UNASSIGNED: To summarise the findings on the effect of the clinical use of 0.1% polyhexanide-propylbetaine (PHMB/betaine) solution/gel on acute and hard-to-heal (chronic) wound healing.
UNASSIGNED: A literature search was conducted in MEDLINE, CINAHL, Embase, Scopus and the CENTRAL Trials Registry of the Cochrane Collaboration. Paired reviewers conducted title and abstract screening and full-text screening to identify experimental, quasi-experimental and observational studies. Study quality and risk of bias were not formally evaluated.
UNASSIGNED: A total of 17 studies met the eligibility criteria. The findings from 12 studies indicated that the use of 0.1% PHMB/betaine solution/gel had: a low risk of contact sensitivity; could help debridement during wound cleansing; aided effective wound bed preparation; reduced wound size, odour and exudate; improved pain control; reduced microbial load; and enhanced wound healing. The results of three studies indicated that both 0.1% PHMB and saline solution were effective in reducing bacterial load, while another showed that adding 0.1% PHMB to tie-over dressings had no effect on reducing bacterial loads in wounds. Another study concluded that disinfection and granulation of pressure ulcers with hydrobalance dressing with 0.3% PHMB was faster and more effective than using 0.1% PHMB/betaine.
UNASSIGNED: The findings of this literature review showed that 0.1% PHMB/betaine solution/gel appeared to be useful and safe for wound cleansing, was effective in removing soft debris and slough from the wound bed, and created a wound environment optimal for healing. Although these actions cannot be attributed solely to this treatment modality, these results do highlight the unique action of this combined product. However, more robust studies are needed to confirm these results.

Previous studies have reported that polyhexamethylene biguanide (PHMB) and betaine solution and gels remove biofilm, improve wound healing and reduce infection rates. Quality of life (QoL) outcomes are not commonly reported on when it comes to wound care. This review aims to summarise QoL data from a cohort of case studies previously published on chronic lower limb ulcers using PHMB products (Prontosan® Solution, Prontosan® Wound Gel X and Prontosan® Debridement Pad). Here, we report on and review a total of 38 case studies describing 56 wounds. From these 38 case studies, 36 reported that all the wounds involved had either healed or improved by the end of their respective study period. QoL themes explore malodour, slough, and exudate, pain, mobility, hair growth, antibiotic intake, return to work, social life and mood. This case series demonstrates that treatment with Prontosan® products improves many QoL outcomes for patients with non-healing wounds.

This is a comprehensive review after a thorough literature search in PubMed-indexed journals, incorporating current information on the pathophysiology, clinical features, diagnosis, medical and surgical therapy, as well as outcomes of Acanthamoeba keratitis (AK). AK is a significant cause of ocular morbidity, and early diagnosis with timely institution of appropriate therapy is the key to obtaining good outcomes. The varied presentations result in frequent misdiagnosis, and co-infections can increase the morbidity of the disease. The first line of therapy continues to be biguanides and diamidines, with surgery as a last resort.

Background: Post-operative infections are a substantial cause of morbidity and mortality worldwide. Polyhexamethylene biguanide (PHMB) is an antimicrobial agent that has been used in various surgical settings to prevent infections. However, the literature on its efficacy in reducing post-operative infections remains unclear. Materials and Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of PHMB in reducing post-operative infections. The risk of bias and methodologic quality of the included studies were also assessed. Results: The systematic review included nine RCTs, and eight were included in the meta-analysis that showed that the use of PHMB was associated with a reduction in the rate of post-operative infections. The overall effect size was statistically significant, with moderate heterogeneity across the included studies (log Peto\'s odds ratio [OR], -0.890; 95% confidence interval [CI], -1.411 to -0.369; I2 = 41.89%). However, the diversity in the application of PHMB and the potential influence of other factors, such as adherence to infection prevention protocols and organizational-level variables, underscore the need for further primary studies. Conclusions: Polyhexamethylene biguanide appears to be a promising intervention for reducing post-operative infections. However, more high-quality, well-designed RCTs are needed to confirm these findings and to explore the most effective ways to use PHMB within specific infection prevention bundles. Future research should also aim to control for potential confounding factors to provide a more comprehensive understanding of the efficacy of PHMB in reducing post-operative infections.

Diabetes medications may modify the risk of certain cancers. We systematically searched MEDLINE, Embase, Web of Science, and Cochrane CENTRAL from 2011 to March 2021 for studies evaluating associations between diabetes medications and the risk of breast, lung, colorectal, prostate, liver, and pancreatic cancers. A total of 92 studies (3 randomized controlled trials, 64 cohort studies, and 25 case-control studies) were identified in the systematic review, involving 171 million participants. Inverse relationships with colorectal (n = 18; RR = 0.85; 95% CI = 0.78-0.92) and liver cancers (n = 10; RR = 0.55; 95% CI = 0.46-0.66) were observed in biguanide users. Thiazolidinediones were associated with lower risks of breast (n = 6; RR = 0.87; 95% CI = 0.80-0.95), lung (n = 6; RR = 0.77; 95% CI = 0.61-0.96) and liver (n = 8; RR = 0.83; 95% CI = 0.72-0.95) cancers. Insulins were negatively associated with breast (n = 15; RR = 0.90; 95% CI = 0.82-0.98) and prostate cancer risks (n = 7; RR = 0.74; 95% CI = 0.56-0.98). Positive associations were found between insulin secretagogues and pancreatic cancer (n = 5; RR = 1.26; 95% CI = 1.01-1.57), and between insulins and liver (n = 7; RR = 1.74; 95% CI = 1.08-2.80) and pancreatic cancers (n = 8; RR = 2.41; 95% CI = 1.08-5.36). Overall, biguanide and thiazolidinedione use carried no risk, or potentially lower risk of some cancers, while insulin secretagogue and insulin use were associated with increased pancreatic cancer risk.

A wound offers an ideal environment for the growth and proliferation of a variety of microorganisms which, in some cases, may lead to localised or even systemic infections that can be catastrophic for the patient; the development of biofilms exacerbates these infections. Over the past few decades, there has been a progressive development of antimicrobial resistance (AMR) in microorganisms across the board in healthcare sectors. Such resistant microorganisms have arisen primarily due to the misuse and overuse of antimicrobial treatments, and the subsequent ability of microorganisms to rapidly change and mutate as a defence mechanism against treatment (e.g., antibiotics). These resistant microorganisms are now at such a level that they are of grave concern to the World Health Organization (WHO), and are one of the leading causes of illness and mortality in the 21st century. Treatment of such infections becomes imperative but presents a significant challenge for the clinician in that treatment must be effective but not add to the development of new microbes with AMR. The strategy of antimicrobial stewardship (AMS) has stemmed from the need to counteract these resistant microorganisms and requires that current antimicrobial treatments be used wisely to prevent amplification of AMR. It also requires new, improved or alternative methods of treatment that will not worsen the situation. Thus, any antimicrobial treatment should be effective while not causing further development of resistance. Some antiseptics fall into this category and, in particular, polyhexamethylene hydrochloride biguanide (PHMB) has certain characteristics that make it an ideal solution to this problem of AMR, specifically within wound care applications. PHMB is a broad-spectrum antimicrobial that kills bacteria, fungi, parasites and certain viruses with a high therapeutic index, and is widely used in clinics, homes and industry. It has been used for many years and has not been shown to cause development of resistance; it is safe (non-cytotoxic), not causing damage to newly growing wound tissue. Importantly there is substantial evidence for its effective use in wound care applications, providing a sound basis for evidence-based practice. This review presents the evidence for the use of PHMB treatments in wound care and its alignment with AMS for the prevention and treatment of wound infection.

There is increasing interest in drug therapy for preventing aneurysmal subarachnoid hemorrhage (aSAH). We aimed to comprehensively evaluate the association between drug use and the risk of aSAH. We searched PubMed and Scopus from the databases\' inception until December 2021. Observational studies reporting the association between any drug therapy and aSAH were included. The odds ratios (ORs) for each drug used in aSAH were meta-analyzed with a random-effect model. According to the systematic review, 25 observational studies were eligible for the present study. Four therapeutic purpose-based classes (e.g., lipid-lowering agents) and 14 mechanism-based classes (e.g., statins) were meta-analyzed. Anti-hypertensive agents (OR, 0.50; 95% confidence interval [95% CI], 0.33-0.74), statins (OR, 0.55; 95% CI, 0.35-0.85), biguanides (OR, 0.57; 95% CI, 0.34-0.96), and acetylsalicylic acid (ASA) (OR, 0.62; 95% CI, 0.41-0.94) were inversely associated with the risk of aSAH. Non-ASA non-steroidal anti-inflammatory drugs (OR, 1.73; 95% CI, 1.07-2.79), selective cyclooxygenase-2 inhibitors (OR, 2.04; 95% CI, 1.24-3.35), vitamin K antagonists (OR, 1.50; 95% CI, 1.18-1.91), and dipyridamole (OR, 1.77; 95% CI, 1.23-2.54) were positively associated with the incidence of aSAH. There was also a trend toward a positive association between glucocorticoids (OR, 1.38; 95% CI, 0.97-1.94) and aSAH. The present study suggests that anti-hypertensive agents, statins, biguanides, and ASA are candidate drugs for preventing aSAH. By contrast, several drugs (e.g., anti-thrombotic drugs) may increase the risk of aSAH. Thus, the indications of these drugs in patients with intracranial aneurysms should be carefully determined.

Surgical site infection (SSI) is the most common postoperative complication and substantially increases health-care costs. Published meta-analyses and international guidelines differ with regard to which preoperative skin antiseptic solution and concentration has the highest efficacy. We aimed to compare the efficacy of different skin preparation solutions and concentrations for the prevention of SSIs, and to provide an overview of current guidelines.
This systematic review and network meta-analysis compared different preoperative skin antiseptics in the prevention of SSIs in adult patients undergoing surgery of any wound classification. We searched for randomised controlled trials (RCTs) in MEDLINE, Embase, and Cochrane CENTRAL, published up to Nov 23, 2021, that directly compared two or more antiseptic agents (ie, chlorhexidine, iodine, or olanexidine) or concentrations in aqueous and alcohol-based solutions. We excluded paediatric, animal, and non-randomised studies, and studies not providing standard preoperative intravenous antibiotic prophylaxis. Studies with no SSIs in both groups were excluded from the quantitative analysis. Two reviewers screened and reviewed eligible full texts and extracted data. The primary outcome was the occurrence of SSI (ie, superficial, deep, and organ space). We conducted a frequentist random effects network meta-analysis to estimate the network effects of the skin preparation solutions on the prevention of SSIs. A risk-of-bias and Grading of Recommendations, Assessment, Development, and Evaluation assessment were done to determine the certainty of the evidence. This study is registered with PROSPERO, CRD42021293554.
Overall, 2326 articles were identified, 33 studies were eligible for the systematic review, and 27 studies with 17 735 patients reporting 2144 SSIs (overall incidence of 12·1%) were included in the quantitative analysis. Only 2·0-2·5% chlorhexidine in alcohol (relative risk 0·75, 95% CI 0·61-0·92) and 1·5% olanexidine (0·49, 0·26-0·92) significantly reduced the rate of SSIs compared with aqueous iodine. For clean surgery, we found no difference in efficacy between different concentrations of chlorhexidine in alcohol. Seven RCTs were at high risk of bias, 24 had some concerns, and two had low risk of bias. Heterogeneity across the studies was moderate (I2=27·5%), and netsplitting did not show inconsistencies between direct and indirect comparisons. Five of ten studies that mentioned adverse events related to the skin preparation solutions reported no adverse events, and five reported a total of 56 mild events (mainly erythema, pruritus, dermatitis, skin irritation, or mild allergic symptoms); none reported a substantial difference in adverse events between groups.
For adult patients undergoing a surgical procedure of any wound classification, skin preparation using either 2·0-2·5% chlorhexidine in alcohol or 1·5% olanexidine is most effective in the prevention of SSIs. For clean surgery, no specific concentration of chlorhexidine in alcohol can be recommended. The efficacy of olanexidine was established by a single randomised trial and further investigation is needed.
Dutch Association for Quality Funds Medical Specialists.

The COVID-19 pandemic is a global public health emergency and patients with diabetes mellitus (DM) are disproportionately affected, exhibiting more severe outcomes. Recent studies have shown that metformin is associated with improved outcomes in patients with COVID-19 and DM and may be a potential candidate for drug repurposing. We aimed to investigate the effects of metformin on outcomes in patients with COVID-19 and DM.
Databases (PubMed, Scopus, Web of Science, EMBASE, Clinicaltrials.gov and Cochrane library) were searched up to 10 April 2021 for studies reporting data on metformin use in COVID-19 patients with DM. The risk of bias was assessed using the Newcastle-Ottawa scale. Certainty of evidence was rated using the GRADE approach. The primary outcome was mortality reported as odds ratio (OR). A random-effects meta-analysis was carried out on both unadjusted and adjusted ORs. This study is registered with PROSPERO, CRD42020221842.
In total, 2 916 231 patients from 32 cohort studies were included in the quantitative and qualitative synthesis. The meta-analysis showed that metformin was significantly associated with lower mortality in COVID-19 patients with DM in both unadjusted (OR 0.61 [95% confidence interval: 0.53-0.71], P < .00001, I2  = 70%) and adjusted (OR 0.78 [95% confidence interval: 0.69-0.88], P < .00001, I2  = 67%) models.
Poor outcomes in COVID-19 patients with DM can be attributed to inadequate glycaemic control and weakened immune responses. Metformin has multiple effects that can improve outcomes in patients with DM and our findings highlight a possible role of its use. However, robust randomised trials are needed to thoroughly assess its use.

Maintenance of oral microbiota balance is the simplest way to prevent infectious oral diseases, through controlling dental biofilm. Combined use of mouthwash and mechanical removal has been shown to be a very effective way for this.
To identify clinical studies comparing the antimicrobial effect and possible adverse effects and/or side effects of chlorhexidine-based mouthwashes with those of mouthwashes containing chlorine dioxide and/or polyhexanide, for controlling oral microbiota.
Systematic review designed by the stomatology sector of postgraduation in applied dental sciences of Bauru Dentistry School, University of São Paulo, Brazil.
A systematic review was conducted using online databases (PubMed, Embase, Web of Science and Science Direct) up to April 8, 2020. The search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
The studies included comprised eight articles published between 2001 and 2017. A total of 295 young adults, adults and elderly people were evaluated (males 44.75% and females 55.25%). Three articles compared polyhexanide with chlorhexidine and five articles compared chlorine dioxide with chlorhexidine. No studies comparing all three mouthwashes were found. The concentrations of the study solutions were quite varied, and all rinses had an antimicrobial effect. In four studies, it was stated that no side effects or adverse effects had been found. Three studies did not address these results and only one study addressed side effects and/or adverse effects.
Mouthwashes containing chlorine dioxide and polyhexanide are viable alternatives to chlorhexidine, since they reduce oral biofilm and have little or no reported side or adverse effects.