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Purpose: To compare the effectiveness and adverse event profile of standalone polystyrene-isobutylene-styrene (SIBS) microshunt implantation with adjunct mitomycin C (MMC) 0.2 mg/ml and MMC 0.4 mg/ml., Design: Mega-analysis using individual patient data from international prospective and retrospective clinical studies., Participants: Patients with glaucoma who underwent implantation of a SIBS microshunt with MMC as a standalone procedure., Methods: A comparison of eyes that received MMC 0.2 mg/ml or 0.4 mg/ml., Main Outcomes Measures: Primary outcome was complete success defined as the proportion of eyes at 1 year with all of the following: (1) no 2 consecutive intraocular pressures (IOPs) > 17 mmHg; (2) no clinical hypotony; (3) ≥ 20% IOP reduction from baseline; and (4) no use of glaucoma medications. Secondary outcomes included IOP thresholds of 12 mmHg, 14 mm Hg, and 21 mmHg, median IOP, number of medications, risk factors for failure, interventions, adverse events, and reoperations., Results: At 1 year, the complete success rate was significantly higher (71.3% vs. 50.46%; P < 0.001) and the median IOP was significantly lower (13.0 vs 14.2 mmHg; P < 0.05) in the MMC 0.4 mg/ml group. Mitomycin C 0.2 mg/ml was found to be a significant risk factor for failure (hazard ratio 1.75; 95% confidence interval 1.14-2.67). Needling and surgical revision occurred at a lower rate in the MMC 0.4 mg/ml group (7% vs 18.8%; P = 0.002 and 4.3% vs 13.7% P = 0.0087, respectively). Adverse events occurred at a similar frequency in both groups (26.6% MMC 0.2 mg/ml vs 29.6% MMC 0.4 mg/ml; P = 0.46), most of which were early and transient., Conclusion: Polystyrene-isobutylene-styrene microshunt implantation with MMC 0.4 mg/ml resulted in a higher success rate with greater IOP reduction compared with MMC 0.2 mg/ml. Higher MMC concentration was not associated with increased serious adverse events., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance: Sex-based research in medicine has revealed inequities against females on almost every metric at almost every career stage; ophthalmology is no exception., Objective: To systematically review the experiences of females in ophthalmology (FiO) from training through practice in high-income countries (HICs)., Evidence Review: A systematic review of English-language studies, published between January 1990 and May 2022, relating to FiO in HICs was performed. PubMed, MEDLINE, and Embase electronic databases were searched, as well as the Journal of Academic Ophthalmology as it was not indexed in the searched databases. Studies were organized by theme at each career stage, starting in medical school when an interest in ophthalmology is expressed, and extending up to retirement., Findings: A total of 91 studies, 87 cross-sectional and 4 cohort, were included. In medical school, mentorship and recruitment of female students into ophthalmology was influenced by sex bias, with fewer females identifying with ophthalmologist mentors and gender stereotypes perpetuated in reference letters written by both male and female referees. In residency, females had unequal learning opportunities, with lower surgical case volumes than male trainees and fewer females pursued fellowships in lucrative subspecialties. In practice, female ophthalmologists had lower incomes, less academic success, and poorer representation in leadership roles. Female ophthalmologists had a greater scholarly impact factor than their male counterparts, but this was only after approximately 30 years of publication experience. Pervasive throughout all stages of training and practice was the experience of greater sexual harassment among females from both patients and colleagues. Despite these disparities, some studies found that females reported equal overall career satisfaction rating with males in ophthalmology, whereas others suggested higher burnout rates., Conclusions and Relevance: Ophthalmology is approaching sex parity, however, the increase in the proportion of females in ophthalmology had not translated to an increase in female representation in leadership positions. Sex disparities persisted across many domains including recruitment, training, practice patterns, academic productivity, and income. Interventions may improve sex equity in the field.

Competing Interests: The authors report no conflicts of interest.

Purpose: To determine intermediate intraocular pressure (IOP)-lowering and adverse event profile of the 63-μm gelatin microstent (Xen63) with mitomycin C (MMC) compared with the 45-μm gelatin microstent (Xen45) with MMC., Design: Single center, consecutive, retrospective cohort study., Participants: Eighty-four glaucomatous eyes (42 63-μm gelatin microstent and 42 45-μm gelatin microstent) with or without previous subconjunctival glaucoma surgery., Methods: Consecutive eyes that underwent 63-μm gelatin microstent implantation with MMC from February 2020 to June 2021 were compared with eyes that underwent 45-μm gelatin microstent implantation with MMC. Standalone and combined cases with phacoemulsification were included., Main Outcome Measures: Primary outcome was the hazard ratio of failure of 45-μm gelatin microstent vs. 63-μm gelatin microstent eyes at 12 months, with failure defined as 2 consecutive IOPs, (1) >17 mmHg, (2) <6 mmHg with 2 lines of vision loss, or (3) <20% reduction from baseline IOP, without (complete) or with (qualified) glaucoma medications. Secondary outcomes included IOP thresholds of 14 mmHg and 21 mmHg, postoperative IOP, medications, adverse events, interventions, and reoperations., Results: The complete success rate was higher in the 63-μm gelatin microstent group (59.5% vs. 28.6%, P = 0.009) at the primary IOP threshold of 6 to 17 mmHg but did not differ significantly for qualified success (66.7% vs. 45.2%, P = 0.08). The crude hazard ratio of failure of 45-μm gelatin microstent relative to 63-μm gelatin microstent was 2.28 (95% confidence interval [CI], 1.21-4.32), and the adjusted hazard ratio was 7.90 (95% CI, 2.12-29.43). 63-μm gelatin microstent eyes had significantly lower mean IOP (12.7 ± 4.8 vs. 15.5 ± 5.1 mmHg, P = 0.001) and fewer medication classes (0.6 ± 1.1 vs. 1.7 ± 1.6 medications, P = 0.0005), with the degree of reduction in IOP and medication count being significantly greater in 63-μm gelatin microstent eyes. There were 28 and 21 distinct interventions in 63-μm gelatin microstent and 45-μm gelatin microstent eyes respectively, with 11.9% of eyes undergoing needling in each group. There were 34 and 19 distinct adverse events, in 63-μm gelatin microstent and 45-μm gelatin microstent eyes, respectively, most of which were early and transient. Nine Xen63 eyes (21.4%) and 6 45-μm gelatin microstent eyes (14.3%) underwent reoperation., Conclusions: 63-μm gelatin microstent resulted in higher surgical success rates and fewer medications compared with 45-μm gelatin microstent. This was tempered by more postoperative interventions and adverse events, although most were transient., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Vaccination and the emergence of SARS-CoV-2 variants mark the second year of the pandemic. Variants have amino acid mutations at the spike region, a viral protein central in the understanding of COVID-19 pathogenesis and vaccine response. Variants may dominate local epidemics, as Gamma (P.1) in Brazil, emerging in 2020 and prevailing until mid-2021. Different obstacles hinder a wider use of Next-Generation Sequencing for genomic surveillance. We describe Sanger based sequencing protocols: i) Semi-nested RT-PCR covering up to 3.684 kb (>96 %) spike gene; ii) One-Step RT-PCR for key Receptor Binding Domain (RBD) mutations (codons 417-501); iii) One-Step RT-PCR of partial N region to improve genomic capability. Protocols use leftovers of RNA extracted from nasopharyngeal swabs for quantitative RT-PCR diagnosis; with retro-transcribed DNA sequenced at ABI 3500 using dye termination chemistry. Analyses of sequences from 95 individuals (late 2020/early 2021) identified extensive amino acid variation, 57 % with at least one key mutation at the Receptor Binding Domain, with B.1.1.28 lineage most prevalent, followed by Gamma and Zeta variants, with no Delta variant observed. The relatively low cost and simplicity may provide an accessible tool to improve surveillance of SARS-CoV-2 evolution, monitor new variants and vaccinated breakthroughs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Various requirements for the repair of complex bone defects have motivated to development of scaffolds with adjustable degradation rates and biological functions. Tricalcium phosphate (TCP) and calcium sulfate are the most commonly used bone repair materials in the clinic, how to better combine TCP and calcium sulfate and play their greatest advantages in the repair of osteoporotic bone defect is the focus of our research. In this study, a series of scaffolds with multistage-controlled degradation properties composed of strontium-doped calcium sulfate (SrCSH) and strontium-doped tricalcium phosphate (Sr-TCP) microspheres scaffolds were prepared, and their osteogenic activity, in vivo degradation and bone regeneration ability in tibia of osteoporotic rats were evaluated. In vitro studies revealed that different components of SrCSH/Sr-TCP scaffolds significantly promoted the proliferation and differentiation of MC3T3-E1 cells, which showed a good osteogenic induction activity. In vivo degradation results showed that the degradation time of composite scaffolds could be controlled in a large range (6-12 months) by controlling the porosity and phase composition of Sr-TCP microspheres. The results of osteoporotic femoral defect repair showed that when the degradation rate of scaffold matched with the growth rate of new bone, the parameters such as bone mineral density, bone volume/total volume ratio, trabecular thickness, angiogenesis marker platelet endothelial cell adhesion molecule-1 and new bone formation marker osteocalcin expression were higher, which promoted the rapid repair of osteoporotic bone defects. On the contrary, the slow degradation rate of scaffolds hindered the growth of new bone to a certain extent. This study elucidates the importance of the degradation rate of scaffolds for the repair of osteoporotic bone defects, and the design considerations can be extended to other bone repair materials, which is expected to provide new ideas for the development of tissue engineering materials in the future., (© 2021 IOP Publishing Ltd.)

Background During the coronavirus disease 2019 pandemic, three-dimensional (3D) printing was utilized to rapidly produce face shields for frontline workers in response to an acute shortage of personal protective equipment (PPE). In this study, we examine the perceived utility and performance of 3D-printed (3DP) face shields through a survey of frontline workers in Ontario, Canada. Methodology Frontline workers who received community-produced 3DP face shields from the Canadian initiative "3DPPE GTHA" (March-December 2020) were invited to participate in the study. The survey response rate was 54.3%. Of 63 respondents, 39 were patient-facing and 24 were community-facing frontline workers. Participants were asked to rate performance measures in 10 categories on a five-point Likert scale. Data were categorized by organization and frontline worker type, and a t-test was used to determine statistically significant differences among subgroups. Results The mean preference for 3DP face shields among respondents was 3.2 out of 5 (95% confidence interval [CI]: 2.1-4.3). Community-facing respondents reported significantly greater overall utility scores for 3DP face shields (3.58, 95% CI: 3.38-3.79) compared to respondents working in a patient-facing profession (2.95, 95% CI: 2.77-3.13; p < 0.05). However, no differences were reported in portability and compatibility with other PPE. Respondents from organizations with large service volumes reported significantly lower overall utility scores (2.67, 95% CI: 2.44-2.89) than respondents in organizations with smaller service volumes (3.45, 95% CI: 3.28-3.62; p < 0.05). Conclusions Community-facing frontline workers and those from smaller service volume organizations endorse higher utility for 3DP face shields than patient-facing frontline workers. Despite this, frontline workers generally rate 3DP face shields positively. 3DP face shields are a viable option for personal and community use and can be used to supplement supply in a community setting., Competing Interests: All authors were volunteer members of the now concluded 3DPPE GTHA grassroots not-for-profit initiative. No personal benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2021, Daud et al.)

Background: As the healthcare system faced an acute shortage of personal protective equipment (PPE) during the COVID-19 pandemic, the use of 3D printing technologies became an innovative method of increasing production capacity to meet this acute need. Due to the emergence of a large number of 3D printed face shield designs and community-led PPE printing initiatives, this case study examines the methods and design best optimized for community printers who may not have the resources or experience to conduct such a thorough analysis., Case Presentation: We present the optimization of the production of 3D printed face shields by community 3D printers, as part of an initiative aimed at producing PPE for healthcare workers. The face shield frames were manufactured using the 3DVerkstan design and were coupled with an acetate sheet to assemble a complete face shield. Rigorous quality assurance and decontamination protocols ensured community-printed PPE was satisfactory for healthcare use., Conclusion: Additive manufacturing is a promising method of producing adequate face shields for frontline health workers because of its versatility and quick up-start time. The optimization of stacking and sanitization protocols allowed 3D printing to feasibly supplement formal public health responses in the face of a global pandemic.

Background: Tofacitinib is an oral Janus kinase (JAK) inhibitor which blocks cytokine signaling involved in the pathogenesis of autoimmune diseases including ulcerative colitis (UC). The etiology of UC is poorly understood, however research suggests the development and progression of the disease is due to a dysregulated immune response leading to inflammation of the colonic mucosa in genetically predisposed individuals. Additional medications are currently required since some patients do not respond to the available medications and some medications are associated with serious adverse events (SAEs). JAK inhibitors have been widely studied in diseases including rheumatoid arthritis and Crohn's disease and may represent a promising and novel therapeutic option for the treatment of UC., Objectives: The primary objective was to assess the efficacy and safety of oral JAK inhibitors for the maintenance of remission in participants with quiescent UC., Search Methods: We searched the following databases from inception to 20 September 2019: MEDLINE, Embase, CENTRAL, and the Cochrane IBD Group Specialized Register, WHO trials registry and clinicaltrials.gov. References and conference abstracts were searched to identify additional studies., Selection Criteria: Randomized control trial (RCTs) in which an oral JAK inhibitor was compared with placebo or active comparator in the treatment of quiescent UC were eligible for inclusion., Data Collection and Analysis: Two review authors independently screened studies for inclusion and extraction. Bias was assessed using the Cochrane 'Risk of bias' tool. The primary outcome was the proportion of participants who failed to maintain remission as defined by any included studies. Secondary outcomes included failure to maintain clinical response, failure to maintain endoscopic remission, failure to maintain endoscopic response, disease-specific quality of life, adverse events (AEs), withdrawal due to AEs and SAEs. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for each dichotomous outcome. Data were analyzed on an intention-to-treat basis. The overall certainty of the evidence supporting the outcomes was evaluated using the GRADE criteria., Main Results: One RCT (593 participants) including patients with moderately to severely active UC met the inclusion criteria. Patients were randomly assigned in a 1:1:1 ratio to receive maintenance therapy with tofacitinib at 5 mg twice daily, 10 mg twice daily or placebo for 52 weeks. The primary endpoint was remission at 52 weeks and the secondary endpoints included mucosal healing at 52 weeks, sustained remission at 24 and 52 weeks and glucocorticosteroid-free remission. This study was rated as low risk of bias. The study reported on most of the pre-specified primary and secondary outcomes for this review including clinical remission, clinical response, endoscopic remission, AEs, SAEs and withdrawal due to AEs. However, the included study did not report on endoscopic response or disease-specific quality of life. Sixty-three per cent (247/395) of tofacitinib participants failed to maintain clinical remission at 52 weeks compared to 89% (176/198) of placebo participants (RR 0.70, 95% CI 0.64 to 0.77; high-certainty evidence). Forty-three per cent (171/395) of tofacitinib participants failed to maintain clinical response at 52 weeks compared to 80% (158/198) of placebo participants (RR 0.54, 95% CI 0.48 to 0.62; high-certainty evidence). Eighty-four per cent (333/395) of tofacitinib participants failed to maintain endoscopic remission at 52 weeks compared to 96% (190/198) of placebo participants (RR 0.88, 95% CI 0.83 to 0.92; high-certainty evidence). AEs were reported in 76% (299/394) of tofacitinib participants compared with 75% (149/198) of placebo participants (RR 1.01, 95% CI 0.92 to 1.11; high-certainty evidence). Commonly reported AEs included worsening UC, nasopharyngitis, arthralgia (joint pain)and headache. SAEs were reported in 5% (21/394) of tofacitinib participants compared with 7% (13/198) of placebo participants (RR 0.81, 95% CI 0.42 to 1.59; low-certainty evidence). SAEs included non-melanoma skin cancers, cardiovascular events, cancer other than non-melanoma skin cancer, Bowen's disease, skin papilloma and uterine leiomyoma (a tumour in the uterus). There was a higher proportion of participants who withdrew due to an AE in the placebo group compared to the tofacitinib group. Nine per cent (37/394) of participants taking tofacitinib withdrew due to an AE compared to 19% (37/198) of participants taking placebo (RR 0.50, 95% CI 0.33 to 0.77; moderate-certainty evidence). The most common reason for withdrawal due to an AE was worsening UC. The included study did not report on endoscopic response or on mean disease-specific quality of life scores., Authors' Conclusions: High-certainty evidence suggests that tofacitinib is superior to placebo for maintenance of clinical and endoscopic remission at 52 weeks in participants with moderate-to-severe UC in remission. The optimal dose of tofacitinib for maintenance therapy is unknown. High-certainty evidence suggests that there is no increased risk of AEs with tofacitinib compared to placebo. However, we are uncertain about the effect of tofacitinib on SAEs due to the low number of events. Further studies are required to look at the long-term effectiveness and safety of using tofacitinib and other oral JAK inhibitors as maintenance therapy in participants with moderate-to-severe UC in remission., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background and Aims: Nocebo effects, adverse outcomes occurring in patients receiving inert therapy, contribute to adverse event [AE] reporting in randomized controlled trials [RCTs]. High placebo AE rates may result in inaccurate estimation of treatment-related AEs. We estimate the pooled rate of AEs in patients randomized to placebo compared to active therapy in inflammatory bowel disease [IBD] RCTs., Methods: MEDLINE, EMBASE and CENTRAL were searched to March 1, 2017 for RCTs of conventional medical therapies for Crohn's disease [CD] or ulcerative colitis [UC]. Rates of AEs, serious AEs [SAEs], AE-related trial withdrawal, infections and worsening IBD were pooled using a random-effects model., Results: We included 124 CD [n = 26 042] and 71 UC RCTs [n = 16 798]. The pooled placebo AE rate was 70.6% (95% confidence interval [CI]: 65.3%, 75.4%) and 54.5% [47.8%, 61.1%] in CD and UC RCTs, respectively. There was no significant risk difference [RD] in AE, SAE or AE-related withdrawal rates between CD patients receiving placebo or active drug. A 1.6% [95% CI: 0.1%, 3.1%] increase in AE rates was observed among UC patients randomized to active therapy. Patients receiving active therapy had a higher risk of infection (RD 1.0% [95% CI: 0.4%, 1.7%] for CD, 2.9% [95% CI: 1.4%, 4.4%] for UC) although a lower risk of worsening CD (RD -3.2% [95% CI: -4.8%, -1.5%]) or UC (RD -3.7% [95% CI: -5.7%, -1.8%])., Conclusions: AEs are commonly reported by patients randomized to either placebo or active treatment in IBD RCTs. Clinically relevant differences in AE, SAE and AE-related withdrawal were not observed., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background & Aims: Endpoints in randomized controlled trials (RCTs) of Crohn's disease (CD) are changing. We performed a systematic review of efficacy and safety outcomes reported in placebo-controlled RCTs of patients with CD., Methods: We searched the MEDLINE, EMBASE, and the Cochrane Library through March 1, 2017 for placebo-controlled RCTs of adult patients with CD treated with aminosalicylates, immunomodulators, corticosteroids, biologics, and oral small molecules. Efficacy and safety outcomes, definitions, and measurement tools were collected and stratified by decade of publication., Results: Our final analysis included 116 RCTs (81 induction, 44 maintenance, 7 postoperative prevention trials, comprising 27,263 patients). Clinical efficacy endpoints were reported in all trials; the most common endpoint was CD activity index score. We identified 38 unique definitions of clinical response or remission and 32 definitions of loss of response. Definitions of endoscopic response, remission, and endoscopic healing were also heterogeneous, evaluated using the CD endoscopic index of severity, the simple endoscopic score for CD, ulcer resolution, and Rutgeerts' Score for postoperative endoscopic appearance. Histologic outcomes were reported in 11.1% of induction trials, 2.3% of maintenance trials, and 14.3% of postoperative prevention trials. Biomarker outcomes were reported in 81.5% induction trials, 68.2% of maintenance trials, and 42.9% of postoperative prevention trials. Safety outcomes were reported in 93.8% of induction trials, 97.7% of maintenance trials, and 85.7% of postoperative prevention trials., Conclusions: In this systematic review, we demonstrate heterogeneity in definitions of response and remission, and changes in outcomes reported in RCTs of CD. It is a priority to select a core set of outcomes to standardize efficacy and safety evaluation in trials of patients with CD., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

This study aimed at the identification of the spectrum of mutations in patients with β-thalassemia (β-thal) in the western province of Saudi Arabia. Screening for the mutations was done using the polymerase chain reaction-amplification refractory mutation system (PCR-ARMS) technique to test for 12 mutations, and direct automated DNA sequencing for the unknown samples. The study included 172 patients; of these 15 patients had sickle cell anemia and one Hb S [β6(A3)Glu→Val, GAG>GTG]/β-thal. A total of 23 mutations were identified to cause the disease in the western area. Seven common mutations were responsible for the β-thal alleles in 78% of patients and could be detected by the ARMS technique: IVS-II-1 (G>A), IVS-I-110 (G>A), IVS-I-5 (G>C), codon 39 (C>T), codon 26 (G>A) [Hb E or β26(B8)Glu→Lys, GAG>AAG], frameshift codons (FSC) 8/9 (+G), and IVS-I-1 (G>A). DNA sequencing of uncharacterized alleles detected eight less common mutations: FSC 41/42 (-TCTT), IVS-I 25 bp deletion, codon 37 (G>A), FSC 44 (-C), Cap site +1 (A>C), IVS-I-6 (T>C), FSC 5 (-CT) and IVS-I-1 (G>T), and eight rare mutations: -87 (C>G), initiation codon -1 (T>G), codon 15 (G>A), FSC 16 (-C), FSC 20/21 (+G), codon 27 (G>A), IVS-I-130 (G>C) and IVS-II-837 (A>C). Four alleles were normal by DNA sequencing. Genetic heterogeneity was observed in this study, 10 mutations were of Asian or Asian/Indian origin, two were Kurdish, one Chinese, one Turkish, one Saudi, and the remainder were of Mediterranean origin. The presence of a large population of immigrants in the western province is responsible for the great heterogeneity at the molecular level, and for the difference observed in the frequencies of mutations from those reported in the eastern province of Saudi Arabia. Screening for β-thal mutations using PCR-ARMS for the seven most frequent mutations in the Saudi population followed by DNA sequencing of the unknown alleles could be useful for the implementation of a strategy for carrier detection and preimplantation genetic diagnosis in high risk families.

The combined effects of increasing demand for health services and declining real public resources have recently led many governments in the developing world to explore various health financing alternatives. Faced with a significant decline during the 1980s in its real per capita expenditures, the Kenya Ministry of Health (MOH) introduced a new cost sharing programme in December 1989. The programme was part of a comprehensive health financing strategy which also included social insurance, efficiency measures, and private sector development. Early implementation problems led to the suspension in September 1990 of the outpatient registration fee, the major revenue source at the time. In 1991, the Ministry initiated a programme of management improvement and gradual re-introduction of an outpatient fee, but this time as a treatment fee. The new programme was carried out in phases, beginning at the national and provincial levels and proceeding to the local level. The impact of these changes was assessed with national revenue collection reports, quality of care surveys in 6 purposively selected indicator districts, and time series analysis of monthly utilization in these same districts. In contrast to the significant fall in revenue experienced over the period of the initial programme, the later management improvements and fee adjustments resulted in steady increases in revenue. As a percentage of total non-staff expenditures, fiscal year 1993-1994 revenue is estimated to have been 37% at provincial general hospitals, 20% at smaller hospitals, and 21% at health centres. Roughly one third of total revenue is derived from national insurance claims. Quality of care measures, though in some respects improved with cost sharing, were in general somewhat mixed and inconsistent. The 1989 outpatient registration fee led to an average reduction in utilization of 27% at provincial hospitals, 45% at district hospitals, and 33% at health centres. In contrast, phased introduction of the outpatient treatment fee beginning in 1992, combined with somewhat broader exemptions, was associated with much smaller decreases in outpatient utilization. It is suggested that implementing user fees in phases by level of health facility is important to gain patient acceptance, to develop the requisite management systems, and to orient ministry staff to the new systems.