Rachelle Buchbinder

Background: Stem cells are specialised precursor cells that can replace aged or damaged cells and thereby maintain healthy tissue function. Stem cell therapy is increasingly used as a treatment for knee osteoarthritis, despite the lack of clarity around the mechanism by which stem cell therapy may slow down disease progression in osteoarthritis, and uncertainty regarding its benefits and harms. Objectives: To assess the benefits and harms of stem cell injections for people with osteoarthritis of the knee. A secondary objective is to maintain the currency of the evidence, using a living systematic review approach. Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase on 15 September 2023, unrestricted by date or language of publication. We also searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) for relevant trial protocols and ongoing trials. Selection criteria: We included randomised controlled trials (RCTs), or trials using quasi-randomised methods of participant allocation, comparing stem cell injection with placebo injection, no treatment or usual care, glucocorticoid injection, other injections, exercise, drug therapy, surgical interventions, and supplements and complementary therapies in people with knee osteoarthritis. Data collection and analysis: Two review authors selected studies for inclusion, extracted trial characteristics and outcome data, assessed risk of bias and assessed the certainty of evidence using the GRADE approach. The primary comparison was stem cell injection compared with placebo injection. The primary time point for pain, function and quality of life was three to six months, and the end of the trial period for participant-reported success, joint structure changes and adverse event outcomes. Major outcomes were pain, function, quality of life, global assessment of success, radiographic joint progression, withdrawals due to adverse events and serious adverse events. Main Results: We found 25 randomised trials (1341 participants) comparing stem cell injections with placebo injection (eight trials), no treatment or usual care (analgesia, weight loss and exercise) (two trials), glucocorticoid injection (one trial), hyaluronic acid injection (seven trials), platelet-rich plasma injections (two trials), oral acetaminophen (paracetamol) (one trial), non-steroidal anti-inflammatory drugs plus physical therapy plus hyaluronic acid injection (one trial) and stem cell injection plus intra-articular co-intervention versus co-intervention alone (three trials) in people with osteoarthritis of the knee. Trials were predominantly small, with sample sizes ranging from 6 to 252 participants, with only two trials having more than 100 participants. The average age of participants across trials ranged from 51 to 66 years, and symptom duration varied from one to 10 years. Placebo-controlled trials were largely free from bias, while most trials without a placebo control were susceptible to performance and detection biases. Here, we limit reporting to the main comparison, stem cell injection versus placebo injection. Compared with placebo injection, stem cell injection may slightly improve pain and function up to six months after treatment. Mean pain (0 to 10 scale, 0 no pain) was 4.5 out of 10 points with placebo injection and 1.2 points better (2.5 points better to 0 points better) with stem cell injection (I2 = 80%; 7 studies, 445 participants). Mean function (0 to 100 scale, 0 best function) was 46.3 points with placebo injection and 14.2 points better (25.3 points better to 3.1 points better) with stem cell injection (I2 = 82%; 7 studies, 432 participants). We are uncertain whether stem cell injections improve quality of life or increase the number of people who report treatment success compared to placebo injection, because the certainty of the evidence was very low. Mean quality of life was 45.3 points with placebo injection and 22.8 points better (18.0 points worse to 63.7 points better) with stem cell injection (I2 = 96%; 2 studies, 288 participants) at up to six months follow-up. At the end of follow-up, 89/168 participants (530 per 1000) in the placebo injection group reported treatment success compared with 126/180 participants (683 per 1000) in the stem cell injection group (risk ratio (RR) 1.29, 95% CI 1.10 to 1.53; I2 = 0%; 4 trials, 348 participants). We downgraded the evidence to low certainty for pain and function due to indirectness (as the source, method of preparation and dose of stem cells varied across studies), and suspected publication bias (up to three larger RCTs have been conducted but withdrawn prior to reporting of results). For quality of life and treatment success, we further downgraded the evidence to very low certainty due to imprecision in addition to indirectness and suspected publication bias. We are uncertain of the potential harms associated with stem cell injection, as there were very low event rates for serious adverse events. At the end of follow-up, 5/219 participants (23 per 1000) in the placebo injection group experienced serious adverse events compared with 4/242 participants (16 per 1000) in the stem cell injection group (RR 0.72, 95% CI 0.20 to 2.64; I2 = 0%; 7 trials, 461 participants) and there were no reported withdrawals due to adverse events. We downgraded the evidence to very low certainty due to indirectness, suspected publication bias and imprecision. Radiographic progression was not assessed in any of the included studies. Authors' Conclusions: Compared with placebo injections and based upon low-certainty evidence, stem cell injections for people with knee osteoarthritis may slightly improve pain and function. We are uncertain of the effects of stem cell injections on quality of life or the number who report treatment success. Although the putative benefits of stem cell therapies for osteoarthritis include potential regenerative effects on damaged tissues, particularly articular cartilage, we remain uncertain of the effect of stem cell injections on structural progression in the knee (measured by radiographic appearance). There is also uncertainty regarding the safety of stem cell injections. Serious adverse events were infrequently reported, although all invasive joint procedures (including injections) carry a small risk of septic arthritis. The risk of other important harms, including potential concerns related to the use of a therapy with the theoretical capacity to promote cell growth, or to the use of allogeneic cells, remains unknown.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: The primary objective is to assess the effects of implementation interventions aimed at improving the uptake of evidence-based opioid prescribing by healthcare prescribers for adults with acute non-cancer pain, compared with no intervention. The secondary objectives are. To explore whether the effects vary by intervention type (e.g. audit and feedback), target (e.g. healthcare prescribers), setting of implementation intervention (e.g. primary care), and type of pain (e.g. postsurgical pain). To summarise the availability and principal findings of eligible economic evaluations of the implementation interventions.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: The primary objective is to assess the effects of implementation interventions aimed at improving the uptake of evidence-based opioid deprescribing by healthcare professionals for adults with chronic non-cancer pain, compared with no intervention. The secondary objectives are: To explore whether the effects vary by intervention type (e.g. audit and feedback), target (e.g. healthcare organisations), setting of implementation intervention (e.g. primary care) and duration of opioid use (e.g. < 12 months, ≥ 12 months). To summarise the availability and principal findings of eligible economic evaluations of the implementation interventions.

Background: The efficacy and safety of SMS text message-delivered interventions for providing pain self-management education and improving clinical pain outcomes have been demonstrated in several randomised controlled trials. However, little is known about the feasibility and effectiveness of these interventions within Australian hospital settings. The current protocol describes a trial designed to evaluate the effectiveness and implementation of an SMS text message-delivered intervention designed to support patients' engagement with pain self-management strategies and improve clinical pain outcomes after total knee replacement surgery. Methods: A hybrid, type 1 effectiveness-implementation trial will be conducted at a private hospital in Australia. Participants (n=130) will be randomised to either the intervention group (receiving a pain self-management educational video prior to surgery, plus daily SMS text message reminders for 3 weeks after surgery) or an active control group (receiving the pre-surgery video alone, without text message reminders) in addition to usual care. Effectiveness outcomes will be pain intensity (primary), opioid dose, knee function and pain-related distress and will be recorded at baseline, 3 days, 3 weeks, 6 weeks, 3 months and 6 months after surgery using self-reported surveys. Pain self-efficacy and health-related quality of life will be measured at 6 weeks, 3 months and 6 months post-surgery. Implementation outcomes (Reach, Experience, Adoption, Implementation, Maintenance) will be evaluated using mixed (qualitative and quantitative) methods. This trial represents a first step towards the translation of digitally delivered postoperative support for engaging with pain self-management in the Australian healthcare system. Background: The study protocol was reviewed and approved by the Austin Health Human Ethics Research Committee (Australia, HREC/110142/Austin-2024). Study results will be published in a peer-reviewed journal and presented at scientific and professional meetings. Background: ACTRN12624001060538.

Nepal continues to face significant challenges with high maternal and neonatal mortality. To improve health and achieve the Sustainable Development Goals of reducing maternal and newborn mortality by 2030, Nepal needs to focus on addressing high-burden maternal and neonatal disorders. The objective of the study was to examine the current burden of maternal and neonatal disorders in Nepal and to assess any changes over time. We examined the annual Global Burden of Disease Study data on prevalence, deaths, Years Lived with Disability, and Disability-Adjusted Life Years for maternal and neonatal disorders in Nepal for the 1990-2019 period. Estimated annual percentage changes were also calculated to assess the trends of the age-standardised rates of these burden metrics. The analysis found that the prevalence of overall maternal disorder in Nepal decreased by 37% from 128,176 in 1990 to 80,724 in 2019 with Age-Standarised Ratio of 432.07 per 100,000 in 2019 and Estimated Annual Percentange Change of -4.34 (CI 95%: -4.49 to -4.18). Similarly, the overall prevalence of neonatal disorder increased by 57% from 303,146 in 1990 to 475,544 in 2019 with Age-Standarised Ratio of 1521.14 per 100,000 in 2019 and Estimated Annual Percentage Change of 0.98 (95% CI: 0.67-1.29). Our findings emphasise the need to address maternal haemorrhage, indirect maternal deaths, maternal abortion and neonatal disorders in Nepal in future national health programs.