistently reported within trials. We noted less certainty in the strength of evidence to support the safety of restrictive transfusion thresholds for the following predefined clinical subgroups: myocardial infarction, vascular surgery, haematological malignancies, and chronic bone-marrow disorders. AUTHORS' CONCLUSIONS: Transfusion at a restrictive haemoglobin concentration decreased the proportion of people exposed to RBC transfusion by 41% across a broad range of clinical contexts. Across all trials, no evidence suggests that a restrictive transfusion strategy impacted 30-day mortality, mortality at other time points, or morbidity (i.e. cardiac events, myocardial infarction, stroke, pneumonia, thromboembolism, infection) compared with a liberal transfusion strategy. Despite including 17 more randomised trials (and 8846 participants), data remain insufficient to inform the safety of transfusion policies in important and selected clinical contexts, such as myocardial infarction, chronic cardiovascular disease, neurological injury or traumatic brain injury, stroke, thrombocytopenia, and cancer or haematological malignancies, including chronic bone marrow failure.  Further work is needed to improve our understanding of outcomes other than mortality. Most trials compared only two separate thresholds for haemoglobin concentration, which may not identify the actual optimal threshold for transfusion in a particular patient. Haemoglobin concentration may not be the most informative marker of the need for transfusion in individual patients with different degrees of physiological adaptation to anaemia. Notwithstanding these issues, overall findings provide good evidence that transfusions with allogeneic RBCs can be avoided in most patients with haemoglobin thresholds between the range of 7.0 g/dL and 8.0 g/dL. Some patient subgroups might benefit from RBCs to maintain higher haemoglobin concentrations; research efforts should focus on these clinical contexts.

Hypertonic saline versus other intracranial pressure-lowering agents for people with acute traumatic brain injury.

BACKGROUND: Increased intracranial pressure has been shown to be strongly associated with poor neurological outcomes and mortality for patients with acute traumatic brain injury. Currently, most efforts to treat these injuries focus on controlling the intracranial pressure. Hypertonic saline is a hyperosmolar therapy that is used in traumatic brain injury to reduce intracranial pressure. The effectiveness of hypertonic saline compared with other intracranial pressure-lowering agents in the management of acute traumatic brain injury is still debated, both in the short and the long term. OBJECTIVES: To assess the comparative efficacy and safety of hypertonic saline versus other intracranial pressure-lowering agents in the management of acute traumatic brain injury. SEARCH METHODS: We searched Cochrane Injuries' Specialised Register, CENTRAL, PubMed, Embase Classic+Embase, ISI Web of Science: Science Citation Index and Conference Proceedings Citation Index-Science, as well as trials registers, on 11 December 2019. We supplemented these searches with searches of four major Chinese databases on 19 September 2018. We also checked bibliographies, and contacted trial authors to identify additional trials. SELECTION CRITERIA: We sought to identify all randomised controlled trials (RCTs) of hypertonic saline versus other intracranial pressure-lowering agents for people with acute traumatic brain injury of any severity. We excluded cross-over trials as incompatible with assessing long-term outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results to identify potentially eligible trials and extracted data using a standard data extraction form. Outcome measures included: mortality at end of follow-up (all-cause); death or disability (as measured by the Glasgow Outcome Scale (GOS)); uncontrolled intracranial pressure (defined as failure to decrease the intracranial pressure to target and/or requiring additional intervention); and adverse events e.g. rebound phenomena; pulmonary oedema; acute renal failure during treatment). MAIN RESULTS: Six trials, involving data from 287 people, met the inclusion criteria. The majority of participants (91%) had a diagnosis of severe traumatic brain injury. We had concerns about particular domains of risk of bias in each trial, as physicians were not reliably blinded to allocation, two trials contained participants with conditions other than traumatic brain injury and in one trial, we had concerns about missing data for important outcomes. The original protocol was available for only one trial and other trials (where registered) were registered retrospectively. Meta-analysis for both the primary outcome (mortality at final follow-up) and for 'poor outcome' as per conventionally dichotomised GOS criteria, was only possible for two trials. Synthesis of long-term outcomes was inhibited by the fact that two trials ceased data collection within two hours of a single bolus dose of an intracranial pressure-lowering agent and one at discharge from the intensive care unit (ICU). Only three trials collected data after participants were released from hospital, one of which did not report mortality and reported a 'poor outcome' by GOS criteria in an unconventional way. Substantial missing data in a key trial meant that in meta-analysis we report 'best-case' and 'worst-case' estimates alongside available case analysis. In no scenario did we discern a clear difference between treatments for either mortality or poor neurological outcome. Due to variation in modes of drug administration (including whether it followed or did not follow cerebrospinal fluid (CSF) drainage, as well as different follow-up times and ways of reporting changes in intracranial pressure, as well as no uniform definition of 'uncontrolled intracranial pressure', we did not perform meta-analysis for this outcome and report results narratively, by individual trial. Trials tended to report both treatments to be effective in reducing elevated intracranial pressure but that hypertonic saline had increased benefits, usually adding that pretreatment factors need to be considered (e.g. serum sodium and both system and brain haemodynamics). No trial provided data for our other outcomes of interest. We consider evidence quality for all outcomes to be very low, as assessed by GRADE; we downgraded all conclusions due to imprecision (small sample size), indirectness (due to choice of measurement and/or selection of participants without traumatic brain injury), and in some cases, risk of bias and inconsistency. Only one of the included trials reported data on adverse effects; a rebound phenomenon, which was present only in the comparator group (mannitol). None of the trials reported data on pulmonary oedema or acute renal failure during treatment. On the whole, trial authors do not seem to have rigorously sought to collect data on adverse events. AUTHORS' CONCLUSIONS: This review set out to find trials comparing hypertonic saline to a potential range of other intracranial pressure-lowering agents, but only identified trials comparing it with mannitol or mannitol in combination with glycerol. Based on limited data, there is weak evidence to suggest that hypertonic saline is no better than mannitol in efficacy and safety in the long-term management of acute traumatic brain injury. Future research should be comprised of large, multi-site trials, prospectively registered, reported in accordance with current best practice. Trials should investigate issues such as the type of traumatic brain injury suffered by participants and concentration of infusion and length of time over which the infusion is given.

Decompressive craniectomy for the treatment of high intracranial pressure in closed traumatic brain injury.

BACKGROUND: High intracranial pressure (ICP) is the most frequent cause of death and disability after severe traumatic brain injury (TBI). It is usually treated with general maneuvers (normothermia, sedation, etc.) and a set of first-line therapeutic measures (moderate hypocapnia, mannitol, etc.). When these measures fail, second-line therapies are initiated, which include: barbiturates, hyperventilation, moderate hypothermia, or removal of a variable amount of skull bone (secondary decompressive craniectomy). OBJECTIVES: To assess the effects of secondary decompressive craniectomy (DC) on outcomes of patients with severe TBI in whom conventional medical therapeutic measures have failed to control raised ICP. SEARCH METHODS: The most recent search was run on 8 December 2019. We searched the Cochrane Injuries Group's Specialised Register, CENTRAL (Cochrane Library), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic + Embase (OvidSP) and ISI Web of Science (SCI-EXPANDED & CPCI-S). We also searched trials registries and contacted experts. SELECTION CRITERIA: We included randomized studies assessing patients over the age of 12 months with severe TBI who either underwent DC to control ICP refractory to conventional medical treatments or received standard care. DATA COLLECTION AND ANALYSIS: We selected potentially relevant studies from the search results, and obtained study reports. Two review authors independently extracted data from included studies and assessed risk of bias. We used a random-effects model for meta-analysis. We rated the quality of the evidence according to the GRADE approach. MAIN RESULTS: We included three trials (590 participants). One single-site trial included 27 children; another multicenter trial (three countries) recruited 155 adults, the third trial was conducted in 24 countries, and recruited 408 adolescents and adults. Each study compared DC combined with standard care (this could include induced barbiturate coma or cooling of the brain, or both). All trials measured outcomes up to six months after injury; one also measured outcomes at 12 and 24 months (the latter data remain unpublished). All trials were at a high risk of bias for the criterion of performance bias, as neither participants nor personnel could be blinded to these interventions. The pediatric trial was at a high risk of selection bias and stopped early; another trial was at risk of bias because of atypical inclusion criteria and a change to the primary outcome after it had started. Mortality: pooled results for three studies provided moderate quality evidence that risk of death at six months was slightly reduced with DC (RR 0.66, 95% CI 0.43 to 1.01; 3 studies, 571 participants; I2 = 38%; moderate-quality evidence), and one study also showed a clear reduction in risk of death at 12 months (RR 0.59, 95% CI 0.45 to 0.76; 1 study, 373 participants; high-quality evidence). Neurological outcome: conscious of controversy around the traditional dichotomization of the Glasgow Outcome Scale (GOS) scale, we chose to present results in three ways, in order to contextualize factors relevant to clinical/patient decision-making. First, we present results of death in combination with vegetative status, versus other outcomes. Two studies reported results at six months for 544 participants. One employed a lower ICP threshold than the other studies, and showed an increase in the risk of death/vegetative state for the DC group. The other study used a more conventional ICP threshold, and results favoured the DC group (15.7% absolute risk reduction (ARR) (95% CI 6% to 25%). The number needed to treat for one beneficial outcome (NNTB) (i.e. to avoid death or vegetative status) was seven. The pooled result for DC compared with standard care showed no clear benefit for either group (RR 0.99, 95% CI 0.46 to 2.13; 2 studies, 544 participants; I2 = 86%; low-quality evidence). One study reported data for this outcome at 12 months, when the risk for death or vegetative state was clearly reduced by DC compared with medical treatment (RR 0.68, 95% CI 0.54 to 0.86; 1 study, 373 participants; high-quality evidence). Second, we assessed the risk of an 'unfavorable outcome' evaluated on a non-traditional dichotomized GOS-Extended scale (GOS-E), that is, grouping the category 'upper severe disability' into the 'good outcome' grouping. Data were available for two studies (n = 571). Pooling indicated little difference between DC and standard care regarding the risk of an unfavorable outcome at six months following injury (RR 1.06, 95% CI 0.69 to 1.63; 544 participants); heterogeneity was high, with an I2 value of 82%. One trial reported data at 12 months and indicated a clear benefit of DC (RR 0.81, 95% CI 0.69 to 0.95; 373 participants). Third, we assessed the risk of an 'unfavorable outcome' using the (traditional) dichotomized GOS/GOS-E cutoff into 'favorable' versus 'unfavorable' results. There was little difference between DC and standard care at six months (RR 1.00, 95% CI 0.71 to 1.40; 3 studies, 571 participants; low-quality evidence), and heterogeneity was high (I2 = 78%). At 12 months one trial suggested a similar finding (RR 0.95, 95% CI 0.83 to 1.09; 1 study, 373 participants; high-quality evidence). With regard to ICP reduction, pooled results for two studies provided moderate quality evidence that DC was superior to standard care for reducing ICP within 48 hours (MD -4.66 mmHg, 95% CI -6.86 to -2.45; 2 studies, 182 participants; I2 = 0%). Data from the third study were consistent with these, but could not be pooled. Data on adverse events are difficult to interpret, as mortality and complications are high, and it can be difficult to distinguish between treatment-related adverse events and the natural evolution of the condition. In general, there was low-quality evidence that surgical patients experienced a higher risk of adverse events. AUTHORS' CONCLUSIONS: Decompressive craniectomy holds promise of reduced mortality, but the effects of long-term neurological outcome remain controversial, and involve an examination of the priorities of participants and their families. Future research should focus on identifying clinical and neuroimaging characteristics to identify those patients who would survive with an acceptable quality of life; the best timing for DC; the most appropriate surgical techniques; and whether some synergistic treatments used with DC might improve patient outcomes.

Hypertonic saline versus other intracranial pressure-lowering agents for people with acute traumatic brain injury.

BACKGROUND: Increased intracranial pressure (ICP) has been shown to be strongly associated with poor neurological outcomes and mortality for patients with acute traumatic brain injury (TBI). Currently, most efforts to treat these injuries focus on controlling the ICP. Hypertonic saline (HTS) is a hyperosmolar therapy that is used in traumatic brain injury to reduce intracranial pressure. The effectiveness of HTS compared with other ICP-lowering agents in the management of acute TBI is still debated, both in the short and the long term. OBJECTIVES: To assess the comparative efficacy and safety of hypertonic saline versus other ICP-lowering agents in the management of acute TBI. SEARCH METHODS: We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, PubMed, Embase Classic+Embase (OvidSP), ISI Web of Science: Science Citation Index and Conference Proceedings Citation Index-Science, as well as trials registers, on 11 December 2019. We supplemented these searches using four major Chinese databases on 19 September 2018. We also checked bibliographies, and contacted study authors to identify additional studies. SELECTION CRITERIA: We sought to identify all randomised controlled trials (RCTs) of HTS versus other intracranial pressure-lowering agents for people with acute TBI of any severity. We excluded cross-over trials as incompatible with assessing long term outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results to identify potentially eligible trials and extracted data using a standard data extraction form. Outcome measures included: mortality at end of follow-up (all-cause); death or disability (as measured by the Glasgow Outcome Scale (GOS)); uncontrolled ICP (defined as failure to decrease the ICP to target and/or requiring additional intervention); and adverse events (AEs) (e.g. rebound phenomena; pulmonary oedema; acute renal failure during treatment). MAIN RESULTS: Six trials, involving data from 295 people, met the inclusion criteria. The majority of participants (89%) had a diagnosis of severe TBI. We had concerns about particular domains of risk of bias in each trial, as physicians were not reliably blinded to allocation, two trials contained participants with conditions other than TBI and in one trial, there were concerns about missing data for important outcomes. The original protocol was available for only one study and other trials (where registered) were registered retrospectively. Meta-analysis for both the primary outcome (mortality at final follow up) and for 'poor outcome' as per conventionally dichotomised GOS criteria, was only possible for two studies. Synthesis of long-term outcomes was inhibited by the fact that two ceased data collection within two hours of a single bolus dose of an ICP-lowering agent and one at discharge from ICU. Only three studies collected data after release from hospital. Due to variation in modes of drug administration, follow-up times, and ways of reporting changes in ICP, as well as no uniform definition of 'uncontrolled ICP', we did not perform meta-analysis for this outcome and report results narratively, by individual trial. Trials tended to report both treatments to be effective in reducing elevated ICP but that HTS had increased benefits, usually adding that pretreatment factors need to be considered (e.g. serum sodium and both system and brain hemodynamics). No trial provided data for our other outcomes of interest. Evidence for all outcomes is considered very low, as assessed by GRADE. All conclusions were downgraded due to imprecision (small sample size), indirectness (due to choice of measurement and/or selection of patients without TBI), and in some cases, risk of bias and inconsistency. Only one of the included trials reported data on adverse effects (AEs) - a rebound phenomenon, which was present only in the comparator group (mannitol). No data were reported on pulmonary oedema or acute renal failure during treatment. On the whole, investigators do not seem to have rigorously sought to collect data on AEs. AUTHORS' CONCLUSIONS: This review set out to find trials comparing HTS to a potential range of other ICP-lowering agents, but only identified trials comparing it with mannitol or mannitol in combination with glycerol. Based on limited data, there is weak evidence to suggest that HTS is no better than mannitol in efficacy and safety in the long-term management of acute TBI. Future research should be comprised of large, multi-site trials, prospectively registered, reported in accordance with current best practice. Issues such as the type of TBI suffered by participants and concentration of infusion and length of time over which the infusion is given should be investigated.

Pharmacological interventions for those who have sexually offended or are at risk of offending.

BACKGROUND: Sexual offending is a serious social problem, a public health issue, and a major challenge for social policy. Victim surveys indicate high incidence and prevalence levels and it is accepted that there is a high proportion of hidden sexual victimisation. Surveys report high levels of psychiatric morbidity in survivors of sexual offences.Biological treatments of sex offenders include antilibidinal medication, comprising hormonal drugs that have a testosterone-suppressing effect, and non-hormonal drugs that affect libido through other mechanisms. The three main classes of testosterone-suppressing drugs in current use are progestogens, antiandrogens, and gonadotropin-releasing hormone (GnRH) analogues. Medications that affect libido through other means include antipsychotics and serotonergic antidepressants (SSRIs). OBJECTIVES: To evaluate the effects of pharmacological interventions on target sexual behaviour for people who have been convicted or are at risk of sexual offending. SEARCH METHODS: We searched CENTRAL (2014, Issue 7), Ovid MEDLINE, EMBASE, and 15 other databases in July 2014. We also searched two trials registers and requested details of unidentified, unpublished, or ongoing studies from investigators and other experts. SELECTION CRITERIA: Prospective controlled trials of antilibidinal medications taken by individuals for the purpose of preventing sexual offences, where the comparator group received a placebo, no treatment, or 'standard care', including psychological treatment. DATA COLLECTION AND ANALYSIS: Pairs of authors, working independently, selected studies, extracted data, and assessed the risk of bias of included studies. We contacted study authors for additional information, including details of methods and outcome data. MAIN RESULTS: We included seven studies with a total of 138 participants, with data available for 123. Sample sizes ranged from 9 to 37. Judgements for categories of risk of bias varied: concerns were greatest regarding allocation concealment, blinding of outcome assessors, and incomplete outcome data (dropout rates in the five community-based studies ranged from 3% to 54% and results were usually analysed on a per protocol basis).Participant characteristics in the seven studies were heterogeneous, but the vast majority had convictions for sexual offences, ranging from exhibitionism to rape and child molestation.Six studies examined the effectiveness of three testosterone-suppressing drugs: cyproterone acetate (CPA), ethinyl oestradiol (EO), and medroxyprogesterone acetate (MPA); a seventh evaluated two antipsychotics (benperidol and chlorpromazine). Five studies were placebo-controlled; in two, MPA was administered as an adjunctive treatment to a psychological therapy (assertiveness training or imaginal desensitisation). Meta-analysis was not possible due to heterogeneity of interventions, comparators, study designs, and other issues. The quality of the evidence overall was poor. In addition to methodological issues, much evidence was indirect. PRIMARY OUTCOME: recividism. Two studies reported recidivism rates formally. One trial of intramuscular MPA plus imaginal desensitisation (ID) found no reports of recividism at two-year follow-up for the intervention group (n = 10 versus one relapse within the group treated by ID alone). A three-armed trial of oral MPA, alone or in combination with psychological treatment, reported a 20% rate of recidivism amongst those in the combined treatment arm (n = 15) and 50% of those in the psychological treatment only group (n = 12). Notably, all those in the 'oral MPA only' arm of this study (n = 5) dropped out immediately, despite treatment being court mandated.Two studies did not report recidivism rates as they both took place in one secure psychiatric facility from which no participant was discharged during the study, whilst another three studies did not appear directly to measure recividism but rather abnormal sexual activity alone. SECONDARY OUTCOMES: The included studies report a variety of secondary outcomes. Results suggest that the frequency of self reported deviant sexual fantasies may be reduced by testosterone-suppressing drugs, but not the deviancy itself (three studies). Where measured, hormonal levels, particularly levels of testosterone, tended to correlate with measures of sexual activity and with anxiety (two studies). One study measured anxiety formally; one study measured anger or aggression. Adverse events: Six studies provided information on adverse events. No study tested the effects of testosterone-suppressing drugs beyond six to eight months and the cross-over design of some studies may obscure matters (given the 'rebound effect' of some hormonal treatments). Considerable weight gain was reported in two trials of oral MPA and CPA. Side effects of intramuscular MPA led to discontinuation in some participants after three to five injections (the nature of these side effects was not described). Notable increases in depression and excess salivation were reported in one trial of oral MPA. The most severe side effects (extra-pyramidal movement disorders and drowsiness) were reported in a trial of antipsychotic medication for the 12 participants in the study. No deaths or suicide attempts were reported in any study. The latter is important given the association between antilibidinal hormonal medication and mood changes. AUTHORS' CONCLUSIONS: We found only seven small trials (all published more than 20 years ago) that examined the effects of a limited number of drugs. Investigators reported issues around acceptance and adherence to treatment. We found no studies of the newer drugs currently in use, particularly SSRIs or GnRH analogues. Although there were some encouraging findings in this review, their limitations do not allow firm conclusions to be drawn regarding pharmacological intervention as an effective intervention for reducing sexual offending.The tolerability, even of the testosterone-suppressing drugs, was uncertain given that all studies were small (and therefore underpowered to assess adverse effects) and of limited duration, which is not consistent with current routine clinical practice. Further research is required before it is demonstrated that their administration reduces sexual recidivism and that tolerability is maintained.It is a concern that, despite treatment being mandated in many jurisdictions, evidence for the effectiveness of pharmacological interventions is so sparse and that no RCTs appear to have been published in two decades. New studies are therefore needed and should include trials with larger sample sizes, of longer duration, evaluating newer medications, and with results stratified according to category of sexual offenders. It is important that data are collected on the characteristics of those who refuse and those who drop out, as well as those who complete treatment.

Alexander technique for chronic asthma.

BACKGROUND: 'The Alexander technique' is a taught form of physical therapy involving a series of movements designed to correct posture and bring the body into natural alignment with the object of helping it to function efficiently, and is reported to aid relaxation. Some practitioners claim benefits for those who desire greater ease and efficiency of breathing, including asthmatics. OBJECTIVES: The objective of this review was to evaluate the efficacy of the Alexander technique in people with chronic, stable asthma. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register, the Cochrane Complementary Medicine Field trials register and the bibliographies of relevant articles. The most recent search was run in June 2012. SELECTION CRITERIA: Randomised controlled trials of Alexander technique (AT) for the improvement of the symptoms of chronic, stable asthma, comparing the treatment with either another intervention or no intervention. DATA COLLECTION AND ANALYSIS: No trials were found that met the selection criteria. MAIN RESULTS: No meta-analysis could be performed. AUTHORS' CONCLUSIONS: Robust, well-designed randomised controlled trials are required in order to test claims by practitioners that AT can have a positive effect on the symptoms of chronic asthma and thereby help people with asthma to reduce medication.

Psychological interventions for adults who have sexually offended or are at risk of offending.

BACKGROUND: Sexual offending is a legal construct that overlaps, but is not entirely congruent with, clinical constructs of disorders of sexual preference. Sexual offending is both a social and a public health issue. Victim surveys illustrate high incidence and prevalence levels, and it is commonly accepted that there is considerable hidden sexual victimisation. There are significant levels of psychiatric morbidity in survivors of sexual offences.Psychological interventions are generally based on behavioural or psychodynamic theories.Behavioural interventions fall into two main groups: those based on traditional classical conditioning and/or operant learning theory and those based on cognitive behavioural approaches. Approaches may overlap. Interventions associated with traditional classical and operant learning theory are referred to as behaviour modification or behaviour therapy, and focus explicitly on changing behaviour by administering a stimulus and measuring its effect on overt behaviour. Within sex offender treatment, examples include aversion therapy, covert sensitisation or olfactory conditioning. Cognitive behavioural therapies are intended to change internal processes - thoughts, beliefs, emotions, physiological arousal - alongside changing overt behaviour, such as social skills or coping behaviours. They may involve establishing links between offenders' thoughts, feelings and actions about offending behaviour; correction of offenders' misperceptions, irrational beliefs and reasoning biases associated with their offending; teaching offenders to monitor their own thoughts, feelings and behaviours associated with offending; and promoting alternative ways of coping with deviant sexual thoughts and desires.Psychodynamic interventions share a common root in psychoanalytic theory. This posits that sexual offending arises through an imbalance of the three components of mind: the id, the ego and the superego, with sexual offenders having temperamental imbalance of a powerful id (increased sexual impulses and libido) and a weak superego (a low level of moral probation), which are also impacted by early environment.This updates a previous Cochrane review but is based on a new protocol. OBJECTIVES: To assess the effects of psychological interventions on those who have sexually offended or are at risk of offending. SEARCH METHODS: In September 2010 we searched: CENTRAL, MEDLINE, Allied and Complementary Medicine (AMED), Applied Social Sciences Index and Abstracts (ASSIA), Biosis Previews, CINAHL, COPAC, Dissertation Abstracts, EMBASE, International Bibliography of the Social Sciences (IBSS), ISI Proceedings, Science Citation Index Expanded (SCI), Social Sciences Citation Index (SSCI), National Criminal Justice Reference Service Abstracts Database, PsycINFO, OpenSIGLE, Social Care Online, Sociological Abstracts, UK Clinical Research Network Portfolio Database and ZETOC. We contacted numerous experts in the field. SELECTION CRITERIA: Randomised trials comparing psychological intervention with standard care or another psychological therapy given to adults treated in institutional or community settings for sexual behaviours that have resulted in conviction or caution for sexual offences, or who are seeking treatment voluntarily for behaviours classified as illegal. DATA COLLECTION AND ANALYSIS: At least two authors, working independently, selected studies, extracted data and assessed the studies' risk of bias. We contacted study authors for additional information including details of methods and outcome data. MAIN RESULTS: We included ten studies involving data from 944 adults, all male.Five trials involved primarily cognitive behavioural interventions (CBT) (n = 664). Of these, four compared CBT with no treatment or wait list control, and one compared CBT with standard care. Only one study collected data on the primary outcome. The largest study (n = 484) involved the most complex intervention versus no treatment. Long-term outcome data are reported for groups in which the mean years 'at risk' in the community are similar (8.3 years for treatment (n = 259) compared to 8.4 in the control group (n = 225)). There was no difference between these groups in terms of the risk of reoffending as measured by reconviction for sexual offences (risk ratio (RR) 1.10; 95% CI 0.78 to 1.56).Four trials (n = 70) compared one behavioural programme with an alternative behavioural programme or with wait list control. No meta-analysis was possible for this comparison. For two studies (both cross-over, n = 29) no disaggregated data were available. The remaining two behavioural studies compared imaginal desensitisation with either covert sensitisation or as part of adjunctive drug therapy (n = 20 and 21, respectively). In these two studies, results for the primary outcome (being 'charged with anomalous behaviour') were encouraging, with only one new charge for the treated groups over one year in the former study, and in the latter study, only one new charge (in the drug-only group) over two years.One study compared psychodynamic intervention with probation. Results for this study (n = 231) indicate a slight trend in favour of the control group (probation) over the intervention (group therapy) in terms of sexual offending as measured by rearrest (RR 1.87; 95% CI 0.78 to 4.47) at 10-year follow-up.Data for adverse events, 'sexually anomalous urges' and for secondary outcomes thought to be 'dynamic' risk factors for reoffending, including anger and cognitive distortions, were limited. AUTHORS' CONCLUSIONS: The inescapable conclusion of this review is the need for further randomised controlled trials. While we recognise that randomisation is considered by some to be unethical or politically unacceptable (both of which are based on the faulty premise that the experimental treatment is superior to the control - this being the point of the trial to begin with), without such evidence, the area will fail to progress. Not only could this result in the continued use of ineffective (and potentially harmful) interventions, but it also means that society is lured into a false sense of security in the belief that once the individual has been treated, their risk of reoffending is reduced. Current available evidence does not support this belief. Future trials should concentrate on minimising risk of bias, maximising quality of reporting and including follow-up for a minimum of five years 'at risk' in the community.

Parent training interventions for Attention Deficit Hyperactivity Disorder (ADHD) in children aged 5 to 18 years.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterised by high levels of inattention, hyperactivity and impulsivity that are present before the age of seven years, seen in a range of situations, inconsistent with the child's developmental level and causing social or academic impairment. Parent training programmes are psychosocial interventions aimed at training parents in techniques to enable them to manage their children's challenging behaviour. OBJECTIVES: To determine whether parent training interventions are effective in reducing ADHD symptoms and associated problems in children aged between five and eigtheen years with a diagnosis of ADHD, compared to controls with no parent training intervention. SEARCH METHODS: We searched the following electronic databases (for all available years until September 2010): CENTRAL (2010, Issue 3), MEDLINE (1950 to 10 September 2010), EMBASE (1980 to 2010 Week 36), CINAHL (1937 to 13 September 2010), PsycINFO (1806 to September Week 1 2010), Dissertation Abstracts International (14 September 2010) and the metaRegister of Controlled Trials (14 September 2010). We contacted experts in the field to ask for details of unpublished or ongoing research. SELECTION CRITERIA: Randomised (including quasi-randomised) studies comparing parent training with no treatment, a waiting list or treatment as usual (adjunctive or otherwise). We included studies if ADHD was the main focus of the trial and participants were over five years old and had a clinical diagnosis of ADHD or hyperkinetic disorder that was made by a specialist using the operationalised diagnostic criteria of the DSM-III/DSM-IV or ICD-10. We only included trials that reported at least one child outcome. DATA COLLECTION AND ANALYSIS: Four authors were involved in screening abstracts and at least 2 authors looked independently at each one. We reviewed a total of 12,691 studies and assessed five as eligible for inclusion. We extracted data and assessed the risk of bias in the five included trials. Opportunities for meta-analysis were limited and most data that we have reported are based on single studies. MAIN RESULTS: We found five studies including 284 participants that met the inclusion criteria, all of which compared parent training with de facto treatment as usual (TAU). One study included a nondirective parent support group as a second control arm.  Four studies targeted children's behaviour problems and one assessed changes in parenting skills. Of the four studies targeting children's behaviour, two focused on behaviour at home and two focused on behaviour at school. The two studies focusing on behaviour at home had different findings: one found no difference between parent training and treatment as usual, whilst the other reported statistically significant results for parent training versus control. The two studies of behaviour at school also had different findings: one study found no difference between groups, whilst the other reported positive results for parent training when ADHD was not comorbid with oppositional defiant disorder. In this latter study, outcomes were better for girls and for children on medication.We assessed the risk of bias in most of the studies as unclear at best and often as high. Information on randomisation and allocation concealment did not appear in any study report. Inevitably, blinding of participants or personnel was impossible for this intervention; likewise, blinding of outcome assessors (who were most often the parents who had delivered the intervention) was impossible.We were only able to conduct meta-analysis for two outcomes: child 'externalising' behaviour (a measure of rulebreaking, oppositional behaviour or aggression) and child 'internalising' behaviour (for example, withdrawal and anxiety). Meta-analysis of three studies (n = 190) providing data on externalising behaviour produced results that fell short of statistical significance (SMD -0.32; 95% CI -0.83 to 0.18, I(2) = 60%). A meta-analysis of two studies (n = 142) for internalising behaviour gave significant results in the parent training groups (SMD -0.48; 95% CI -0.84 to -0.13, I(2) = 9%). Data from a third study likely to have contributed to this outcome were missing, and we have some concerns about selective outcome reporting bias.Individual study results for child behaviour outcomes were mixed. Positive results on an inventory of child behaviour problems were reported for one small study (n = 24) with the caveat that results were only positive when parent training was delivered to individuals and not groups. In another study (n = 62), positive effects (once results were adjusted for demographic and baseline data) were reported for the intervention group on a social skills measure.The study (n = 48) that assessed parenting skill changes compared parent training with a nondirective parent support group. Statistically significant improvements were reported for the parent training group. Two studies (n = 142) provided data on parent stress indices that were suitable for combining in a meta-analysis. The results were significant for the 'child' domain (MD -10.52; 95% CI -20.55 to -0.48) but not the 'parent' domain (MD -7.54; 95% CI -24.38 to 9.30). Results for this outcome from a small study (n = 24) suggested a long-term benefit for mothers who received the intervention at an individual level; in contrast, fathers benefited from short-term group treatment. A fourth study reported change data for within group measures of parental stress and found significant benefits in only one of the two active parent training group arms (P ≤ 0.01).No study reported data for academic achievement, adverse events or parental understanding of ADHD. AUTHORS' CONCLUSIONS: Parent training may have a positive effect on the behaviour of children with ADHD. It may also reduce parental stress and enhance parental confidence. However, the poor methodological quality of the included studies increases the risk of bias in the results. Data concerning ADHD-specific behaviour are ambiguous. For many important outcomes, including school achievement and adverse effects, data are lacking.Evidence from this review is not strong enough to form a basis for clinical practice guidelines. Future research should ensure better reporting of the study procedures and results.

Parent training interventions for attention deficit hyperactivity disorder.

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine whether parent-training interventions are effective in reducing ADHD symptoms and associated problems (e.g. disruptive behaviour disorders or child-specific impairments such as learning difficulties) in children and young people aged 5-18 with ADHD, compared to controls with no parent-training interventions.

Personal assistance for children and adolescents (0-18) with physical impairments.

BACKGROUND: There is a high and increasing prevalence of impairments among children and adolescents in the West. Many countries offer personal assistance in the form of individualised support for people living in the community by a paid assistant other than a healthcare professional for at least 20 hours per week. OBJECTIVES: To assess the effectiveness of personal assistance for children and adolescents with physical impairments, and the impacts of personal assistance on others, compared to other interventions. SEARCH STRATEGY: Electronic databases including CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC, Dissertation Abstracts International and a variety of specialist Swedish databases were searched from 1980 to June 2005; reference lists were checked; 345 experts, organisations, government bodies and charities were contacted in an attempt to locate relevant research. SELECTION CRITERIA: Children and adolescents with physical impairments (0-18 years) living in the community who require assistance to perform tasks of daily living (e.g., bathing and eating) and participate in normal activities due to permanent impairments. Controlled studies of personal assistance in which participants were prospectively assigned to study groups and in which control group outcomes were measured concurrently with intervention group outcomes were included. DATA COLLECTION AND ANALYSIS: Titles and abstracts were examined by two reviewers. 130 full papers were examined. None met the inclusion criteria. MAIN RESULTS: No eligible studies were found. AUTHORS' CONCLUSIONS: Research in this field is limited. When implementing new programmes, recipients could be randomly assigned to different forms of assistance. While advocates may support personal assistance for myriad reasons, this review demonstrates that further studies are required to determine which models of personal assistance are most effective and efficient for particular people.

Personal assistance for adults (19-64) with physical impairments.

BACKGROUND: There is a high incidence of impairments among working age adults. Many countries offer personal assistance in the form of individualised support for people living in the community by a paid assistant other than a healthcare professional for at least 20 hours per week. OBJECTIVES: To assess the effectiveness of personal assistance for adults with physical impairments, and the impacts of personal assistance on others, compared to other interventions. SEARCH STRATEGY: Electronic databases including CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC, Dissertation Abstracts International and a variety of specialist Swedish databases were searched from 1980 to June 2005; reference lists were checked; 345 experts, organisations, government bodies and charities were contacted in an attempt to locate relevant research. SELECTION CRITERIA: Adults (19-64) with physical impairments living in the community who require assistance to perform tasks of daily living (e.g., bathing and eating) and participate in normal activities due to permanent impairments. Controlled studies of personal assistance in which participants were prospectively assigned to study groups and in which control group outcomes were measured concurrently with intervention group outcomes were included. DATA COLLECTION AND ANALYSIS: Titles and abstracts were examined by two reviewers. Outcome data were extracted. Studies were assessed for the possibility of bias. Results and potential sources of bias are presented for included studies. MAIN RESULTS: One randomised controlled trial involving 817 participants compared personal assistance versus usual care was identified. Whilst personal assistance was generally preferred over other services, some people prefer other models of care. This review indicates that personal assistance may have some benefits for some recipients and may benefit caregivers. Whilst paid assistance probably substitutes for informal care and may cost government more than alternatives, the total costs to recipients and society are currently unknown. AUTHORS' CONCLUSIONS: Research in this field is limited. When implementing new programmes, recipients could be randomly assigned to different forms of assistance. While advocates may support personal assistance for myriad reasons, this review demonstrates that further studies are required to determine which models of personal assistance are most effective and efficient for particular people.

Personal assistance for children and adolescents (0-18) with both physical and intellectual impairments.

BACKGROUND: There is a high and increasing prevalence of impairments among children and adolescents in the West. Many countries offer personal assistance in the form of individualised support for people living in the community by a paid assistant other than a healthcare professional for at least 20 hours per week. OBJECTIVES: To assess the effectiveness of personal assistance for children and adolescents with both physical and intellectual impairments, and the impacts of personal assistance on others, compared to other interventions. SEARCH STRATEGY: Electronic databases including CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC, Dissertation Abstracts International and a variety of specialist Swedish databases were searched from 1980 to June 2005; reference lists were checked; 345 experts, organisations, government bodies and charities were contacted in an attempt to locate relevant research. SELECTION CRITERIA: Children and adolescents with both physical and intellectual impairments (0-18 years) living in the community who require assistance to perform tasks of daily living (e.g., bathing and eating) and participate in normal activities due to permanent impairments. Controlled studies of personal assistance in which participants were prospectively assigned to study groups and in which control group outcomes were measured concurrently with intervention group outcomes were included. DATA COLLECTION AND ANALYSIS: Titles and abstracts were examined by two reviewers. 130 full papers were examined. None met the inclusion criteria. MAIN RESULTS: No eligible studies were found. AUTHORS' CONCLUSIONS: Research in this field is limited, though one related review provides some evidence of the effectiveness of personal assistance for children and adolescents with intellectual impairments. When implementing new programmes, recipients could be randomly assigned to different forms of assistance. While advocates may support personal assistance for myriad reasons, this review demonstrates that further studies are required to determine which models of personal assistance are most effective and efficient for particular people.

Personal assistance for children and adolescents (0-18) with intellectual impairments.

BACKGROUND: There is a high and increasing prevalence of intellectual impairments among children and adolescents in the West. Many countries offer personal assistance in the form of individualised support for people living in the community by a paid assistant other than a healthcare professional for at least 20 hours per week. OBJECTIVES: To assess the effectiveness of personal assistance for children and adolescents with intellectual impairments, and the impacts of personal assistance on others, compared to other interventions. SEARCH STRATEGY: Electronic databases including CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC, Dissertation Abstracts International and a variety of specialist Swedish databases were searched from 1980 to June 2005; reference lists were checked; 345 experts, organisations, government bodies and charities were contacted in an attempt to locate relevant research. SELECTION CRITERIA: Children and adolescents with intellectual impairments (0-18 years) living in the community who require assistance to perform tasks of daily living (e.g., bathing and eating) and participate in normal activities due to permanent impairments. Controlled studies of personal assistance in which participants were prospectively assigned to study groups and in which control group outcomes were measured concurrently with intervention group outcomes were included. DATA COLLECTION AND ANALYSIS: Titles and abstracts were examined by two reviewers. Outcome data were extracted. Studies were assessed for the possibility of bias. Results and potential sources of bias are presented for included studies. MAIN RESULTS: One included study randomised 1002 participants to personal assistance or usual care. Whilst personal assistance was generally preferred over other services, some people prefer other models of care. This review indicates that personal assistance may have some benefits for some recipients and may benefit caregivers. However, near complete dependence on proxy respondents raises concerns about the validity of these results. Paid assistance probably substitutes for informal care and may cost government more than alternatives; however, the total costs to recipients and society are currently unknown. AUTHORS' CONCLUSIONS: Research in this field is limited. When implementing new programmes, recipients could be randomly assigned to different forms of assistance. While advocates may support personal assistance for myriad reasons, this review demonstrates that further studies are required to determine which models of personal assistance are most effective and efficient for particular people.