Assessing the cost-effectiveness of integrated case management of Neglected Tropical Diseases in Liberia.

BACKGROUND: In 2017, Liberia became one of the first countries in the African region to develop and implement a national strategy for integrated case management of Neglected Tropical Diseases (CM-NTDs), specifically Buruli ulcer, leprosy, lymphatic filariasis morbidities, and yaws. Implementing this plan moves the NTD program from many countries' fragmented (vertical) disease management. This study explores to what extent an integrated approach offers a cost-effective investment for national health systems. METHODS: This study is a mixed-method economic evaluation that explores the cost-effectiveness of the integrated CM-NTDs approach compared to the fragmented (vertical) disease management. Primary data were collected from two integrated intervention counties and two non-intervention counties to determine the relative cost-effectiveness of the integrated program model vs. fragmented (vertical) care. Data was sourced from the NTDs program annual budgets and financial reports for integrated CM-NTDs and Mass Drug Administration (MDA) to determine cost drivers and effectiveness. RESULTS: The total cost incurred by the integrated CM-NTD approach from 2017 to 2019 was US$ 789,856.30, with the highest percentage of costs for program staffing and motivation (41.8%), followed by operating costs (24.8%). In the two counties implementing fragmented (vertical) disease management, approximately US$ 325,000 was spent on the diagnosis of 84 persons and the treatment of twenty-four persons suffering from NTDs. While 2.5 times as much was spent in integrated counties, 9-10 times more patients were diagnosed and treated. CONCLUSIONS: The cost of a patient being diagnosed under the fragmented (vertical) implementation is five times higher than integrated CM-NTDs, and providing treatment is ten times as costly. Findings indicate that the integrated CM-NTDs strategy has achieved its primary objective of improved access to NTD services. The success of implementing an integrated CM-NTDs approach in Liberia, presented in this paper, demonstrates that NTD integration is a cost-minimizing solution.

Antimicrobial blue light: A 'Magic Bullet' for the 21st century and beyond?

Over the past decade, antimicrobial blue light (aBL) at 400 - 470 nm wavelength has demonstrated immense promise as an alternative approach for the treatment of multidrug-resistant infections. Since our last review was published in 2017, there have been numerous studies that have investigated aBL in terms of its, efficacy, safety, mechanism, and propensity for resistance development. In addition, researchers have looked at combinatorial approaches that exploit aBL and other traditional and non-traditional therapeutics. To that end, this review aims to update the findings from numerous studies that capitalize on the antimicrobial effects of aBL, with a focus on: efficacy of aBL against different microbes, identifying endogenous chromophores and targets of aBL, Resistance development to aBL, Safety of aBL against host cells, and Synergism of aBL with other agents. We will also discuss our perspective on the future of aBL.

The rationale for including osteopathic manipulative treatment in the management of infections: a hermeneutic review.

INTRODUCTION: As the prevalence of drug-resistant infections continues to outpace the development of new antibiotics, we must explore all reasonable options for enhancing the effectiveness of existing anti-infectives. The emergence of novel pathogens without initial drug treatments or vaccines, typified by the severe acute respiratory syndrome coronavirus-2 pandemic, further underscores the need for non-pharmacologic adjunctive measures for infection management. Osteopathic manipulative treatment (OMT) may represent such an adjunct. AREAS COVERED: PubMed, CINAHL, Google Scholar, Cochrane databases and relevant chapters of major osteopathic texts were searched for animal experiments, case reports, observational studies, non-randomized, and randomized trials pertaining to infection, OMT, and the complications or safety of OMT. OMT was associated with one or more of the following: decreased bacterial colony counts in lung tissue; changes in immunologic profiles manifested by significant differences dendritic cells and levels of IL-8, MCP-1, MIP-1a, and G-CSF; shorter durations of IV antibiotics; decreased length of hospitalization; decreased rates of respiratory failure and death; decreased post-surgical lengths of stay; and enhanced patient satisfaction. EXPERT OPINION: Preliminary, lower-grade evidence suggests that OMT can improve some infection-related outcomes, and is safe. The role of OMT in infection management should undergo further controlled trials without delay.

Hyperbaric Oxygen Therapy: An Effective Auxiliary Treatment Method for Large Jaw Cysts.

Background: To evaluate hyperbaric oxygen therapy (HBOT) on infection rates and repair rates during the treatment of large jaw cysts. Methods: A prospective randomized, non-blinded, controlled clinical trial included 90 patients with jaw cysts, randomly divided into three groups. Patients were treated with enucleations and bone substitute was used in the experimental and control groups. The experimental group received HBOT. The primary predictor variable was HBOT. The infection rate, repair rate, preoperative volume of the jaw cysts, age, and sex were statistically analyzed. The Fisher exact test was used to compare the infection rate and postoperative complications. The repair rate of the bone defects was analyzed using the repeated-measures analysis of variance and the least significant difference tests. The Kendall's coefficient of concordance and Kappa statistics were calculated to evaluate the consistency between the two investigators. Results: The infection rate was 3.4% in the experimental group, 14.3% in the blank group, and 32.1% in the control group (P<0.05). The repair rate in the experimental group was significantly higher than in the control and blank groups at 1, 3 and 6 months after surgery (P<0.05). Conclusion: The results showed that HBOT reduced the postoperative infection rate following the enucleation of large jaw cysts with bone substitute filling, and it also improved the bone repair rate.

Does UV Light as an Adjunct to Conventional Treatment Improve Healing and Reduce Infection in Wounds? A Systematic Review.

OBJECTIVE: To examine the effect of UV light on wound healing and infection in patients with skin ulcers or surgical incisions. Outcomes of interest included healing time, wound size and appearance, bacterial burden, and infection. DATA SOURCES: Ovid MEDLINE, Embase, Cochrane, PubMed, CINAHL, and Web of Science. STUDY SELECTION: Comparative and noncomparative clinical studies were considered, including observational cohort, retrospective, and randomized controlled studies. They addressed the research question: "Does the use of UV light as an adjunct to conventional treatment help improve healing and reduce infection in wounds?" Selection criteria included any English language study in adults who used UV light to improve wound healing and prevent or treat wound infection. DATA EXTRACTION: Authors extracted information pertaining to patient demographics, treatment protocols, and the following wound outcomes: appearance, healing time, infection, and bacterial burden. DATA SYNTHESIS: The search yielded 30,986 articles, and screening resulted in 11 studies that underwent final analysis. Of these (N = 27,833), seven (64%) demonstrated an improvement in healing outcomes with adjunctive UV therapy, and the results of four (36%) achieved statistical significance. CONCLUSIONS: There is limited research on the utility of adjunctive UV therapy to improve wound healing outcomes in humans. The majority of literature included in this review supported improved wound healing outcomes with adjuvant UV therapy. Future well-designed randomized controlled trials will be essential in further determining the benefit and utility of UV therapy in wound healing.

Development of Antimicrobial Phototreatment Tolerance: Why the Methodology Matters.

Due to rapidly growing antimicrobial resistance, there is an urgent need to develop alternative, non-antibiotic strategies. Recently, numerous light-based approaches, demonstrating killing efficacy regardless of microbial drug resistance, have gained wide attention and are considered some of the most promising antimicrobial modalities. These light-based therapies include five treatments for which high bactericidal activity was demonstrated using numerous in vitro and in vivo studies: antimicrobial blue light (aBL), antimicrobial photodynamic inactivation (aPDI), pulsed light (PL), cold atmospheric plasma (CAP), and ultraviolet (UV) light. Based on their multitarget activity leading to deleterious effects to numerous cell structures-i.e., cell envelopes, proteins, lipids, and genetic material-light-based treatments are considered to have a low risk for the development of tolerance and/or resistance. Nevertheless, the most recent studies indicate that repetitive sublethal phototreatment may provoke tolerance development, but there is no standard methodology for the proper evaluation of this phenomenon. The statement concerning the lack of development of resistance to these modalities seem to be justified; however, the most significant motivation for this review paper was to critically discuss existing dogma concerning the lack of tolerance development, indicating that its assessment is more complex and requires better terminology and methodology.

Vaccines Against Antimicrobial Resistance.

In the last century, life expectancy has increased considerably, thanks to the introduction of antibiotics, hygiene and vaccines that have contributed to the cure and prevention of many infectious diseases. The era of antimicrobial therapy started in the nineteenth century with the identification of chemical compounds with antimicrobial properties. However, immediately after the introduction of these novel drugs, microorganisms started to become resistant through different strategies. Although resistance mechanisms were already present before antibiotic introduction, their large-scale use and mis-use have increased the number of resistant microorganisms. Rapid spreading of mobile elements by horizontal gene transfer such as plasmids and integrative conjugative elements (ICE) carrying multiple resistance genes has dramatically increased the worldwide prevalence of relevant multi drug-resistant human pathogens such as Staphylococcus aureus, Neisseria gonorrhoeae, and Enterobacteriaceae. Today, antimicrobial resistance (AMR) remains one of the major global concerns to be addressed and only global efforts could help in finding a solution. In terms of magnitude the economic impact of AMR is estimated to be comparable to that of climate global change in 2030. Although antibiotics continue to be essential to treat such infections, non-antibiotic therapies will play an important role in limiting the increase of antibiotic resistant microorganisms. Among non-antibiotic strategies, vaccines and therapeutic monoclonal antibodies (mAbs) play a strategic role. In this review, we will summarize the evolution and the mechanisms of antibiotic resistance, and the impact of AMR on life expectancy and economics.

Assessment of latent infections in patients receiving biological therapies.

The use of biological (or targeted) therapies constitutes a major advance in the management of autoinflammatory and malignant diseases. However, due to the selective effect of these agents on the host's immune response, reactivation of certain pathogens that cause latent infection is to be expected. The most relevant concern is the risk of reactivation of latent tuberculosis infection (LTBI) and progression to active tuberculosis among patients treated with agents targeting tumor necrosis factor (TNF)-α. Systematic screening for LTBI at base-line with appropriate initiation of antituberculous treatment, if needed, is mandatory in this patient population as risk minimization strategy. In addition, reactivation of hepatitis B virus induced by B-cell-depleting (anti-CD20) and anti-TNF-α agents should be also prevented among HBsAg-positive patients and those with isolated anti-HBc IgG positivity (risk of "occult HBV infection"). The present review summarizes available evidence regarding the risk of reactivation of these latent infections induced by newer biological agents, as well as the recommendations included in the most recent guidelines.

Ozone therapy: a potential therapeutic adjunct for improving female reproductive health.

Ozone is emerging as a new adjunct therapeutic agent for female infertility. We here present a review of the literature, to date, pertaining to the effect of ozone therapy on tubal, ovarian, endometrial, and vaginal factors that could potentially affect female fertility. It also presents data pertaining to the relationship of ozone therapy on pelvic adhesion formation. Most data were performed on animals and very few human studies existed in the literature. Results suggested that ozone therapy could have beneficial effect on tubal occlusion, could protect from endometritis and vaginitis, might protect ovaries from ischemia and oocyte loss and finally might lead to less formation of pelvic adhesions. There is a critical need for human studies pertaining to ozone therapy, especially using safe methods of administration, such as transdermally or intravaginally, on female fertility.

Non-Nutritional Use of Human Milk Part 1: A Survey of the Use of Breast Milk as a Therapy for Mucosal Infections of Various Types in Poland.

The use of home remedies for the treatment of moderately severe ailments is a common practice in the Polish population. Currently, the topic of the potential non-nutritional properties of human milk is attracting the attention of breastfeeding mothers. This study was aimed at understanding lactating women's knowledge, attitudes, and practices of non-nutritional breast milk on mucous membranes. The study was conducted among lactating women, who filled out a questionnaire consisting of questions about their knowledge and experiences with non-nutritional use of human milk. Statistical calculations were conducted with chi-square test and c-Pearson coefficient. A total of 1187 women were acted on, whereby 768 of respondents claimed to have knowledge of the non-nutritional use of human milk on mucous membranes, whilst 404 of them claimed that they had used at least one method. Among the most frequently used methods were the treatment of rhinorrhea, lacrimal canaliculi obstruction, and conjunctivitis. A correlation between length of breastfeeding (p < 0.001) and knowledge of non-nutritional human milk usage in prophylaxis and treatment of mucous membrane inflammation was found. Breastfeeding duration (p < 0.001) and parity (p < 0.005) were correlated with the application of those methods in practice. Due to a high propensity to testing those methods, parents' education in the field of possible risks and importance of medical consultations is necessary.

[Efferent methods and hyperbaric oxygen therapy for great vessels injuries of extremities]. / Rezul'taty primeneniia éfferentnykh metodov i giperbaricheskoi oksigenatsii pri travmakh krupnykh arterii konechnostei.

AIM: To evaluate an efficacy of efferent therapy of great vessels injuries of extremities and acute limb ischemia. MATERIAL AND METHODS: There were 197 patients (main group -107, control group - 90 patients) with great vessels injuries of extremities and acute limb ischemia. The patients of the main group underwent plasmapheresis, ultraviolet irradiation of blood (UVIB) and hyperbaric oxygen (HBO) therapy. Efferent methods were used depending on the severity of acute ischemia, intoxication and infection (intoxication - plasmapheresis, ischemia - plasmapheresis + HBO, infections - UVIB, their combination - plasmapheresis + UVIB + HBO). RESULTS: Limb amputation and necrectomy were required only in 2 (1.96%) and 3 (2.8%) patients of the main group, mortality - 0.94% (n=1). In the control group these values were 16 (17.8%), 10 (11.1%) and 7 (7.8%), respectively. CONCLUSION: Efferent methods are effective in patients with traumatic vascular injuries and acute limb ischemia regarding improvement of clinical outcomes and 2-fold reduction of hospital-stay, less number of amputations and decreased mortality rate.

Incorporating Voluntary Medical Male Circumcision Into Traditional Circumcision Contexts: Experiences of a Local Consortium in Zimbabwe Collaborating With an Ethnic Group.

Employing voluntary medical male circumcision (VMMC) within traditional settings may increase patient safety and help scale up male circumcision efforts in sub-Saharan Africa. In Zimbabwe, the VaRemba are among the few ethnic groups that practice traditional male circumcision, often in suboptimal hygienic environments. ZAZIC, a local consortium, and the Zimbabwe Ministry of Health and Child Care (MoHCC) established a successful, culturally sensitive partnership with the VaRemba to provide safe, standardized male circumcision procedures and reduce adverse events (AEs) during traditional male circumcision initiation camps. The foundation for the VaRemba Camp Collaborative (VCC) was established over a 4-year period, between 2013 and 2017, with support from a wide group of stakeholders. Initially, ZAZIC supported VaRemba traditional male circumcisions by providing key commodities and transport to help ensure patient safety. Subsequently, 2 male VaRemba nurses were trained in VMMC according to national MoHCC guidelines to enable medical male circumcision within the camp. To increase awareness and uptake of VMMC at the upcoming August-September 2017 camp, ZAZIC then worked closely with a trained team of circumcised VaRemba men to create demand for VMMC. Non-VaRemba ZAZIC doctors were granted permission by VaRemba leaders to provide oversight of VMMC procedures and postoperative treatment for all moderate and severe AEs within the camp setting. Of 672 male camp residents ages 10 and older, 657 (98%) chose VMMC. Only 3 (0.5%) moderate infections occurred among VMMC clients; all were promptly treated and healed well. Although the successful collaboration required many years of investment to build trust with community leaders and members, it ultimately resulted in a successful model that paired traditional circumcision practices with modern VMMC, suggesting potential for replicability in other similar sub-Saharan African communities.

The Combined Use of Tea Polyphenols and Lactobacillus Plantarum ST8SH Bacteriocin in a Rabbit Model of Infection Following Femoral Fracture with Internal Fixation.

BACKGROUND Worldwide, the increasing use of antibiotics has resulted in antimicrobial resistance, leading to studies to find alternative antimicrobial treatments. Tea polyphenols have antibacterial properties. Bacteriocins produced by probiotic lactobacilli can inhibit Gram-positive bacteria. This study used a rabbit model of infection, following femoral fracture with internal fixation, to evaluate the efficacy of the combined use of tea polyphenols and Lactobacillus plantarum ST8SH bacteriocin. MATERIAL AND METHODS Twenty-four New Zealand White rabbits underwent femoral fracture, internal fixation, and insertion of a mini-titanium implant, and were inoculated intravenously with suspensions of Staphylococcal bacteria. Four treatment groups included group A, injected with tea polyphenols and bacteriocins (N=6); group B, injected with cefradine and bacteriocins (N=6); group C, injected with tea polyphenols and cefradine (N=6); and group D (controls), injected with saline (N=6). Blood samples were collected at 1, 6, 12, 24, and 48 hours after the injection of bacteriocins. Biofilms that formed on the mini-titanium implant were studied by fluorescence microscopy. Serum levels of level of interleukin (IL)-8, IL-6, and tumor necrosis factor-α (TNF-α) were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS The combination of tea polyphenols and bacteriocins (group A) had a significant inhibitory effect on Staphylococcus aureus (P<0.05) and significant differences in serum levels of IL-8, TNF-α, and IL-6 levels in serum (P<0.05) when compared with groups, B, C, and D. CONCLUSIONS In a rabbit model of femoral fracture with internal fixation, the combined use of tea polyphenols and Lactobacillus plantarum ST8SH bacteriocin effectively controlled Staphylococcus aureus infection.

Effect of Natural Compounds on NK Cell Activation.

Natural killer (NK) cells are lymphocytes of the innate immune system that survey the body for stressed and abnormal cells. The integration of signals that they receive through various inhibitory and activating cell surface receptors controls their activation and ability to kill target cells and produce cytokines. In this manner, phenotypically and functionally distinct subsets of NK cells help protect against microbial infections and cancer and shape the adaptive immune response. NK cells can use two different mechanisms to kill their targets, either by cytotoxic granule exocytosis or by induction of death receptor-mediated apoptosis. Death ligands belong to the tumor necrosis factor (TNF) family of ligands. Upon release in close proximity to a cell slated for killing, perforin forms pores in the cell membrane of the target cell through which granzymes and associated molecules can enter and induce apoptosis. NK cells are also involved in antibody-dependent cellular toxicity via the CD16 receptor. In addition to target recognition, NK cells can be also activated by treatment with multiple compounds with stimulatory properties. Apart from interleukins, which belong to the best characterized group of NK cell-stimulating compounds, vitamins and constituents extracted from plants also display the ability to activate NK cells. The current review characterizes several groups of NK cell-activating compounds: vitamins belonging to classes A, B, C, D, and E, polysaccharides, lectins, and a number of phytochemicals used in cancer research, exhibiting stimulatory properties when applied to NK cells. Although in most cases the exact mechanism of action is not known, constituents described in this review seem to be promising candidates for NK cell-stimulating drugs.

Management of infections in rheumatic patients receiving biological therapies. The Portuguese Society of Rheumatology recommendations.

INTRODUCTION: Infections are a major cause of morbidity and mortality in systemic inflammatory rheumatic diseases and the management of infectious complications in patients under biological therapies deserves particular attention. OBJECTIVE: Develop evidence-based recommendations for the management of infections in rheumatic patients receiving biological therapies. METHODS: A search in PubMed (until 10 November 2014) and EMBASE (until 20 December 2014) databases was performed. Patients with systemic inflammatory rheumatic diseases treated with approved biologics in whom infections occurred were included. Search results were submitted to title and abstract selection, followed by detailed review of suitable studies. Information regarding presentation of the infectious complication, its diagnosis, treatment, and outcome, as well as maintenance or discontinuation of the biological agent was extracted and subsequently pooled according to the type of infection considered. Results of literature review were presented and critically reviewed in a dedicated meeting by a multidisciplinary panel. Recommendations were then formulated using the Delphi method. Finally, the level of agreement among rheumatologists was voted using an online survey. RESULTS: Fifteen recommendations were issued. Nine general recommendations concerned the assessment of infectious risk before and while on biologics, the procedures in case of suspected infection and the management of biologics during infectious complications. Six specific recommendations were developed for respiratory, urinary, gastrointestinal, skin, osteoarticular and disseminated infections. CONCLUSION: These fifteen recommendations are intended to help rheumatologists in the management of infections in patients on biological therapy. They integrate an extensive literature review, expert opinion and inputs from Portuguese rheumatologists.

Functional training and timed nutrition intervention in infectious medical patients.

BACKGROUND/OBJECTIVES: Bed rest and decreased nutrition intake in hospitalized patients have been shown to impair the clinical course negatively, including reduced function after hospital stay. Recent reviews have shown that early physical rehabilitation for acute hospitalized old adults leads to functional benefits. The aim of our study was to assess whether it was possible to influence nutrition intake, loss of muscle function and quality of life, with an evidence-based intervention in acutely ill hospitalized infectious medical patients. SUBJECTS/METHODS: For potentially frail patients, functional training three times weekly, and an individually adjusted self-training program for use 1-2 times daily, was given by a physiotherapist. Oral nutritional supplement with 5-10 g whey protein was timed straight after training 2 times daily, and dietetic advice was provided. A historical control group was used to compare nutrition intake. Functional measures and health-related quality of life (HRQoL) were done on admission and discharge. RESULTS: The study included 59 patients in the intervention group. Historic control included 145. Energy and protein intake increased by 3053 kJ (P<0.001) and 28 g of protein (P<0.001), compared with historic controls. Functional parameters (De Mortons Mobility Index (DEMMI), Timed Up and Go and the 30-s chair test) and HRQoL improved significantly for the overall group, most remarkably in patients >70 years of age, from hospitalization to discharge. CONCLUSION: The intervention with dietician and timed oral supplement to functional training by physiotherapist in hospitalized infectious medical patients improved function as well as nutrition intake and HRQoL.