Duration Of Administration Research Articles

Cytomegalovirus infection during daratumumab therapy in patients with newly diagnosed multiple myeloma.

The introduction of daratumumab has improved treatment outcomes for multiple myeloma (MM). However, infectious complications are a concern in patients receiving daratumumab. Although some reports have explored the association between daratumumab and cytomegalovirus (CMV) infection, most of these have focused on relapsed or refractory cases, and few describe patients with newly diagnosed MM (NDMM). In this study, we retrospectively analyzed CMV infections in 53 patients with NDMM who received daratumumab as induction therapy. CMV infection was defined as CMV antigenemia positivity. The median age at treatment initiation was 71years (range, 50-82years), and 50.9% of the patients were female. The median duration of daratumumab administration was 10.0months (range, 0.3-63.8months). Nine patients developed CMV infection, and the cumulative incidence rate at six months was 18.1% (95% confidence interval: 8.9-30.1%). One patient experienced CMV retinitis and required antiviral therapy, while the remaining eight patients did not require treatment and could be managed through observation. Few cases of CMV infection during daratumumab treatment for NDMM required treatment. However, the incidence of CMV infection was not negligible, suggesting that regular monitoring for CMV is worth considering to ensure more appropriate management during daratumumab treatment.

Preventive and Therapeutic Effects of Crocetin in Rats with Heart Failure.

Gardenia is both a food and medicine plant. It is widely used for cardiovascular protection, and its main bioactive ingredient is crocetin. This study aims to observe the therapeutic effects of crocetin on chronic heart failure in rats induced by various etiologies. It further compares the efficacy differences between preventative and treatment administration, varying dosages, and treatment durations, to provide improved guidance for medication in heart failure rats and determine which categories of chronic heart failure rats might benefit most from crocetin. Chronic heart failure models induced by abdominal aorta constriction, renal hypertension, and coronary artery ligation were constructed. By examining cardiac function, blood biochemistry, and histopathology, the study assessed the preventive and therapeutic effects of crocetin on load-induced and myocardial ischemia-induced heart failure. The results showed that in all three models, both treatment and preventative administration of crocetin significantly improved chronic heart failure in rats, especially in preventative administration. The results indicate crocetin may be beneficial for improving symptoms and functional capacity in rats with heart failure. Furthermore, long-term administration was more effective than short-term administration across all three rat models, with therapeutic onset observed over 6 weeks.

Efficacy of inhaled iloprost in children with pulmonary hypertension after pediatric cardiac surgery: a case series

BackgroundThe postoperative phase of cardiac surgery in pediatric patients with congenital heart disease often involves the management of pulmonary hypertension, which can significantly affect recovery and long-term prognosis. Inhaled iloprost is a potent acute pulmonary vasodilator with a rapid onset of action and has been shown to be effective and safe in patients with pulmonary arterial hypertension, improving clinical parameters by lowering pulmonary artery pressure. In our study, we will share the results of patients with pulmonary hypertension after pediatric cardiac surgery in whom we used inhaled iloprost.ResultsA total of 9 patients who received inhaled iloprost between 2020 and 2023 were included in the retrospective study. The age of the patients ranged between 10 days and 11 months, with a mean of 207.77 days (6.92 months) ± 105.78 days (3.52 months). Five patients were male (55.55%), and four were female (44.45%). Three of the patients had trisomy 21 (33.3%) genetic mutations.ConclusionsThe limited number of case series in the literature support the potential of inhaliloprost as an effective and safe therapeutic option for the treatment of pulmonary hypertension in the pediatric population after congenital heart surgery. The findings of this study support the literature and suggest that inhaliloprost is effective. Due to the limited number of patients, further research is needed to determine the safety and efficacy of these drugs, especially to determine the dose, route, and duration of administration in intubated patients.

Calcium-based phosphate binders and bone mineral density in patients undergoing hemodialysis: a retrospective cohort study.

Calcium supplements are commonly prescribed to prevent fractures in patients with osteoporosis. Nonetheless, they are generally eschewed in hemodialysis patients because they increase vascular calcification and induce cardiovascular disease. This retrospective cohort study aimed to investigate the effect of calcium-based phosphate binders (CBPB) on bone mineral density (BMD) in hemodialysis patients. Outpatients on dialysis who underwent BMD measurement from January to December 2017, whose data on BMD trends and CBPB administration were recorded over the next 4years, were enrolled. Patients receiving anti-osteoporotic medications were excluded. The association between the presence and duration of CBPB administration and changes in BMD was evaluated. The femoral neck's BMD decreased from 0.836g/cm2 (0.702-0.952) to 0.764g/cm2 (0.636-0.896) (P < 0.001) in the non-CBPB group (patients who never received CBPB over 4years, n = 32). The CBPB group (n = 56) exhibited only a minute decrease from 0.833g/cm2 (0.736-0.965) to 0.824g/cm2 (0.706-0.939) (P = 0.004). Multivariate linear regression analysis revealed better BMD maintenance in the CBPB group [β-coefficient (95% CI): 0.033 (0.001-0.065); P = 0.046] than in the non-CBPB group. Additionally, the prolonged-CBPB administration group showed superior BMD preservation [β-coefficient (95% CI): 0.038 (0.001-0.076); P = 0.042]. CBPB administration may be associated with BMD maintenance.

BREAST CANCER ASSISTANCE JOURNEY FROM THE PERSPECTIVE OF THE PUBLIC HEALTHCARE SERVICE OF RIO GRANDE DO SUL

Objective: This study aims to characterize the breast cancer (BC) patient journey in Rio Grande do Sul (RS), Brazil, through the perspectives of the High Complexity Oncology Assistance Centers (CACONs) and High Complexity Oncology Assistance Units (UNACONs). Methods: Conducted between March and May 2023 across 17 RS Oncology public healthcare services, the cross-sectional study utilized a 54-question questionnaire administered to healthcare professionals. The survey covered various aspects, including diagnosis, treatment, funding, and multidisciplinary teamwork. Results: Descriptive analysis revealed that BC patients undergo screening tests upon treatment entry (88.2%), with immunohistochemistry commonly performed externally (64.7%) and PCR often requested (82.4%) for adjuvant therapy initiation, taking an average of 90 to 250 days for all procedures. Patients encounter challenges such as lengthy hospital stays, extensive travel to treatment centers, treatment side effects, and high transportation expenses, often leading to treatment discontinuation. The most time-consuming stage is treatment, with subcutaneous infusion proving more time-efficient than intravenous administration. Physical limitations, mobility issues, late diagnosis (90-day average), and limited access to care significantly impact patients' quality of life. Healthcare teams face difficulties with outdated guidelines, lack of intravenous treatment facilities, and extended administration durations. Institutions confront barriers like drug shortages, guideline disparities, and logistical challenges. Conclusion: The study concludes by emphasizing the identified hurdles in BC patients' public healthcare journey, underscoring the need to address delays in screening, resource constraints, and disparities in access to care based on geographical, socioeconomic, and racial/ethnic factors to enhance overall quality of care and equity within the system.

How Is the Nociceptive Withdrawal Reflex Influenced by Increasing Doses of Propofol in Pigs?

The nociceptive withdrawal reflex (NWR) is a physiological, polysynaptic spinal reflex occurring in response to noxious stimulations. Continuous NWR threshold (NWRt) tracking has been shown to be possibly useful in the depth of anesthesia assessment. The primary aim of this study was to describe how propofol modulates the NWRt over time in pigs. Five juvenile pigs (anesthetized three times) were included. An intravenous (IV) infusion of propofol (20 mg/kg/h) was started, and boli were administered to effect until intubation. Afterwards, the infusion was increased every ten minutes by 6 mg/kg/h, together with an IV bolus of 0.5 mg/kg, until reaching an electroencephalographic suppression ratio (SR) of between 10% and 30%. The NWRt was continuously monitored. For data analysis, the time span between 15 min following intubation and the end of propofol infusion was considered. Individual durations of propofol administration were divided into five equal time intervals for each pig (TI1-TI5). A linear regression between NWRt and TI was performed for each pig. Moreover, the baseline NWRt and slopes of the linear regression (b1) were compared among days using a Friedman Repeated Measures Analysis of Variance on Ranks. The NWRt always increased with the propofol dose (b1 = 4.71 ± 3.23; mean ± standard deviation). No significant differences were found between the baseline NWRt and the b1 values. Our results suggest that the NWRt may complement the depth of anesthesia assessment in pigs receiving propofol.

Rationality of antibiotic prescribing in basic- and intermediate-level accredited primary health centres in Depok, Indonesia

Background: Previous research has identified a high irrationality of antibiotic usage among accredited primary health centres (PHCs). Implementing health system accreditation in Indonesia will encourage health facilities to rationalise antibiotic use. Objective: To evaluate antibiotics' prescribing pattern and rationality in basic and intermediate accredited PHCs after implementing health system accreditation. Method: A cross-sectional study was conducted at each of two basic- and intermediate-accredited PHCs in Depok, Indonesia. All antibiotic prescriptions from January to March 2020 were included in the prescribing pattern, while 384 prescriptions from each PHC were randomly sampled to evaluate the rationality using the PHCs clinical guidelines. Result: Amoxicillin was the most prescribed in the basic accredited PHCs (61%) and intermediate accredited PHCs (83.9%). Most of the antibiotics were used to treat respiratory tract (64.1%), teeth (12.0%), skin (7.8%), and other kind of infections. Irrational prescribing of antibiotics was found in basic and intermediate health centres in the form of duration of administration (75.7% and 79.3%), selection (18.6% and 14.2%), frequency (14.4% and 3.4%), and dosage (11.8% and 1.4%) respectively. Conclusion: After implementing the accreditation system, irrational use of antibiotics remains common, but PHCs with higher accreditation levels tend to show more rational antibiotic use.

Maxillary osteonecrosis of the jaw. A multidisciplinary approach, communication strategies, and technological tools for prophylaxis

Background. Maxillary osteonecrosis, particularly medication-related osteonecrosis of the jaw (MRONJ), necessitates prompt identification and a comprehensive approach for effective management. Early diagnosis and proactive dental care are crucial in mitigating the complications associated with this condition. Aims. This study aims to outline the importance of early detection, multidisciplinary collaboration, patient education, and proactive dental care in the management of maxillary osteonecrosis. Methods. The study emphasizes the utilization of standardized medical letters to facilitate communication between prescribing physicians and dentists, while ensuring the timely exchange of essential patient information. Additionally, patient education plays a pivotal role, with the distribution of informative leaflets at the initiation of Bone Modifying Agents (BMA) treatment, emphasizing the risks associated with MRONJ and the significance of maintaining oral health and making appropriate lifestyle choices. Results. Dentists are key stakeholders in the prophylaxis of MRONJ, undertaking primary and secondary prevention measures. Primary prophylaxis encompasses various dental procedures aimed at reducing bacterial load and mucosal irritation. Secondary prophylaxis involves educating patients on maintaining optimal oral health and adopting lifestyle modifications. Furthermore, an Android application assists dentists in assessing MRONJ risk factors and making informed treatment decisions based on factors such as BMA type, dose, duration of administration, and the presence of dental and general risk factors. Conclusions. In conclusion, a proactive approach to managing Maxillary Osteonecrosis involves early detection, multidisciplinary collaboration, patient education, and proactive dental care. By integrating standardized communication tools, patient education materials, and risk assessment technology, healthcare providers can optimize patient outcomes and minimize the incidence and severity of MRONJ complications.

Effect of vibratory device on the time of administration of vaccines and on patient satisfaction measures.

Previous studies have demonstrated that Buzzy® is effective for pain reduction during vaccination. This study aimed to determine if Buzzy® would have an effect on either duration of vaccine administration and/or patient satisfaction. Pediatric patients aged birth to 18 years old receiving a vaccination were randomized to either a control group receiving no intervention, or the experimental group, utilizing Buzzy®. Time of administration was measured by the number of seconds required by nursing to administer vaccines. Patient satisfaction was measured with a survey given to guardians. Time required was reduced by almost 2 min when utilizing Buzzy®, with median time dropping to 190, 95% CI [26.99, 415.92] seconds from 333, 95% CI [51.35, 627.21] seconds. Patient satisfaction surveys showed positive impacts of using the device, with 100% that used the device reporting that it "made a difference in the pain level experienced," but did not demonstrate statistical significance. This study shows that use of Buzzy® increases efficiency of appointments with possible positive effect on patient satisfaction.

Inhaled nitric oxide and postoperative outcomes in cardiac surgery with cardiopulmonary bypass: A systematic review and meta-analysis

Cardiac surgeries under cardiopulmonary bypass (CPB) are complex procedures with high incidence of complications, morbidity and mortality. The inhaled nitric oxide (iNO) has been frequently used as an important composite of perioperative management during cardiac surgery under CPB. We conducted a meta-analysis of published randomized clinical trials (RCTs) to assess the effects of iNO on reducing postoperative complications, including the duration of postoperative mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay, mortality, hemodynamic improvement (the composite right ventricular failure, low cardiac output syndrome, pulmonary arterial pressure, and vasoactive inotropic score) and myocardial injury biomarker (postoperative troponin I levels). Subgroup analyses were performed to assess the effect of modification and interaction. These included iNO dosage, the timing and duration of iNO therapy, different populations (children and adults), and comparators (other vasodilators and placebo or standard care). A comprehensive search for iNO and cardiac surgery was performed on online databases. Twenty-seven studies were included after removing the duplicates and irrelevant articles. The results suggested that iNO could reduce the duration of mechanical ventilation, but had no significance in the ICU stay, hospital stay, and mortality. This may be attributed to the small sample size of the most included studies and heterogeneity in timing, dosage and duration of iNO administration. Well-designed, large-scale, multicenter clinical trials are needed to further explore the effect of iNO in improving postoperative prognosis in cardiovascular surgical patients.

Randomized, controlled, multi-center phase II study of postoperative enoxaparin treatment for venous thromboembolism prophylaxis in patients undergoing surgery for hepatobiliary-pancreatic malignancies.

Postoperative venous thromboembolism (VTE) risk is pronounced after abdominal cancer surgery. Enoxaparin shows promise in preventing VTE in gastrointestinal, gynecological, and urological cancers, but its application after surgery for hepatobiliary-pancreatic malignancy has been under-evaluated due to bleeding concerns. We confirmed the safety of enoxaparin administration in patients undergoing curative hepatobiliary-pancreatic surgery for malignancies in a prospective, multi-center, phase I study. The study was conducted from April 2015 to May 2021 across eight specialized centers. Patients (n = 262) were randomized to enoxaparin prophylaxis given postoperatively for 8 days (n = 131) or control (n = 131). The primary endpoint was the efficacy in reducing VTE. Secondary endpoints examined safety. The full analysis set included 259 patients (131 control, 129 enoxaparin). The per-protocol population included 233 patients (117 control, 116 enoxaparin). Most cases were hepatic malignancies (111 control, 111 enoxaparin). The median administration duration of enoxaparin was 7 days, with 92% receiving 4000 units/day. Despite a reduction in the relative risk (RR) of VTE due to postoperative enoxaparin administration, the results were not significant (control: four cases, 3.4% vs. treatment: two cases, 1.7%; RR 0.50, 95% CI 0.09-2.70; p = 0.6834). No significant difference was found in the incidence of bleeding events (control: five cases, 4.3% vs. treatment: five cases, 4.3%, RR 1.00, 95% CI 0.53-1.89; p = 1.0000). The perioperative administration of enoxaparin in hepatobiliary-pancreatic malignancies is feasible and safe. However, further case accumulation and investigation are necessary to assess its potential in reducing the occurrence of VTE.

Research Progress on Anti-tumor Mechanism of Artesunate Combined Drugs

Artesunate (ART) is a semi-synthetic artemisinin derivative of hemiterpene lactones, which is widely used in clinical antimalarial therapy. In recent years, studies have shown that artesunate also has anti-inflammatory, anti-tumor, anti-fibrosis, antiviral, antibacterial, immunomodulatory and other pharmacological activities. Artesunate can play an anti-tumor role by inhibiting tumor cell proliferation, invasion and migration, promoting tumor cell apoptosis and blocking cell cycle. At the same time, when combined with other anti-tumor drugs, it can enhance the anti-tumor efficacy, shorten the duration of administration, reduce the dose and adverse reactions. In this paper, the main keywords of "artesunate", "pharmacology", "anti-tumor" and "combined drug" were searched and integrated in Pubmed, Web of Science and CNKI electronic databases to review the anti-tumor mechanism of artesunate combined with other drugs in recent 5 years. The prospect of clinical application of artesunate as an antitumor drug was prospected to provide some theoretical basis for further rational development and utilization of artesunate and new drug research and development.

Evaluation of Administration Prophylactic Antibiotic against Incidence of Surgical Site Infection in Post Appendectomy at Panembahan Senopati Hospital, Indonesia

Appendicitis is a prevalent abdominal surgical emergency in Indonesia, occurring at a rate of 5 per 1,000 people, with around 10 million cases each year. Appendectomy, the surgical removal of the vermiform, is the primary treatment for appendicitis but carries a high risk of surgical site infections. Prophylactic antibiotics are given to minimize the risk of infection resulting from surgery, administered in accordance with established guidelines. This study aims to evaluate the administration of antibiotic prophylactic against SSIs. This study used a mixed-methods approach to evaluate prophylactic antibiotic administration and the incidence of surgical site infection in post-appendectomy patients. The researchers conducted in-depth interviews with surgeons and nurses and an analytical observational study with a cross-sectional design, observing various indicators such as the timing and duration of prophylactic antibiotic administration and the presence of surgical site infections. The study found that the duration of antibiotic administration ≤24 hours had a higher number of infection-free patients (62.50%). The researchers analyzed the relationship between the duration of antibiotic administration and surgical site infection in post-appendectomy patients and found a significant relationship (p &lt;0.05) at the hospital. There is a relationship between prophylactic antibiotic administration and surgical site infection. All patients were given prophylactic antibiotics with appropriate timing, duration, and method of administration.

Effectiveness of antibiotic therapy for early recurrence of peritonsillar cellulitis and abscesses: A retrospective cohort study

ObjectiveShort-term recurrence is common in patients with peritonsillar cellulitis and abscesses, leading to socioeconomic problems. Early switching from intravenous to oral antibiotics is feasible for treating certain diseases. However, reports on early switching and total antibiotic administration duration in peritonsillar cellulitis and abscesses are limited. This study aimed to determine the appropriate antibiotic therapy duration and examine the impact of early oral switch therapy on peritonsillar cellulitis and abscesses. MethodsWe retrospectively identified 98,394 patients who received antibiotic therapy during hospitalization for peritonsillar cellulitis and abscesses between July 1, 2010, and December 31, 2019, using the Japanese Diagnosis Procedure Combination database. ResultsPropensity score matching analysis revealed no significant between-group difference in the rehospitalization rate (early oral switch therapy and long intravenous therapy: 1.7 % [198 of 11,621] vs. 2.0 % [234 of 11,621], odds ratio [OR] 0.84, 95 % confidence interval [CI] 0.70–1.02). A long total duration of antibiotic therapy (reference: 1–9 days) was associated with a low risk of rehospitalization (10–14 days: OR 0.86, 95 % CI 0.78–0.95; 15+ days: OR 0.51, 95 % CI 0.38–0.66). ConclusionEarly oral switch therapy may be a viable option for treating patients with peritonsillar cellulitis and abscesses in good condition who can tolerate oral intake. No less than 10 days of antibiotic therapy is desirable.

Anabolic steroids induced changes at the level of protein expression: Effects of prolonged administration of testosterone and nandrolone to pigs

Synthetic derivatives of steroid hormones, specifically anabolic-androgenic steroids (AAS), have gained prominence due to their observed benefits in enhancing meat quality. The study replicated the administration of banned AAS and investigated their impacts on pigs to contribute to the understanding of animal biochemistry and to explore the feasibility of detecting AAS administration by employing a non-targeted analysis. The effects were corroborated by evaluating changes in the expression of selected proteins, as well as examining haematological and biochemical profiles and histological alterations. Exposure to AAS influenced the expression of proteins related to drug-metabolizing enzymes, muscle and lipid metabolism, kidney function, reproductive processes, immune system functions, and carcinogenic changes. The effects of AAS appear intricate and contingent on factors such as the specific drug used, dosage, and duration of administration. The results underscore that protein expression analysis holds promise as a valuable tool for detecting illicit AAS use in the fattening process.

Development of opioid analgesic tolerance in rat to extended-release buprenorphine formulated for laboratory subjects.

Buprenorphine in an extended-release formulation intended for use in laboratory subjects is frequently administered to rats to provide extended analgesia without repeated handling. While levels of buprenorphine may persist in serum once extended-release buprenorphine has been introduced, exposure to opioids can cause opioid tolerance or opioid-induced hypersensitivity. This work examined the analgesic duration and efficacy of a single administration of extended-release buprenorphine intended for use in laboratory subjects in models of inflammatory pain and post-operative pain and the development of opioid tolerance in rat. After subcutaneous administration of 1 mg/kg extended-release buprenorphine, analgesic efficacy did not persist for the expected 72 hours. No changes were observed in mechanical thresholds in the hindpaws that were contralateral to the injury, suggesting a lack of centrally mediated opioid-induced hypersensitivity. To determine whether opioid tolerance arose acutely after one exposure to extended-release buprenorphine, we conducted the warm water tail flick assay; on Day 1 we administered either saline or extended-release buprenorphine (1 mg/kg) and on Day 3 we quantified the standard buprenorphine dose-response curve (0.1-3 mg/kg). Rats previously given extended-release buprenorphine displayed decreased analgesic responses after administration of standard buprenorphine as compared to the robust efficacy of standard buprenorphine in control subjects. Males appeared to show evidence of acute opioid tolerance, while females previously exposed to opioid did not demonstrate a decreased response at the doses examined. Taken together, these results suggest that opioid tolerance arises quickly in male rats after exposure to the extended-release formulation of buprenorphine. This tolerance may account for the brief period of antinociception observed.

An anti-TNF-glucocorticoid receptor modulator antibody-drug conjugate is efficacious against immune-mediated inflammatory diseases.

Glucocorticoids (GCs) are efficacious drugs used for treating many inflammatory diseases, but the dose and duration of administration are limited because of severe side effects. We therefore sought to identify an approach to selectively target GCs to inflamed tissue. Previous work identified that anti-tumor necrosis factor (TNF) antibodies that bind to transmembrane TNF undergo internalization; therefore, an anti-TNF antibody-drug conjugate (ADC) would be mechanistically similar, where lysosomal catabolism could release a GC receptor modulator (GRM) payload to dampen immune cell activity. Consequently, we have generated an anti-TNF-GRM ADC with the aim of inhibiting pro-inflammatory cytokine production from stimulated human immune cells. In an acute mouse model of contact hypersensitivity, a murine surrogate anti-TNF-GRM ADC inhibited inflammatory responses with minimal effect on systemic GC biomarkers. In addition, in a mouse model of collagen-induced arthritis, single-dose administration of the ADC, delivered at disease onset, was able to completely inhibit arthritis for greater than 30 days, whereas an anti-TNF monoclonal antibody only partially inhibited disease. ADC treatment at the peak of disease was also able to attenuate the arthritic phenotype. Clinical data for a human anti-TNF-GRM ADC (ABBV-3373) from a single ascending dose phase 1 study in healthy volunteers demonstrated antibody-like pharmacokinetic profiles and a lack of impact on serum cortisol concentrations at predicted therapeutic doses. These data suggest that an anti-TNF-GRM ADC may provide improved efficacy beyond anti-TNF alone in immune mediated diseases while minimizing systemic side effects associated with standard GC treatment.

Perioperative antibiotic prophylaxis in the setting of cochlear implantation: a retrospective analysis of 700 cases

PurposePostoperative wound infections after cochlear implantation are rare but sometimes serious and can lead to explantation. Therefore, perioperative antibiotic administration is often recommended. However, in clinical practice, the type and duration of antibiotic prophylaxis varies between different centers. The aim of this study was to investigate the role of perioperative antibiotic prophylaxis in preventing postoperative complications.Methods700 patients who underwent cochlear implantation between 2007 and 2019 were retrospectively evaluated with regard to wound infections within the first 28 postoperative days. These were classified into major and minor complications. Data were analyzed using the IBM statistical program SPSS.ResultsIn 670 out of 700 patients the type and duration of perioperative antibiotic administration could be reconstructed from the records. Of these 67 patients (10%) received antibiotics as a single shot, 158 patients (23.6%) were treated with antibiotics for a period of 48 h, and 445 patients (66.4%) received prolonged antibiotic therapy for more than 72 h. In total 64 patients (9.5%) showed abnormalities in wound assessment within the first 28 postoperative days after implantation. Major infections (1.6%) were detected in 11 patients. Overall, there was no statistically significant difference in wound infection rates between the group receiving single-shot antibiosis and the group receiving 48 h prophylaxis or antibiotic treatment > 72 h (p = 0.46).ConclusionPatients receiving an antibiotic single shot do not appear to be at significantly increased risk for postoperative wound infections compared with patients with prolonged antibiotic treatment. Continuation of data collection across centers seems reasonable.

Prevention of hypotension after induction of general anesthesia using point-of-care ultrasound to guide fluid management: a randomized controlled trial.

Hypotension after induction of general anesthesia (GAIH) is common and is associated with postoperative complications including increased mortality. Collapsibility of the inferior vena cava (IVC) has good performance in predicting GAIH; however, there is limited evidence whether a preoperative fluid bolus in patients with a collapsible IVC can prevent this drop in blood pressure. We conducted a single-centre randomized controlled trial with adult patients scheduled to undergo elective noncardiac surgery under general anesthesia (GA). Patients underwent a preoperative point-of-care ultrasound scan (POCUS) to identify those with a collapsible IVC (IVC collapsibility index ≥ 43%). Individuals with a collapsible IVC were randomized to receive a preoperative 500mL fluid bolus or routine care (control group). Surgical and anesthesia teams were blinded to the results of the scan and group allocation. Hypotension after induction of GA was defined as the use of vasopressors/inotropes or a decrease in mean arterial pressure < 65mm Hg or > 25% from baseline within 20min of induction of GA. Forty patients (20 in each group) were included. The rate of hypotension after induction of GA was significantly reduced in those receiving preoperative fluids (9/20, 45% vs 17/20, 85%; relative risk, 0.53; 95% confidence interval, 0.32 to 0.89; P = 0.02). The mean (standard deviation) time to complete POCUS was 4 (2) min, and the duration of fluid bolus administration was 14 (5) min. Neither surgical delays nor adverse events occurred as a result of the study intervention. A preoperative fluid bolus in patients with a collapsible IVC reduced the incidence of GAIH without associated adverse effects. ClinicalTrials.gov (NCT05424510); first submitted 15 June 2022.

Elimination of transmission of onchocerciasis (river blindness) with long-term ivermectin mass drug administration with or without vector control in sub-Saharan Africa: a systematic review and meta-analysis

WHO has proposed elimination of transmission of onchocerciasis (river blindness) by 2030. More than 99% of cases of onchocerciasis are in sub-Saharan Africa. Vector control and mass drug administration of ivermectin have been the main interventions for many years, with varying success. We aimed to identify factors associated with elimination of onchocerciasis transmission in sub-Saharan Africa. For this systematic review and meta-analysis we searched for published articles reporting epidemiological or entomological assessments of onchocerciasis transmission status in sub-Saharan Africa, with or without vector control. We searched MEDLINE, PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, African Index Medicus, and Google Scholar databases for all articles published from database inception to Aug 19, 2023, without language restrictions. The search terms used were "onchocerciasis" AND "ivermectin" AND "mass drug administration". The three inclusion criteria were (1) focus or foci located in Africa, (2) reporting of elimination of transmission or at least 10 years of ivermectin mass drug administration in the focus or foci, and (3) inclusion of at least one of the following assessments: microfilarial prevalence, nodule prevalence, Ov16 antibody seroprevalence, and blackfly infectivity prevalence. Epidemiological modelling studies and reviews were excluded. Four reviewers (NM, AJ, AM, and TNK) extracted data in duplicate from the full-text articles using a data extraction tool developed in Excel with columns recording the data of interest to be extracted, and a column where important comments for each study could be highlighted. We did not request any individual-level data from authors. Foci were classified as achieving elimination of transmission, being close to elimination of transmission, or with ongoing transmission. We used mixed-effects meta-regression models to identify factors associated with transmission status. This study is registered in PROSPERO, CRD42022338986. Of 1525 articles screened after the removal of duplicates, 75 provided 282 records from 238 distinct foci in 19 (70%) of the 27 onchocerciasis-endemic countries in sub-Saharan Africa. Elimination of transmission was reported in 24 (9%) records, being close to elimination of transmission in 86 (30%) records, and ongoing transmission in 172 (61%) records. I2 was 83·3% (95% CI 79·7 to 86·3). Records reporting 10 or more years of continuous mass drug administration with 80% or more therapeutic coverage of the eligible population yielded significantly higher odds of achieving elimination of transmission (log-odds 8·5 [95% CI 3·5 to 13·5]) or elimination and being close to elimination of transmission (42·4 [18·7 to 66·1]) than those with no years achieving 80% coverage or more. Reporting 15-19 years of ivermectin mass drug administration (22·7 [17·2 to 28·2]) and biannual treatment (43·3 [27·2 to 59·3]) were positively associated with elimination and being close to elimination of transmission compared with less than 15 years and no biannual mass drug administration, respectively. Having had vector control without vector elimination (-42·8 [-59·1 to -26·5]) and baseline holoendemicity (-41·97 [-60·6 to -23·2]) were associated with increased risk of ongoing transmission compared with no vector control and hypoendemicity, respectively. Blackfly disappearance due to vector control or environmental change contributed to elimination of transmission. Mass drug administration duration, frequency, and coverage; baseline endemicity; and vector elimination or disappearance are important determinants of elimination of onchocerciasis transmission in sub-Saharan Africa. Our findings underscore the importance of improving and sustaining high therapeutic coverage and increasing treatment frequency if countries are to achieve elimination of onchocerciasis transmission. The Bill & Melinda Gates Foundation and Neglected Tropical Diseases Modelling Consortium, UK Medical Research Council, and Global Health EDCTP3 Joint Undertaking. For the Swahili, French, Spanish and Portuguese translations of the abstract see Supplementary Materials section.