Single-dose HPV vaccine immunity: is there a role for non-neutralizing antibodies?

A single dose of human papillomavirus (HPV) vaccine against HPV infection (prerequisite for cervical cancer) appears to be as efficacious as two or three doses, despite inducing lower antibody titers. Neutralizing antibodies are thought to be the primary mediator of protection, but the threshold for protection is unknown. Antibody functions beyond neutralization have not been explored for HPV vaccines. Here, we discuss the immune mechanisms of HPV vaccines, with a focus on non-neutralizing antibody effector functions. In the context of single-dose HPV vaccination where antibody is limiting, we propose that non-neutralizing antibody functions may contribute to preventing HPV infection. Understanding the immunological basis of protection for single-dose HPV vaccination will provide a rationale for implementing single-dose HPV vaccine regimens.

Sertaconazole 300 mg versus clotrimazole 500 mg vaginal suppository for treating pregnant women with acute vaginal candidiasis: a double-blinded, randomized trial.

BACKGROUND: Vaginal candidiasis (VC) commonly affects pregnant women. Traditionally, clotrimazole vaginal tablets (CLO) have been the cornerstone of management. However, sertaconazole ovules (SER) offer a novel topical antimycotic option. This double-blinded, randomized trial evaluated the efficacy of single-dose SER and CLO in treating acute VC during pregnancy. METHODS: From June 2020 to May 2021, this trial recruited pregnant women aged ≥ 18 years with VC symptoms (abnormal vaginal discharge and/or vulvar/vaginal itching) confirmed by microscopy. Participants with ≥ 4 VC episodes in the prior year, immunocompromised status, or imidazole contraindications and those who were absent at the 2-week follow-up were excluded. Participants were randomized to receive either 300 mg SER or 500 mg CLO. Evaluations 2 weeks after the initial medication administration included clinical cure (self-reported resolution of all symptoms), microscopic cure (pseudohyphal absence), patient satisfaction, side effects, and time to clinical cure. Participants with persistent VC received weekly SER doses until delivery. Assessments of recurrence and pregnancy outcomes were done. RESULTS: The analysis included 96 participants (48 per group, mean age 27.4 ± 7.4 years, gestational age at diagnosis 22.9 ± 6.4 weeks). Without statistical significance, SER achieved a higher clinical cure rate (62.5% vs 50%, p = 0.217; a mean difference of 12.5%, 95%CI: -17.5% to 42.5%; and a rate ratio of 1.25, 95%CI: 0.71 to 2.23) and a lower microscopic cure (47.9% vs. 62.5%, p = 0.151; a mean difference of -14.6%, 95%CI: -44.3% to 15.1%; and a rate ratio of 0.77, 95%CI: 0.43 to 1.37). The two groups had comparable times to clinical cure (SER: 3.1 ± 1.8 days, CLO: 3.4 ± 2.7 days; p = 0.848) and substantial satisfaction rates (SER: 66.7%, CLO: 60.4%; p = 0.753). No side effects were reported. Of 60 participants who gave birth at Siriraj Hospital, there were no significant differences in pregnancy outcomes. Repeated SER dosing eradicated symptoms and enhanced the microscopic cure rate. Recurrence was observed in four SER and two CLO participants within 1-2 months. CONCLUSION: In the treatment of acute VC during pregnancy, 300 mg SER and 500 mg CLO exhibited comparable efficacy in terms of clinical and microscopic cure rates, satisfaction, side effects, time to clinical cure, recurrence rates, and pregnancy outcomes. TRIAL REGISTRATION: TCTR20190308004 (registration date March 8, 2019).

"Dirty Dry Eye"- A waste volume analysis from topical therapy in keratoconjunctivitis sicca.

PURPOSE: The healthcare system is responsible for around 5% of CO2 emissions globally and in Germany. So far, there are no data on the amount of waste from dry eye disease (DED) therapy in ophthalmology. The aim of this project was to evaluate the amount and type of waste from single- and multi-dose units (SDU/MDU) generated by eyedrops used to treat DED in Germany. METHODS: The net waste weight (outer/inner packaging, instruction leaflet, empty container) from factory-sealed products was determined using a precision scale. Based on prescription data from PharMaAnalyst, a database of medical prescriptions from over 70 million patients in Germany, the total annual waste volume for 2016-2021 and the net weight of a 30-day treatment were calculated. RESULTS: The total annual waste volume increased significantly (p < 0.0001) from 7.13 tons in 2016 to 20.64 tons in 2021. A 30-day treatment with MDUs (without/with filter) results in a significantly lower mean waste volume (paper: SDU 24.3 ± 18.7 g; MDU 4.8 ± 1.7 g/8.8 g ± 1.7 g; SDU/MDU p = 0.0003, with filter p = 0.0034; plastic: SDU 35.0 ± 4.0, MDU 6.6 ± 0.7 g/ 15.1 g ± 5.8 g, SDU/MDU p < 0.0001, with filter p < 0.0001). CONCLUSION: Prescription-based treatment of DED in Germany causes an increasing and substantial waste volume. The use of SDUs is considerably more resource-intensive than MDUs. Due to the large and rising number of patients suffering from DED improvements in packaging could considerably reduce the CO2 footprint of DED treatment.

Comparison between a single dose of PEG G-CSF and multiple doses of non-PEG G-CSF: a systematic review and meta-analysis from Clinical Practice Guidelines for the use of G-CSF 2022.

BACKGROUD: Granulocyte colony-stimulating factor (G-CSF) is widely used for the primary prophylaxis of febrile neutropenia (FN). Two types of G-CSF are available in Japan, namely G-CSF chemically bound to polyethylene glycol (PEG G-CSF), which provides long-lasting effects with a single dose, and non-polyethylene glycol-bound G-CSF (non-PEG G-CSF), which must be sequentially administrated for several days. METHODS: This current study investigated the utility of these treatments for the primary prophylaxis of FN through a systematic review of the literature. A detailed literature search for related studies was performed using PubMed, Ichushi-Web, and the Cochrane Library. Data were independently extracted and assessed by two reviewers. A qualitative analysis or meta-analysis was conducted to evaluate six outcomes. RESULTS: Through the first and second screenings, 23 and 18 articles were extracted for qualitative synthesis and meta-analysis, respectively. The incidence of FN was significantly lower in the PEG G-CSF group than in the non-PEG G-CSF group with a strong quality/certainty of evidence. The differences in other outcomes, such as overall survival, infection-related mortality, the duration of neutropenia (less than 500/µL), quality of life, and pain, were not apparent. CONCLUSIONS: A single dose of PEG G-CSF is strongly recommended over multiple-dose non-PEG G-CSF therapy for the primary prophylaxis of FN.

Single Intravenous Dose Dalbavancin Pathway for the Treatment of Acute Bacterial Skin and Skin Structure Infections: Considerations for Emergency Department Implementation and Cost Savings.

BACKGROUND: A pathway for the treatment of acute bacterial skin and skin structure infections (ABSSSI) with a single intravenous (IV) dose of dalbavancin was previously shown to reduce hospital admissions and shorten inpatient length of stay (LOS). OBJECTIVES: To describe pathway implementation at the emergency department (ED) and evaluate cost-effectiveness of a single-dose dalbavancin administered to ED patients who would otherwise be hospitalized to receive usual care with multidose IV antibiotics. METHODS: The dalbavancin pathway was previously implemented at 11 U.S. EDs (doi:10.1111/acem.14258). Patients with ABSSSI, without an unstable comorbidity or infection complication requiring complex management, were treated with a single dose of dalbavancin. At the emergency physicians' discretion, patients were either discharged and received outpatient follow-up or were hospitalized for continued management. A decision analytic cost-effectiveness model was developed from the U.S. healthcare's perspective to evaluate costs associated with the dalbavancin pathway compared with inpatient usual care. Costs (2021 USD) were modeled over a 14-day horizon and included ED visits, drug costs, inpatient stay, and physician visits. One-way and probabilistic sensitivity analyses examined input parameter uncertainty. RESULTS: Driven largely by the per diem inpatient cost and LOS for usual care, the dalbavancin pathway was associated with savings of $5133.20 per patient and $1211.57 per hospitalization day avoided, compared with inpatient usual care. The results remained robust in sensitivity and scenario analyses. CONCLUSION: The new single-dose dalbavancin ED pathway for ABSSSI treatment, which was previously implemented at 11 U.S. EDs, offers robust cost savings compared to inpatient usual care.

Global impact and cost-effectiveness of one-dose versus two-dose human papillomavirus vaccination schedules: a comparative modelling analysis.

BACKGROUND: To eliminate cervical cancer as a public health problem, the World Health Organization had recommended routine vaccination of adolescent girls with two doses of the human papillomavirus (HPV) vaccine before sexual initiation. However, many countries have yet to implement HPV vaccination because of financial or logistical barriers to delivering two doses outside the infant immunisation programme. METHODS: Using three independent HPV transmission models, we estimated the long-term health benefits and cost-effectiveness of one-dose versus two-dose HPV vaccination, in 188 countries, under scenarios in which one dose of the vaccine gives either a shorter duration of full protection (20 or 30 years) or lifelong protection but lower vaccine efficacy (e.g. 80%) compared to two doses. We simulated routine vaccination with the 9-valent HPV vaccine in 10-year-old girls at 80% coverage for the years 2021-2120, with a 1-year catch-up campaign up to age 14 at 80% coverage in the first year of the programme. RESULTS: Over the years 2021-2120, one-dose vaccination at 80% coverage was projected to avert 115.2 million (range of medians: 85.1-130.4) and 146.8 million (114.1-161.6) cervical cancers assuming one dose of the vaccine confers 20 and 30 years of protection, respectively. Should one dose of the vaccine provide lifelong protection at 80% vaccine efficacy, 147.8 million (140.6-169.7) cervical cancer cases could be prevented. If protection wanes after 20 years, 65 to 889 additional girls would need to be vaccinated with the second dose to prevent one cervical cancer, depending on the epidemiological profiles of the country. Across all income groups, the threshold cost for the second dose was low: from 1.59 (0.14-3.82) USD in low-income countries to 44.83 (3.75-85.64) USD in high-income countries, assuming one dose confers 30-year protection. CONCLUSIONS: Results were consistent across the three independent models and suggest that one-dose vaccination has similar health benefits to a two-dose programme while simplifying vaccine delivery, reducing costs, and alleviating vaccine supply constraints. The second dose may become cost-effective if there is a shorter duration of protection from one dose, cheaper vaccine and vaccination delivery strategies, and high burden of cervical cancer.

Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk breast cancer patients: the ABLATIVE-2 trial-a study protocol.

BACKGROUND: Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients. METHODS: The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy. DISCUSSION: This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6-8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients. TRIAL REGISTRATION: The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).

Real-life effectiveness of anti-malarial treatment regimens: what are we aiming for?

Three-day artemisinin-based combination therapy (ACT) is the current standard of care for the treatment of malaria. However, specific drug resistance associated with reduced efficacy of ACT has been observed, therefore necessitating the clinical development of new anti-malarial drugs and drug combinations. Previously, Single Encounter Radical Cure and Prophylaxis (SERCAP) has been proposed as ideal target-product-profile for any new anti-malarial drug regimen as this would improve treatment adherence besides ensuring complete cure and prevention of early reinfection. Arguably, this concept may not be ideal as it (1) necessitates administration of an excessively high dose of drug to achieve plasmodicidal plasma levels for a sufficient time span, (2) increases the risk for drug related adverse drug reactions, and (3) leaves the patient with a one-time opportunity to achieve-or not-cure by a single drug intake. Over the past years, SERCAP has led to the halt of promising drug development programmes, leading to potentially unnecessary attrition in the anti-malarial development pipeline. One proposition could be the concept of single-day multi-dose regimens as a potentially better alternative, as this allows to (1) administer a lower dose of the drug at each time-point leading to better tolerability and safety, (2) increase treatment adherence based on the intake of the anti-malarial drug within 24 h when malaria-related symptoms are still present, and (3) have more than one opportunity for adequate intake of the drug in case of early vomiting or other factors causing reduced bioavailability. In line with a recently published critical viewpoint on the concept of SERCAP, an alternative proposition is-in contrast to the current World Health Organization (WHO) treatment guidelines-to aim for less than three days, but still multiple-dose anti-malarial treatment regimens. This may help to strike the optimal balance between improving treatment adherence, maximizing treatment effectiveness, while keeping attrition of new drugs and drug regimens as low as possible.

Protocol, rationale and design of BE-PEOPLE (Bedaquiline enhanced exposure prophylaxis for LEprosy in the Comoros): a cluster randomized trial on effectiveness of rifampicin and bedaquiline as post-exposure prophylaxis of leprosy contacts.

BACKGROUND: Leprosy is an ancient infectious disease with an annual global incidence of around 200,000 over the past decade. Since 2018, the World Health Organization (WHO) recommends single-dose rifampicin as post-exposure prophylaxis (SDR-PEP) for contacts of leprosy patients. The Post ExpOsure Prophylaxis for Leprosy (PEOPLE) trial evaluated PEP with a double dose of rifampicin in Comoros and Madagascar. Preliminary results of this trial show some reduction in leprosy incidence in intervention villages but a stronger regimen may be beneficial. The objective of the current Bedaquiline Enhanced ExpOsure Prophylaxis for LEprosy trial (BE-PEOPLE) is to explore effectiveness of a combination of bedaquiline and rifampicin as PEP. METHODS: BE-PEOPLE is a cluster-randomized trial in which 44 clusters in Comoros will be randomized to two study arms. Door-to-door screening will be conducted annually during four years, leprosy patients identified will be offered standard of care treatment. Based on study arm, contacts aged five years and above and living within a 100-meter radius of an index case will either receive bedaquiline (400-800 mg) and rifampicin (150-600 mg) or only rifampicin (150-600 mg). Contacts aged two to four years will receive rifampicin only. Household contacts randomized to the bedaquiline plus rifampicin arm will receive a second dose four weeks later. Incidence rate ratios of leprosy comparing contacts who received either of the PEP regimens will be the primary outcome. We will monitor resistance to rifampicin and/or bedaquiline through molecular surveillance in all incident tuberculosis and leprosy patients nationwide. At the end of the study, we will assess anti-M. leprae PGL-I IgM seropositivity as a proxy for the population burden of M. leprae infection in 8 villages (17,000 individuals) that were surveyed earlier as part of the PEOPLE trial. DISCUSSION: The COLEP trial on PEP in Bangladesh documented a reduction of 57% in incidence of leprosy among contacts treated with SDR-PEP after two years, which led to the WHO recommendation of SDR-PEP. Preliminary results of the PEOPLE trial show a lesser reduction in incidence. The BE-PEOPLE trial will explore whether reinforcing SDR-PEP with bedaquiline increases effectiveness and more rapidly reduces the incidence of leprosy, compared to SDR-PEP alone. TRIAL REGISTRATION: NCT05597280. Protocol version 5.0 on 28 October 2022.

Single-dose replicating poxvirus vector-based RBD vaccine drives robust humoral and T cell immune response against SARS-CoV-2 infection.

The coronavirus disease 2019 (COVID-19) pandemic requires the continued development of safe, long-lasting, and efficacious vaccines for preventive responses to major outbreaks around the world, and especially in isolated and developing countries. To combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we characterize a temperature-stable vaccine candidate (TOH-Vac1) that uses a replication-competent, attenuated vaccinia virus as a vector to express a membrane-tethered spike receptor binding domain (RBD) antigen. We evaluate the effects of dose escalation and administration routes on vaccine safety, efficacy, and immunogenicity in animal models. Our vaccine induces high levels of SARS-CoV-2 neutralizing antibodies and favorable T cell responses, while maintaining an optimal safety profile in mice and cynomolgus macaques. We demonstrate robust immune responses and protective immunity against SARS-CoV-2 variants after only a single dose. Together, these findings support further development of our novel and versatile vaccine platform as an alternative or complementary approach to current vaccines.

Durable immunogenicity, adaptation to emerging variants, and low-dose efficacy of an AAV-based COVID-19 vaccine platform in macaques.

The COVID-19 pandemic continues to have devastating consequences on health and economy, even after the approval of safe and effective vaccines. Waning immunity, the emergence of variants of concern, breakthrough infections, and lack of global vaccine access and acceptance perpetuate the epidemic. Here, we demonstrate that a single injection of an adenoassociated virus (AAV)-based COVID-19 vaccine elicits at least 17-month-long neutralizing antibody responses in non-human primates at levels that were previously shown to protect from viral challenge. To improve the scalability of this durable vaccine candidate, we further optimized the vector design for greater potency at a reduced dose in mice and non-human primates. Finally, we show that the platform can be rapidly adapted to other variants of concern to robustly maintain immunogenicity and protect from challenge. In summary, we demonstrate this class of AAV can provide durable immunogenicity, provide protection at dose that is low and scalable, and be adapted readily to novel emerging vaccine antigens thus may provide a potent tool in the ongoing fight against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Formation of phosphatidylethanol and ethylglucuronide after low to moderate alcohol consumption in volunteers with a previous three-week alcohol abstinence.

AIMS: Phosphatidylethanol (PEth) is only formed when ethanol is present in blood. This direct alcohol marker has been widely discussed, including the minimum amount of ethanol being necessary to form as much PEth as to exceed the threshold of 20 ng/mL in previously PEth negative subjects. In order to corroborate hitherto existing results, a drinking study including 18 participants after a 3-week alcohol abstinence was performed. METHODS: They consumed a pre-calculated amount of ethanol to reach a blood alcohol concentration (BAC) of at least 0.6 g/kg. Blood was drawn before and periodically seven times after alcohol administration on day 1. Blood and urine were also collected the next morning. Dried blood spots (DBS) were prepared immediately from collected venous blood. BAC was determined by head space gas chromatography and the concentrations of both PEth (16:0/18:1, 16:0/18:2 and five additional homologues) and ethyl glucuronide (EtG) were analysed using liquid chromatography-tandem mass spectrometry. RESULTS: Out of 18, 5 participants had concentrations of PEth 16:0/18:1 above the threshold of 20 ng/mL, and 11 out of the 18 subjects had concentrations between 10 and 20 ng/mL. In addition, four persons had PEth 16:0/18:2 concentrations above 20 ng/mL the following morning. All test subjects tested positive for EtG in DBS (≥ 3 ng/mL) and urine (≥100 ng/mL) upon 20-21 h after alcohol administration. CONCLUSION: By combining both a lower cutoff of 10 ng/mL and the homologue PEth 16:0/18:2, the sensitivity to detect a single alcohol intake after a 3-week abstinence increases to 72.2%.

Do the change in ß-hCG values between the 0th and 4th days in tubal ectopic pregnancy treatment with a single-dose methotrexate (MTX) protocol predict the need for a second dose of MTX?

AIM: The single-dose methotrexate (MTX) regimen is effective and minimizes side effects but an additional second dose is needed in case of failure in an ectopic pregnancy (EP). We aimed to predict the additional MTX dose by evaluating the change in ß-hCG values between day 0 and day 4 in EPs with administered single-dose MTX regimen. METHOD: A total of 454 tubal EPs between 2013 and 2019 were evaluated retrospectively. Cases cured with a single dose of MTX without an additional dose were accepted as the control group, and cases under a single-dose regimen were cured by applying a second dose of MTX on the 7th day were accepted as the study group. Obstetric and demographic characteristics and the change in ß-hCG values compared in both groups. RESULTS: Age, body mass index (BMI), gravida, smoking, abdominal surgery, presence of IUDs, initial ß-hCG levels (0th day), and EP size were similar in both groups, but the presence of previous EP history was significantly higher in the study group. The change of ß-hCG from days 0 and 4 determined that a 20% increase predicts the need for a second dose of MTX with 72.4% sensitivity, and 87.8% negative predictive value (NPV). CONCLUSION: The single-dose MTX protocol is successful in 83.3% of convenient cases (as the control group), but an increase of 20% in ß-hCG between days 0 and 4 predicts the patients who need to be administered second-dose MTX, and thus, a double-dose MTX protocol will be achieved early.

Single and repeat-dose toxicity and local tolerance assessment of newly developed oil emulsion adjuvant formulations for veterinary purposes.

Adjuvants are components of vaccines that boost the intensity, duration, and breadth of the immune response. Insight into the mechanisms responsible for the immunotoxicity of both local and systemic adverse reactions following the use of adjuvants has been gained through research over the past twenty years. In the present study, single and repeated-dose toxicity and local tolerance of newly developed Water-in-Oil (W/O) and Water-in-Oil-in-Water (W/O/W) Emulsion adjuvants (Coralvac RZ 528, Coralvac RZ 506, Coralvac AT 318, Coralvac AT 318 SIS and Coralvac 252) by Coral Biotechnology Industry and Trade Incorporated Company were demonstrated after intramuscular injection in mice. In both toxicity studies, no adverse reactions such as death, general appearance, behavior, or weight loss were observed in the mice in the experimental groups. The results indicate that clinical chemistry parameters demonstrated normal function of the major organs and no irreversible damage to the mice in all adjuvant groups compared to the control group. In histopathologic investigation of single dose toxicity study, inflammation, edema, and large amounts of lipid droplets were observed on the 7th day in all experimental groups. On the 14th day, when the control group and the experimental groups were compared, it was seen that inflammation and edema had decreased considerably. Similarly, repeated dose toxicity study showed mild inflammation and edema in the control group, while quite widespread and severe inflammation, edema, and diffuse lipid droplets of varying sizes were observed in all adjuvant groups compared to the control group. These observations would be useful for the future development of oil-based adjuvants and their use in veterinary inactive vaccines.

Efficacy and safety of postoperative single-dose anticoagulant treatment in preventing venous thromboembolism after revision hip arthroplasty: a retrospective cohort study.

PURPOSE: The purpose of the study is to determine the efficacy and safety of postoperative single-dose anticoagulant treatment in preventing venous thromboembolism (VTE) after revision THA, in comparison with a multiple-dose chemoprophylaxis protocol. METHODS: We retrospectively compared 295 patients undergoing revision THA who received multiple-dose chemoprophylaxis protocol (40 mg low-molecular-weight heparin once and oral rivaroxaban for 10 days) or single-dose chemoprophylaxis protocol (40 mg low-molecular-weight heparin once) for VTE. The patients in both groups performed active lower limb exercises. Each group was further stratified into subgroups based on the aetiology of revision. The incidence of VTE, wound complications within three months, hidden blood loss (HBL), transfusion rate, and surgical drainage duration were recorded. RESULTS: The incidence rates of VTE (P = 0.870) did not differ between the two prophylaxis protocols. However, significant differences were observed in wound complications within three months (P = 0.002), HBL (P = 0.015), transfusion rate (P = 0.028). Surgical drainage duration was also shorter in the single-dose chemoprophylaxis group (P = 0.0023). In the subgroup analysis, the use of single-dose chemoprophylaxis protocol cannot significantly reduce HBL and transfusion rate after septic revision THA. The use of multiple-dose chemoprophylaxis protocol (OR = 2.89, P = 0.002) and high BMI (OR = 1.09, P = 0.037) were independent risk factors of wound complications. CONCLUSIONS: Single-dose chemoprophylaxis protocol effectively and safely prevented VTE after revision THA compared with multiple-dose chemoprophylaxis protocol. The effect in reducing HBL and postoperative transfusion rate was limited in septic revision.

Antibiotics for preventing infection at the surgical site: Single dose vs. multiple doses.

Background: Surgical site infections are common and expensive infections that can cause fatalities or poor patient outcomes. To prevent these infections, antibiotic prophylaxis is used. However, excessive antibiotic use is related to higher costs and the emergence of antimicrobial resistance. Objectives: The present meta-analysis aimed to compare the effectiveness of a single dosage versus several doses of antibiotics in preventing the development of surgical site infections. Methods: PubMed was used to find clinical trials evaluating the effectiveness of a single dosage versus several doses of antibiotics in avoiding the development of surgical site infections. The study included trials that were published between 1984 and 2022. Seventy-four clinical trials were included in the analysis. Odds ratios were used to compare groups with 95% confidence intervals. The data were displayed using OR to generate a forest plot. Review Manager (RevMan version 5.4) was used to do the meta-analysis. Results: Regarding clean operations, there were 389 surgical site infections out of 5,634 patients in a single dose group (6.90%) and 349 surgical site infections out of 5,621 patients in multiple doses group (6.21%) (OR = 1.11, lower CI = 0.95, upper CI = 1.30). Regarding clean-contaminated operations, there were 137 surgical site infections out of 2,715 patients in a single dose group (5.05%) and 137 surgical site infections out of 2,355 patients in multiple doses group (5.82%) (OR = 0.87, lower CI = 0.68, upper CI = 1.11). Regarding contaminated operations, there were 302 surgical site infections out of 3,262 patients in a single dose group (9.26%) and 276 surgical site infections out of 3,212 patients in multiple doses group (8.59%) (OR = 1.11, lower CI = 0.84, upper CI = 1.47). In general, there were 828 surgical site infections out of 11,611 patients in a single dose group (7.13%) and 762 surgical site infections out of 11,188 patients in multiple doses group (6.81%) (OR = 1.05, lower CI = 0.93, upper CI = 1.20). The difference between groups was not significant. Conclusion: The present study showed that using a single-dose antimicrobial prophylaxis was equally effective as using multiple doses of antibiotics in decreasing surgical site infections.

Stable Recombinant Invasion Plasmid Antigen C (IpaC)-Based Single Dose Nanovaccine for Shigellosis.

Shigellosis, caused by the bacteria Shigella, is the leading cause of bacterial diarrhea and the second leading cause of diarrheal death among children under the age of five. Unfortunately, Shigella strains have acquired resistance to antibiotics, and a commercial vaccine is yet to be available. We have previously demonstrated that Shigella dysenteriae serotype 1 (Sd1)-based recombinant, stabilized, "invasion plasmid antigen C" (IpaC; 42 kDa) protein can induce robust immune responses in BALB/c mice against a challenge of a high dose of heterologous Shigella when immunized via three intranasal doses of IpaC without an adjuvant. In this work, in order to reduce the frequency of dosing and increase possible patient compliance, based on our previous screening, the minimum protective dose of stabilized IpaC (20 µg) was encapsulated in biodegradable polymeric poly(lactide-co-glycolide) nanoparticles (∼370 nm) and intranasally administered in BALB/c mice in a single dose. Interestingly, a single intranasal dose of the developed vaccine particles encapsulating only 20 µg of Sd1 IpaC led to a temporal increase in the antibody production with an improved cytokine response compared to free IpaC administered three times as described in our previous report. Upon intraperitoneal challenge with a high dose of heterologous Shigella flexneri 2a (common in circulation), the immunized animals were protected from diarrhea, lethargy, and weight loss with ∼67% survival, while all the control animals died by 36 h of the challenge. Overall, the developed nanovaccine could be explored as a potential noninvasive, cross-protective, single-dose, single-antigen Shigella vaccine amenable for scale-up and eventual mass immunization.

Boosting maternal and neonatal humoral immunity following SARS-CoV-2 infection using a single messenger RNA vaccine dose.

BACKGROUND: Post-COVID-19 vaccine boosting is a potent tool in the ongoing pandemic. Relevant data regarding this approach during pregnancy are lacking, which affects vaccination policy guidance, public acceptance, and vaccine uptake during pregnancy. We aimed to investigate the dynamics of anti-SARS-CoV-2 antibody levels following SARS-CoV-2 infection during pregnancy and to characterize the effect of a single postinfection vaccine booster dose on the anti-SARS-CoV-2 antibody levels in parturients in comparison with the levels in naïve vaccinated and convalescent, nonboosted parturients. STUDY DESIGN: Serum samples prospectively collected from parturients and umbilical cords at delivery at our university-affiliated urban medical center in Jerusalem, Israel, from May to October 2021, were selected and analyzed in a case-control manner. Study groups comprised the following participants: a consecutive sample of parturients with a polymerase chain reaction-confirmed history of COVID-19 during any stage of pregnancy; and comparison groups selected according to time of exposure comprising (1) convalescent, nonboosted parturients with polymerase chain reaction-confirmed COVID-19; (2) convalescent parturients with polymerase chain reaction-confirmed COVID-19 who received a single booster dose of the BNT162b2 messenger RNA vaccine; and (3) infection-naïve, fully vaccinated parturients who received 2 doses of the BNT162b2 messenger RNA vaccine. Outcomes that were determined included maternal and umbilical cord blood anti-SARS-CoV-2 antibody levels detected at delivery, the reported side effects, and pregnancy outcomes. RESULTS: A total of 228 parturients aged 18 to 45 years were included. Of those, samples from 64 were studied to characterize the titer dynamics following COVID-19 at all stages of pregnancy. The boosting effect was determined by comparing (1) convalescent (n=54), (2) boosted convalescent (n=60), and (3) naïve, fully vaccinated (n=114) parturients. Anti-SARS-CoV-2 antibody levels detected on delivery showed a gradual and significant decline over time from infection to delivery (r=0.4371; P=.0003). Of the gravidae infected during the first trimester, 34.6% (9/26) tested negative at delivery, compared with 9.1% (3/33) of those infected during the second trimester (P=.023). Significantly higher anti-SARS-CoV-2 antibody levels were observed among boosted convalescent than among nonboosted convalescent (17.6-fold; P<.001) and naïve vaccinated parturients (3.2-fold; P<.001). Similar patterns were observed in umbilical cord blood. Side effects in convalescent gravidae resembled those in previous reports of mild symptoms following COVID-19 vaccination during pregnancy. CONCLUSION: Postinfection maternal humoral immunity wanes during pregnancy, leading to low or undetectable protective titers for a marked proportion of patients. A single boosting dose of the BNT162b2 messenger RNA vaccine induced a robust increase in protective titers for both the mother and newborn with moderate reported side effects.

Is split-dose better than single-dose? Results of Turkish Stem Cell Coordination Center (TURKOK) donors in the era of rising biosimilar G-CSF.

BACKGROUND: Turkish Stem Cell Coordination Center (TURKOK) carries out the procurement process of unrelated allogeneic hematopoietic stem cells in Turkey. This study aims to compare the efficacy of both once-daily and divided-dose G-CSF administration and the original and biosimilar G-CSF use and the frequency and severity of adverse events in TURKOK donors. METHOD: The study was conducted retrospectively with 142 healthy TURKOK donors. For PBSC mobilization, two different subcutaneous G-CSF programs were used as 10 µ/kg/day single-dose and 5 µ/kg/12 h. Neupogen (Amgen, Puerto Rico) and Tevagrastim (Teva, Kfar Saba, Israel) were used as G-CSF. All donors started apheresis on the fifth day, and all side effects were recorded during the procedure. RESULTS: Stem cell yield was similar between single-dose and divided-doses based on donor weight, favoring the split-dose based on recipient weight (P = .506 and P = .023, respectively). Both G-CSF posologies were comparable if the target CD34+ cell yield was ≥4 × 106 /kg. CD34+ cell yield was equivalent when evaluated against recipient weight, significantly favoring Tevagrastim vs Neupogen by donor weight (P = .740 and P = .021, respectively). Side effects, duration of pain, and need for analgesia favor Tevagratim over Neupogen. CONCLUSION: Split-dose may be recommended for cases where the need for large numbers of CD34+ cells to be harvested is anticipated due to significant cell yield relative to recipient weight. However, sufficient hematopoietic stem cells can be collected with both posology. Tevagrastim is non-inferiority effective to Neupogen. Side effects during administration are both low-grade and temporary.

The economic impact of the switch from single- to multi-dose PCV13 vial in Benin.

BACKGROUND: Little is known on the economic implications of multi-dose 13 valent pneumococcal conjugate vaccine (PCV13) introduction in expanded program on immunization (EPI). Based on evidence of PCV13's reduced pressure on vaccine cold chain, Benin, a third world country in West Africa, introduced the multi-dose PCV13 starting in April 2018 in its EPI program in replacement of the single-dose presentation. The objective of this study was to conduct a rapid assessment of the costs and economic impact of switching from single- to multi-dose PCV13 vial in Benin. METHODS: The data collected retrospectively between January 1 and February 16, 2019 using a quantitative questionnaire was analyzed using Excel 2010 and Stata 13. Resources consumed from April 1st to September 30th, 2017 for the single-dose PCV13 and from April 1st to September 30th, 2018 for multi-dose were analyzed. For both presentations, costs analyzed included vaccines, injections supplies, waste management, cold chain, personnel (salaries and per diems), supervision and monitoring, training, social mobilization and overheads. Moreover, additional costs incurred for the introduction of multi-dose PCV13 were also collected. Costs were estimated for each presentation of PCV13 vaccine by calculating the half-year value of recurrent and capital costs, discounted at a rate of 3% for capital items. To enable comparisons, costs pertaining to 2017 were converted to 2018 equivalent values taking inflation in US$ into account. RESULTS: The economic costs of the single-dose PCV13 exceeded that of the multi-dose: US$ 3,708,795 versus US$ 3,698,795, respectively. Three cost items, including costs of vaccines, injection supplies, and cold chain appeared to be the main drivers of the observed reduction in costs of multi-dose PCV13. Moreover, the cost per infant vaccinated was lower with the single-dose PCV13 than the multi-dose, respectively US$ 6.28 versus US$ 10.92, and costs of vaccines wasted higher for the multi-dose PCV13. CONCLUSIONS: This evaluation seemed to show that the switch from single- to multi-dose PCV13 resulted in reduced economic costs of PCV13. Vaccinating more infants together with a rigorous application of vaccine open vial policy could lead to the change being more cost-effective.