Key Message

Evidence regarding the clinical efficacy of continuously diffused oxygen was identified in three unique randomized controlled trials and a systematic review. The key contributions to the findings of this report were from two recently published, double-blinded, placebo controlled, randomized controlled trials associated with few methodological limitations, however both observed high patient attrition. These two studies had conflicting findings which prevented evidence-based conclusions regarding clinical efficacy of continuously diffused oxygen for patients with diabetic foot ulcers. Limited evidence from these studies suggested that the patient population most likely to benefit from continuously diffused oxygen treatment of diabetic foot ulcers has yet to be defined. Two smaller unblinded randomized controlled trials, one identified in the systematic review, observed benefits of continuously derived oxygen for diabetic foot ulcers but both were associated with methodological limitations. While consensus was reached in all identified evidence that continuously diffused oxygen is safe, the best safety evidence was from patients with diabetic foot ulcers and limited comorbidities. For patients with other chronic wounds, evidence for the efficacy of continuously diffused oxygen was generally favourable however this evidence consisted of two small case series identified by the systematic review included in this report. No evidence regarding the cost-effectiveness of continuously diffused oxygen therapy was identified. Relevant guidelines from the International Working Group of the Diabetic Foot were published in 2020. The guideline development group recommended not to use topical oxygen therapy, of which continuously diffused oxygen is a subtype, as a primary or adjunctive intervention for diabetic foot ulcers. The strength of this recommendation was weak, and it rated the supporting evidence as low quality. Further studies to resolve the conflicting evidence identified in this report, and further studies on patients with chronic wounds other than diabetic foot ulcers, are required before an evidence-based assessment of the potential role for continuously diffused oxygen therapy in wound healing can be well established.

Key Message

Fourteen randomized controlled trials (RCTs) regarding the comparative clinical effectiveness of vaccines administered using a needleless injector versus a needle syringe (N-S) were identified in this review. Five RCTs were for influenza vaccine, four for inactivated polio vaccine (IPV), two for measles, mumps and rubella (MMR) vaccination, one for the diphtheria–tetanus–pertussis, hepatitis B, and hemophilus influenza type B (DTP-HB-Hib) vaccine, one for human papillomavirus vaccination (HPV) and one for Bacille Calmette-Guérin (BCG) vaccination. Four needle-free jet injectors (NFJIs) used in the included trials are PharmaJet Injector, Med-Jet H4 injector, Biojector and LectraJet injector.

For influenza vaccine: the findings observed in five RCTs indicated that influenza vaccine administered by NFJI, intradermally achieved similar immune response (e.g., seroconversion, seroprotection, antibody titer) compared with that administered by traditional N-S, intramuscularly. No evidence of a dose-sparing strategy for influenza vaccine using NFJI was identified.

For IPV vaccine: the findings reported in four RCTs showed that compared with conventional full dose IPV (i.e., 0.5 ml) given by N-S, intramuscularly, a fractional dose of IPV (i.e. 0.1 ml or 1/5 of full dose), given by NFJI, intradermally demonstrated a similar seroconversion rate (both initial and boosting response), but lower antibody titer.

The findings from two RCTs for MMR vaccination indicated that there was no statistically significant difference observed between NFJI, subcutaneously and N-S, subcutaneously in terms of immune response (e.g., seroconversion rate, antibody titer).

For DTP-HB-Hib, HPV and BCG vaccine, the immune response (e.g., seroconversion rate, or seroprotection rate/ antibody titer or T-cell [CD4/CD8] response) introduced by NFJI were also similar to that observed in the N-S group.

Regardless of the type of vaccine, or type of NFJI, numerically more unsolicited and solicited local adverse reactions (e.g., redness, swelling, induration and infiltration) were observed with NFJIs than with traditional N-S injection. However, the frequency of unsolicited and solicited systemic AEs (e.g., fever, headache, muscles aches, tiredness, nausea) were numerically lower in NFJI, intradermal injection group compared with N-S intramuscular injection group.

In conclusion, the vaccines administered by NFJI were reported to be as immunogenic as that by N-S. However, more local injection reaction, but fewer systemic adverse events associated with NFJI were also reported. Despite some limitations of the study designs, the comparative effectiveness and safety profile of vaccines (e.g., influenza, IPV or MMR) administered by NFJI and N-S were consistent regardless the type of vaccine and the type of NFJIs. Future studies assessing NFJI as a dose–sparing strategy comparing with conventional N-S are needed, especially for the influenza vaccine.

Key Message

This report summarized the evidence regarding the clinical effectiveness and cost-effectiveness of conservative management in advanced chronic kidney disease (CKD) or end stage renal disease (ESRD). Three systematic reviews, seven non-randomized studies and one economic evaluation were included in this report.Conservative care and dialysis were found to have comparable patient outcomes in elderly patients with CKD. Conservative care was associated with shorter survival and increased mortality compared to dialysis in ESRD patients. However, in the presence of severe comorbidities, no differences were found between the two. Quality of life, symptom prevalence and functional outcomes were similar in conservatively managed CKD patients and those receiving dialysis care. Conservatively managed ESRD patients reported a higher burden of kidney disease compared to dialysis although overall quality of life was not different. No evidence regarding repatriation, frailty, renal function and safety outcomes comparing CM and dialysis care were identified.Overall, the body of evidence had several limitations and biases such as differences between patients who receive dialysis and conservative care making objective comparisons between the groups less meaningful, methodological and ethical difficulties in conducting well-designed randomized studies, and potential confounding factors such as age and other comorbidities that could independently affect outcomes.Evidence regarding the cost-effectiveness of conservative management was limited, low to moderate quality and not generalizable to Canadian settings. One cost effective study conducted in Indonesia found that supportive care was the most cost-effective treatment option at willingness to pay threshold of 43 million Indonesian Rupiah.

Key Message

This rapid qualitative review analyzed 12 studies describing podiatrists’ and patients’ experiences using offloading devices. This review identified several challenges that patients face adhering to various offloading modalities. The most common challenges were mobility and autonomy, patients’ perceptions of the device effectiveness, and how offloading devices affected patients’ self-image and social interactions. First, patients cited how some offloading devices were heavy and difficult to use, which decreased their willingness to use them consistently in their daily lives. Patients also preferred not to use offloading devices in their homes because they were not designed for comfortable movement around the house. Second, patients who believed that the device provided quick ulcer healing were more likely to use offloading devices in the long-term. However, when patients’ expectations for healing were not met, their adherence to offloading decreased. Some patients were also concerned about how some devices may increase the risk of falls or cause new ulcers, particularly with devices that did not fully immobilize affected areas. Third, patients’ adherence depended on how their new self-image with the offloading device fit with family and community norms. Some patients viewed the device as a symbol of a disability that affected their social status in their communities, especially when strangers reacted negatively to the device in public. Patients needed time to reflect on how they would use the offloading device in their daily lives; adequate time enabled patients to accept a new self-image that incorporated offloading device use, thereby increasing adherence in the long-term. Patients also expressed challenges with purchasing offloading devices, particularly older patients who were on a fixed income and had to negotiate between broader self-management costs. Maintaining, repairing, and replacing offloading devices was also costly for these patients. Finally, this review found two studies examining podiatrists’ perspectives, which generally mirrored patients’ experiences and challenges using offloading devices. Podiatrists adopted two approaches to recommending offloading: an aggressive modality that was changed to a less aggressive version because of adverse outcomes, or a moderate modality that was changed to a more aggressive version because of slow healing.

Key Message

The eight relevant publications identified comprised two systematic reviews with network meta-analysis (NMA), four randomized controlled trials (RCTs) and two economic evaluations. Six publications reported on clinical efficacy (related to pain relief) of capsaicin compared to other drugs. Four publications reported on neuropathic pain (peripheral neuropathic pain [PNP] or painful diabetic neuropathy [DPN]); these comprised one systematic review with network analysis (NMA) (with comparators: pregabalin, gabapentin, and duloxetine) and three non-inferiority randomized controlled trials (with comparators: pregabalin, amitriptyline, or clonidine; one each). For neuropathic pain, similar or non-inferior efficacy was reported for capsaicin (8%) patch compared to oral drugs (pregabalin, gabapentin, and duloxetine), and capsaicin (0.75%) cream compared to topical drugs (amitriptyline and clonidine). One systematic review with NMA involving patients with pain due to osteoarthritis, reported similar efficacy with capsaicin (0.0125% or 0.025%) compared to topical non-steroidal anti-inflammatory drugs. One randomized controlled trial involving patients with acute back and neck pain suggested greater efficacy with capsaicin (0.075%) compared with diclofenac, statistical significance was not reported. Four publications reported on safety outcomes (related to adverse events). These comprised one systematic review with NMA and three RCTs (two being non-inferiority trials). Capsaicin was associated with dermatological complications (application site pain, erythema, itching, and burning sensation) whereas pregabalin, gabapentin, and duloxetine were associated with somnolence, dizziness, and nausea. There was no statistically significant difference in headache events with capsaicin compared to pregabalin, gabapentin, or duloxetine. Itching was greater with capsaicin compared to amitriptyline or clonidine; statistical significance was not reported.One cost utility analysis showed that for patients with PNP, the probability of capsaicin (8%) patch being cost-effective versus optimized dose pregabalin was 97%, at a willingness to pay threshold of £20,000 per QALY. Another cost utility analysis showed that for patients with post-herpetic neuropathy (PHN), treatment with capsaicin (8%) patch versus oral agents (tricyclic antidepressant [TCA], gabapentin, pregabalin, or duloxetine) was cost-effective at a willingness to pay threshold of US$50,000 to US$100,000.Findings need to be interpreted with caution considering the limitations, such as limited quantity of evidence, variable quality of evidence, limited number of head-to-head trials comparing capsaicin with other agents, concerns related to reliability of findings from indirect comparisons, unclear long term effects, and potential biases; and for economic evaluations, findings are dependent on the assumptions on which the evaluations were based.

Key Message

This review identified 1,342 citations and included 17 publications reporting on the results of 15 studies on people’s experiences of engaging in the diagnosis and treatment of pancreatic diseases. With a focus on pancreatic cancer, the included studies provided limited information about those with suspected or diagnosed acute or chronic pancreatitis. Additionally, the included studies provided limited information on diagnostic testing and decision-making. The key findings from this review are: Many who were investigated for suspected pancreatic cancer became aware of their symptoms over time, seeking medical care once their symptoms worsened and they could no longer explain them or self-manage them. People with a familial risk of pancreatic cancer saw engaging in surveillance as a way of ‘doing something’ to prevent cancer. Some questioned the tests and the usefulness of their results, and all found waiting for results a time fraught with worry. Receiving a diagnosis of pancreatic cancer was often a shock and emotionally charged. For those diagnosed with acute pancreatitis, a formal diagnosis was found to be comforting and helped them self-manage their condition. People who had received diagnosis of pancreatic cancer placed their trust in and deferred to their physician’s treatment recommendations. People with a diagnosis of pancreatic cancer found it important to continually find ways to be optimistic and have hope in light of their prognosis. In the face of a poor prognosis of pancreatic cancer, people had varying views on when and how to decide to stop active treatment. Once discharged from care, people were left feeling that they were no longer supported.

Key Message

Transgender youth and adults faced numerous obstacles when seeking gender affirming care. Their journey required self-advocacy, and they often encountered stigma and discrimination. There was no evidence that the decision to undergo hormone replacement therapy was a shared decision between patients and providers. Transgender youth developed an understanding of the transgender experience through their own research. Primary care physicians often lacked knowledge about hormone replacement therapy and would sometimes refer patients elsewhere. This treatment delay could result in increased levels of anxiety and suicidality. Participants described educating their primary care physicians by providing them with resources or information about continuing education. Participants noted that it can be difficult to access gender affirming care because the assessment criteria for gender dysphoria are highly subjective. Some individuals described efforts to present in a way that is consistent with the assessment criteria. Individuals with complex mental health problems, or those with financial insecurity, faced particular barriers to care, as clinicians could make the decision that they were not ready to transition. Non-binary individuals also face unique challenges because their needs regarding hormone therapy and surgeries are not consistent with a binary narrative. In general, participants expressed a preference for having primary care physicians rather than specialists provide hormone replacement therapy and surgery referrals. Primary care physicians were viewed as preferable because of their greater accessibility and because they were viewed as more able to provide holistic care that included medical, psychological and social needs.Social and environmental factors are also relevant. Participants sought supportive primary care physicians who could provide positive spaces. However, participants frequently reported experiencing discriminatory encounters in the health care setting, such as misgendering, deadnaming or being outed in the health care space, which often led to the avoidance of health care, including gender affirming care. Both clinicians and transgender patients thought that primary care physicians lack foundational knowledge regarding transgender health needs. Clinicians reported that they had received virtually no formal education regarding transgender health. Many clinicians were aware of the discrimination and stigma faced by their transgender patients. However, clinicians did not seem aware of other aspects of the health care environment that are important to transgender individuals, such as the need for privacy and sensitivities regarding the physical exam.

Key Message

Six evidence-based guidelines regarding the use of preoperative interventions for the prevention of surgical site infections were included in this report. Four included guidelines were of high quality, while two guidelines were of moderate quality due to unclear reporting of methodological details.Of these guidelines, for the purpose of infection prevention, four recommend nasal decolonization with mupirocin, body washing with chlorhexidine gluconate, and bathing with antimicrobial or non-antimicrobial soap prior to surgery. Furthermore, four guidelines recommend the use of alcohol-based solutions for skin antiseptic preparation but recommend against hair removal unless absolutely required. Three guidelines recommend mechanical bowel preparation with oral antibiotics for elective colorectal surgery, while one guideline recommends against its use with no mention of specific indications or concurrent antibiotic use. Two guidelines made recommendations on perioperative blood glucose control with different target levels. Four guidelines made recommendations on the optimal time for administering antibiotic prophylaxis (i.e., at one or two hours before incision, or at the time of anesthesia). Overall, these recommendations ranged from conditional to strong and were based on evidence that ranged in quality from very low to high (when reported).