Tamsulosin 0.8 mg daily dose in management of BPH patients with failed tamsulosin 0.4 mg monotherapy and unfit for surgical intervention.

AIM: This study aims to evaluate the effectiveness and safety of administering double-dose tamsulosin (0.8 mg) for treating patients with benign prostatic hyperplasia (BPH) who have not responded to the standard single dose of tamsulosin (0.4 mg) and are deemed unsuitable for transurethral resection (TUR) intervention. MATERIALS AND METHODS: Between November 2022 and July 2023, we prospectively analyzed 111 patients who were experiencing severe BPH symptoms. These patients received a double dose of tamsulosin for one month. We collected baseline characteristics such as age, body mass index, and underlying medical conditions. Various parameters including the International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) levels, prostate volume, peak urinary flow rate (Qmax), voided volume, and post-void residual volume were evaluated before and after treatment. RESULTS: All 111 patients completed the study. The mean age, PSA level, and prostate volume were 63.12 ± 4.83 years, 3.42 ± 0.93 ng/ml, and 50.37 ± 19.23 ml, respectively. Of these patients, 93 showed improvement in Qmax, post-void residual volume, and IPSS score (p-value = 0.001). The total IPSS score and total Qmax improved from 24.03 ± 2.49 and 7.72 ± 1.64 ml/sec to 16.41 ± 3.84 and 12.08 ± 2.37 ml/sec, respectively. CONCLUSION: Double-dose 0.8mg tamsulosin as an alpha-blocker therapy appears to be a viable temporary management option for BPH patients who have not responded to the standard single dose 0.4mg tamsulosin and are not suitable candidates for TUR intervention.

Effects of double-dose algebra on college persistence and degree attainment.

In 2003, Chicago Public Schools introduced double-dose algebra, requiring two periods of math-one period of algebra and one of algebra support-for incoming ninth graders with eighth-grade math scores below the national median. Using a regression discontinuity design, earlier studies showed promising results from the program: For median-skill students, double-dose algebra improved algebra test scores, pass rates, high school graduation rates, and college enrollment. This study follows the same students 12 y later. Our findings show that, for median-skill students in the 2003 cohort, double-dose significantly increased semesters of college attended and college degree attainment. These results were not replicated for the 2004 cohort. Importantly, the impact of the policy on median-skill students depended largely on how classes were organized. In 2003, the impacts on college persistence and degree attainment were large in schools that strongly adhered to the cut-score-based course assignment, but without grouping median-skill students with lower-skill peers. Few schools implemented the policy in such a way in 2004.

Efficacy of combination therapy with ezetimibe and statins versus a double dose of statin monotherapy in participants with hypercholesterolemia: a meta-analysis of literature.

BACKGROUND: The aim of this study was to compare and summarize the lipid-altering effects of combination therapy with ezetimibe and statins (E/S) and a double dose of statin (D/S) monotherapy on patients with hypercholesterolemia. METHODS: We conducted search on 2 medical databases, PubMed and EMBASE to identify all relevant studies. A meta-analysis was performed to clarify the efficacy in the two groups. Only double-blind Randomized controlled study (RCTs) of efficacy evaluation in the two groups with ezetimibe and statins and a double dose of statin in participants with hypercholesterolemia that examined low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein (HDL) were included. Two reviewers extracted data from all primary studies independently. The primary data were the level of LDL-C, TC and HDL-C concentrations at the end point and are expressed as mean and standard deviation (SD). RESULTS: A total of 11 double-blind, active or placebo-controlled studies with 1926 hypercholesterolemia adults randomized to ezetimibe 10 mg added to ongoing statins (N = 994) or statin titration (doubling) (N = 932) were pooled for the global meta-analysis. The effect size between treatment groups within individual studies was assessed by weighted mean difference (MD) using a random- or fixed-effect model. The result showed that the participants in E/S group get obvious lower LDL-C [MD = -13.14 mg/dL, 95%CI (-16.83, -9.44), p = 0.00001] and TC concentration [MD = -23.79 mg/dL, 95%CI (-38.65, -8.93), p = 0.002] from baseline to follow-up, comparing to the D/S group. Besides, no significant between-group differences were observed for concentrations of HDL-C [MD = 0.46 mg/dL, 95%CI (- 1.14, 2.06), p = 0.57]. According to subgroup analysis, the combination of ezetimibe and atorvastatin (10 mg) [MD = -16.98 mg/dL, p < 0 .0001] or simvastatin (20 mg) [MD = -17.35 mg/dL, p < 0 .0001] showed stronger ability of reducing LDL-C than combination of ezetimibe and rosuvastatin (10 mg) [MD = -9.29 mg/dL, p = 0.05]. The efficacy of short-term (endpoint time between 6 to 16 week) and long-term (52 week) treatment in the LDL-C between two groups did not show significant differences. Besides, only participants from Asia treated with combination therapy were associated with a significant lower LDL-C concentration [MD = -14.7 mg/dL, p < 0 .0001]. CONCLUSIONS: The addition of ezetimibe to statin appears to be more effective on reducing LDL-C and TC concentrations than doubling the statin dose. Moreover, the ability to reduce cholesterol levels of combinations therapy with ezetimibe and different statins or to participants from different geographic location may vary, based on this meta-analysis, while more samples are needed to verify.

Comparison of double-dose vs standard-dose oseltamivir in the treatment of influenza: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: The effect of double-dose oseltamivir on mortality in patients with influenza remains controversial. We systematically reviewed the literature to investigate whether double-dose oseltamivir influences mortality in patients with influenza. METHODS: PubMed, Excerpta Medica Database (Embase) and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized controlled trials (RCTs) and observational studies regarding the effect of double-dose oseltamivir on mortality in patients with influenza. The primary outcome was all-cause mortality. The Mantel-Haenszel method with random effects model was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS AND DISCUSSION: Ten studies (four RCTs and six observational studies), involving 20 947 patients, were included. Pooled analysis suggested that double-dose oseltamivir was not associated with decreased mortality in patients with influenza, both in RCTs (OR, 1.29; 95% CI, 0.52-3.15; P = .58) and observational studies (OR, 1.59; 95% CI, 0.79-3.19; P = .20; I2  = 51%). Double-dose oseltamivir did not show statistical benefit on the virologic clearance rate (OR, 1.26; 95% CI, 0.85-1.88; P = .25; I2  = 0%) or the incidence of adverse events (AEs) (OR, 1.52; 95% CI, 0.85-2.72; P = .15; I2  = 59%). WHAT IS NEW AND CONCLUSION: Current evidence indicates that double-dose oseltamivir does not decrease mortality or have advantages on the outcome of virologic clearance rate and incidence of AEs. However, the finding largely relied on the data from observational studies, which may potentially have led to selection bias. Therefore, high-quality and adequately powered RCTs are warranted.

Quercetin exerts bidirectional regulation effects on the efficacy of tamoxifen in estrogen receptor-positive breast cancer therapy: An in vitro study.

Tamoxifen was widely applied in the therapy of estrogen receptor (ER)-positive breast cancer. With the purpose of determining the potential impacts of quercetin on its effectiveness, MCF-7 cells were selected as the in vitro model and several cellular biological behaviors (ie, cell proliferation, migration, invasion, cycle, apoptosis, and oxidative stress) were investigated. As results, quercetin showed contrasting dose-response to cellular behaviors dependent on the ROS-regulated p53 signaling pathways. In detail, quercetin promoted cell proliferation and inhibited cell apoptosis at low concentrations, whereas high-concentration resulted in apoptosis induction. Moreover, quercetin at a low concentration significantly inhibited tamoxifen-induced antiproliferation in MCF-7 cells, whereas high concentrations enhanced cell apoptosis in a synergetic manner. The real-time quantitative polymerase chain reaction analysis further implied that quercetin exerted its dual roles in tamoxifen-induced antiproliferative effects by regulated the gene expression involved in cell metastasis, cycle, and apoptosis through the ER pathways. Our present study provides a considerable support to the combination of quercetin and tamoxifen on human ER-positive breast carcinoma management.

Effects of fixed time AI and AI at detected estrus on conception rate in smallholder zebu and crossbred heifers and cows subjected to double PGF2α administration.

The study was conducted to evaluate estrus response, time to the onset of estrus, and conception rate at fixed time AI and AI at detected estrus in local and crossbred heifers and cows subjected to double administration of PGF2α. One hundred twenty local (heifers, n = 27; cows, n = 33) and crossbreds (heifers, n = 21; cows, n = 39) were used for the study. About 63 and 85.7 % of the local and crossbred heifers, respectively, exhibited estrus. Similarly, all crossbred cows and 90.9 % of local cows showed estrus. Most heifers came to estrus between 48 and 72 h while cows exhibited behavioral signs of estrus between 72 and 96 h. AI at detected estrus resulted in higher conception rate than fixed time AI. Pregnancy per artificial insemination was higher in AI at detected estrus than fixed time AI. Accurate estrus detection followed by insemination are crucial factors in maximizing pregnancy, and this study has demonstrated that conception rate in smallholder heifers and cows should be inseminated following estrus detection to maximize the conception rate of the animals.

Combining Double-Dose and High-Dose Pulsed Dapsone Combination Therapy for Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome and Co-Infections, Including Bartonella: A Report of 3 Cases and a Literature Review.

Three patients with relapsing and remitting borreliosis, babesiosis, and bartonellosis, despite extended anti-infective therapy, were prescribed double-dose dapsone combination therapy (DDDCT) for 8 weeks, followed by one or several two-week courses of pulsed high-dose dapsone combination therapy (HDDCT). We discuss these patients' cases to illustrate three important variables required for long-term remission. First, diagnosing and treating active co-infections, including Babesia and Bartonella were important. Babesia required rotations of multiple anti-malarial drug combinations and herbal therapies, and Bartonella required one or several 6-day HDDCT pulses to achieve clinical remission. Second, all prior oral, intramuscular (IM), and/or intravenous (IV) antibiotics used for chronic Lyme disease (CLD)/post-treatment Lyme disease syndrome (PTLDS), irrespective of the length of administration, were inferior in efficacy to short-term pulsed biofilm/persister drug combination therapy i.e., dapsone, rifampin, methylene blue, and pyrazinamide, which improved resistant fatigue, pain, headaches, insomnia, and neuropsychiatric symptoms. Lastly, addressing multiple factors on the 16-point multiple systemic infectious disease syndrome (MSIDS) model was important in achieving remission. In conclusion, DDDCT with one or several 6-7-day pulses of HDDCT, while addressing abnormalities on the 16-point MSIDS map, could represent a novel effective clinical and anti-infective strategy in CLD/PTLDS and associated co-infections including Bartonella.

Effect of double dose plateletpheresis on target yield and donor platelet recovery.

INTRODUCTION: The demand for apheresis platelets has increased in the recent past and the shrinking donor pool has shifted the trend to collection of double-dose or higher yield of platelets. OBJECTIVE: The present study aimed to determine the effect of double-dose plateletpheresis on the target yield and donor platelet recovery. METHODS: The study was conducted on 100 healthy plateletpheresis donors, 50 of whom were in the study group, which underwent double-dose plateletpheresis (DDP), and 50 of whom were in the control group for single-donor plateletpheresis. Pre- and post-procedure samples of donors were subjected to a complete blood count. The DDP product was sampled for platelet yield and then split into two parts. Platelet yield, collection efficiency, collection rate, recruitment factor and donor platelet loss were calculated. RESULTS: The mean platelet yield in the SDP was 4.09 ±â€¯1.15 × 1011 and in the DDP, 5.93 ±â€¯1.04 × 1011. There was a significant correlation between the pre-donation platelet count and platelet yield. The total of platelets processed for the SDP were 5.42 ±â€¯1.08 × 1011 and for the DDP, 7.94 ±â€¯0.77 × 1011. The collection efficiency was 71.93 ±â€¯25.14% in the SDP and 72.94 ±â€¯16.28% in the DDP, while the collection rates were 0.78 × 1011 and 0.94 × 1011 per minute, respectively. The average recruitment factor observed was 0.98 in the SDP, while it was 0.99 in the DDP. The mean platelet loss observed in the SDP was 35.55 ± 8.53% and in the DDP, 37.76 ± 8.65%. CONCLUSION: The double-dose plateletpheresis supplements the platelet inventory in developing countries where the apheresis donor pool is limited. It is prudent to ensure stringent donor selection criteria for donors donating high-yield platelet products, thus enhancing donor safety and retention.

Comparing oxygen demand in critical covid-19 patients using single versus double doses of tocilizumab.

OBJECTIVES: To compare the outcomes of single versus double doses of tocilizumab in patients with severe COVID-19, especially on different types of oxygenation requirements. METHODS: This cross-sectional study was carried out from January 2020 to March 2020. Patients diagnosed with COVID-19, who received at least one dose of tocilizumab, were included. The dependent variable was tocilizumab dose (single versus double). The primary outcome variable was oxygen demand on the first and last day of hospitalization. A series of comparisons between patients administered one dose of tocilizumab versus 2 doses were conducted. RESULTS: Herein, 80 patients with severe COVID-19 infection were included, of whom 68.8% received one dose of tocilizumab, while 31.3% received a double dose. Two-thirds of the patients were male, with an overall average age of 58 years. In patients receiving 2 doses, oxygen demand tended to worsen by the seventh day, while in those who received one dose. The group that received 2 doses had a longer length of hospital stay. CONCLUSION: This study could not capture the additional value of the second dose for different health outcomes. However, the results can inform clinician from experience when facing uncertainty due to new virus or variant.

Efficacy and safety of single- and double-dose intravenous tranexamic acid in hip and knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: With the increasing prevalence of osteoarthritis of the hip and knee, total joint replacement, the end-stage treatment, provides pain relief and restoration of function, but is often associated with massive blood loss. Tranexamic acid (TXA) has been reported to reduce perioperative blood loss in hip or knee arthroplasty. However, the optimal dose of TXA administration remains controversial. Therefore, we performed a meta-analysis combining data from 5 trials comparing the efficacy and safety of one fixed dose of 1 g intravenously administered TXA with two doses of 1 g each administered intravenously for hip or knee arthroplasty. METHODS: PubMed, Medline, Embase, Web of Science, and The Cochrane Library were searched from January 2000 to February 2023. Our meta-analysis included randomized controlled trials and cohort studies comparing the efficacy and safety of different doses of intravenous TXA (IV-TXA) for THA or TKA. The observation endpoints included total blood loss, postoperative hemoglobin drop, blood transfusion rate, length of hospital stay, incidence of deep venous thrombosis (DVT), and incidence of pulmonary embolism (PE). Meta-analysis was performed according to Cochrane's guidelines and PRISMA statement. The Danish RevMan5.3 software was used for data merging. RESULTS: Five cohort studies involving 5542 patients met the inclusion criteria. Our meta-analysis showed that the two groups were significantly higher in total blood loss (mean difference (MD) = - 65.60, 95% confidence interval (CI) [- 131.46, 0.26], P = 0.05); blood transfusion rate (risk difference (RD) = 0.00, 95% CI [- 0.01, 0.02], P = 0.55); postoperative hemoglobin (MD = 0.02, 95% CI [- 0.09, 0.13], P = 0.31); postoperative hospital stay days (MD = - 0.13), 95% CI [- 0.35, 0.09], P = 0.25); DVT (RD = 0.00, 95% CI [- 0.00, 0.01], P = 0.67); PE (RD = 0.00, 95% CI [- 0.01, 0.00], P = 0.79). There was some inherent heterogeneity due to variance in sample size across each major study. CONCLUSION: 1 dose of 1 g and 2 doses of 1 g IV-TXA each time have similar effects on reducing blood loss, blood transfusion rate, postoperative hemoglobin level, and postoperative hospital stay after TKA or THA, without increasing the risk of postoperative complications risk. For patients at high risk of thromboembolic events, one dose of 1 g TXA throughout surgery may be preferred. However, higher-quality RCT is needed to explore the optimal protocol dose to recommend the widespread use of TXA in total joint arthroplasty. Trial registration We conducted literature selection, eligibility criteria evaluation, data extraction and analysis on the research program registered in Prospero (CRD42023405387) on March 16, 2023.

Efficacy of Hepatitis B Vaccine in Adults with Chronic Liver Disease.

Background & Aims: Although HBV vaccine has a 95% seroconversion rate in the general population, patients with chronic liver disease have reduced seroconversion rates (16-79%). The aim of the study was to describe seroconversion rates with HBV vaccines in patients with chronic liver disease. Approach & Results: Retrospective chart review was performed among 652 patients who received a complete HBV vaccine series in the hepatology clinic. Of those, 126 patients that were included, 111 received a single dose series, and 15 patients received a double dose series. The seroconversion rate was overall low at 35%, and stayed the same at 35% with double dose and at 33% with single dose. Patients who received a single dose series were further analyzed to review risk factors for seroconversion. Overall, 65% of patients had cirrhosis. Patients were more likely to seroconvert if no cirrhosis (51% vs 72%, P=.04), higher aminotransferase levels, intermediate anti-HBs (2.5-11.9 mIU/mL) at baseline (87.5% vs 14%). Conclusion: Patients with chronic liver disease had a low rate (35%) of response to HBV vaccination. The response rates did not improve in patients that received double dose series. Patients with cirrhosis, lower aminotransferase levels and with a lower baseline anti-HBs had decreased response rates.

Comparison of the Efficacy of Longer versus Shorter Pulsed High Dose Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome with Bartonellosis and Associated Coinfections.

Twenty-five patients with relapsing and remitting Borreliosis, Babesiosis, and bartonellosis despite extended anti-infective therapy were prescribed double-dose dapsone combination therapy (DDDCT), followed by one or several courses of High Dose Dapsone Combination Therapy (HDDCT). A retrospective chart review of these 25 patients undergoing DDDCT therapy and HDDCT demonstrated that 100% improved their tick-borne symptoms, and patients completing 6-7 day pulses of HDDCT had superior levels of improvement versus 4-day pulses if Bartonella was present. At the completion of treatment, 7/23 (30.5%) who completed 8 weeks of DDDCT followed by a 5-7 day pulse of HDDCT remained in remission for 3-9 months, and 3/23 patients (13%) who recently finished treatment were 1 ½ months in full remission. In conclusion, DDDCT followed by 6-7 day pulses of HDDCT could represent a novel, effective anti-infective strategy in chronic Lyme disease/Post Treatment Lyme Disease Syndrome (PTLDS) and associated co-infections, including Bartonella, especially in individuals who have failed standard antibiotic protocols.

Double the dose, double the impact? Effects of iTBS on salivary cortisol in stressed healthy volunteers.

There is a growing interest in applying double-dose repetitive transcranial Magnetic Stimulation (rTMS) as a therapeutic tool for stress-related psychiatric disorders. Such stimulation protocols may shorten the treatment duration and may result in faster symptom improvement. Currently, theta-burst stimulation (TBS) protocols have gained attention because of their significantly reduced treatment duration, compared to conventional rTMS. However, the effect of one or twice daily rTMS sessions remains unclear in relation to stress. Using a two-period cross-over design, we examined the impact of double-dosed intermittent (TBS) over the left dorsolateral prefrontal cortex on stress responses (salivary cortisol) in thirty-eight healthy participants after being stressed by a validated psychosocial stress task: the Trier Social Stress Test. After the first active iTBS session, as contrasted to sham, no differential effects on salivary output were observed. However, after the second active session, there was a significantly smaller decrease of salivary cortisol concentrations in the active iTBS condition compared to sham. Our results suggest that double-dosed iTBS after being stressed might differently affect stress recovery compared to a single session of iTBS.

Naringenin and Quercetin Exert Contradictory Cytoprotective and Cytotoxic Effects on Tamoxifen-Induced Apoptosis in HepG2 Cells.

Tamoxifen is commonly used to treat estrogen receptor-positive breast cancer and hepatocellular carcinoma. Phytoconstituents are considered candidates for chemopreventive drugs in cancer treatment. However, it remains unknown what would happen if tamoxifen and phytoconstituents were administrated simultaneously. We aimed to observe the synergistic antitumor effects of tamoxifen and naringenin/quercetin on human hepatic carcinoma and to explore the potential underlying molecular mechanisms. The HepG2 cell line was used as an in vitro model. Cell proliferation, invasion, migration, cycle progression and apoptosis were investigated along with reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨm) repression. The signaling pathways involved were identified using real-time quantitative polymerase chain reaction analysis. As the results show, tamoxifen in combination with higher concentrations of naringenin or quercetin significantly inhibited cell growth compared to either agent alone. These antiproliferative effects were accompanied by the inhibition of cell migration and invasion but the stimulation of cell apoptosis and loss of ΔΨm, which depended on the ROS-regulated p53 signaling cascades. Conversely, lower concentrations of naringenin and quercetin inhibited the tamoxifen-induced cell antiproliferative effects by regulating cell migration, invasion, cycle and apoptosis. Taken together, our findings revealed that phytoconstituents exerted contradictory cytoprotective and cytotoxic effects induced by tamoxifen in human hepatic cancer.

Double-dose icotinib may induce the emergence of the EGFR exon 20 T790M mutation in non-small cell lung cancer patients harboring EGFR-sensitive mutation.

Background: Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) inevitably occurs in non-small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations. There are approximately half of the patients who developed resistance to EGFR-TKIs treatment, the mechanism of which remains undiscovered. We occasionally found that double-dose icotinib as further-line salvage treatment may induce the emerging mutation of EGFR exon 20 T790M in NSCLC patients. The present study, therefore, was conducted to explore the probability of the emerging T790M mutation after exposure to double-dose icotinib in metastatic NSCLC patients. Patients and Methods: Metastatic NSCLC patients who received double-dose icotinib as salvage treatment after progression on first-generation TKIs and systematic chemotherapy were screened. Thereafter, patients who received a repeated next-generation sequencing (NGS) test with tumor sample were further enrolled. The procedure of NGS was performed with the standard criteria. Finally, the clinical characteristics, treatment procedures, and outcomes of eligible patients were reviewed and presented. Results: Three patients have been detected with the emerging T790M mutation after double-dose icotinib exposure, with a mutation frequency of 19.6%, 8.2%, and 87.5%. During the treatment of targetable TKIs including almonertinib or osimertinib, partial response was observed in two patients, and stable disease was observed in the other. The progression-free survival by targetable TKIs for the patients was 3.7+ months (still in extension), 4.9+ months (still in extension), and 6.3 months. Manageable adverse events were observed during the treatment of TKIs. Conclusion: The results of the present study revealed that the emerging EGFR exon 20 T790M mutation might be induced by double-dose icotinib exposure in further-line treatment. Patients with the emerging T790M mutation responded well to the treatment of targetable TKIs including almonertinib or osimertinib.

Double-dose cefuroxime concentrations in bone, synovial fluid of the knee joint and subcutaneous adipose tissue-A randomised porcine microdialysis study.

This study evaluated target tissue concentrations of double dose cefuroxime administered intravenously as either one 15 min infusion of 3000 mg (Group 1) or two single 15 min infusions of 1500 mg administered 4 h apart (Group 2). Sixteen pigs were randomised into two groups of eight. Cortical and cancellous bone, synovial fluid of the knee joint and subcutaneous adipose tissue concentrations were measured based on sampling via microdialysis. Plasma samples were collected as a reference. Comparison of the groups was based on time with concentrations above relevant minimal inhibitory concentrations (fT>MIC) of 4 µg/mL. The mean time fT>MIC (4 µg/mL) across compartments was longer for Group 2 (280-394 min) than for Group 1 (207-253 min) (p<0.01). Cortical bone showed a tendency towards longer fT>MIC (4 µg/mL) in Group 2 (280 min) than in Group 1 (207 min) (p = 0.053). Within 50 min after administration, the mean concentration of 4 µg/mL was reached in all compartments for both groups. The mean concentrations decreased below 4 µg/mL after approximately 4 h (Group 1) and 3 h (Group 2) from initiation of administration (time zero). During an 8 h interval, double-dose cefuroxime administered as 2 × 1500 mg with a 4 h interval provides longer time above MIC breakpoint for Staphylococcus aureus (4 µg/mL) than a single bolus of 3000 mg cefuroxime. To maintain sufficient tissue concentrations during longer surgeries, re-administration of cefuroxime (1500 mg) should be considered 3 h after the first administration.

Effects of double-dose statin therapy for the prevention of post-stroke epilepsy: A prospective clinical study.

BACKGROUND: To determine treatment effects on the incidence of post-stroke epilepsy (PSE) using different doses of statin, a prospective hospital-based cohort study was designed to explore whether a double-dose statin treatment can better prevent the occurrence of PSE. METHODS: A total of 1152 patients with newly diagnosed ischemic stroke admitted to our hospital from March to August 2017 were selected, 1033 of whom were followed-up. Patients were divided into two treatment groups:(1) standard-dose (20 mg atorvastatin or 10 mg rosuvastatin,daily oral; 788 patients); and (2) double-dose (40 mg atorvastatin or 20 mg rosuvastatin, daily oral; 245 patients).At 18 months follow-up was conducted to compare the incidence of PSE between groups. RESULTS: In general, in the standard-dose group we observed two cases of early seizure (ES) (0.25%), 22 cases oflate seizure (LS) (2.79%) and 20 cases of PSE (2.54%). In the double-dose group, onepatient had ES (0.41%), two patients had LS (0.82%), and onepatient had PSE (0.41%). The incidence of PSE was significantly lower in the double-dose group as compared to the standard-dose group. There was a higher proportion of PSE in patients younger than 65 years and in males. Three patients had ES; one presented with focal aware seizure (FAS), and two had focal to bilateral tonic-clonic seizure (FBTCS). Among the 21 patients with PSE, there were two cases of FAS, five cases of focal impaired awareness seizure (FIAS), five cases of FBTCS, and nine cases of GTCS, suggesting that partial seizure is the most common type of PSE. Cerebral cortex was involved in 85.75% of cases with PSE, and multiple lobes were involved in 61.9% of cases with PSE. CONCLUSION: Increasing the dose of statin treatment during the acute phase of ischemic stroke reduces the incidence of PSE. Further research is needed to understand the mechanisms underlying the potential preventative effects of statins against PSE.

Deep surgical site infections following double-dose perioperative antibiotic prophylaxis in adult obese orthopedic patients.

BACKGROUND: Obesity is a risk factor for surgical site infections (SSI). Based on retrospective comparisons and pharmacology, many orthopedic centers have adopted weight- or body mass index (BMI)-related antibiotic prophylaxis. METHODS: Double-dose prophylaxis was introduced in March 2017 for patients weighting >80 kg. The period April 2014 to March 2017 ('before') was compared to the period March 2017 to June 2019 ('after') regarding the impact on deep SSIs. RESULTS: A total of 9318 surgeries 'before' were compared to 7455 interventions 'after' the introduction of double-dose prophylaxis. Baseline demographic characteristics (age, sex, BMI, American Society of Anesthesiologists score, and duration of surgery) were similar. In the period 'after', 3088 cases (3088/16 773; 18%) received double-dose prophylaxis. Overall, 82 deep SSIs were observed (0.5%). The pathogens were resistant to the standard cefuroxime prophylaxis in 30 cases (30/82; 37%). Excluding these prophylaxis-resistant cases and all of the five hematogenous SSIs, the remaining 47 SSIs (57%) could have been prevented by the preceding prophylaxis. Double-dosing of parenteral cefuroxime from 1.5 g to 3.0 g in obese patients did not reduce deep SSIs (hazard ratio 0.7, 95% confidence interval 0.3-1.6). In the direct group comparison among obese patients >80 kg, the double-dose prophylaxis equally failed to alter the SSI risk (3088/16 726 non-infections vs 8/47 SSI despite double-dose prophylaxis; Chi-square test, P = 0.78). CONCLUSIONS: In this single-center before-and-after study with almost 17 000 orthopedic surgeries in adult patients, systemic doubling of the perioperative antibiotic prophylaxis in obese patients clinically failed to reduce the overall deep SSI risk.

Current perspectives for SARS-CoV-2 vaccination efficacy improvement in patients with active treatment against cancer.

A higher risk of death from coronavirus disease 19 has been shown for patients with solid cancers or haematological malignancies (HM). Thanks to the accelerated development of anti-SARS-SoV-2 vaccines in less than a year since the start of the global pandemic, patients with cancer were quickly prioritised in early 2021 for vaccination, however dependent on the very unequal availability at the global level. Impaired immunogenicity of SARS-CoV-2 mRNA vaccines in immunocompromised patients was rapidly reported as early as April 2021, although the vaccination fortunately appears to be generally effective without increasing the spacing. Worryingly, the humoral response of the SARS-CoV-2 vaccination is, however, considered insufficient in patients followed for HM, in particular when they are on anti-CD20 treatment. Thus, improving vaccination coverage by strengthening immune stimulation should be evaluated in patients under active treatment against cancer. Here, we discuss three different approaches: a third dose of early vaccine (repeated immune stimulation), heterologous prime-boost vaccination (multimodal immune stimulation) and a double-dose strategy (maximisation of immune response). Dedicated therapeutic trials, currently almost non-existent, seem rapidly necessary.

Doubling the Dose of Bevacizumab Beyond Progression in Metastatic Colorectal Cancer-the Experience of a Tertiary Cancer Center.

Background: Colorectal cancer (CRC) is the third most common cancer in Europe, with an annual increase in incidence ranging between 0.4 and 3.6% in various countries. Although the development of CRC was extensively studied, limited number of new therapies were developed in the last few years. Bevacizumab is frequently used as first- and second-line therapy for management of metastatic CRC (mCRC). The aim of this study is to present our experience with using bevacizumab beyond disease progression at different dosage levels in mCRC patients, in terms of overall survival, progression-free survival, time to treatment failure, and toxicities. Methods: We performed a consecutive retrospective analysis of patients with confirmed mCRC who were treated with bevacizumab at "Prof Dr. Ion Chiricuta" Institute of Oncology, Cluj-Napoca, Romania. We included patients who had received bevacizumab as first- or second-line therapy and further stratified them according to the dose administered as a second-line (either standard dose of 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks, or double dose of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks-depending on the classical chemotherapy partner). All patients had received bevacizumab beyond progression (BYP) which is defined as continuing bevacizumab administration through second-line treatment despite disease progression. In each group, we evaluated the prognostic factors that influenced survival and treatment outcome. Results: One hundred and fifty-one (151) patients were included in the study. Themedian age of patients receiving double dose bevacizumab (DDB) and standard dose bevacizumab (SDB) was 58 years (range 41-71) and 57 years (range 19-75), respectively. The median overall survival in the DDB group was 41 months (range 27-49) compared to 25 months (range 23-29) in the SDB group (p = 0.01 log-rank test). First-line oxaliplatin-based treatment was used more frequently regardless of group, while irinotecan-based more frequently used as a second-line treatment (p = 0.014). Both oxaliplatin- and irinotecan-based regimens were found to be suitable partners for BYP. Statistical analysis revealed that dose intensity, primary tumor location, and cumulative exposure to BYP had significant influence on survival. Conclusion: Doubling the dose of bevacizumab after first progression may improve survival in mCRC patients. Increasing bevacizumab dose intensity could override the prognostic impact of primary tumor location in patients receiving double the dose of bevacizumab after first disease progression.