Perspectives and Misconceptions of an Online Adult Male Cohort Regarding Prostate Cancer Screening.

INTRODUCTION: Congruent with most guideline publishers, the Canadian Urological Association (CUA) recommends shared decision-making (SDM) on PSA screening (PSAS) for prostate cancer (PCa) following a discussion of its benefits and harms. However, there are limited data on how the general male population feels about these topics. METHODS: A survey was completed by 906 male-identifying participants (age > 18) recruited via Amazon Mechanical Turk (MTurk), which is a crowdsourcing platform providing minimal compensation. Participants answered questions regarding demographics (15), personal/family history (9), PCa/PSA knowledge (41), and opinions regarding PSAS (45). RESULTS: The median age was 38.2 (SD = 12.0), with 22% reporting a family history of PCa and 20% reporting personally undergoing PSAS. Although most participants had heard of PCa (85%) and that they could be screened for it (81%), they generally did not feel knowledgeable about PCa or PSAS guidelines. Most want to talk to their clinician about PCa and PSAS (74%) and are supportive of SDM (48%) or patient-centered decision-making (25%). In general, participants thought PSAS was still worthwhile, even if it led to additional testing or side effects. Similarly, participants thought higher-risk patients should be screened earlier (p < 0.001). A number of misconceptions were evident in the responses. CONCLUSIONS: Men approaching the age of PSAS do not feel knowledgeable about PCa or PSAS and want their clinician to discuss these topics with them. The majority believe in PSAS and would like to undergo this screening following SDM. Clinicians also have a role in correcting common misconceptions about PCa.

Metal binding feature of copper‒induced metallothionein from freshwater crab Sinopotamon henanense reveals its Cu‒thionein character.

Sinopotamon Henanense expresses two metal‒induced metallothioneins (MTs), Cd‒induced MT and Cu‒induced MT (ShCuMT). The Cd‒induced MT has been characterized as a Cd‒thiolate MT. However, it is unknown whether ShCuMT is a Cu‒thiolate MT. In the present study, ShCuMT was expressed heterologously in Escherichia coli and purified by Ni‒NTA column and superdex‒75 column. And its metal‒binding feature was evaluated by DTNB reaction, circular dichroism spectroscopy (CD), isothermal microtitration (ITC), electrospray flight mass spectrometry (ESI‒TOF‒MS), and matrix‒assisted laser desorption ionization flight mass spectrometry (MALDI‒TOF‒MS). Bioinformatics analysis demonstrated that ShCuMT possessed the cysteine‒triplet motif of a Cu‒specific MT. Expression and purification of ShCuMT illustrated that SUMO tag used as the production system for ShCuMT resulted in a high production yield. The stability order of ShCuMT binding metal ions were Cu (Ⅰ) > Cd (Ⅱ) > Zn (Ⅱ). The CD spectrum indicated that ShCuMT binding with Cu (I) exhibited a compact thiol metal clusters structure. Besides, there emerged no a visible nickel‒thiol absorption after Ni‒NTA column affinity chromatography. The ITC results implied that Cu‒ShCuMT possessed the optimal thermodynamic conformation and the highest stoichiometric number of Cu (Ⅰ). Overall, the results suggested that SUMO fusion system is a robust and inexpensive approach for ShCuMT expression and Ni‒NTA column had no influence on metal binding of ShCuMT and Cu(Ⅰ) was considered its cognate metal ion, and ShCuMT possessed canonical Cu‒thiolate characteristics. The metal binding feature of ShCuMT reported here contributes to elucidating the structure‒function relationship of ShCuMT in S. Henanense.

Factors influencing medical expenditures in patients with unresolved facial palsy and pharmacoeconomic analysis of upper eyelid lid loading with gold and platinum weights compared to tarsorrhaphy.

There are no standards in diagnostic and therapeutic approaches to eye care in incomplete eyelid closure due to unresolved facial palsy (FP). Loading of the upper eyelid (UELL) with gold weights (GWs) or platinum chains (PCs) is a highly effective procedure for the correction of lagophthalmos. Despite this, the procedure is used infrequently in our country because of the relatively high price of the implant and the lack of reimbursement. The aim of this research was to assess the factors influencing medical expenditures in this group of patients and to analyze utility costs for the UELL procedure with the use of GW and PC compared to tarsorrhaphy.Material and methods The costs of 88 surgical procedures (40 GWs, 11 PCs and 37 tarsorrhaphies) and medical expenditures before and after surgery were calculated based on reporting of materials, staff salaries and the SF-36 questionnaire. Distribution quartiles of the cost per QALY measure (dependent variable) was assessed via an ordered logistic regression model with eight explanatory variables.Results The calculated total cost of the surgery was US$209 for tarsorrhaphy, US$758 for UELL with a GW and US$1,676 for UELL with a PC. Bootstrapped costs per QALY values (CUI) in 88% of cases were below the US$100,000 cutoff. Etiology and duration of facial palsy and presence of Bell's phenomenon were factors that significantly influenced the CUI. Patient gender and age, history of previous eyelid surgery, and presence of corneal sensation were found to be not significant (p > 0.1). Calculated ICER for GW was US$1,241.74/1QALY and ICER for PC was US$13,181.05/1QALY compared to tarsorrhaphy.Conclusions Eye protection in patients with FP should be a crucial element of health policy. Findings suggest UELL procedure with a GW or a PC to be a cost-effective procedure with GW being the most cost-effective.

Environmental applications of lignin-based hydrogels for Cu remediation in water and soil: adsorption mechanisms and passivation effects.

Heavy metal pollution, particularly the excessive release of copper (Cu), is an urgent environmental concern. In this study, sodium lignosulfonate/carboxymethyl sa-son seed gum (SL-Cg-g-PAA) designed for remediation of Cu-contaminated water and soil was successfully synthesized through a free radical polymerization method using lignin as a raw material. This hydrogel exhibits remarkable Cu adsorption capability when applied to water, with a maximum adsorption capacity reaching 172.41 mg/g. Important adsorption mechanisms include surface complexation and electrostatic attraction between Cu(Ⅱ) and oxygen-containing functional groups (-OH, -COOH), as well as cation exchange involving -COONa and -SO3Na. Furthermore, SL/Cg-g-PAA effectively mitigated the bioavailability of heavy metals within soil matrices, as evidenced by a notable 14.1% reduction in DTPA extracted state Cu (DTPA-Cu) content in the S4 treatment (0.7% SL/Cg-g-PAA) compared to the control group. Concurrently, the Cu content in both the leaves and roots of pakchoi exhibited substantial decreases of 55.19% and 36.49%, respectively. These effects can be attributed to the precipitation and complexation reactions facilitated by the hydrogel. In summary, this composite hydrogel is highly promising for effective remediation of heavy metal pollution in water and soil, with a particular capability for the immobilization of Cu(Ⅱ) and reduction of its adverse effects on ecosystems.

Systematic methodological review of health state values in glaucoma cost-utility analyses.

IMPORTANCE: Describing the characteristics and sources of health state utility values and reporting practice in the literature of cost-utility analyses facilitates an understanding of the level of the transparency, validity, and generalizability of cost-utility analyses. Improving the quality of reporting will support investigators in describing the incremental value of emerging glaucoma interventions. OBJECTIVE: To describe the state of practice among published glaucoma cost-utility analysis studies, focusing on valuation of health and the quality of reporting. EVIDENCE REVIEW: We searched several databases including Medline, CINHAL, Embase, Web of Science, Scopus, Biosis previews, the Health Economic Evaluations Database, and the NHS Economic Evaluation Database (NHS EED). We included full-text, English, published cost-utility analyses of glaucoma interventions with quality-adjusted life years (QALYs) as the primary outcome measure to calculate incremental cost-utility ratios. Excluded studies were non-English language, reviews, editorials, protocols, or other types of economic studies (cost-benefit, cost-minimization, cost-effectiveness). Study characteristics, operational definitions of glaucoma health states and health state utilities were extracted. The original source of the health utility was reviewed to determine the scale of measurement and the source of preference weighting. Items from the Systematic Review of Utilities for Cost-Effectiveness (SpRUCE checklist) were used to assess the reporting and quality of health utilities in glaucoma CUA. FINDINGS: 43 CUAs were included, with 11 unique sources of health utilities. A wide range of health utilities for the same Hodapp-Parrish-Anderson glaucoma health states were reported; ocular hypertension (0.84-0.95), mild (0.68-0.94), moderate (0.57-0.92), advanced (0.58-0.88), severe/blind (0.46-0.76), and bilateral blindness (0.26-0.5). Most studies reported the basis for using health utilities (34, 79%) and any assumptions or adjustments applied to the health utilities (22, 51%). Few studies reported a framework for assessing the relevance of health utilities to a decision context (8, 19%). Even fewer (3, 7%) applied a systematic search strategy to identify health utilities and used a structured assessment of quality for inclusion. Overall, reporting has not improved over time. CONCLUSIONS AND RELEVANCE: This review describes that few CUAs describe important rationale for using health state utility values. Including additional details on the search, appraisal, selection, and inclusion process of health utility values improves transparency, generalizability and supports the assessment of the validity of study conclusions. Future investigations should aim to use health utilities on the same scale of measurement across health states and consider the source and relevance to the decision context/purpose of conducting that cost-utility study.

Using an inexpensive RGB color sensor for field quantitative assessment of soil accessible Cu(â ¡).

Field rapid determination of soil accessible Cu(Ⅱ) was important for environmental safety and human health risk assessment. In this study, an inexpensive red, green, and blue (RGB) color sensor was used for quantitative color difference analysis of the colored solution for soil accessible Cu(Ⅱ) with bis-cyclohexanone oxalydihydrazone as color reagent to develop a new method for analyzing soil accessible under field conditions. First, the calibration curve for RGB color sensor method was established in the standard solutions of Cu(II). Then the "hand shaking + standing" field extraction method for accessible Cu(Ⅱ) was developed. Finally, the method was applied in contaminated soils in the laboratory and in the field, and set the values determined by atomic absorption spectroscopy (AAS) as the standard ones. Results indicated that in the range of 0.1-5 mg L-1 Cu(II), the RGB Euclidean chromogenic difference values were directly linear correlated with the concentration of Cu(II) (R2 > 0.999). The interference of Fe(Ⅲ) and Mn(Ⅱ) could be eliminated by adding citric acid. The "hand shaking + standing" field extraction method could effectively extract the accessible Cu(Ⅱ) from soil with the high extraction rates. The concentrations of accessible Cu(II) in various polluted soils determined by RGB color sensor method were consistent with that determined by AAS, with the relative error within ±5%, the relative standard deviation ≤ 20%. The recovery of Cu(II) in RGB color sensor method was between 97% and 105%, which could meet the requirements of trace analysis of accessible Cu(Ⅱ) in the field. The high accuracy and precision of RGB color sensor method was reconfirmed in the rapid field quantitative assessment of soil accessible Cu(Ⅱ). Due to that the RGB color sensor was low cost, rechargeable, portable, mobile, ambient light resistant, the method would have a great potential for the determination of accessible Cu(Ⅱ) in contaminated soils.

A new Caenorhabditis elegans model to study copper toxicity in Wilson disease.

Wilson disease (WD) is caused by mutations in the ATP7B gene that encodes a copper (Cu) transporting ATPase whose trafficking from the Golgi to endo-lysosomal compartments drives sequestration of excess Cu and its further excretion from hepatocytes into the bile. Loss of ATP7B function leads to toxic Cu overload in the liver and subsequently in the brain, causing fatal hepatic and neurological abnormalities. The limitations of existing WD therapies call for the development of new therapeutic approaches, which require an amenable animal model system for screening and validation of drugs and molecular targets. To achieve this objective, we generated a mutant Caenorhabditis elegans strain with a substitution of a conserved histidine (H828Q) in the ATP7B ortholog cua-1 corresponding to the most common ATP7B variant (H1069Q) that causes WD. cua-1 mutant animals exhibited very poor resistance to Cu compared to the wild-type strain. This manifested in a strong delay in larval development, a shorter lifespan, impaired motility, oxidative stress pathway activation, and mitochondrial damage. In addition, morphological analysis revealed several neuronal abnormalities in cua-1 mutant animals exposed to Cu. Further investigation suggested that mutant CUA-1 is retained and degraded in the endoplasmic reticulum, similarly to human ATP7B-H1069Q. As a consequence, the mutant protein does not allow animals to counteract Cu toxicity. Notably, pharmacological correctors of ATP7B-H1069Q reduced Cu toxicity in cua-1 mutants indicating that similar pathogenic molecular pathways might be activated by the H/Q substitution and, therefore, targeted for rescue of ATP7B/CUA-1 function. Taken together, our findings suggest that the newly generated cua-1 mutant strain represents an excellent model for Cu toxicity studies in WD.

Boosting Cu─In─Zn─S-based Quantum-Dot Light-Emitting Diodes Enabled by Engineering Cu─NiOx /PEDOT:PSS Bilayered Hole-Injection Layer.

The imbalance of charge injection is considered to be a major factor that limits the device performance of cadmium-free quantum-dot light-emitting diodes (QLEDs). In this work, high-performance cadmium-free Cu─In─Zn─S(CIZS)-based QLEDs are designed and fabricated through tailoring interfacial energy level alignment and improving the balance of charge injection. This is achieved by introducing a bilayered hole-injection layer (HIL) of Cu-doped NiOx (Cu─NiOx )/Poly(3,4-ethylenedioxythiophene): poly (styrene sulfonate) (PEDOT:PSS). High-quality Cu─NiOx film is prepared through a novel and straightforward sol-gel procedure. Multiple experimental characterizations and theoretical calculations show that the incorporation of Cu2+ ions can regulate the energy level structure of NiOx and enhance the hole mobility. The state-of-art CIZS-based QLEDs with Cu─NiOx /PEDOT:PSS bilayered HIL exhibit the maximum external quantum efficiency of 6.04% and half-life time of 48 min, which is 1.3 times and four times of the device with only PEDOT:PSS HIL. The work provides a new pathway for developing high-performance cadmium-free QLEDs.

The long-term impact and value of curative therapy for HIV: a modelling analysis.

INTRODUCTION: Curative therapies (CTx) to achieve durable remission of HIV disease without the need for antiretroviral therapy (ART) are currently being explored. Our objective was to model the long-term health and cost outcomes of HIV in various countries, the impact of future CTx on those outcomes and the country-specific value-based prices (VBPs) of CTx. METHODS: We developed a decision-analytic model to estimate the future health economic impacts of a hypothetical CTx for HIV in countries with pre-existing access to ART (CTx+ART), compared to ART alone. We modelled populations in seven low-and-middle-income countries and five high-income countries, accounting for localized ART and other HIV-related costs, and calibrating variables for HIV epidemiology and ART uptake to reproduce historical HIV outcomes before projecting future outcomes to year 2100. Health was quantified using disability-adjusted life-years (DALYs). Base case, pessimistic and optimistic scenarios were modelled for CTx+ART and ART alone. Based on long-term outcomes and each country's estimated health opportunity cost, we calculated the country-specific VBP of CTx. RESULTS: The introduction of a hypothetical CTx lowered HIV prevalence and prevented future infections over time, which increased life-years, reduced the number of individuals on ART, reduced AIDS-related deaths, and ultimately led to fewer DALYs versus ART-alone. Our base case estimates for the VBP of CTx ranged from $5400 (Kenya) up to $812,300 (United States). Within each country, the VBP was driven to be greater primarily by lower ART coverage, lower HIV incidence and prevalence, and higher CTx cure probability. The VBP estimates were found to be greater in countries where HIV prevalence was higher, ART coverage was lower and the health opportunity cost was greater. CONCLUSIONS: Our results quantify the VBP for future curative CTx that may apply in different countries and under different circumstances. With greater CTx cure probability, durability and scale up, CTx commands a higher VBP, while improvements in ART coverage may mitigate its value. Our framework can be utilized for estimating this cost given a wide range of scenarios related to the attributes of a given CTx as well as various parameters of the HIV epidemic within a given country.

Sodium Thiosulfate for Calciphylaxis Treatment in Patients on Peritoneal Dialysis: A Systematic Review.

Limited data are available on the utilization of sodium thiosulfate (STS) treatment for calciphylaxis in peritoneal dialysis (PD) patients, while it is well-studied in hemodialysis (HD) patients. A systematic literature search was conducted using Ovid MEDLINE, EBM Reviews-Cochrane Central Register of Controlled Trials, and EBM Reviews-Cochrane Database of Systematic Reviews to identify reported cases of PD patients with calciphylaxis who received STS. The search covered the inception of the databases through August 2022. Across 19 articles, this review identified 30 PD patients with calciphylaxis who received STS. These included 15 case reports, 2 case series, and 2 cohort studies. The administration routes and doses varied depending on the study. For intravenous (IV) administration (n = 18), STS doses ranged from 3.2 g twice daily to 25 g three times weekly for 5 weeks to 8 months. Outcomes included 44% of patients experiencing successful wound healing, 6% discontinuing STS due to adverse effects, 67% transitioning to HD, and 50% dying from calciphylaxis complications. For intraperitoneal (IP) administration (n = 5), STS doses ranged from 12.5 to 25 g three to four times weekly for 12 h to 3 months. Results showed 80% of patients achieving successful wound healing, 80% discontinuing STS due to adverse effects, 40% transitioning to HD, and 20% dying from IP STS-related chemical peritonitis. In cases where patients switched from IV to IP STS (n = 3), doses ranged from 12.5 to 25 g two to three times weekly for 2.5 to 5 months. Among them, 67% experienced successful wound healing, while 33% died from sepsis. Two cases utilized oral STS at a dose of 1500 mg twice daily for 6 and 11 months, resulting in successful wound healing without adverse effects or need for HD. However, one patient (50%) died due to small bowel obstruction. This systematic review provides an overview of STS treatment for PD patients with calciphylaxis. Although successful treatment cases exist, adverse effects were significant. Further research, including larger clinical studies and pharmacokinetic data, is necessary to establish the optimal route, dose, and efficacy of STS in PD patients.

Cost-effectiveness analysis of sarcopenia management interventions in Iran.

OBJECTIVES: Identification the optimal management intervention of sarcopenia is a concern of health systems. We aimed to analyze the cost-effectiveness of sarcopenia management strategies in Iran. METHODS: We constructed a lifetime Markov model based on natural history. The strategies comparedincluded exercise training, nutritional supplements, whole body vibration (WBV), and various exercise interventions and nutritional supplement combinations. A total of 7 strategies was evaluated in addition to the non-intervention strategy. Parameter values were extracted from primary data and the literature, and the costs and Quality-adjusted life years (QALYs) were calculated for each strategy. Deterministic and probabilistic sensitivity analysis, including the expected value of perfect information (EVPI), was also performed to determine the robustness of the model. Analyses were performed using the 2020 version of TreeAge Pro software. RESULTS: All seven strategies increased lifetime effectiveness (QALYs). The protein and Vitamin D3 (P + D) strategy had the highest effectiveness values among all strategies. After removing the dominated strategies, the estimated ICER for the P + D compared to Vitamin D3 alone (D) strategy was calculated as $131,229. Considering the cost-effectiveness threshold ($25,249), base-case results indicated that the D strategy was the most cost-effective strategy in this evaluation. Sensitivity analysis of model parameters also demonstrated the robustness of results. Also, EVPI was estimated at $273. CONCLUSIONS: Study results, as the first economic evaluation of sarcopenia management interventions, showed that despite the higher effectiveness of D + P, the D strategy was the most cost-effective. Completing clinical evidence of various intervention options can lead to more accurate results in the future.

Fully Delocalized Mixed-Valent Cu1.5 Cu1.5 Complex: Strong Cu-Cu interaction and Fast Electron Self-Exchange Rate Despite Large Structural Changes.

A flexible macrocyclic ligand with two tridentate {CNC} compartments can host two Cu ions in reversibly interconvertible states, CuI CuI (1) and mixed-valent Cu1.5 Cu1.5 (2). They were characterized by XRD and multiple spectroscopic methods, including EPR, UV/Vis absorption and MCD, in combination with TD-DFT and CASSCF calculations. 2 features a short Cu⋅⋅⋅Cu distance (≈2.5 Å; compared to ≈4.0 Šin 1) and a very high delocalization energy of 13 000 cm-1 , comparable to the mixed-valent state of the biological CuA site. Electron self-exchange between 1 and 2 is rapid despite large structural reorganization, and is proposed to proceed via a sequential mechanism involving an active conformer of 1, viz. 1'; the latter has been characterized by XRD. Such electron transfer (ET) process is reminiscent of the conformationally gated ET proposed for biological systems. This redox couple is a unique pair of flexible dicopper complexes, achieving fast electron self-exchange closely related to the function of the CuA site.

Preparation of Hydrophobic Cryogel Containing Hydroxyoxime Extractant and Its Extraction Properties of Cu(â ¡).

Hydrophobic cryogels with monolithic supermacropores based on poly-trimethylolpropane trimethacrylate (pTrim) containing 1-(2-Hydroxyl-5-nonyphenyl)ethanone oxime (LIX84-I) were successfully prepared by a cryo-polymerization technique using organic solvents with freezing points between room temperature and around 0 °C as solvents. The prepared cryogels were characterized in terms of macroscopic shape and porous structure. The cryogels had a monolithic supermacroporous structure and high contents of LIX84-I depending on the added amount of the extractant to the monomer solution. The amount of LIX84-I impregnated in the cryogel had a linear relationship with the added amount of LIX84-I in the monomer solution for cryo-polymerization. Cu(II) in the aqueous solution was immediately adsorbed into the cryogel containing LIX84-I.

Health economics of health justice partnerships: A rapid review of the economic returns to society of promoting access to legal advice.

Background: Welfare legal problems and inadequate access to support services follow both the socioeconomic and the health inequalities gradients. Health Justice Partnership (HJP) is an international practitioner-led movement which brings together legal and healthcare professionals to address the root causes of ill health from negative social determinants. The aim of this paper was to identify the current evidence base for the cost-effectiveness of HJP or comparable welfare advice services. Methods: A rapid review format was used, with a literature search of PubMed, CINAHL, ASSIA, PsycINFO, Medline, Cochrane Library, Global Health and Web of Science identifying 496 articles. After removal of duplicates, 176 papers were screened on titles and abstracts, and 20 papers met the eligibility criteria. Following a full-text screening, a further 14 papers were excluded due to lack of economic evaluations. Excluded papers' reference lists were scanned, with a further 3 further papers identified which met the inclusion criteria. A final pool of nine studies were included in this review. Results: Studies focused on the financial benefit to service users, with only three studies reporting on cost effectiveness of the interventions. Only one study reported on the economic impact of change of health in service users and one study reported on changes in health service use. Conclusion: This review highlights the current evidence gap in evaluating the cost-effectiveness of adequate access to free legal welfare advice and representation. We propose that an interdisciplinary research agenda between health economics and legal-health services is required to address this research gap.

Fish species composition, diversity, and migration in the Mekong Delta: a study in the Cua Tieu River, Vietnam.

Southern Vietnam, particularly the Mekong Delta, is popular in inland fish species diversity. In this study, fish species diversity across six stations from the estuary to the upstream of Cua Tieu River, which is situated in the Tien Giang province in Southern Vietnam, has been studied from January 2018 to June 2020. Altogether, 2088 specimens were collected and classified, and these belonged to 115 species, 98 genera, and 54 families of 15 orders that were recognized and identified. The names of species, genera, families, and orders are cited. In the total of 115 species, the Perch-like order (Perciformes) is the most diverse group, with 50 species (consist of 43.48% of total species). The catfish order (Siluriformes) is the second-most diverse group, consisting of 19 species (16.52% of total species). The carp order (Cypriniformes) consists of 8 species (6.96%), and the herring order (Clupeiformes) consists of 7 species (6.09%). Three orders of fishes, needle fish order (Beloniformes), Spiny eel order (Synbranchiformes), and flounder order (Pleuronectiformes), consist of 6 species (5.22%), and other orders consist of 1-3 species (0.87-2.61%). Among the 115 species recorded, 4 species were classified as vulnerable (VU) in the Red Data Book of Viet Nam (2007) (which is 3.48% of the total species collected). These are Elops saurus, Anodontostoma chacunda, Datnioides polota, and Toxotes chatareus. According to the IUCN Red list (2020), 1 species is endangered (EN) (0.87%), 1 species is vulnerable (VU) (0.87%), 3 species of fish are near threatened (NT) (2.61%), 6 species are data deficient (DD) (5.22%), and 58 species are least concern (LC) (50.43%). The result also recorded 41 fish as migratory species (26 freshwater species and 15 marine species), which is 35.65% of total species collected. Some migratory species are important and endemic species of the Mekong River, such as Bagarius yarrelli, Boesemania microlepis, Yasuhikotakia modesta, Cyclocheilos enoplos, Pangasianodon hypophthalmus, Pangasius conchophilus, Pangasius krempfi, Pangasius pleurotaenia, Phalacronotus bleekeri.

Health economics and manual small-incision cataract surgery: An illustrative mini review.

Cataract extraction is one of the most common surgical procedures performed worldwide. Manual small-incision cataract surgery (MSICS) is a popular technique of cataract extraction. Full economic evaluation of different techniques is of value to policy makers. This was a systematic review of published literature to present a brief overview of evidence available in respect of economic evaluation measures like cost effectiveness, cost utility, and cost parameters in cataract patients regarding MSICS. The data on these was sparse and heterogeneous. Direct costs of MSICS were lower than phacoemulsification (PE): $25.55 (PE) to $17.03 (MSICS) in India, $15 (MSICS) to $70 (PE) in Nepal, and $62.25 (MSICS) to $104.15 (PE) in Thailand. The cost utility analysis for MSICS demonstrated savings of $79.57 (INR6175) per gain in LogMAR BCVA, $8.91 (INR691) per QALY gained and $1.42 (INR110) per VF 14 score increment in India. Incremental cost-effectiveness ratio (ICER) $368.20 (13,215.50 Baht) for MSICS was better than $489.30 (17,561.70 Baht) for PE in Thailand. ICER for femto laser-assisted cataract surgery (FLACS) compared to was €10,703 in femtosecond laser-assisted versus phacoemulsification cataract surgery (FEMCAT) study. The corrected ICER for PE against MSICS is €146.50. The limited data available demonstrates that MSICS is the most cost-effective technique among FLACS, PE, and MSICS. MSICS scores over other existing alternatives of cataract extraction from cost-effectiveness and cost-minimization approaches. Further research is required in this area.

Plascua: Programming Language Support for Continuous User Authentication.

Compared to traditional user authentication methods, continuous user authentication (CUA) provide enhanced protection, guarantees against unauthorized access and improved user experience. However, developing effective continuous user authentication applications using the current programming languages is a daunting task mainly because of lack of abstraction methods that support continuous user authentication. Using the available language abstractions developers have to write the CUA concerns (e.g., extraction of behavioural patterns and manual checks of user authentication) from scratch resulting in unnecessary software complexity and are prone to error. In this paper, we propose new language features that support the development of applications enhanced with continuous user authentication. We develop Plascua, a continuous user authentication language extension for event detection of user bio-metrics, extracting of user patterns and modelling using machine learning and building user authentication profiles. We validate the proposed language abstractions through implementation of example case studies for CUA.

Cost-Utility Analysis of Community Case Management for Malaria Control in Burundi.

BACKGROUND: The community case management (CCM) program for malaria control is a community-based strategy implemented to regulate malaria in children in Burundi. This study compared the cost and utility of implementing the CCM program combined with health facility management (HFM) versus HFM alone for malaria control in children under five in Burundi. METHODS: This study constructed a five-year Markov model with one-week cycles to estimate cost-utility and budget impact analysis (BIA). The model defined 10 health states, simulating the progression of the disease and the risk of recurrent malaria in children under five years of age. Cost data were empirically collected and presented for 2019. Incremental cost per disability-adjusted life year (DALY) averted, and a five-year budget was estimated. One-way and probabilistic sensitivity analyses (PSAs) were then performed. RESULTS: From provider and societal perspectives, combining the CCM program with HFM for malaria control in Burundi was more cost-effective than implementing HFM alone. The addition of CCM, using artesunate amodiaquine (ASAQ) as the first-line treatment, increased by US$1.70, and US$ 1.67 per DALY averted from the provider and societal perspectives, respectively. Using Artemether Lumefantrine (AL) as the first-line treatment, adding the CCM program to HFM increased by US$ 1.92, and US$ 1.87 per DALY averted from the provider and societal perspectives. At a willingness-to-pay of one GDP/capita, the CCM program remained a 100% chance of being cost-effective. In addition, implementing the program for five years requires a budget of US$ 15 800 486-19 765 117. CONCLUSION: Implementing the CCM program and HFM is value for money for malaria control in Burundi. The findings can support decision-makers in Burundi in deciding on resource allocation, especially during the program's scale up.

Meta-analysis of economic evaluation studies: data harmonisation and methodological issues.

BACKGROUND: In the context of ever-growing health expenditure and limited resources, economic evaluations aid in making evidence-informed policy decisions. Cost-utility analysis (CUA) is often used, and CUA data synthesis is also desirable, but methodological issues are challenged. Hence, we aim to provide a step-by-step process to prepare the CUA data for meta-analysis. METHODS: Data harmonisation methods were constructed specifically considering CUA methodology, including inconsistent reports, economic parameters, heterogeneity (i.e., country's income, time horizon, perspective, modelling approaches, currency, willingness to pay). An incremental net benefit (INB) and its variance were estimated and pooled across studies using a basic meta-analysis by COMER. RESULTS: Five scenarios show how to obtain INB and variance with various reported data: Study reports the mean and variance (Scenario 1) or 95% confidence interval (Scenario 2) of ΔC, ΔE, and ICER for INB/variance calculations. Scenario 3: ΔC, ΔE, and variances are available, but not for the ICER; a Monte Carlo was used to simulate ΔC and ΔE data, variance and covariance can be then estimated leading INB calculation. Scenario-4: Only the CE plane was available, ΔC and ΔE data can be extracted; means of ΔC, ΔE, and variance/covariance can be estimated accordingly, leading to INB/variance estimates. Scenario-5: Only mean cost/outcomes and ICER are available but not for variance and the CE-plane. A variance INB can be borrowed from other studies which are similar characteristics, including country income, ICERs, intervention-comparator, time period, country region, and model type and inputs (i.e., discounting, time horizon). CONCLUSION: Out data harmonisation and meta-analytic methods should be useful for researchers for the synthesis of economic evidence to aid policymakers in decision making.

The Role of COA6 in the Mitochondrial Copper Delivery Pathway to Cytochrome c Oxidase.

Copper is essential for the stability and activity of cytochrome c oxidase (CcO), the terminal enzyme of the mitochondrial respiratory chain. Copper is bound to COX1 and COX2, two core subunits of CcO, forming the CuB and CuA sites, respectively. Biogenesis of these two copper sites of CcO occurs separately and requires a number of evolutionarily conserved proteins that form the mitochondrial copper delivery pathway. Pathogenic mutations in some of the proteins of the copper delivery pathway, such as SCO1, SCO2, and COA6, have been shown to cause fatal infantile human disorders, highlighting the biomedical significance of understanding copper delivery mechanisms to CcO. While two decades of studies have provided a clearer picture regarding the biochemical roles of SCO1 and SCO2 proteins, some discrepancy exists regarding the function of COA6, the new member of this pathway. Initial genetic and biochemical studies have linked COA6 with copper delivery to COX2 and follow-up structural and functional studies have shown that it is specifically required for the biogenesis of the CuA site by acting as a disulfide reductase of SCO and COX2 proteins. Its role as a copper metallochaperone has also been proposed. Here, we critically review the recent literature regarding the molecular function of COA6 in CuA biogenesis.