Search

Background: Needle and syringe programs (NSPs) are effective at preventing HIV and hepatitis C virus (HCV) among people who inject drugs (PWID), yet global coverage is low, partly because governments lack data on the cost and cost-effectiveness of NSP in their countries to plan and fund their responses. We conducted a global systematic review of unit costs of NSP provision to inform estimation of cost drivers and extrapolated costs to other countries., Methods: We conducted a systematic review to extract data on the cost per syringe distributed and its cost drivers. We estimated the impact of country-level and program-level variables on the cost per syringe distributed using linear mixed-effects models. These models were used to predict unit costs of NSP provision, with the best performing model used to extrapolate the cost per syringe distributed for 137 countries. The total cost for a comprehensive NSP (200 syringes per PWID/year) was also estimated for 68 countries with PWID population size estimates., Results: We identified 55 estimates of the unit cost per syringe distributed from 14 countries. Unit costs were extrapolated for 137 countries, ranging from $0.08 to $20.77 (2020 USD) per syringe distributed. The total estimated spend for a high-coverage, comprehensive NSP across 68 countries with PWID size estimates is $5 035 902 000 for 10 887 500 PWID, 2.1-times higher than current spend., Conclusion: Our review identified cost estimates from high-income, upper-middle-income, and lower-middle-income countries. Regression models may be useful for estimating NSP costs in countries without data to inform HIV/HCV prevention programming and policy., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Although climate change poses a threat to health and well-being globally, a regional approach to addressing climate-related health equity may be more suitable, appropriate, and appealing to under-resourced communities and countries. In support of this argument, this commentary describes an approach by a network of researchers, practitioners, and policymakers dedicated to promoting climate-related health equity in Small Island Developing States and low- and middle-income countries in the Pacific. We identify three primary sets of needs related to developing a regional capacity to address physical and mental health disparities through research, training, and assistance in policy and practice implementation: (1) limited healthcare facilities and qualified medical and mental health providers; (2) addressing the social impacts related to the cooccurrence of natural hazards, disease outbreaks, and complex emergencies; and (3) building the response capacity and resilience to climate-related extreme weather events and natural hazards.

VEGF inhibitor drugs are part of standard care in oncology and ophthalmology, but not all patients respond to them. Combinations of drugs are likely to be needed for more effective therapies of angiogenesis-related diseases. In this paper we describe naturally occurring combinations of receptors in endothelial cells that might help to understand how cells communicate and to identify targets for drug combinations. We also develop and share a new software tool called DECNEO to identify them. Single-cell gene expression data are used to identify a set of co-expressed endothelial cell receptors, conserved among species (mice and humans) and enriched, within a network, of connections to up-regulated genes. This set includes several receptors previously shown to play a role in angiogenesis. Multiple statistical tests from large datasets, including an independent validation set, support the reproducibility, evolutionary conservation and role in angiogenesis of these naturally occurring combinations of receptors. We also show tissue-specific combinations and, in the case of choroid endothelial cells, consistency with both well-established and recent experimental findings, presented in a separate paper. The results and methods presented here advance the understanding of signaling to endothelial cells. The methods are generally applicable to the decoding of intercellular combinations of signals., (© 2022. The Author(s).)

Workers in climate exposed industries such as agriculture, construction, and manufacturing face increased health risks of working on high temperature days and may make decisions to reduce work on high-heat days to mitigate this risk. Utilizing the American Time Use Survey (ATUS) for the period 2003 through 2018 and historical weather data, we model the relationship between daily temperature and time allocation, focusing on hours worked by high-risk laborers. The results indicate that labor allocation decisions are context specific and likely driven by supply-side factors. We do not find a significant relationship between temperature and hours worked during the Great Recession (2008-2014), perhaps due to high competition for employment, however during periods of economic growth (2003-2007, 2015-2018) we find a significant reduction in hours worked on high-heat days. During periods of economic growth, for every degree above 90 on a particular day, the average high-risk worker reduces their time devoted to work by about 2.6 minutes relative to a 90-degree day. This effect is expected to intensify in the future as temperatures rise. Applying the modeled relationships to climate projections through the end of century, we find that annual lost wages resulting from decreased time spent working on days over 90 degrees across the United States range from $36.7 to $80.0 billion in 2090 under intermediate and high emission futures, respectively., Competing Interests: The authors have declared that no competing interests exist.

Workers trained in STEM are generally viewed as essential for innovation-led economic growth. Yet, recent statistics suggest that a majority of STEM undergraduates do not go on to pursue innovation-focused careers in their fields of study. We investigate whether STEM students who do not self-select into innovative tasks are doing so because they are less capable than their peers who do. We find that monetary inducement among STEM students increases aggregate innovative output, but that low-GPA students who were induced significantly underperform relative to low-GPA students who self-selected; however, induced and self-selected high-GPA students perform statistically the same. In contrast, words of encouragement appears to benefit those students with the lowest GPAs. Our results highlight the value of efforts to increase the pool of STEM students who pursue innovative careers and underscore the importance of interventions targeted at specific student subgroups to maximize the returns on those efforts., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To determine cost-effectiveness of three community-based acute HIV infection (AHI) testing algorithms compared to HIV antibody testing alone by focusing on the potential of averting new infections occurring within a one-year time horizon among men who have sex with men (MSM)., Methods: Data sources for model parameters included actual cost and prevalence data derived from a community-based AHI screening program in San Diego, and published studies. Main outcome measure was costs per infection averted (IA). The lower end of the cost range of discounted lifetime costs of an HIV infection (i.e. $236,948) was used for defining cost-effectiveness., Results: The most sensitive algorithm for AHI detection, which was based on HIV nucleic acid amplification testing, was estimated to prevent between 5 and 45 transmissions, with simulated costs per infection averted between $965 and $141,256 when compared to HIV antibody testing alone., Conclusion: AHI testing was cost-effective in preventing new HIV infections among at risk MSM in San Diego, and also among other MSM populations with similar HIV prevalence but lower proportions of AHI diagnoses. These results indicate that community-based AHI testing among MSM in the United States can pay for itself over the long run., Competing Interests: Dr. Hoenigl served on the speakers’ bureau of Merck. Dr. Little reported grant funding from Gilead Sciences, Inc. All other authors no conflicts., (Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: We evaluated the cost-effectiveness of combined single session brief behavioral intervention, either didactic or interactive (Mujer Mas Segura, MMS) to promote safer-sex and safer-injection practices among female sex workers who inject drugs (FSW-IDUs) in Tijuana (TJ) and Ciudad-Juarez (CJ) Mexico. Data for this analysis was obtained from a factorial RCT in 2008-2010 coinciding with expansion of needle exchange programs (NEP) in TJ, but not in CJ., Methods: A Markov model was developed to estimate the incremental cost per quality adjusted life year gained (QALY) over a lifetime time frame among a hypothetical cohort of 1,000 FSW-IDUs comparing a less intensive didactic vs. a more intensive interactive format of the MMS, separately for safer sex and safer injection combined behavioral interventions. The costs for antiretroviral therapy was not included in the model. We applied a societal perspective, a discount rate of 3% per year and currency adjusted to US$2014. A multivariate sensitivity analysis was performed. The combined and individual components of the MMS interactive behavioral intervention were compared with the didactic formats by calculating the incremental cost-effectiveness ratios (ICER), defined as incremental unit of cost per additional health benefit (e.g., HIV/STI cases averted, QALYs) compared to the next least costly strategy. Following guidelines from the World Health Organization, a combined strategy was considered highly cost-effective if the incremental cost per QALY gained fell below the gross domestic product per capita (GDP) in Mexico (equivalent to US$10,300)., Findings: For CJ, the mixed intervention approach of interactive safer sex/didactic safer injection had an incremental cost-effectiveness ratio (ICER) of US$4,360 ($310-$7,200) per QALY gained compared with a dually didactic strategy. Using the dually interactive strategy had an ICER of US$5,874 ($310-$7,200) compared with the mixed approach. For TJ, the combination of interactive safer sex/didactic safer injection had an ICER of US$5,921 ($104-$9,500) per QALY compared with dually didactic. Strategies using the interactive safe injection intervention were dominated due to lack of efficacy advantage. The multivariate sensitivity analysis showed a 95% certainty that in both CJ and TJ the ICER for the mixed approach (interactive safer sex didactic safer injection intervention) was less than the GDP per capita for Mexico. The dual interactive approach met this threshold consistently in CJ, but not in TJ., Interpretation: In the absence of an expanded NEP in CJ, the combined-interactive formats of the MMS behavioral intervention is highly cost-effective. In contrast, in TJ where NEP expansion suggests that improved access to sterile syringes significantly reduced injection-related risks, the interactive safer-sex combined didactic safer-injection was highly cost-effective compared with the combined didactic versions of the safer-sex and safer-injection formats of the MMS, with no added benefit from the interactive safer-injection component.

Background: In nonhealthcare settings, widespread screening for acute human immunodeficiency virus (HIV) infection (AHI) is limited by cost and decision algorithms to better prioritize use of resources. Comparative cost analyses for available strategies are lacking., Methods: To determine cost-effectiveness of community-based testing strategies, we evaluated annual costs of 3 algorithms that detect AHI based on HIV nucleic acid amplification testing (EarlyTest algorithm) or on HIV p24 antigen (Ag) detection via Architect (Architect algorithm) or Determine (Determine algorithm) as well as 1 algorithm that relies on HIV antibody testing alone (Antibody algorithm). The cost model used data on men who have sex with men (MSM) undergoing community-based AHI screening in San Diego, California. Incremental cost-effectiveness ratios (ICERs) per diagnosis of AHI were calculated for programs with HIV prevalence rates between 0.1% and 2.9%., Results: Among MSM in San Diego, EarlyTest was cost-savings (ie, ICERs per AHI diagnosis less than $13.000) when compared with the 3 other algorithms. Cost analyses relative to regional HIV prevalence showed that EarlyTest was cost-effective (ie, ICERs less than $69.547) for similar populations of MSM with an HIV prevalence rate >0.4%; Architect was the second best alternative for HIV prevalence rates >0.6%., Conclusions: Identification of AHI by the dual EarlyTest screening algorithm is likely to be cost-effective not only among at-risk MSM in San Diego but also among similar populations of MSM with HIV prevalence rates >0.4%., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Objectives: Traditional economic evaluations for most health technology assessments (HTAs) have previously not included environmental outcomes. With the growing interest in reducing the environmental impact of human activities, the need to consider how to include environmental outcomes into HTAs has increased. We present a simple method of doing so., Methods: We adapted an existing clinical-economic model to include environmental outcomes (carbon dioxide [CO2] emissions) to predict the consequences of adding insulin to an oral antidiabetic (OAD) regimen for patients with type 2 diabetes mellitus (T2DM) over 30 years, from the United Kingdom payer perspective. Epidemiological, efficacy, healthcare costs, utility, and carbon emissions data were derived from published literature. A scenario analysis was performed to explore the impact of parameter uncertainty., Results: The addition of insulin to an OAD regimen increases costs by 2,668 British pounds per patient and is associated with 0.36 additional quality-adjusted life-years per patient. The insulin-OAD combination regimen generates more treatment and disease management-related CO2 emissions per patient (1,686 kg) than the OAD-only regimen (310 kg), but generates fewer emissions associated with treating complications (3,019 kg versus 3,337 kg). Overall, adding insulin to OAD therapy generates an extra 1,057 kg of CO2 emissions per patient over 30 years., Conclusions: The model offers a simple approach for incorporating environmental outcomes into health economic analyses, to support a decision-maker's objective of reducing the environmental impact of health care. Further work is required to improve the accuracy of the approach; in particular, the generation of resource-specific environmental impacts.

Background: Patient navigation (PN) is being used increasingly to help patients complete screening colonoscopy (SC) to prevent colorectal cancer. At their large, urban academic medical center with an open-access endoscopy system, the authors previously demonstrated that PN programs produced a colonoscopy completion rate of 78.5% in a cohort of 503 patients (predominantly African Americans and Latinos with public health insurance). Very little is known about the direct costs of implementing PN programs. The objective of the current study was to perform a detailed cost analysis of PN programs at the authors' institution from an institutional perspective., Methods: In 2 randomized controlled trials, average-risk patients who were referred for SC by primary care providers were recruited for PN between May 2008 and May 2010. Patients were randomized to 1 of 4 PN groups. The cost of PN and net income to the institution were determined in a cost analysis., Results: Among 395 patients who completed colonoscopy, 53.4% underwent SC alone, 30.1% underwent colonoscopy with biopsy, and 16.5% underwent snare polypectomy. Accounting for the average contribution margins of each procedure type, the total revenue was $95,266.00. The total cost of PN was $14,027.30. Net income was $81,238.70. In a model sample of 1000 patients, net incomes for the institutional completion rate (approximately 80%), the historic PN program (approximately 65%), and the national average (approximately 50%) were compared. The current PN program generated additional net incomes of $35,035.50 and $44,956.00, respectively., Conclusions: PN among minority patients with mostly public health insurance generated additional income to the institution, mainly because of increased colonoscopy completion rates., (Copyright © 2012 American Cancer Society.)

Purpose: Acute skin toxicity is one of the most common side effects of breast cancer radiotherapy. To date, no one has estimated the nonmedical out-of-pocket expenses associated with this side effect. The primary aim of the present descriptive, exploratory study was to assess the feasibility of a newly developed skin toxicity costs questionnaire. The secondary aims were to: (1) estimate nonmedical out-of-pocket costs, (2) examine the nature of the costs, (3) explore potential background predictors of costs, and (4) explore the relationship between patient-reported dermatologic quality of life and expenditures., Methods: A total of 50 patients (mean age = 54.88, Stage 0-III) undergoing external beam radiotherapy completed a demographics/medical history questionnaire as well as a seven-item Skin Toxicity Costs (STC) questionnaire and the Skindex-16 in week 5 of treatment., Results: Mean skin toxicity costs were $131.64 (standard error [SE] = $23.68). Most frequently incurred expenditures were new undergarments and products to manage toxicity. Education was a significant unique predictor of spending, with more educated women spending more money. Greater functioning impairment was associated with greater costs. The STC proved to be a practical, brief measure which successfully indicated specific areas of patient expenditures and need., Conclusions: Results reveal the nonmedical, out-of-pocket costs associated with acute skin toxicity in the context of breast cancer radiotherapy. To our knowledge, this study is the first to quantify individual costs associated with this treatment side effect, as well as the first to present a scale specifically designed to assess such costs., Relevance: In future research, the STC could be used as an outcome variable in skin toxicity prevention and control research, as a behavioral indicator of symptom burden, or as part of a needs assessment.

Background: One approach postulated to improve the provision of health care is effective utilization of team-based care including pharmacists., Objective: The objective of this study was to conduct a comprehensive systematic review with focused meta-analyses to examine the effects of pharmacist-provided direct patient care on therapeutic, safety, and humanistic outcomes., Methods: The following databases were searched from inception to January 2009: NLM PubMed; Ovid/MEDLINE; ABI/INFORM; Health Business Fulltext Elite; Academic Search Complete; International Pharmaceutical Abstracts; PsycINFO; Cochrane Database of Systematic Reviews; National Guideline Clearinghouse; Database of Abstracts of Reviews of Effects; ClinicalTrials.gov; LexisNexis Academic Universe; and Google Scholar. Studies selected included those reporting pharmacist-provided care, comparison groups, and patient-related outcomes. Of these, 56,573 citations were considered. Data were extracted by multidisciplinary study review teams. Variables examined included study characteristics, pharmacists' interventions/services, patient characteristics, and study outcomes. Data for meta-analyses were extracted from randomized controlled trials meeting meta-analysis criteria., Results: A total of 298 studies were included. Favorable results were found in therapeutic and safety outcomes, and meta-analyses conducted for hemoglobin A1c, LDL cholesterol, blood pressure, and adverse drug events were significant (P < 0.05), favoring pharmacists' direct patient care over comparative services. Results for humanistic outcomes were favorable with variability. Medication adherence, patient knowledge, and quality of life-general health meta-analyses were significant (P < 0.05), favoring pharmacists' direct patient care., Conclusions: Pharmacist-provided direct patient care has favorable effects across various patient outcomes, health care settings, and disease states. Incorporating pharmacists as health care team members in direct patient care is a viable solution to help improve US health care.

Purpose: A systematic review examining the economic effects of pharmacist-provided direct patient care on health outcomes in the United States was conducted., Methods: A comprehensive literature search was conducted using 13 academic and medical databases. Studies were included in the analysis if they described pharmacist-provided direct patient care, used comparison groups, evaluated economic outcomes, and were conducted in the United States. Outcome results were categorized as (1) favorable, indicating significant improvement as a result of pharmacists' interventions or services, (2) not favorable, indicating significant improvement as a result of nonpharmacist care, (3) mixed, having favorable results on one measure of a study variable but not favorable results or no effect on another, (4) having no effect, indicating no significant difference between pharmacists' interventions or services and the comparison, or (5) unclear, indicating the outcome could not be determined based on presented data., Results: Of the 56,573 citations considered, a total of 126 studies met the criteria for inclusion in this systematic review. Results favoring pharmacist-provided care were found in 20 studies (15.9%), mixed results were seen in 53 studies (42.1%), no effect was found in 6 studies (4.8%), and unclear results were found in 47 studies (37.3%)., Conclusion: A majority of studies examining the economic effects of pharmacist-provided direct patient care in the United States were limited by their partial cost analyses, study design, and other analysis considerations. A majority of the 20 studies that found positive economic benefits examined pharmacists' interventions involving technical methods or multimodal approaches.

The influence of current medical technology adoption decisions on the use of future potential interventions is often overlooked. Some health interventions, once exercised, restrict future potential interventions for both related and unrelated medical conditions. For example, treatment of a patient with an antibiotic may lead to resistance in that patient that precludes future treatment with the same or related compounds. This irreversibility raises the value of treatment modalities that preserve future treatment options. Surprisingly, partial reversibility with or without learning can either increase or decrease this value, depending on the distribution of patient types within the treated population. Evaluations that ignore these option values miss an important part of the welfare equation that is becoming increasingly important as individuals live longer and the stock of medical treatments increases., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

Purpose: Colorectal cancer (CRC) screening remains underutilized in the United States. Prior studies reporting the cost effectiveness of randomized interventions to improve CRC screening have not been replicated in the setting of small physician practices. We recently conducted a randomized trial evaluating an academic detailing intervention in 264 small practices in geographically diverse New York City communities. The objective of this secondary analysis is to assess the cost effectiveness of this intervention., Methods: A total of 264 physician offices were randomly assigned to usual care or to a series of visits from trained physician educators. CRC screening rates were measured at baseline and 12 months. The intervention costs were measured and the incremental cost-effectiveness ratio (ICER) was derived. Sensitivity analyses were based on varying cost and effectiveness estimates., Results: Academic detailing was associated with a 7% increase in CRC screening with colonoscopy. The total intervention cost was $147,865, and the ICER was $21,124 per percentage point increase in CRC screening rate. Sensitivity analyses that varied the costs of the intervention and the average medical practice size were associated with ICERs ranging from $13,631 to $36,109 per percentage point increase in CRC screening rates., Conclusion: A comprehensive, multicomponent academic detailing intervention conducted in small practices in metropolitan New York was clinically effective in improving CRC screening rates, but was not cost effective.

Objective: To evaluate the cost-effectiveness of telemedicine and standard ophthalmoscopy for retinopathy of prematurity (ROP) management., Methods: Models were developed to represent ROP examination and treatment using telemedicine and standard ophthalmoscopy. Cost-utility analysis was performed using decision analysis, evidence-based outcome data from published literature, and present value modeling. Visual outcome data were converted to patient preference-based time trade-off utility values based on published literature. Costs of disease management were determined based on 2006 Medicare reimbursements. Costs per quality-adjusted life year gained by telemedicine and ophthalmoscopy for ROP management were compared. One-way sensitivity analysis was performed on the following variables: discount rate (0%-7%), incidence of treatment-requiring ROP (1%-20%), sensitivity and specificity of ophthalmoscopic diagnosis (75%-100%), percentage of readable telemedicine images (75%-100%), and sensitivity and specificity of telemedicine diagnosis (75%-100%)., Results: For infants with birth weight less than 1500 g using a 3% discount rate for costs and outcomes, the costs per quality-adjusted life year gained were $3193 with telemedicine and $5617 with standard ophthalmoscopy. Sensitivity analysis resulted in ranges of costs per quality-adjusted life year from $1235 to $18,898 for telemedicine and from $2171 to $27,215 for ophthalmoscopy., Conclusions: Telemedicine is more cost-effective than standard ophthalmoscopy for ROP management. Both strategies are highly cost-effective compared with other health care interventions.

Background: Breast cancer surgery is associated with side effects, including postsurgical pain, nausea, and fatigue. We carried out a randomized clinical trial to test the hypotheses that a brief presurgery hypnosis intervention would decrease intraoperative anesthesia and analgesic use and side effects associated with breast cancer surgery and that it would be cost effective., Methods: We randomly assigned 200 patients who were scheduled to undergo excisional breast biopsy or lumpectomy (mean age 48.5 years) to a 15-minute presurgery hypnosis session conducted by a psychologist or nondirective empathic listening (attention control). Patients were not blinded to group assignment. Intraoperative anesthesia use (i.e., of the analgesics lidocaine and fentanyl and the sedatives propofol and midazolam) was assessed. Patient-reported pain and other side effects as measured on a visual analog scale (0-100) were assessed at discharge, as was use of analgesics in the recovery room. Institutional costs and time in the operating room were assessed via chart review., Results: Patients in the hypnosis group required less propofol (means = 64.01 versus 96.64 microg; difference = 32.63; 95% confidence interval [CI] = 3.95 to 61.30) and lidocaine (means = 24.23 versus 31.09 mL; difference = 6.86; 95% CI = 3.05 to 10.68) than patients in the control group. Patients in the hypnosis group also reported less pain intensity (means = 22.43 versus 47.83; difference = 25.40; 95% CI = 17.56 to 33.25), pain unpleasantness (means = 21.19 versus 39.05; difference = 17.86; 95% CI = 9.92 to 25.80), nausea (means = 6.57 versus 25.49; difference = 18.92; 95% CI = 12.98 to 24.87), fatigue (means = 29.47 versus 54.20; difference = 24.73; 95% CI = 16.64 to 32.83), discomfort (means = 23.01 versus 43.20; difference = 20.19; 95% CI = 12.36 to 28.02), and emotional upset (means = 8.67 versus 33.46; difference = 24.79; 95% CI = 18.56 to 31.03). No statistically significant differences were seen in the use of fentanyl, midazolam, or recovery room analgesics. Institutional costs for surgical breast cancer procedures were $8561 per patient at Mount Sinai School of Medicine. Patients in the hypnosis group cost the institution $772.71 less per patient than those in the control group (95% CI = 75.10 to 1469.89), mainly due to reduced surgical time., Conclusions: Hypnosis was superior to attention control regarding propofol and lidocaine use; pain, nausea, fatigue, discomfort, and emotional upset at discharge; and institutional cost. Overall, the present data support the use of hypnosis with breast cancer surgery patients.

Objective: To evaluate the effect of central corneal thickness determination on the clinical management of patients with glaucoma and glaucoma suspect., Methods: A cross-sectional retrospective study was performed on 188 consecutive patients. Mean ultrasound pachymetry measurements of central corneal thickness and corresponding Goldmann applanation tonometry measurements were obtained. Intraocular pressures (IOPs) were corrected using linear and mathematical (Orssengo-Pye) algorithms. Measurement-significant outcomes were defined as an IOP adjustment of 1.5 mm Hg or greater and outcomes-significant results as an IOP adjustment of 3.0 mm Hg or greater. Changes in therapy such as the use of eyedrops and addition or cancellation of laser therapy or surgery were then noted for those individuals with measurement- or outcomes-significant changes., Results: Using the linear correction scale, 105 (55.9%) of 188 patients had at least a measurement-significant adjustment in their IOP measurements: 67 (35.6%) had adjustments between 1.5 and 3.0 mm Hg, while 38 (20.2%) had an outcomes-significant IOP adjustment (> or =3.0 mm Hg). Among the 188 patients, 16 (8.5%) had a change in eyedrop therapy, 4 (2.1%) had a change regarding laser therapy, and 6 (3.2%) had a change in the decision regarding glaucoma surgery. Using the exponential correction (Orssengo-Pye) scale, similar percentages were obtained., Conclusion: Pachymetry-measured central corneal thickness has a significant effect on the clinical management of patients with glaucoma and glaucoma suspect.