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Introduction: The purpose of this study is to identify the factors affecting neovascular age-related macular degeneration (nAMD) disease stability after brolucizumab treatment. Methods: We retrospectively analyzed the medical records of 31 patients (31 eyes) with recalcitrant nAMD who were switched to brolucizumab after conventional anti-vascular endothelial growth factor (VEGF) treatment. We divided patients into two groups by treatment extension (TE) period: group 1 with TE < 12 weeks (N = 16) and group 2 with TE ≥ 12 weeks (N = 15). We compared outcomes between the groups at 2, 4, 8, and 12 weeks, including morphological characteristics of choroidal neovascularization (CNV). Logistic regression analysis identified factors associated with TE ≥ 12 weeks. Results: Group 2 had a significantly greater proportion of patients with dry macula (subretinal and intraretinal fluids absent) than group 1 (60 vs. 12.5%) at 2 weeks (P < 0.05). Best-corrected visual acuity (BCVA) and subfoveal choroidal thickness (SFCT) did not differ significantly between groups at all timepoints. Central subfield retinal thickness (CST) was significantly lower in group 2 at 2 (237.1 vs. 280.8 μm; P < 0.05), 4 (224.0 vs. 262.9 μm; P < 0.05), and 8 weeks (216.8 vs. 331.1 μm; P < 0.05). Group 2 had less vessel area (0.63 vs. 1.27 mm2; P < 0.05) and total vessel length (0.22 vs. 0.42 mm; P < 0.05). Choriocapillaris flow deficit (CCFd) was significantly lower in group 2 (42.7 vs. 48.2%; P < 0.05). Dry macula at 2 weeks (odds ratio [OR] = 8.3; P < 0.05) and a lower CCFd (OR = 0.73; P < 0.05) were associated with TE ≥ 12 weeks. Conclusions: Early fluid-free status after switching to brolucizumab and choriocapillary function around CNV were prognostic factors for disease stability in nAMD refractory to anti-VEGF treatment. [ABSTRACT FROM AUTHOR]

Abstract Introduction The purpose of this study is to identify the factors affecting neovascular age-related macular degeneration (nAMD) disease stability after brolucizumab treatment. Methods We retrospectively analyzed the medical records of 31 patients (31 eyes) with recalcitrant nAMD who were switched to brolucizumab after conventional anti-vascular endothelial growth factor (VEGF) treatment. We divided patients into two groups by treatment extension (TE) period: group 1 with TE

Background: This study investigates clinical and biomarker differences between standard interval dosing (SID) and extended interval dosing (EID) of ocrelizumab therapy in multiple sclerosis (MS). Methods: This is a prospective, double-arm, open-label, multi-center study in Denmark. Participants diagnosed with MS on ocrelizumab therapy >12 months were included (n = 184). Clinical, radiological, and blood-based biomarker outcomes were evaluated. MRI disease activity, relapses, worsening of neurostatus, and No Evidence of Disease Activity-3 (NEDA-3) were used as a combined endpoint. Results: Out of 184 participants, 107 participants received EID (58.2%), whereas 77 participants received SID (41.8%). The average extension was 9 weeks with a maximum of 78 weeks. When comparing EID to SID, we found higher levels of B-cells, lower serum concentrations of ocrelizumab, and similar levels of age-adjusted NFL and GFAP in the two groups. No difference in NEDA-3 between EID and SID was demonstrated (hazard ratio: 1.174, p = 0.69). Higher levels of NFL were identified in participants with disease activity. Body mass index correlated with levels of ocrelizumab and B-cells. Conclusion: Extending one treatment interval of ocrelizumab on average 9 weeks and up to 78 weeks did not result in clinical, radiological, or biomarker evidence of worsening compared with SID. [ABSTRACT FROM AUTHOR]

Abstract Objective The optimal timing for surgery following neoadjuvant immunochemotherapy for lung squamous cell carcinoma appears to be a topic of limited data. Many clinical studies lack stringent guidelines regarding this timing. The objective of this study is to explore the effect of the interval between neoadjuvant immunochemotherapy and surgery on survival outcomes in patients with lung squamous cell carcinoma. Methods This study conducted a retrospective analysis of patients with lung squamous cell carcinoma who underwent neoadjuvant immunochemotherapy between January 2019 and October 2022 at The First Affiliated Hospital, Zhejiang University School of Medicine. Patients were divided into two groups based on the treatment interval: ≤33 days and > 33 days. The primary observational endpoints of the study were Disease-Free Survival (DFS) and Overall Survival (OS). Secondary observational endpoints included Objective response rate (ORR), Major Pathological Response (MPR), and Pathological Complete Remission (pCR). Results Using the Kaplan-Meier methods, the ≤ 33d group demonstrated a superior DFS curve compared to the > 33d group (p = 0.0015). The median DFS for the two groups was 952 days and 590 days, respectively. There was no statistical difference in the OS curves between the groups (p = 0.66), and the median OS was not reached for either group. The treatment interval did not influence the pathologic response of the tumor or lymph nodes. Conclusions The study observed that shorter treatment intervals were associated with improved DFS, without influencing OS, pathologic response, or surgical safety. Patients should avoid having a prolonged treatment interval between neoadjuvant immunochemotherapy and surgery.

Objective: The optimal timing for surgery following neoadjuvant immunochemotherapy for lung squamous cell carcinoma appears to be a topic of limited data. Many clinical studies lack stringent guidelines regarding this timing. The objective of this study is to explore the effect of the interval between neoadjuvant immunochemotherapy and surgery on survival outcomes in patients with lung squamous cell carcinoma. Methods: This study conducted a retrospective analysis of patients with lung squamous cell carcinoma who underwent neoadjuvant immunochemotherapy between January 2019 and October 2022 at The First Affiliated Hospital, Zhejiang University School of Medicine. Patients were divided into two groups based on the treatment interval: ≤33 days and > 33 days. The primary observational endpoints of the study were Disease-Free Survival (DFS) and Overall Survival (OS). Secondary observational endpoints included Objective response rate (ORR), Major Pathological Response (MPR), and Pathological Complete Remission (pCR). Results: Using the Kaplan-Meier methods, the ≤ 33d group demonstrated a superior DFS curve compared to the > 33d group (p = 0.0015). The median DFS for the two groups was 952 days and 590 days, respectively. There was no statistical difference in the OS curves between the groups (p = 0.66), and the median OS was not reached for either group. The treatment interval did not influence the pathologic response of the tumor or lymph nodes. Conclusions: The study observed that shorter treatment intervals were associated with improved DFS, without influencing OS, pathologic response, or surgical safety. Patients should avoid having a prolonged treatment interval between neoadjuvant immunochemotherapy and surgery. [ABSTRACT FROM AUTHOR]

Introduction: AZURE was a 76-week, randomized, open-label, parallel-group, phase IIIb noninferiority study comparing the efficacy and safety of intravitreal aflibercept (IVT-AFL) in a treat-and-extend (T&E) regimen with fixed dosing in patients with neovascular age-related macular degeneration (nAMD) previously receiving IVT-AFL for ≥ 1 year. Methods: Patients were aged ≥ 51 years and had completed ≥ 1 year of IVT-AFL treatment prior to enrollment (IVT-AFL once per month [– 1 or + 2 weeks] for 3 months followed by IVT-AFL every 2 months [6–12 weeks]). Patients were randomly assigned (1:1) to receive IVT-AFL 2 mg in either a T&E (minimum treatment interval of 8 weeks with no upper limit, adjusted according to functional and anatomic outcomes, as assessed by the investigator; n = 168), or a fixed dosing regimen (treatment every 8 weeks [± 3 days]; n = 168). The primary endpoint was best-corrected visual acuity (BCVA) change from baseline to week (W) 52. The key secondary endpoint was the proportion of patients maintaining vision (< 15-letter loss) at W52. Results: The full analysis set comprised 332 patients (T&E: n = 165; fixed dosing: n = 167). Mean BCVA change (baseline to W52) was − 0.3 ± 7.5 vs. − 0.5 ± 8.4 letters (T&E vs. fixed dosing; least-squares mean difference [95% CI]: 0.22 [− 1.51 to 1.96] letters; P < 0.0001 for noninferiority test [5-letter margin]). From baseline to W52, 95.2% (T&E) and 94.0% (fixed dosing) of patients maintained vision. Mean central subfield thickness change from baseline to W52 was − 24 ± 55 (T&E) and − 33 ± 47 (fixed dosing) µm. Last treatment interval to W76 was ≥ 12 weeks for 37.0% of T&E patients. No new safety signals were identified. Conclusion: IVT-AFL T&E can achieve similar functional and anatomic outcomes to fixed dosing every 8 weeks over 52 weeks in patients with nAMD who have completed ≥ 1 year of treatment, while reducing treatment burden. Trial Registration: ClinicalTrials.gov Identifier: NCT02540954. [ABSTRACT FROM AUTHOR]

Background: Dupilumab is a fully humanized monoclonal antibody that blocks interleukin-4 and interleukin-13 signals. Several large clinical trials have demonstrated the efficacy of dupilumab in patients with severe asthma. However, few studies have examined a switch to dupilumab from other biologics. Methods: This retrospective, multi-center observational study was conducted by the Okayama Respiratory Disease Study Group. Consecutive patients with severe asthma who were switched to dupilumab from other biologics without a treatment interval between May 2019 and September 2021 were enrolled. Patients with a treatment interval of more than twice the standard dosing interval for the previous biologic prior to dupilumab administration were excluded. Results: The median patient age of the 27 patients enrolled in this study was 57 years (IQR, 45–68 years). Eosinophilic chronic rhinosinusitis (ECRS)/chronic rhinosinusitis with nasal polyp (CRSwNP) was confirmed in 23 patients. Previous biologics consisted of omalizumab (n = 3), mepolizumab (n = 3), and benralizumab (n = 21). Dupilumab significantly improved FEV1 (median improvement: +145 mL) and the asthma control test score (median improvement: +2). The overall response rate in patients receiving dupilumab for asthma as determined using the Global Evaluations of Treatment Effectiveness (GETE) was 77.8%. There were no significant differences in the baseline characteristics of the GETE-improved group vs. the non-GETE-improved group. ECRS/CRSwNP improved in 20 of the 23 patients (87.0%). Overall, 8 of the 27 patients (29.6%) developed transient hypereosinophilia (>1500/μL), but all were asymptomatic and able to continue dupilumab therapy. Conclusions: Dupilumab was highly effective for the treatment of severe asthma and ECRS/CRSwNP, even in patients switched from other biologics without a treatment interval. [ABSTRACT FROM AUTHOR]

Objective: Timely cancer treatment improves survival and anxiety for some sites. Patients with esophageal cancer require specific workup before treatment, which can prolong the time from diagnosis to treatment (treatment interval [TI]). The geographical variation of this interval remains uninvestigated in patients with esophageal cancer. Methods: This retrospective population-level study conducted in Ontario used linked administrative health care databases. Patients treated for esophageal cancer between 2013 and 2018 were included. The TI was time from diagnosis to treatment. Patients were assigned a geographical Local Health Integration Network on the basis of postal code. Covariates included patient, disease, and diagnosing physician characteristics. Quantile regression modeled TI length at the 50th and 90th percentile and identified associated factors. Results: Of 7509 patients, 78% were male and most were aged between 60 and 69 years. The 50th and 90th percentile TI was 36 (interquartile range, 22-55) and 77 days, respectively. The difference between the Local Health Integration Network with the longest and shortest TI at the 50th and 90th percentile was 18 and 25 days, respectively. Older age (P

Patients with resectable esophageal cancer are recommended to undergo chemoradiotherapy before esophagectomy. A longer time to surgery (TTS) and/or time to consultation (TTC) may be associated with inferior cancer-related outcomes and heightened anxiety. Thoracic cancer surgery centers (TCSCs) oversee esophageal cancer management, but differences in TTC/TTS between centers have not yet been examined. This Ontario population-level study used linked administrative healthcare databases to investigate patients with esophageal cancer between 2013–2018, who underwent neoadjuvant chemoradiotherapy and then surgery. TTC and TTS were time from diagnosis to the first surgical consultation and then to surgery, respectively. Patients were assigned a TCSC based on the location of the surgery. Patient, disease, and diagnosing physician characteristics were investigated. Quantile regression was used to model TTS/TTC at the 50th and 90th percentiles and identify associated factors. The median TTS and TTC were 130 and 29 days, respectively. The adjusted differences between the TCSCs with the longest and shortest median TTS and TTC were 32 and 18 days, respectively. Increasing age was associated with a 16-day longer median TTS. Increasing material deprivation was associated with a 6-day longer median TTC. Significant geographic variability exists in TTS and TTC. Therefore, the investigation of TCSC characteristics is warranted. Shortening wait times may reduce patient anxiety and improve the control of esophageal cancer.

Patients with resectable esophageal cancer are recommended to undergo chemoradiotherapy before esophagectomy. A longer time to surgery (TTS) and/or time to consultation (TTC) may be associated with inferior cancer-related outcomes and heightened anxiety. Thoracic cancer surgery centers (TCSCs) oversee esophageal cancer management, but differences in TTC/TTS between centers have not yet been examined. This Ontario population-level study used linked administrative healthcare databases to investigate patients with esophageal cancer between 2013–2018, who underwent neoadjuvant chemoradiotherapy and then surgery. TTC and TTS were time from diagnosis to the first surgical consultation and then to surgery, respectively. Patients were assigned a TCSC based on the location of the surgery. Patient, disease, and diagnosing physician characteristics were investigated. Quantile regression was used to model TTS/TTC at the 50th and 90th percentiles and identify associated factors. The median TTS and TTC were 130 and 29 days, respectively. The adjusted differences between the TCSCs with the longest and shortest median TTS and TTC were 32 and 18 days, respectively. Increasing age was associated with a 16-day longer median TTS. Increasing material deprivation was associated with a 6-day longer median TTC. Significant geographic variability exists in TTS and TTC. Therefore, the investigation of TCSC characteristics is warranted. Shortening wait times may reduce patient anxiety and improve the control of esophageal cancer. [ABSTRACT FROM AUTHOR]

Introduction: High-intensity Focused Ultrasound (HIFU) treatment is a non-invasive technology. The purpose of this study was to explore the effects of different treatment depths, tissue types and treatment interval on biological tissue thermal lesions under continuous and intermittent treatment modes. Material and Methods: A simulation model of biological tissue irradiated by HIFU was established by finite difference time domain (FDTD). The thermal lesion of biological tissue irradiated by HIFU was calculated using the spherical beam equation (SBE) and Pennes biological heat transfer equation (PBHTE). Parameters such as treatment depth, tissue type, and treatment interval were varied to explore their effects on the thermal lesion to biological tissues in both continuous and intermittent treatment modes. Results: For the same biological tissue or treatment depth, with the increase of HIFU irradiation time, the focal temperature under continuous treatment was higher than that under intermittent treatment, and the thermal lesion area under continuous treatment was greater than that under intermittent treatment. Whether continuous or intermittent treatment, with the increase of treatment depth, the temperature rise rate of deep tissue was slower than that of superficial tissue, and the thermal lesion area decreased gradually. Moreover, in the intermittent treatment mode with a long single treatment time and short treatment interval, the focal temperature rase quickly and the thermal lesion area was large. Conclusion: For the same tissue type, treatment depth, or any treatment interval, the focal temperature and thermal lesion area corresponding to continuous treatment were greater than those corresponding to intermittent treatment. [ABSTRACT FROM AUTHOR]

Introduction: To explore the efficacy and safety of intravitreal aflibercept (IVT-AFL) proactive, individualized treat-and-extend (T&E) regimens in exudative age-related macular degeneration (AMD) in the subgroup of patients with polypoidal choroidal vasculopathy (PCV) enrolled in the ALTAIR study. Methods: This was a PCV subgroup analysis of ALTAIR, a 96-week, randomized, open-label, phase 4 study in treatment-naïve patients with exudative AMD in Japan. Following three initial monthly doses, patients received IVT-AFL at week 16 and were randomized 1:1 to T&E regimens with either 2-week (IVT-AFL-2W) or 4-week (IVT-AFL-4W) adjustments. The primary endpoint of ALTAIR was the mean change in best-corrected visual acuity (BCVA) from baseline to week 52. Endpoints were assessed at weeks 52 and 96. Safety analyses were conducted. Results: A total of 90 patients with PCV were included within the full analysis set. From baseline to week 52, mean [standard deviation (SD)] change in BCVA was + 7.5 (14.7) letters and + 8.2 (11.6) letters in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. From baseline to week 96, 91.3% and 90.9% of patients maintained vision in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. From baseline to week 52, mean (SD) change in central retinal thickness was − 153 (177) µm and −112 (122) µm in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. Overall, 51.1% of patients (IVT-AFL-2W, 43.5%; IVT-AFL-4W, 59.1%) achieved a treatment interval of 16 weeks between weeks 16 and 96. The safety profile of IVT-AFL was consistent with previous studies. Conclusion: In treatment-naïve patients with PCV, IVT-AFL administered using two different T&E regimens improved and maintained functional and anatomic outcomes over 96 weeks while minimizing treatment burden. Trial registration: ClinicalTrials.gov identifier, NCT02305238. [ABSTRACT FROM AUTHOR]

Abstract Background Breast cancer patients in sub-Saharan Africa experience long time intervals between their first presentation to a health care facility and the start of cancer treatment. The role of the health system in the increasing treatment time intervals has not been widely investigated. This review aimed to identify existing information on health system factors that influence diagnostic and treatment intervals in women with breast cancer in sub-Saharan Africa to contribute to the reorientation of health policies in the region. Methods PubMed, ScienceDirect, African Journals Online, Mendeley, ResearchGate and Google Scholar were searched to identify relevant studies published between 2010 and July 2020. We performed a qualitative synthesis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Related health system factors were extracted and classified according to the World Health Organization’s six health system building blocks. The quality of qualitative and quantitative studies was assessed by using the Critical Appraisal Skills Program Quality-Assessment Tool and the National Institute of Health Quality Assessment Tool, respectively. In addition, we used the Confidence in the Evidence from Reviews of Qualitative Research tool to assess the evidence for each qualitative finding. Results From 14,184 identified studies, this systematic review included 28 articles. We identified a total of 36 barriers and 8 facilitators that may influence diagnostic and treatment intervals in women with breast cancer. The principal health system factors identified were mainly related to human resources and service delivery, particularly difficulty accessing health care, diagnostic errors, poor management, and treatment cost. Conclusion The present review shows that diagnostic and treatment intervals among women with breast cancer in sub-Saharan Africa are influenced by many related health system factors. Policy makers in sub-Saharan Africa need to tackle the financial accessibility to breast cancer treatment by adequate universal health coverage policies and reinforce the clinical competencies for health workers to ensure timely diagnosis and appropriate care for women with breast cancer in this region.

Abstract Background Prophylactic uterine artery embolization (UAE) combined with subsequent curettage is suggested as an effective and minimally invasive treatment strategy for cesarean scar pregnancy (CSP) with a high bleeding risk. However, the timing of curettage after UAE remains to be studied. Thus, we aimed to identify the optimal time interval to perform curettage after UAE in patients with CSP. Methods We conducted a retrospective cohort study in a large medical center for women and children in Southwest China. CSP patients treated by UAE combined with subsequent curettage were included and grouped by the treatment time interval between these two procedures. The clinical outcomes among arms were compared by univariate and multivariable analysis. Results Our study included 314 CSP patients who received this combination treatment in our department from January 2014 to December 2019. The median time interval between UAE and curettage was 48 h, with a range of 12-168 h among all participants. Thirty-two patients (10.2%) experienced intraoperative hemorrhage (blood loss ≥200 mL). Intrauterine balloon tamponade was used in 17 cases (5.4%). In 14 cases (4.5%), the procedure was converted to laparoscopy (or laparotomy). In the cohort study, patients with longer treatment intervals had more intraoperative blood loss and a higher incidence of complications than those with shorter intervals (P 72 h had an adjusted odds ratio of 3.37 (95% confidence interval: 1.40-8.09). Conclusion We suggest that curettage not be delayed longer than 72 h after UAE in this combined treatment of CSP.

Background: There is limited information on the management and outcomes of oligometastases (OM) in adenoid cystic carcinoma (ACC). Methods: Retrospective study of 42 patients with metastatic ACC of the head and neck. Imaging studies were analyzed to identify patients with OM (1–5 lesions) at any point during follow‐up. Results: There was radiographic evidence of OM in 33/42 (79%) patients. Eighteen patients had OM when treated for metastases, with median overall survival (OS) of 36.0 versus 9.2 years for patients with polymetastases (6+ lesions, HR 0.38, 95%CI 0.14–0.89). Earlier locally ablative treatment, but not systemic treatment, of patients with OM predicted improved survival 3 years after metastasis (HR 0.15, 95%CI 0.02–0.63) and postponed systemic treatment by 80 more months (HR 0.22, 95%CI 0.07–0.71). Conclusions: There is a considerable population of ACC patients with detectable oligometastases, and early locally ablative treatment of oligometastases may be associated with improved outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Secondary cytoreductive surgery (SCS) is possible in selected patients with recurrent epithelial ovarian cancer (EOC). The goal of SCS is complete resection, although chemotherapy is always followed. Delayed intervals between primary debulking surgery and adjuvant chemotherapy was reported to be associated with poorer survivals, however, the role of intervals in recurrent disease is still unknown. Materials and methods This retrospective cohort study reviewed data from electronic medical records of women with recurrent EOC treated at Samsung Medical Centre, Seoul, Korea, between January 1, 2002, and December 31, 2015. Patients who underwent SCS with adjuvant chemotherapy for recurrent EOC were eligible. We defined intervals as the period between the day of SCS and the first cycle of adjuvant chemotherapy. Results Seventy-nine patients were eligible for this study. Their median age was 48 (range, 18–69) years and median interval between the date of SCS and initiation of adjuvant chemotherapy was 10 (range, 4–115) days. The rate of complete resection was 72.2% (57/79). Division of the patients by interval (Group 1, interval ≤ 10 days; Group 2, interval > 10 days) revealed no difference in clinical parameters. No gross residual disease after SCS (no vs. any gross residual, p = 0.002) and longer platinum-free survival (over 12 vs. 6–12 months, p = 0.023) were independent favorable prognostic factors in Cox model; however, the intervals did not affect survival. Conclusions Delayed intervals to adjuvant chemotherapy after secondary cytoreductive surgery is not associated with decreased survivals. It is important to identify recurrent EOC patients who might have no gross residual disease following SCS. Moreover, surgeons should strive for complete resection.

Background: We assessed the proportion of eyes with neovascular age‐related macular degeneration (nAMD) in routine clinical practice that reach ≥14 week treatment intervals and their outcomes. Method: We analysed data from the Fight Retinal Blindness! (FRB!) Project database, a prospectively designed registry of 'real‐world' outcomes. Treatment‐naive eyes starting vascular endothelial growth factor (VEGF) inhibitors for nAMD from 1st January 2006 were included. Eyes were defined to have reached the ≥14 week treatment interval if they received ≥2 consecutive injections at treatment intervals of ≥14 week but not exceeding 26 weeks. Outcomes were reported in a subgroup of eyes that had 12 months of follow‐up from reaching this interval. Results: Of the 3907 treatment‐naïve eyes that started treatment during the identified periods on a treat‐and‐extend regimen and received at least 8 injections over the first 2 years, 402 (10%) eyes received at least 2 consecutive injections at an interval of ≥14 week during their follow‐up. Fifty‐two percent of these eyes maintained vision to 12 months, however only 40% stayed at this interval and 25% of the lesions reactivated. Conclusion: We found that only 10% of eyes with nAMD were extended beyond a 13‐week injection interval and that over half had returned to a shorter interval by 12 months. Eyes that stayed at this extended treatment interval maintained stable vision. More data on the outcomes of eyes treated with intervals longer than 3 months are required to establish whether emerging VEGF inhibitors provide a more sustained effect than the currently available drugs. [ABSTRACT FROM AUTHOR]

Background: Breast cancer patients in sub-Saharan Africa experience long time intervals between their first presentation to a health care facility and the start of cancer treatment. The role of the health system in the increasing treatment time intervals has not been widely investigated. This review aimed to identify existing information on health system factors that influence diagnostic and treatment intervals in women with breast cancer in sub-Saharan Africa to contribute to the reorientation of health policies in the region.Methods: PubMed, ScienceDirect, African Journals Online, Mendeley, ResearchGate and Google Scholar were searched to identify relevant studies published between 2010 and July 2020. We performed a qualitative synthesis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Related health system factors were extracted and classified according to the World Health Organization's six health system building blocks. The quality of qualitative and quantitative studies was assessed by using the Critical Appraisal Skills Program Quality-Assessment Tool and the National Institute of Health Quality Assessment Tool, respectively. In addition, we used the Confidence in the Evidence from Reviews of Qualitative Research tool to assess the evidence for each qualitative finding.Results: From 14,184 identified studies, this systematic review included 28 articles. We identified a total of 36 barriers and 8 facilitators that may influence diagnostic and treatment intervals in women with breast cancer. The principal health system factors identified were mainly related to human resources and service delivery, particularly difficulty accessing health care, diagnostic errors, poor management, and treatment cost.Conclusion: The present review shows that diagnostic and treatment intervals among women with breast cancer in sub-Saharan Africa are influenced by many related health system factors. Policy makers in sub-Saharan Africa need to tackle the financial accessibility to breast cancer treatment by adequate universal health coverage policies and reinforce the clinical competencies for health workers to ensure timely diagnosis and appropriate care for women with breast cancer in this region. [ABSTRACT FROM AUTHOR]

Background: Prophylactic uterine artery embolization (UAE) combined with subsequent curettage is suggested as an effective and minimally invasive treatment strategy for cesarean scar pregnancy (CSP) with a high bleeding risk. However, the timing of curettage after UAE remains to be studied. Thus, we aimed to identify the optimal time interval to perform curettage after UAE in patients with CSP.Methods: We conducted a retrospective cohort study in a large medical center for women and children in Southwest China. CSP patients treated by UAE combined with subsequent curettage were included and grouped by the treatment time interval between these two procedures. The clinical outcomes among arms were compared by univariate and multivariable analysis.Results: Our study included 314 CSP patients who received this combination treatment in our department from January 2014 to December 2019. The median time interval between UAE and curettage was 48 h, with a range of 12-168 h among all participants. Thirty-two patients (10.2%) experienced intraoperative hemorrhage (blood loss ≥200 mL). Intrauterine balloon tamponade was used in 17 cases (5.4%). In 14 cases (4.5%), the procedure was converted to laparoscopy (or laparotomy). In the cohort study, patients with longer treatment intervals had more intraoperative blood loss and a higher incidence of complications than those with shorter intervals (P < 0.05). The rates of intraoperative bleeding were 5.0% for patients who received curettage within 24 h after UAE (Arm 1) and 19.4% for those who had a treatment interval longer than 72 h (Arm 4). In the multivariable logistic regression model of bleeding, a treatment interval > 72 h had an adjusted odds ratio of 3.37 (95% confidence interval: 1.40-8.09).Conclusion: We suggest that curettage not be delayed longer than 72 h after UAE in this combined treatment of CSP. [ABSTRACT FROM AUTHOR]

The efficacy and safety of incobotulinumtoxinA ≤400 U was demonstrated in subjects with post-stroke upper-limb spasticity in a randomized, double-blind Phase 3 study with an open-label extension (OLEX; EudraCT number 2005-003951-11, NCT00432666). We report a post-hoc analysis of the duration of the treatment effect. Subjects completing the placebo-controlled main period (single injection cycle with 12–20-week observation) entered the OLEX and received a maximum of five further treatments (maximum duration 69 weeks) with incobotulinumtoxinA ≤400 U at flexible intervals with a minimum duration of 12 weeks, based on clinical need. Intervals between two consecutive incobotulinumtoxinA injections, excluding treatment intervals prior to the end-of-study visit, were evaluated. Of 437 incobotulinumtoxinA treatment intervals, 415 received by 136 subjects were included in the post-hoc analysis. More than half (52.3%; 217/415) of all incobotulinumtoxinA reinjections were administered at Week ≥14, 31.1% (129/415) at Week ≥16, 19.0% (79/415) at Week ≥18, and 11.6% (48/415) at Week ≥20. The duration of effect may vary and can exceed 20 weeks or more, which was observed in at least one injection cycle in 29.4% (40/136) subjects over the course of their treatment. Data show that incobotulinumtoxinA retreatment for upper-limb spasticity may not be required at 12-week intervals and provides evidence for flexible treatment intervals beyond this time frame.

The efficacy and safety of incobotulinumtoxinA ≤400 U was demonstrated in subjects with post-stroke upper-limb spasticity in a randomized, double-blind Phase 3 study with an open-label extension (OLEX; EudraCT number 2005-003951-11, NCT00432666). We report a post-hoc analysis of the duration of the treatment effect. Subjects completing the placebo-controlled main period (single injection cycle with 12–20-week observation) entered the OLEX and received a maximum of five further treatments (maximum duration 69 weeks) with incobotulinumtoxinA ≤400 U at flexible intervals with a minimum duration of 12 weeks, based on clinical need. Intervals between two consecutive incobotulinumtoxinA injections, excluding treatment intervals prior to the end-of-study visit, were evaluated. Of 437 incobotulinumtoxinA treatment intervals, 415 received by 136 subjects were included in the post-hoc analysis. More than half (52.3%; 217/415) of all incobotulinumtoxinA reinjections were administered at Week ≥14, 31.1% (129/415) at Week ≥16, 19.0% (79/415) at Week ≥18, and 11.6% (48/415) at Week ≥20. The duration of effect may vary and can exceed 20 weeks or more, which was observed in at least one injection cycle in 29.4% (40/136) subjects over the course of their treatment. Data show that incobotulinumtoxinA retreatment for upper-limb spasticity may not be required at 12-week intervals and provides evidence for flexible treatment intervals beyond this time frame. [ABSTRACT FROM AUTHOR]

Introduction: Recently, treatment with proteasome inhibitors and immunomodulators has improved the prognosis of multiple myeloma (MM). However, in a complex real-world situation, the patient's ability to undergo regular and timely treatment as prescribed in clinical trials has not been studied, as well as the impact of extended treatment intervals due to different reasons. This study aimed to evaluate the treatment interval and clinical characteristics of 122 patients with primary myeloma in our hospital and explore the prognostic effects of different treatment intervals. Methods: In total, 122 patients with MM were analyzed retrospectively in our hospital from January 2007 to June 2018. The clinical and laboratory data (such as age, International Staging System [ISS] stage, chromosome, etc.) and subsequent treatment intervals were analyzed. The Cox proportional hazard regression model was used for univariate and multivariate analyses of overall survival (OS) and progression-free survival. The Kaplan-Meier method was used in survival analysis, and the log-rank test was used to test survival difference. p < 0.05 was considered to indicate statistical significance. Results: We found that prolonging the interval treatments (>28 days) shortened the OS in the younger and high-risk subgroups. On the contrary, the OS of the older and low-risk subgroups was not shortened. OS was also shortened in patients who were suitable for transplantation but did not receive a transplant. Univariate and multivariate analyses showed that extension of treatment interval was a risk factor for OS shortening. In addition, prolonged treatment interval was due to iatrogenic and family reasons. Conclusion: Extended treatment interval is unfavorable in young and high-risk MM patients and those suitable for transplantation but who did not receive a transplant. However, it has a faint impact on the elderly and low-risk subgroups. [ABSTRACT FROM AUTHOR]

Background Breast assessment sites (bass) were developed to provide expedited and coordinated care for patients being evaluated for breast cancer (bca) in Ontario. We compared the diagnostic and treatment intervals for patients diagnosed at a bas and for those diagnosed through a usual care (uc) route. Methods This population-based, cross-sectional study of patients diagnosed with bca in Ontario during 2007-2015 used linked administrative data. "Diagnostic interval" was the time from the earliest cancer-related health care encounter before diagnosis to diagnosis; "treatment interval" was the time from diagnosis to treatment. Diagnosis at a bas was determined from the patient's biopsy and mammography institutions. Interval lengths for the bas and uc groups were compared using multivariable quantile regression, stratified by detection method. Results The diagnostic interval was shorter for patients who were bas-diagnosed than for those who were uc-diagnosed, with adjusted median differences of -4.0 days [95% confidence interval (ci): -3.2 days to -4.9 days] for symptomatic patients and -5.4 days (95% ci: -4.7 days to -6.1 days) for screen-detected patients. That association was modified by stage at diagnosis, with larger differences in patients with early-stage cancers. In contrast, the treatment interval was longer in patients who were bas-diagnosed than in those who were uc-diagnosed, with adjusted median differences of 4.2 days (95% ci: 3.8 days to 4.7 days) for symptomatic patients and 4.2 days (95% ci: 3.7 days to 4.8 days) for screen-detected patients. Conclusions Diagnosis of bca through a bas was associated with a shorter diagnostic interval, but a longer treatment interval. Although efficiencies in the diagnostic interval might help to reduce distress experienced by patients, the longer treatment intervals for patients who are bas-diagnosed remain a cause for concern. [ABSTRACT FROM AUTHOR]

Background: It is known that daily divided doses and high doses of iron increase hepcidin and reduce iron absorption. Aim: This study aimed to compare treatments of iron replacement every other day at low doses, once a day and twice a day in terms of their effectiveness and frequencies of side effects. Methods: For a month, Group I received 270 mg ferrous sulphate twice a day (total elemental iron dose: 160 mg/day), Group II received 270 mg ferrous sulphate once a day (total elemental iron dose: 80 mg/day), and Group III received 270 mg ferrous sulphate every other day (total elemental iron dose: 80 mg/every other day). Intragroup and intergroup statistical analyses were carried out. Results: Haemoglobin (Hb) increased significantly in all three groups (P = 0.00). The increase in Hb levels was similar among the groups (P = 0.09). Ferritin significantly increased in all three groups after the treatment (P = 0.00). The increase in ferritin in Group I was significantly higher than those in Groups II and III (P < 0.05). Gastrointestinal tract (GIS) side effects were also significantly higher in Group I in comparison to the others (P = 0.001). Conclusions: A low‐dosage of iron treatment every other day may be used in the place of providing iron once or twice every day with similar effectiveness and lower rates of GIS side effects. [ABSTRACT FROM AUTHOR]

Background: Secondary cytoreductive surgery (SCS) is possible in selected patients with recurrent epithelial ovarian cancer (EOC). The goal of SCS is complete resection, although chemotherapy is always followed. Delayed intervals between primary debulking surgery and adjuvant chemotherapy was reported to be associated with poorer survivals, however, the role of intervals in recurrent disease is still unknown. Materials and methods: This retrospective cohort study reviewed data from electronic medical records of women with recurrent EOC treated at Samsung Medical Centre, Seoul, Korea, between January 1, 2002, and December 31, 2015. Patients who underwent SCS with adjuvant chemotherapy for recurrent EOC were eligible. We defined intervals as the period between the day of SCS and the first cycle of adjuvant chemotherapy. Results: Seventy-nine patients were eligible for this study. Their median age was 48 (range, 18–69) years and median interval between the date of SCS and initiation of adjuvant chemotherapy was 10 (range, 4–115) days. The rate of complete resection was 72.2% (57/79). Division of the patients by interval (Group 1, interval ≤ 10 days; Group 2, interval > 10 days) revealed no difference in clinical parameters. No gross residual disease after SCS (no vs. any gross residual, p = 0.002) and longer platinum-free survival (over 12 vs. 6–12 months, p = 0.023) were independent favorable prognostic factors in Cox model; however, the intervals did not affect survival. Conclusions: Delayed intervals to adjuvant chemotherapy after secondary cytoreductive surgery is not associated with decreased survivals. It is important to identify recurrent EOC patients who might have no gross residual disease following SCS. Moreover, surgeons should strive for complete resection. [ABSTRACT FROM AUTHOR]

Lipoprotein (Lp-) apheresis is a life-long therapy, usually performed in weekly intervals. In some cases, however, atherosclerotic disease progresses despite adequate therapy with weekly Lp-apheresis and maximal lipid lowering medication. In an attempt to improve the effectiveness of therapy, we temporarily shortened treatment intervals of Lp-apheresis in patients with elevated lipoprotein(a) (Lp(a)) and further progression of coronary atherosclerosis despite weekly Lp-apheresis and maximal lipid lowering medication. We illustrate three case reports of patients with elevated Lp(a), who underwent regular weekly Lp-apheresis treatment for secondary prevention. The intensified treatment protocol contained three therapies in two weeks (alternating 2 per week and 1 per week). The shortening of treatment intervals achieved a stabilization of atherosclerotic disease in case 1. After a total of 68 therapies in 52 weeks (1.31 sessions/week) the elective coronary angiography revealed excellent long-term results. In case 2, the intensified treatment protocol is still ongoing. The patient reported a decrease in angina pectoris and an increase in exercise capacity since the beginning of more frequent therapy sessions. In some cases, as it is shown in case 3, a fast decision for shortening the treatment intervals is necessary. The intensified treatment regimen resulted in an improvement in clinical symptoms and no further progression of atherosclerosis. In conclusion, shorter therapeutic Lp-apheresis intervals, at least temporarily, should be considered in patients who suffer from clinical and/or angiographic progression of atherosclerosis, despite maximal lipid lowering medication and weekly Lp-apheresis. [ABSTRACT FROM AUTHOR]

Introduction: One of the considerations when investigating neoadjuvant interventions is the prolonging of time from diagnosis to curative surgery (i.e. the treatment interval [TI]). The aim of this study was to investigate the association between the length of TI and overall survival and disease-free survival in patients with deficient mismatch repair (dMMR) colon cancer., Materials and Methods: This retrospective propensity score-adjusted study included all patients of ≥18 years of age undergoing elective curative surgery for stage I-III, dMMR colon cancer. Data were extracted from four Danish patient databases. Outcomes were investigated in groups with TIs of ≤14 days versus >14 days. Propensity scores were computed using all demographics, diagnoses and measurements. Matching was done in a 1:1 ratio., Results: A total of 4130 patients were included in the study with a mean age of 73.8 years and a median follow-up time of 43.9 months. After matching, 2794 patients were included in the analysis of overall survival. No significant difference in overall survival was seen between patients with TIs of ≤14 days versus >14 days (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.81-1.17; p = 0.78). In the analysis of disease-free survival, 1798 patients were included after matching. This showed no significant difference between patients with TIs of ≤14 days versus >14 days (HR, 0.85; 95% CI, 0.69-1.06; p = 0.14)., Conclusion: No associations were found between TI and overall survival and disease-free survival in patients with stage I-III, dMMR colon cancer undergoing elective curative surgery., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. This is also stated in the “author form” which is signed by all the authors as well as in the manuscript., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Sustained drug delivery to the respiratory tract is highly desirable for local treatment of chronic lung diseases. In this context, a correlation of in vitro drug release with in vivo efficacy data is essential to accelerate the application of sustained drug delivery system for inhalation into the clinical setting. In this study, budesonide was incorporated into distinct chitosan-based swellable microparticles, which were characterized, and the in vitro drug release behavior determined. The particles were then given to an allergic asthma animal model as single and successive administrations, and the therapeutic response was determined by measuring cell counts, IL-4 and IL-5 levels in bronchoalveolar lavage fluid, IL-4 and IL-5 mRNA in the lung and by histopathologic examination of lung tissues. After a single administration, the time-dependent therapeutic effect of the swellable microparticles was correlated with the in vitro release behavior, which lasted for 12 or 18 h depending on the molecular weight of the chitosan. After seven days of successive treatment, the number of eosinophils decreased further and IL-4 and IL-5 mRNA expression in the lung tissue was more greatly inhibited. Moreover, the chitosan-based swellable microparticles allowed longer administration intervals (every two days), which decreased the required dose for effectiveness by 50%. These results demonstrate that chitosan-based swellable microparticles can sustain the therapeutic effect of budesonide in the respiratory tract which in principal can be applied to other drugs for the treatment of local lung diseases. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxin (BoNT) is an effective, well-tolerated, and well-established option for the treatment of dystonic and spastic movement disorders. However, a single approach does not suit all patients, even within one disease indication. The degree of flexibility in treatment protocols is determined by individual product licenses, which often lag behind real-world clinical experience. A number of patient/practitioner surveys conducted recently have highlighted a desire for greater flexibility than that currently approved, both in BoNT doses and in the intervals between consecutive doses. New evidence arising from research conducted during the last few years has opened new avenues for tailoring BoNT treatment to patients' needs. Data suggest that escalating incobotulinumtoxinA doses enables treatment of a greater number of spasticity patterns than current dose limitations allow, without compromising safety or tolerability. Similarly, in patients with cervical dystonia (CD), repeated injections of incobotulinumtoxinA at intervals as early as 6 weeks after a previous treatment, based on individual patient need, were effective and well tolerated. Here, the BoNT doses and dosing intervals currently indicated in the USA and European Union are reviewed, together with the use of BoNT for the treatment of spasticity, CD, and blepharospasm. Opportunities for tailored BoNT therapy are also discussed. [ABSTRACT FROM AUTHOR]

Background Because most patients with small-sized nonsmall cell lung cancer (NSCLC) are asymptomatic, their lesions are detected by cancer screenings or routine checkups for other diseases. Incidences of multiple malignancies have been reported to be 27% in patients with stage I-III NSCLC. Some patients have treatment histories for other malignancies, and their small-sized NSCLC was incidentally detected during follow-up. There is no established report regarding the influence of multiple malignancies on small-sized NSCLC prognosis. Therefore, we investigated the correlation between multiple malignancies and surgical outcomes in patients with small-sized NSCLC. Methods In total, 44 patients underwent definitive pulmonary resection for NSCLC of 1 cm or smaller between January 2003 and December 2012. Tumor size was measured by macroscopic findings of the resected specimens, and we then retrospectively investigated their clinical courses. Results One patient had hemoptysis symptoms, whereas 43 patients were asymptomatic; among them, NSCLC was detected by examinations for other diseases in 31 patients and by cancer screening in 12 patients. In total, 20 patients (45%) had multiple malignancies. The median follow-up period was 68 months. One patient had a recurrence from current NSCLC. No patients died of current NSCLC. The overall 5-year survival rate was 90% for all patients. Patients with multiple malignancies had significantly poorer prognoses compared with those without multiple malignancies (P = 0.016). However, patients with treatment intervals of more than 5 years had prognoses equivalent to those of patients without multiple malignancies (P = 0.829). Only the presence of multiple malignancies was a significantly poor prognostic factor in univariate and multivariate analyses. Conclusion NSCLC of 1 cm or smaller showed good prognoses. The presence of multiple malignancies was a significantly poor prognostic factor, and short treatment intervals also correlated with poor prognosis. [ABSTRACT FROM AUTHOR]

Objective: To compare the safety and efficacy of pulsed dye laser (PDL) at different intervals for the treatment of East Asians with Port-Wine Stain (PWS). Background: The population of East Asians around the world is about 1.6 billion, and they are considered to have more melanin in their skin compared with Caucasians. Nevertheless, no studies about the optimal treatment intervals for East Asians with PWS have been carried out. Methods: We prospectively investigated 39 East Asian patients with untreated PWS. Half of the PWS lesion was randomly allocated to be treated at 3 weeks and the other half at 6 weeks. Both halves of the PWS were treated three times in total. The efficacy outcome 2 months post final treatment was evaluated by visual and chromameter evaluation. Results: The average blanching rate was 40.27% and 44.17% for PDL treatments at the 3- and 6-week interval sites, respectively ( p > 0.05). No patient developed scarring or permanent pigmentation change. Limitations: There was no age criteria involved in the enrollment of patients in this study. Additionally, there is no comparison with long-term treatments at different intervals. Conclusions: PDL treatment at 3-week interval proved to be safe for East Asians with PWS. This can reduce the total duration of the course of treatments and had no increase in side effects compared with the standard interval treatments. [ABSTRACT FROM AUTHOR]

Background Pemphigus vulgaris is a chronic autoimmune disease characterized by blisters and erosions forming in the mucous membranes and the skin. Many patients are severely impaired by pain, weight loss and increased risk of infections. The disease is mediated by specific autoantibodies directed against desmogleins that contribute to connect keratinocytes in the epidermis. Autoantibody deposition in the skin causes inflammation and intraepidermal akantholysis. The concentration of autoantibodies in serum correlates with disease activity. Therefore, the removal of autoantibodies by immunoadsorption is a targeted therapeutic intervention for patients with pemphigus vulgaris. Patients and methods A total of 9 patients with pemphigus vulgaris resistant to the standard treatment regimen were treated by immunoadsorption using the TheraSorb™-Ig adsorber system and analyzed retrospectively. Patients received immunoadsorption on two or four consecutive days. Cycles were repeated every two or four weeks, respectively. Treatment was performed for a mean period of 17.5 months (range 6–26). Outcome was measured as improvement in clinical disease analyzed by the investigators global assessment and the reduction of autoantibodies in serum measured by indirect immunofluorescence and ELISA. Tolerability of treatment by patients was evaluated using a visual analog scale. Results Retrospective analysis of 9 patients consecutively treated by immunoadsorption revealed an 80% reduction of the autoantibody concentration in serum after 6 months of treatment, led to a clinical improvement of disease in combination with classical immunosuppression. Steroid consumption could be reduced by 50% after 30 and 75% after 90 days. Therapy resulted in a total response rate of 89%, with 56% of patients reaching partial and 33% complete remission. The bi-weekly treatment regimen resulted in effective improvement of disease and was in favor to the 4-weekly regimen by the subjective judgment of tolerability by the patients. Conclusion Immunoadsorption for the treatment of pemphigus vulgaris is safe and effective. The good tolerability of a bi-weekly treatment regimen shown here might be a valuable therapeutic option in further studies defining the optimal frequency of immunoadsorption required in treatment of pemphigus. [ABSTRACT FROM AUTHOR]

To further increase the cost-effectiveness and sustainability of hot water weed control, the further optimisation of hot water efficacy is needed. Therefore, three dose-response experiments were carried out to evaluate the impact of wetting agents (an ethoxylated triglyceride, an esterified rapeseed oil and a liquid linseed oil-based soap), time of day (2, 4, 6, 8, 10 and 12 h after sunrise) and treatment frequency (1-6 treatments in a 12 week period) on the hot water sensitivity of prevalent weed species (Lolium perenne, Festuca rubra, Taraxacum officinale and Plantago major) on public pavements. Generally, wetting agents did not improve hot water sensitivity. Taraxacum officinale with large planophile leaves showed a higher sensitivity than grasses with an erectophile growth habit. Festuca rubra was more sensitive than L. perenne due to its high leaf dry matter content. The plant species were most sensitive to hot water in the afternoon. This variation in sensitivity during the day was related to the variation in leaf thickness and dry matter content. In general, hot water weed control was highly efficient when conducted four times in a 12 week period at an energy dose of 589 kJ m-2. [ABSTRACT FROM AUTHOR]