Chiral organic chromophores with circularly polarized thermally activated delayed fluorescence (CP-TADF) provide great prospects as circularly polarized luminescence (CPL) emitters owing to the involvement of long-lived triplet excitons. Here, we construct a tailored planar chiral hetero-cyclophane (NBICz-Cy) composed of 1,2:5,6-naphthalene bisimide (1,2:5,6-NBI) and carbazole (Cz) units, which functions as an efficient solution-state CP-TADF emitter. Comprehensive photophysical studies reveal pronounced delayed fluorescence in the orange-red region, with a quantum yield (QY) of 19% in deaerated solution and 12% in an aerated solution-processable matrix. Single-crystal XRD analysis unravels a through-space charge-transfer (CT) interaction between the NBI and Cz moieties, being responsible for delayed fluorescence. The inherent prochirality of the 1,2:5,6-NBI moiety imparts planar chirality in the cyclophane framework, resulting in CP-TADF in both solution and solid state with |glum| values of ∼ 2.5 - 3.3 × 10-3.
Fentanyl is a highly potent synthetic opioid and a major contributor to opioid-related mortality due to central respiratory depression. Inhalational exposure occurs during recreational misuse, polysubstance abuse, occupational handling, and potential chemical threat scenarios. However, whether inhaled fentanyl is associated with pulmonary toxicity independent of central effects remains unclear. Adult male C57BL/6 mice were exposed to aerosolized fentanyl (0.1, 1, or 5 mg/kg; nebulized dose, 5 min) or saline and evaluated 1 and 14 days post-exposure. Within 24 hours, fentanyl exposure was associated with acute lung injury characterized by alveolar hemorrhage, increased bronchoalveolar lavage protein and inflammatory cells, high lactate dehydrogenase levels, elevated lung wet-to-dry ratio, and reduced arterial oxygenation. Systemic hyperglycemia and increased plasma IL-1β and IL-12p70 were observed, with significant upregulation of caspase-1 activity and IL-1β in lung tissue. Similar IL-1β induction occurred in ex vivo human lung tissue and in vitro human macrophages. At 14 days, delayed dose-dependent remodeling was evident. Low-dose exposure (0.1 mg/kg) produced emphysematous changes, airspace enlargement, and increased mean linear intercept, consistent with emphysema-like changes. Higher doses (1 and 5 mg/kg) were associated with fibrotic remodeling, increased collagen deposition, and fibrotic remodeling. High-dose exposure (5 mg/kg) reduced 14-day survival to 65%. In conclusion, these findings demonstrate that aerosolized fentanyl exposure is associated with acute lung injury and subsequent delayed structural remodeling, accompanied by IL-1β-associated inflammatory signaling. These findings highlight potential pulmonary risks of inhaled fentanyl relevant to substance abuse, occupational safety, emergency response preparedness, and regulatory toxicology risk assessment.
The anterior intercostal artery perforator (AICAP) flap has emerged as a viable option in breast reconstructive surgery for salvaging implants compromised by infection or radiotherapy. However, its application in delayed implant exposure following prepectoral reconstruction remains limited in the literature. The authors report the case of a 54-year-old woman who presented with localized infection and implant exposure following nipple-sparing mastectomy and prepectoral breast reconstruction with a silicone implant. Oncologic recurrence was excluded. Conventional conservative therapy failed, and the defect was successfully managed with an AICAP flap for implant salvage. This case highlights the feasibility of this technique as a less invasive alternative to avoid implant removal and secondary reconstruction, particularly in selected patients without extensive soft tissue compromise. Level of Evidence: 5 (Therapeutic).
Current guidelines do not support the addition of stenting to maximal medical therapy (MMT) for severe symptomatic intracranial atherosclerotic disease as first-line treatment. This is largely due to the SAMMPRIS trial (Stenting and Aggressive Medical Management Therapy for Preventing Recurrent Stroke in Intracranial Arterial Stenosis) results, which featured a high periprocedural stroke rate. In this study, we examined the rates of ischemic stroke in the territory of the qualifying artery (stroke in territory [SIT]) over time between MMT alone and stent+MMT. The primary outcome was SIT. Periprocedural stroke was considered <7 days from stent placement. Log-rank analysis, Cox proportional hazards models, and Kaplan-Meier survival curves compared time to SIT between MMT and stent+MMT (day of stenting considered day 0). In total, 435 patients were included (MMT: n=227; stent+MMT: n=208). The SIT event rate was 15.6% (68 events-MMT: n=31/227 (13.7%); stent+MMT: n=37/208 (17.8%). Twenty of the 37 stented patients had periprocedural SIT (7 early; 13 delayed). When periprocedural SIT was excluded, there were zero SIT events in the stent+MMT arm at 30 and 60 days, which was significantly lower than the MMT arm (P<0.01). Similarly, at 1 year, stent+MMT had a significantly lower rate of SIT (hazard ratio, 0.47 [95% CI, 0.23-0.98]; P=0.04). The difference in SIT between MMT and stent+MMT was not significant (P=0.2) over the entire follow-up period (1626 days), with 31 strokes in MMT and 17 nonperiprocedural strokes in stent+MMT (P=0.1). Thirteen patients with SIT were stented early (<7 days from qualifying ischemic event) with similar time of stent insertion to SIT compared to delayed stenting (P=0.9). Of patients with stent+MMT and SIT, there was no difference in periprocedural SIT based on early versus delayed stenting (P=0.9). No significant difference in total SIT was seen over time when compared between early and delayed stenting (P=0.6). Contrary to Food and Drug Administration recommendations, periprocedural SIT rates did not vary by time of stenting after qualifying ischemic event. Most SIT was periprocedural, and the rate of SIT over the study period was higher in MMT when excluding periprocedural strokes. These findings are exploratory but may suggest that MMT alone may not be the most effective treatment for intracranial atherosclerotic disease and that with improvements in periprocedural safety, intracranial stenting may remain a viable treatment option. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00576693.
Studies on unmet needs in long-term care (LTC) have focused on specific time points and have not adopted a dynamic approach that considers changes over time. This study examined the trajectories of unmet needs for care and support with activities of daily living (ADLs) and instrumental ADLs (IADLs) among adults aged 50+ across European countries up to 9 years after the onset of needs. Using the longitudinal data from the SHARE survey (2011-2022; n = 6,154), we used latent profile analysis to identify 5 trajectory types defined by time until onset of unmet needs, number of changes of state, time spent with unmet needs, ADL/IADL limitations, and age at onset of needs. These trajectories are marked by early periods of unmet needs (short-delayed met needs; long-delayed met needs; high needs and delayed), ambivalent (U-shaped met needs), or outright positive (met needs from onset). An overwhelming majority of older adults experienced unmet needs at some point after the onset of needs. Multivariate analysis shows that having a cohabiting spouse/partner and higher income are associated with trajectories where care is available early on. Country-level public expenditure on LTC is also a strong determinant of belonging to different trajectories. We further explored the association between these trajectories and mortality and ADL/IADL limitations. Results confirm the relevance of transition points, such as the time around the onset of needs, highlighting the potential role for case management and discharge teams at such transitions.
ObjectiveCleft lip and palate is the most common craniofacial birth defect. Timely primary cleft surgery is important to achieve good esthetic and speech outcomes and to prevent complications. The aim of this study was to compare outcomes between patients undergoing surgery at a comprehensive cleft center (CCC) and non-CCCs.DesignRetrospective comparative study.SettingsOne CCC and non-CCCs in 5 cities.Patients and InterventionThe study included 300 children who underwent primary cleft surgery at the participating centers between 2020 and 2024.Main Outcome MeasuresThe age at primary cleft surgery, length of hospital stay (LoS), and complications.ResultsPrimary cleft-lip and cleft-palate surgery was delayed in >50% and >60% of patients in the non-CCC group, respectively, which was significantly different compared to the rates in the CCC group. LoS was significantly shorter in the non-CCC group (P = .001). Complications such as bleeding, dehiscence, and return to the operating room after primary cleft surgery were significantly more common in the non-CCC group (P < .01)ConclusionThis study offers an insight into the timing of cleft lip and palate surgery, epidemiology, complication rates, and LoS in CCC and non-CCC settings in Indonesia. The frequency of delayed primary cleft lip and palate surgery and complication rates were significantly higher in non-CCC than in CCC settings. Therefore, strengthening cleft-care infrastructure in remote regions through multidisciplinary training, standardized operative protocols, and improved logistical support is essential to reduce disparities and ensure sustainability.
Organic ionic pairs offer a promising route to thermally activated delayed fluorescence (TADF) by enabling small singlet-triplet energy gaps (ΔE ST) and tunable charge-transfer (CT) interactions. However, balancing between HOMO-LUMO decoupling with moderate SOC and suppression of nonradiative decay remains a challenge. In this work, an electrostatically bound ionic pair, acridinium p-nitrobenzoate (AcPNB) exhibits a well-defined donor-acceptor (D-A) pair, and its physicochemical properties were studied. Single-crystal analysis reveals slipped π-π stacking (3.4 Å) and a slightly twisted D-A geometry (dihedral angle of -11.86°), while strong N-H⋯O and C-H⋯O interactions combinedly stabilize CT states. Density functional theory (DFT) calculations reveal decoupled frontier molecular orbitals, with a small ΔE S1T1 of 6 meV and a SOC of 2.4 cm-1. The AcPNB exhibits atypical broad photoluminescence (PL) emission centred at 578 nm, attributed to CT emission. The prompt and delayed lifetimes in ns and µs, together with non-monotonic temperature-dependent PL confirm a charge-transfer excited state and characteristics of the TADF mechanism. The cyclic voltammetric studies experimentally confirm the charge-transfer process, and this value relates to the DFT calculated HOMO value. The melting transition occurs at 171 °C, indicating strong ionic interactions against thermal decomposition. These findings give insights into the ionic pair-based TADF organic emitter for OLED applications by exploiting the advantages of decoupled HOMO-LUMO, SOC, and low ΔE ST.
Iatrogenic spinal cord herniation is an exceptionally rare complication following spinal surgery involving durotomy. Failure of watertight dural closure may lead to pseudomeningocele formation and progressive spinal cord tethering, ultimately resulting in herniation and neurological deterioration. We report two cases of postoperative spinal cord herniation. A 36-year-old male developed acute conus medullaris herniation 2 weeks after surgical resection of a cystic lesion, presenting with paraparesis, sensory loss, and sphincter dysfunction. A 68-year-old male presented with delayed cervical spinal cord herniation 19 months after C5-C7 meningioma resection, manifesting with progressive paresthesia on all four limbs. Magnetic resonance imaging demonstrated herniation of the spinal cord through a dorsal dural defect in both patients. Surgical revision consisted of extension of the previous durotomy, microsurgical lysis of arachnoid adhesions, reduction of the herniated spinal cord, and watertight dural repair using non-absorbable sutures reinforced with a collagen dural substitute and fibrin sealant. Both patients experienced significant neurological recovery, with complete symptomatic resolution in the cervical case. Postoperative spinal cord herniation requires a high index of suspicion in any patient with delayed neurological deterioration after spinal surgery. Early surgical untethering with watertight dural closure is essential to prevent permanent deficits; pseudomeningoceles identified on postoperative imaging warrant radiological surveillance until resolution.
Delayed cerebrovascular complications after radiotherapy have been well-documented. However, optimal management of acute ischemic stroke secondary to radiation-induced intracranial arterial stenosis remains unclear. A 17-year-old girl developed an acute ischemic stroke secondary to delayed middle cerebral artery stenosis following radiotherapy for recurrent craniopharyngioma after tumor resection. Intravenous alteplase (rt-PA) was administered 4 h after symptom onset, resulting in neurological improvement, and she was discharged with a modified Rankin Scale score of 0. This case suggests that rt-PA may be an effective treatment option for acute ischemic stroke associated with post-radiotherapy arterial stenosis, provided that the standard eligibility criteria are met.
Adverse events related to use of medicinal products are among the significant causes of morbidity and mortality. Quality of adverse event reports is essential for safety risk management. We therefore analyzed trends, timeliness and completeness of individual case safety reports (ICSRs) at a regional pharmacovigilance (PV) centre in Malawi. This was a cross-sectional study involving data extraction from ICSR reports that were submitted from 2017 to 2024. The data included patient demographics, adverse events, suspected products and reporter details. ICSR completeness was assessed using the vigiGrade® tool. The PV centre received a total of 1,057 ICSRs during the targeted period. These included 940 (88.9%) ADR and 117 (11.1%) AEFI cases. Most of the ADRs were serious (56.1%, n=527) while most of the AEFIs were not serious (58.1%, n=68), p<0.001. Highest reporting rates were recorded in 2022. Most of the ADR cases were related to Isoniazid (16.6%, n=156), followed by tenofovir/lamivudine/dolutegravir (14.5%, n=136). For the AEFIs, most cases were related to pneumococcal conjugate (22.2%, n=26), followed by pentavalent vaccine (21.4%, n=25). The median vigiGrade score for the ADRs was 0.7 (95% CI: 0.7-0.9; IQR: 0.57-1). This was significantly lower (P<0.001) as compared to the AEFIs with a median score of 1 (95% CI: 1-1; IQR: 0.7 -1). There was no significant difference in transmission time between ADR and AEFI reports, p=0.106. The median duration for transmission of ADR reports was 19.5 days (95% CI: 17-21 days; IQR: 6-56 days), while the median time AEFI report transmission was 8 days (95% CI: 3-30.9 days; IQR: 1-156 days). The study highlights poor quality and delayed reporting of adverse events. This may hinder safety signal detection, proper regulatory decision making and compromise patient safety. Strengthening digital reporting mechanisms would enhance quality reporting and streamline timely data flow. What is already known and why we conducted the study? Pharmacovigilance decisions rely on voluntary reporting of medicine safety issues such as adverse effects by healthcare providers and patientsGood quality data from the reports is therefore very important for improving patient safety What we did in the study? We assessed the number of reports, completeness and timeliness for submission of adverse effects reports related to medicines and vaccines at a pharmacovigilance centre in Malawi What are the important findings and implications? We found that most of the reports related to medicines are not well documented while most of the reports related to vaccines were well documented according to the World Health Organization standardsHowever, we noted significant delays to transmit both types of reports from the facility to the pharmacovigilance centreSome of the safety reports delayed up to more than 3 months which may affect decision making, especially for serious safety issues.
We study how path-specific delays can be identified from frequency-response measurements in delay-coupled oscillator networks. Although time delays strongly shape collective dynamics, measured transfer curves usually combine many directed routes, making it difficult to determine which delayed path controls a chosen source-detector channel. We show that discrete symmetry can resolve this inverse problem. For delay-coupled Kuramoto populations on a locked Ott-Antonsen branch, a symmetry-preserving operating point enforces an exact detector-source response zero. A controlled symmetry-breaking detuning unfolds this protected zero into a ladder of real-frequency nodal crossings. We prove a general theorem for finite retarded delay networks, solve the minimal four-population motif explicitly, and show that the asymptotic spacing of the nodal ladder reads out a detector-selected delay. In the baseline motif, the recovered spacing matches the predicted delay within 0.08%, while higher-node validations recover effective delays of 2.5027 and 2.7030, in close agreement with the corresponding microscopic path delays. The result provides a swept-frequency protocol for symmetry-assisted delay spectroscopy, requiring only a selected linear detector-source response rather than reconstruction of the full transfer matrix.
Neurobrucellosis is a serious complication of brucellosis, a common zoonotic infection. Its clinical diagnosis is often challenging due to the wide spectrum of clinical manifestations and the limited sensitivity of conventional diagnostic tools, including neuroimaging and cerebrospinal fluid (CSF) analysis, which may be normal or non-diagnostic. A 17-year-old male was recently diagnosed with brucellosis and was on standard triple antibiotic therapy. He presented with worsening systemic symptoms and new dysarthria. Contrast-enhanced brain magnetic resonance imaging was normal despite clear neurologic involvement. Lumbar puncture showed a mildly abnormal CSF with 10 white blood cells/mm3, normal protein and glucose levels. Blood and CSF cultures were negative, but Brucella serology was strongly positive. CSF Brucella PCR returned positive, confirming central nervous system involvement. Due to the high clinical suspicion of neurobrucellosis in the setting of non-diagnostic routine investigations, therapy was escalated to intravenous ceftriaxone for improved central nervous system penetration, in addition to doxycycline and rifampicin. The patient showed rapid and marked clinical improvement following appropriate CNS-targeted therapy, with resolution of dysarthria and systemic symptoms, and was discharged to complete a prolonged antibiotic course. This case highlights the diagnostic challenge of neurobrucellosis when conventional investigations such as MRI and CSF analysis are non-specific or minimally abnormal. Clinicians should maintain a high index of suspicion in endemic areas, as early diagnosis often relies on clinical judgment supported by serology and molecular testing. Recognition of the limitations of routine investigations is essential to avoid delayed treatment and prevent neurological complications.
Bernard "Bernie" Spilka died on Friday, May 23, 2025, in Denver, Colorado. Bernie was born Thursday, August 12, 1926, in New York City, New York. After World War II service in the Army Air Force Medical Corps, he attained a psychology BA (1949) from New York University. Graduate education at Purdue University included both MA (1950; group influence on individual judgment) and PhD (1952; delayed speech feedback) degrees. In 1953, while working for the U.S. Air Force Human Resources Research Center, Combat Crew Laboratory at Randolph Field, Texas, he met and married Ellen Scharlack. He served as president for many psychological associations and in 1985, along with Ralph W. Hood, Jr., and Richard L. Gorsuch summarized the re-emergent psychology of religion. With rotating authorship, that text remains in print today. He was a fierce advocate for the scientific method and never hesitated to chastise "fuzzy" conceptualizations, theories, methods, or overgeneralizations. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
To describe the clinical and radiological outcomes of minimally invasive percutaneous cannulated screw fixation (MIPCSF) in a consecutive series of patients with unstable Tile B/C pelvic fractures, and to explore associations between Tile classification, surgical timing, and outcomes. A single-center retrospective cohort study was conducted on 248 consecutive patients with unstable Tile B/C pelvic fractures who underwent MIPCSF. Fracture reduction and screw placement accuracy were assessed via Matta scoring and Gertzbein-Robbins classification. Functional outcomes were evaluated using Majeed score, SF-36 and VAS. Subgroup analyses were performed by Tile classification (B vs. C) and surgical timing (≤72 h vs. >72 h). Of 248 patients, 63.0% were male (mean age 42.8 ± 10.5 years) and 75.0% underwent early surgery. Mean intraoperative blood loss and operative time were 52.8 ± 18.6 mL and 68.5 ± 12.3 min. The excellent/good rate of Matta scoring was 92.3%, and clinically acceptable screw placement was 96.8%. Mean fracture healing time was 12.8 ± 3.2 weeks (healing rate 98.4%), with 18.5% developing degenerative changes. At final follow-up, mean Majeed score was 86.4 ± 10.2 (excellent/good rate 86.7%) and mean VAS was 1.8 ± 0.9. Tile C patients had longer operative time, more screws per patient, longer healing time, higher SI joint degeneration rate, and inferior functional scores than Tile B (all P-sub < 0.05 after Bonferroni correction). Early surgery was associated with shorter healing time (P-sub < 0.001) and lower SI joint degeneration (P-sub = 0.018) than delayed surgery. Matta excellent/good rate did not differ significantly between groups after correction for multiple comparisons. In this retrospective cohort, MIPCSF was associated with favorable clinical and radiological outcomes. Earlier surgical timing (≤72 h) was associated with shorter healing time and lower rates of SI joint degeneration. Tile C fractures were associated with longer operative times, more screws per patient, longer healing time, higher SI joint degeneration rates, and lower functional scores compared with Tile B fractures.
Hemodynamic failure, defined as insufficient postprocedural improvement in limb perfusion, occurs frequently after endovascular therapy (EVT). However, the predictors of hemodynamic failure and its clinical course have not been adequately investigated. This study aimed to investigate the predictors and clinical course of chronic limb-threatening ischemia (CLTI) with hemodynamic failure after EVT. This retrospective, multicenter analysis of the SAPLING database included 924 patients with CLTI and tissue loss who underwent EVT between April 2010 and March 2023, with skin perfusion pressure (SPP) measured pre- and postprocedure. Hemodynamic failure was defined as postprocedural SPP < 40 mmHg. Kaplan-Meier analysis evaluated cumulative wound healing, reintervention, and wound recurrence. Logistic regression and Cox proportional hazards models identified predictors of hemodynamic failure and wound healing. Hemodynamic failure occurred in 52.2% (482/924) of cases. Multivariable analysis identified lower preprocedural SPP and the absence of wound blush as independent predictors. Stratified analysis revealed the highest hemodynamic failure rate in patients with preprocedural SPP < 20 mmHg and absent wound blush (66.5%). Patients with hemodynamic failure showed significantly lower wound healing rates and higher rates of reintervention and wound recurrence (all p < 0.05). Factors independently associated with delayed wound healing included age ⩾ 75 years, nonambulatory status, hemodialysis, hemodynamic failure, Wound, Ischemia, and foot Infection (WIfI) stage 4, and the absence of wound blush. Hemodynamic failure after EVT was common and strongly associated with delayed wound healing, reintervention, and wound recurrence. Preprocedural SPP and wound blush assessment may be useful for identifying patients at high risk for hemodynamic failure.
The present study builds on conservation of resources theory and the concept of the recovery paradox (Hobfoll, 1989; Sonnentag, 2018) and responds to repeated calls to (a) study recovery processes over midterm time frames of weeks and (b) investigate directions of effects in recovery-well-being relations. Doing so, we employed the recovery activity characteristics approach, a dimensional framework for examining the underlying attributes of recovery activities (physical, social, creative, mental, spiritual, virtual, and outdoor dimensions) and examined the reciprocal lagged relationships between recovery activities and two indicators of employee well-being-emotional exhaustion and work engagement. We use preregistered data from 333 participants answering weekly surveys over an 8-week period to explore how recovery dimensions influence and are influenced by emotional exhaustion and work engagement using a random intercept cross-lagged panel model. Across dimensions, we found little evidence for consistent week-to-week lagged effects between recovery activities and well-being in either direction. One association indicated that higher-than-usual engagement in creative activities was followed by higher work engagement the subsequent week; however, given the number of statistical tests conducted, this finding may reflect a chance result and therefore requires independent replication. Overall, the findings suggest that recovery processes may be temporally bounded, with limited support for delayed within-person carryover effects across working weeks. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Despite the well-documented antimicrobial performance of ZnO nanoparticles, their incorporation into Ordinary Portland cement (OPC) is often accompanied by unfavorable effects, including delayed setting and deterioration of early-age mechanical properties. This investigation evaluates tannic acid (TA), a bio-derived organic compound, as a sustainable alternative cement additive to nano-ZnO. OPC pastes were modified with varying dosages of TA or nano-ZnO, and their influence on setting characteristics, workability, hydration progress, chemically combined water, free lime content, compressive strength, pore structure, phase composition, and microstructural development was systematically investigated. The results show that TA accelerates hydration at low dosage (0.25%) but exhibits a retarding effect at higher content (1%), whereas nano-ZnO consistently retards hydration regardless of concentration. At 3 days of curing, OPC containing 0.25% nano-ZnO attained a compressive strength of 78.3 MPa, while a pronounced reduction to 7 MPa was observed at 1% addition. In contrast, TA-modified systems demonstrated more stable mechanical performance, achieving 68.3 MPa at 0.25% and maintaining approximately 50 MPa at 1%. BET/BJH pore structure analysis revealed that both additives at 0.25% induced significant pore refinement, reducing the mean pore diameter from 67.92 nm to 48.52 nm for TA and 45.57 nm for nano-ZnO. Mineralogical and microstructural analyses (XRD, FTIR, SEM/EDX) indicated that TA promotes silicate dissolution and enhances the formation of portlandite, stratlingite, and tobermorite-like CSH phases. Conversely, nano-ZnO was found to inhibit hydration through the formation of Zn(OH)2 surface layers and calcium zincate hydrates (CZH). Antimicrobial tests confirmed effective inhibition of E. coli, E. faecalis, and C. albicans for both additives. The findings suggest that tannic acid provides improved hydration compatibility and mechanical reliability while retaining antimicrobial functionality, making it a viable alternative additive for cementitious systems.
Drug shortages in Latin America represent a widespread and persistent challenge, with a high proportion of hospitals reporting frequent supply disruptions that affect treatment continuity and quality of care. A cross-sectional study was conducted using a structured survey applied in 144 hospitals across eight Latin American countries between January and April 2025. A non-probabilistic snowball sampling strategy was used to recruit pharmaceutical professionals and personnel responsible for drug procurement. The questionnaire was developed by the research team and reviewed by a panel of hospital pharmacists to ensure content validity. Data were collected anonymously and are based on self-reported perceptions from professionals representing their institutions. Descriptive analyses and exploratory chi-square tests were performed. 75.0% of the responses came from South America, 20.8% from Mexico and 4.2% from Costa Rica. 75.7% of hospitals reported shortages as a serious problem, with a daily frequency in 30.6% and weekly frequency in 27.8% of cases. The most affected categories were antimicrobial, cardiovascular and oncological. Among the most relevant causes were inefficient procurement processes (84.3% in Argentina; 66.7% in Uruguay and Costa Rica), high prices, supply chain disruptions and global shortages of active ingredients. 53.7% of the hospitals had contingency plans, the presence of which was significantly associated with a lower frequency of shortages (p=0.025). The most commonly used strategies were therapeutic substitution (85-90%), inter-institutional collaboration, and the development of alternative formulations (95.5% in Colombia and 75% in Brazil). Shortage of drugs in the region are a multifactorial phenomenon with a relevant clinical and organizational impact. The implementation of contingency plans and inter-institutional cooperation strategies is associated with improved response capacity, understood as a reduced frequency and better management of shortage events. These findings highlight the need to strengthen contingency planning and promote coordinated regional policies based on the observed variability in causes and mitigation strategies. Medicine shortages are a growing problem that affects many hospitals in Latin America. When essential medicines are not available, patients’ treatments can be delayed or interrupted, leading to health complications and stress for both patients and healthcare workers. This study collected information from 144 hospitals in eight Latin American countries, where pharmacists and hospital managers answered a survey about how often medicine shortages occur, what causes them, and what strategies are used to manage them. Most hospitals (about three out of four) reported that shortages are a serious problem. In many cases, the lack of medicines happens every day or every week. The most affected drugs include antibiotics, cardiovascular medicines, and cancer treatments. The main causes of shortages are inefficient purchasing processes, high prices, problems in the global supply chain, and difficulties obtaining active ingredients used to make medicines. More than half of the hospitals have created contingency plans to deal with shortages, and these plans were linked to fewer problems of medicine supply. The most common actions include using therapeutic alternatives, sharing medicines between hospitals, and preparing customized formulations when needed. These results show that medicine shortages are a complex issue with serious consequences for patient care. However, hospitals that plan ahead and cooperate with others can reduce the impact. Stronger regional policies and better coordination between countries are needed to ensure that patients across Latin America always have access to the medicines they need.
Add-ons are non-essential interventions offered in addition to standard infertility treatments, mainly in vitro fertilisation (IVF) and associated procedures, aimed at improving chances of pregnancy and live birth. While existing guidelines provide recommendations on the use of add-ons, they often overlook the trustworthiness of the underlying randomised controlled trials (RCTs), which may lead to misleading conclusions. Furthermore, some add-ons that may offer genuine benefits have been dismissed due to misinterpretation of trial results, or they are reserved for repeated implantation failure based on strategic rather than evidence-based arguments. Here, we propose a framework for an evidence synthesis process to guide the rational use of add-ons. The evaluation should begin with establishing effectiveness through systematic reviews of trustworthy RCTs, ignoring RCTs that do not meet trustworthiness criteria. When assessing effectiveness, the evaluation should consider evidence relating to the biological mechanisms targeted by the add-on, in addition to clinical outcomes such as live birth. For diagnostic add-ons, evaluations should focus on the group of patients whose test result leads to a change in clinical management, rather than analysing all test-exposed patients. Once effectiveness is confirmed, evaluating cost-effectiveness becomes crucial. Its cost per additional live birth should be compared to a benchmark (e.g., $27,000 or £20,000 for a live birth via standard IVF). Finally, once proven cost-effective, add-ons should be offered early, rather than delayed until after repeated treatment failures. It might be that effectiveness and cost-effectiveness increase with progression along the continuum of diagnosis or IVF failure such as recurrent implantation failure. In that case, add-ons may be offered as soon as they are considered cost-effective.
Human adenovirus (HAdV) infection represents a significant cause of morbidity and mortality in patients with hematologic malignancies, particularly following allogeneic hematopoietic stem cell transplant. Clinical manifestations range from asymptomatic DNAemia to pneumonitis, enterocolitis, hepatitis, hemorrhagic cystitis, myocarditis, and central nervous system disease. Advances in molecular diagnostics, including quantitative polymerase chain reaction, have enabled earlier detection and surveillance, yet interpretation remains challenging given the absence of standardized viral load thresholds and international quantitative standards. Reported incidence varies by age, transplant type, geographic regions, and surveillance strategy, with pediatric recipients demonstrating higher infection rates, while mortality among patients with DNAemia or disseminated disease remains substantial. Risk factors include T-cell depletion, cord blood transplant, severe graft-versus-host disease, high-dose corticosteroid exposure, and delayed immune reconstitution. Management relies primarily on immune recovery and reduction of immunosuppression when feasible. Intravenous cidofovir remains the most widely used antiviral despite nephrotoxicity, while intravenous brincidofovir represents a potentially promising emerging approach. The impact of contemporary transplant approaches, including post-transplant cyclophosphamide and novel cellular therapies, on HAdV epidemiology requires further study. This review summarizes contemporary epidemiology, definitions, diagnostic strategies, and evolving therapeutic options for HAdV infection in patients with hematologic malignancies, highlighting ongoing challenges.