Global Dilemma and Needs Assessment Toward Achieving Sustainable Development Goals in Controlling Leishmaniasis.

Leishmaniasis is a disease of poverty that imposes a devastating medical, social, and economic burden on over 1 billion people nationwide. To date, no in-depth study to analyze the major global challenges and needs assessment has been carried out. This investigation aimed to explore a comprehensive narrative review of leishmaniasis's main challenges and initially highlight obstacles that might impede the implementation of control measures. Also, we propose a specific list of priorities for needs assessment. The presence of socioeconomic factors, multiple clinical and epidemiological forms, various Leishmania species, the complexity of the life cycle, the absence of effective drugs and vaccines, and the lack of efficient vector and reservoir control make this organism unique and sophisticated in playing a tangled role to react tricky with its surrounding environments, despite extensive efforts and implementation of all-inclusive former control measures. These facts indicate that the previous strategic plans, financial support, and basic infrastructures connected to leishmaniasis surveillance are still insufficient. Strengthening the leishmaniasis framework in a context of accelerated programmatic action and intensification of cross-cutting activities along with other neglected tropical diseases (NTDs) is confidently expected to result in greater effectiveness, cost-benefit, and fruitful management. Sensitive diagnostics, effective therapeutics, and efficacious vaccines are vital to accelerating advancement toward elimination, and reducing morbidity/mortality and program costs. Collective actions devoted by all sectors and policy-makers can hopefully overcome technical and operational barriers to guarantee that effective and coordinated implementation plans are sustained to meet the road map for NTDs 2021- 2030 goals.

Cutaneous leishmaniasis situation analysis in the Islamic Republic of Iran in preparation for an elimination plan.

Iran has invariably been under the growing public health threat of cutaneous leishmaniasis (CL), a significant barrier to local development that hinders the prevention and control efforts toward eliminating the disease. So far, no comprehensive and in-depth epidemiological analysis of the CL situation has been carried out nationwide. This study aimed to employ advanced statistical models to analyze the data collected through the Center for Diseases Control and Prevention of Communicable Diseases during 1989-2020. However, we emphasized the current trends, 2013-2020, to study temporal and spatial CL patterns. In the country, the epidemiology of CL is incredibly intricate due to various factors. This fact indicates that the basic infrastructure, the preceding supports, and the implementation plan related to preventive and therapeutic measures need crucial support. The leishmaniasis situation analysis is consistent with desperate requirements for efficient information on the control program in the area. This review provides evidence of temporally regressive and spatially expanding incidence of CL with characteristic geographical patterns and disease hotspots, signifying an urgent need for comprehensive control strategies. This information could be a suitable model and practical experience in the Eastern Mediterranean Region, where over 80% of CL is reported.

HIV Continuum of Care Among People Who Inject Drugs in Iran: A Cross-sectional Study.

ABSTRACT: People living with HIV who inject drugs may have lower access to treatment services. We aimed to assess the HIV continuum of care among people who inject drugs (PWID) in Iran. Data were collected from 2,663 PWID who were recruited via respondent-driven sampling from 11 cities of Iran between June 2019 and March 2020. Participants who tested positive for HIV infection were asked questions to calculate the status of HIV cascade of care. Of 95 PWID living with HIV, 67% were aware of their HIV status, 57% were linked to care service and initiated ART, 49% retained on ART, and only 15% had viral load less than 1,000 copies/ml. About half of the PWID diagnosed with HIV ever started ART and less than one in six were virally suppressed. Strategies to improve linkage to ART programs and ART retention may improve HIV care outcomes among PWID in Iran.

Comparison of corneal biomechanical properties in healthy thin corneas with matched keratoconus eyes.

PURPOSE: To compare corneal biomechanical parameters of normal thin corneas with matched keratoconus eyes. SETTING: Eye Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. DESIGN: Cross-sectional comparative study. METHODS: Dynamic corneal response parameters of Corvis ST were compared in 61 eyes with keratoconus with 61 matched healthy thin corneas (corneal thinnest point <500 µm), while corneal thickness, biomechanically corrected intraocular pressure, and age were considered covariates. The receiving operator sensitivity curve analysis was used to determine the cutoff point with the highest sensitivity and specificity, and the area under the curve (AUC) for each parameter. RESULTS: All biomechanical parameters were statistically significant between the 2 groups except for the first ( P = .947) and second ( P = .582) applanation length, first ( P = .783) and second ( P = .301) applanation velocity, and deformation amplitude in the highest concavity phase ( P = .106). The highest mean difference between groups (12.89 ± 2.03 mm Hg/mm) was related to the stiffness parameter at the first applanation (SPA1). Although the Corvis biomechanical index and tomographic biomechanical index had the highest detection ability based on their AUC (0.912 and 0.959, respectively), among the standard and combined biomechanical parameters except for keratoconus screening parameters, the highest discriminative ability was related to SPA1 with AUC, sensitivity, and specificity of 0.793, 60.66%, and 90.16%, respectively. CONCLUSIONS: Keratoconus corneas were significantly softer compared with healthy thin corneas of matched thickness. Optimal cutoff points close to the maximum value defined for screening parameters limit their clinical use for differentiation purposes in these particular types of cases.

A Prospective Study to Evaluate the Impact of Golimumab Therapy on Work Productivity and Activity, and Quality of Life in Patients With Rheumatoid Arthritis, Psoriasis Arthritis and Axial Spondyloarthritis in a Real Life Setting in AUSTRIA. The GO-ACTIVE Study.

Objective: To analyze real-world evidence on work productivity and daily activity impairment (WPAI) and health-related quality of life (HRQoL) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) patients treated with golimumab in Austria. Methods: This was a prospective, non-interventional, multi-center study conducted in RA, PsA and axSpA patients initiating golimumab between April 2016 and May 2020 in 40 centers in Austria. WPAI, HRQoL (RAQoL, ankylosing spondylitis (AS)QoL and PsAQoL) questionnaires and disease activity (Clinical Disease Activity Index, CDAI, in RA and PsA; Bath Ankylosing Spondylitis Disease Activity Index, BASDAI, in axSpA) were assessed at baseline and months 3, 6, 12, 18, and 24. Association between WPAI and disease activity was tested using linear regression. Results: We enrolled 233 patients (RA, n = 95; axSpA, n = 69; PsA, n = 69), 110 patients were followed up to month 24. Mean age was 50.2 ± 14.2 years; 64% were female. Disease activity decreased from baseline to month 24 (RA: CDAI -24.3 ± 13.5; axSpA: BASDAI -4.4 ± 2.1, and PsA: CDAI -21.7 ± 8.5, p < 0.0001, each). Total work productivity impairment (TWPI), activity impairment and presenteeism subscores continuously decreased throughout month 24 in all indications: RA (-58.3 ± 23%, -62.6 ± 23.8% and -61.7 ± 23.3%, respectively as compared to baseline; p < 0.0001, each), axSpA (-34.4 ± 38.3%, p = 0.0117; -60.9 ± 25.9%, and -43.8 ± 26.6%, respectively, p ≤ 0.0001 both) and PsA (-35.8 ± 43.7%, p = 0.0186; -52.3 ± 25.4%, p < 0.0001; and -43.3 ± 33.5%, p = 0.0007, respectively). Absenteeism scores decreased only in RA patients (-9.2 ± 24.9%, p = 0.0234). HRQoL improved between baseline and month 24 (RAQoL: -12.6 ± 7.5; ASQoL: -8.0 ± 4.3; PsAQoL; -8.3 ± 6.4, p < 0.0001, each). TWPI, presenteeism and activity impairment strongly associated with disease activity throughout the study. Conclusions: This real-world study confirms the benefit of golimumab on work productivity/daily activity impairment in Austrian RA, PsA, and axSpA patients.

Dimethyl fumarate is efficacious in severe plaque psoriasis : Post hoc analysis from the BRIDGE trial in Austria.

BACKGROUND: Fumaric acid esters are recommended in European guidelines for induction and maintenance treatment of patients with moderate to severe plaque psoriasis. A systemic medication with pure dimethyl fumarate without monoethyl fumarate salts was recently licensed in Europe. OBJECTIVE: The efficacy and safety of pure dimethyl fumarate were assessed in patients with severe (physician global assessment) plaque psoriasis in Austria in the BRIDGE trial. METHODS: In this double blind, randomized, placebo-controlled trial patients received 16-week treatment with pure dimethyl fumarate in a head to head comparison with dimethyl fumarate with monoethyl fumarate salts, which is licensed in Germany. In this post hoc analysis the efficacy and safety were assessed in patients with severe psoriasis in Austria. RESULTS: Efficacy measures significantly improved in both active treatment arms compared to placebo in 65 patients after 16 weeks of treatment. Physician global assessment of clear/almost clear in the dimethyl fumarate group was non-inferior to the dimethyl fumarate with monoethyl fumarate salts group 2 months after end of treatment. No serious adverse reaction occurred in patients with dimethyl fumarate in contrast to the second active treatment. Efficacy outcome was paralleled by quality of life improvements. CONCLUSION: This is the first report of dimethyl fumarate in a severely affected population with plaque psoriasis. Dimethyl fumarate is effective and safe in the systemic treatment of adults with severe psoriasis (physician global assessment).

Low HIV testing rate and its correlates among men who inject drugs in Iran.

BACKGROUND: Iran has a concentrated HIV epidemic among people who inject drugs (PWID). Low HIV testing uptake could contribute to the significant number HIV-infected PWID, who go undiagnosed. This study aims to assess HIV testing uptake and its correlates among PWID in Iran. METHODS: Data were collected through a national cross-sectional bio-behavioral study in 2010. Adult male HIV-negative PWID were included in the current analysis. All estimates were adjusted for the clustering effect of the sampling sites. Multivariable logistic regression was used to examine the correlates of recent HIV testing and adjusted odds ratios (AOR) were reported. RESULTS: Out of the 2146 eligible PWID for this study, 49.8% reported having ever tested for HIV. However, only 24.9% had tested in the previous year and received their test results. Around 65.2% of PWID knew an HIV testing site. In the multivariable analysis, knowing an HIV testing site (AOR=13.9; P-value<0.001), ≥24 years of age (AOR=3.30; P-value=0.027), and multiple incarcerations (AOR=1.71; P-value<0.001) were positively, and a monthly income of ≥65 US dollar (AOR=0.23; P-value=0.009) was negatively associated with having been tested and received the results. CONCLUSION: Despite the availability of free HIV counselling and testing for PWID in Iran, only one-fourth of adult male PWID had been tested for HIV and received their results. Implementing policies and strategies to normalize routine HIV testing among PWID are crucial steps to help curb the epidemic among Iranian PWID.

Baricitinib in Patients with Refractory Rheumatoid Arthritis.

BACKGROUND: In phase 2 studies, baricitinib, an oral Janus kinase 1 and 2 inhibitor, reduced disease activity in patients with rheumatoid arthritis who had not previously received treatment with biologic disease-modifying antirheumatic drugs (DMARDs). METHODS: In this phase 3 study involving 527 patients with an inadequate response to or unacceptable side effects associated with one or more tumor necrosis factor inhibitors, other biologic DMARDs, or both, we randomly assigned the patients in a 1:1:1 ratio to baricitinib at a dose of 2 or 4 mg daily or placebo for 24 weeks. End points, tested hierarchically at week 12 to control type 1 error, were the American College of Rheumatology 20% (ACR20) response (primary end point), the Health Assessment Questionnaire-Disability Index (HAQ-DI) score, the 28-joint Disease Activity Score based on C-reactive protein level (DAS28-CRP), and a Simplified Disease Activity Index (SDAI) score of 3.3 or less (on a scale of 0.1 to 86.0, with a score of 3.3 or less indicating remission). Comparisons with placebo were made first with the 4-mg dose of baricitinib and then with the 2-mg dose. RESULTS: Significantly more patients receiving baricitinib at the 4-mg dose than those receiving placebo had an ACR20 response at week 12 (55% vs. 27%, P<0.001). Differences between the higher-dose baricitinib group and the placebo group were also significant for the HAQ-DI score and the DAS28-CRP but not for an SDAI score of 3.3 or less. Adverse-event rates through 24 weeks were higher for patients receiving the 2-mg dose of baricitinib and those receiving the 4-mg dose than for patients receiving placebo (71% and 77%, respectively, vs. 64%), including infections (44% and 40%, vs. 31%). The rates of serious adverse events were 4%, 10%, and 7% in the three groups, respectively. Two nonmelanoma skin cancers and two major adverse cardiovascular events, including a fatal stroke, occurred in the higher-dose group. Baricitinib was associated with a small reduction in neutrophil levels and increases in serum creatinine and low-density lipoprotein cholesterol levels. CONCLUSIONS: In patients with rheumatoid arthritis and an inadequate response to biologic DMARDs, baricitinib at a daily dose of 4 mg was associated with clinical improvement at 12 weeks. (Funded by Eli Lilly and Incyte; ClinicalTrials.gov number, NCT01721044.).

Comparison of safety, efficacy and tolerability of dexibuprofen and ibuprofen in the treatment of osteoarthritis of the hip or knee.

In this observer-blinded, multicenter, non-inferiority study, 489 patients suffering from painful osteoarthritis of the hip or knee were included to investigate safety and tolerability of Dexibuprofen vs. Ibuprofen powder for oral suspension. Only patients who had everyday joint pain for the past 3 months and "moderate" to "severe" global pain intensity in the involved hip/knee of within the last 48 h were enrolled. The treatment period was up to 14 days with a control visit after 3 days. The test product was Dexibuprofen 400 mg powder for oral suspension (daily dose 800 mg) compared to Ibuprofen 400 mg powder for oral suspension (daily dose 1,600 mg). Gastrointestinal adverse drug reactions were reported in 8 patients (3.3 %) in the Dexibuprofen group and in 19 patients (7.8 %) in the Ibuprofen group. Statistically significant non-inferiority was shown for Dexibuprofen. Comparing both groups by a Chi square test showed a statistical significant lower proportion of related gastrointestinal events in the Dexibuprofen group. All analyses of secondary tolerability parameters showed the same result of a significantly better safety profile in this therapy setting for Dexibuprofen compared to Ibuprofen. The sum of pain intensity, pain relief and global assessments showed no significant difference between treatment groups. In summary, analyses revealed at least non-inferiority in terms of efficacy and a statistically significant better safety profile for the Dexibuprofen treatment.

Factor structure of the Iranian version of 12-item general health questionnaire.

BACKGROUND: The 12-Item General Health (GHQ-12) questionnaire is one of the most commonly used instruments in screening studies on mental health. OBJECTIVES: The current study aimed to examine the factor structure of the GHQ-12 questionnaire among the students in Iran. MATERIALS AND METHODS: It was a cross-sectional study in which 428 university students were recruited and completed the GHQ-12. Reliability of the GHQ-12 was evaluated using the Cronbach's alpha and the split-half method by applying the Spearman-Brown coefficient. Factor structure of the questionnaire was extracted by exploratory factor analysis (EFA). Confirmatory factor analysis (CFA) was conducted to assess how well the EFA extracted model fitted the observed data. RESULTS: The mean age of the participants was 22.83 years (SD = 3.09). Most of them were female (56.1%) and 81% were unemployed. The Cronbach's alpha coefficient for the Iranian version of GHQ-12 was 0.85. Using the split-half method, the alpha for the social dysfunction was found to be 0.77; it was 0.76 for the psychological distress. The principal component analysis revealed a two-factor structure for the questionnaire including social dysfunction and psychological distress that explained 48% of the observed variances. The confirmatory factor analysis was showed fit for the data. CONCLUSIONS: The current study findings confirm that the Iranian version of GHQ-12 has a good factor structure and is a reliable and valid instrument to measure psychological distress and social dysfunction.

HIV prevalence and related risk behaviours among female sex workers in Iran: results of the national biobehavioural survey, 2010.

OBJECTIVES: To determine the prevalence of HIV and related behavioural risks among Iranian female sex workers (FSW) via the first national biobehavioural surveillance survey. METHODS: In 2010, 1005 FSW were approached and 872 recruited using facility-based sampling from 21 sites in 14 cities in Iran. We collected dried blood samples and conducted face-to-face interviews using a standardised questionnaire. Data were weighted based on the response rate and adjusted for the clustering effect of the sampling site. Adjustment was performed by weighting based on the sampling fraction of each site using a prior estimate of its total size of the FSW population. RESULTS: The prevalence of HIV infection (95% CI) was 4.5% (2.4 to 8.3) overall, 4.8% (2.2 to 9.8) among those who had reported a history of drug use and 11.2% (5.4 to 21.5) among those who had a history of injection drug use. The frequencies of condom use in the last sexual act with paying clients and non-paying partners were 57.1% and 36.3%, respectively. Any drug use was reported by 73.8% of participants, and among this subgroup, 20.5% had a history of injection drug use. CONCLUSIONS: The prevalence of HIV was considerable among FSW particularly those who had a history of drug injection. A combination of prevention efforts addressing unsafe sex and injection are needed to prevent further transmission of HIV infection.

A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study.

OBJECTIVES: To compare the efficacy and safety of innovator infliximab (INX) and CT-P13, an INX biosimilar, in active rheumatoid arthritis patients with inadequate response to methotrexate (MTX) treatment. METHODS: Phase III randomised, double-blind, multicentre, multinational, parallel-group study. Patients with active disease despite MTX (12.5-25 mg/week) were randomised to receive 3 mg/kg of CT-P13 (n=302) or INX (n=304) with MTX and folic acid. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95% CI for the treatment difference was within ±15%. Secondary endpoints included ACR response criteria, European League Against Rheumatism (EULAR) response criteria, change in Disease Activity Score 28 (DAS28), Medical Outcomes Study Short-Form Health Survey (SF-36), Simplified Disease Activity Index, Clinical Disease Activity Index, as well as pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety and immunogenicity. RESULTS: At week 30, ACR20 responses were 60.9% for CT-P13 and 58.6% for INX (95% CI -6% to 10%) in the intention-to-treat population. The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses (C reactive protein (CRP)) at week 30 were 85.8% and 87.1%, respectively. Low disease activity or remission according to DAS28-CRP, ACR-EULAR remission rates, ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30. Incidence of drug-related adverse events (35.2% vs 35.9%) and detection of antidrug antibodies (48.4% vs 48.2%) were highly similar for CT-P13 and INX, respectively. CONCLUSIONS: CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX. CLINICALTRIALS.GOV IDENTIFIER: NCT01217086.

Comparison of two referral strategies for diagnosis of axial spondyloarthritis: the Recognising and Diagnosing Ankylosing Spondylitis Reliably (RADAR) study.

OBJECTIVE: To determine which of two referral strategies, when used by referring physicians for patients with chronic back pain (CBP), is superior for diagnosing axial spondyloarthritis (SpA) by rheumatologists across several countries. METHODS: Primary care referral sites in 16 countries were randomised (1 : 1) to refer patients with CBP lasting >3 months and onset before age 45 years to a rheumatologist using either strategy 1 (any of inflammatory back pain (IBP), HLA-B27 or sacroiliitis on imaging) or strategy 2 (two of the following: IBP, HLA-B27, sacroiliitis, family history of axial SpA, good response to non-steroidal anti-inflammatory drugs, extra-articular manifestations). The rheumatologist established the diagnosis. The primary analysis compared the proportion of patients diagnosed with definite axial SpA by referral strategy. RESULTS: Patients (N=1072) were referred by 278 sites to 64 rheumatologists: 504 patients by strategy 1 and 568 patients by strategy 2. Axial SpA was diagnosed in 35.6% and 39.8% of patients referred by these respective strategies (between-group difference 4.40%; 95% CI -7.09% to 15.89%; p=0.447). IBP was the most frequently used referral criterion (94.7% of cases), showing high concordance (85.4%) with rheumatologists' assessments, and having sensitivity and a negative predictive value of >85% but a positive predictive value and specificity of <50%. Combining IBP with other criteria (eg, sacroiliitis, HLA-B27) increased the likelihood for diagnosing axial SpA. CONCLUSIONS: A referral strategy based on three criteria leads to a diagnosis of axial SpA in approximately 35% of patients with CBP and is applicable across countries and geographical locales with presumably different levels of expertise in axial SpA.

A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus.

OBJECTIVE: To assess the efficacy/safety of the B lymphocyte stimulator inhibitor belimumab plus standard therapy compared with placebo plus standard therapy in active systemic lupus erythematosus (SLE). METHODS: In a phase III, multicenter, randomized, placebo-controlled trial, 819 antinuclear antibody-positive or anti-double-stranded DNA-positive SLE patients with scores ≥6 on the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) were randomized in a 1:1:1 ratio to receive 1 mg/kg belimumab, 10 mg/kg belimumab, or placebo intravenously on days 0, 14, and 28 and then every 28 days for 72 weeks. The primary efficacy end point was the SLE Responder Index (SRI) response rate at week 52 (an SRI response was defined as a ≥4-point reduction in SELENA-SLEDAI score, no new British Isles Lupus Assessment Group [BILAG] A organ domain score and no more than 1 new BILAG B score, and no worsening in physician's global assessment score versus baseline). RESULTS: Belimumab at 10 mg/kg plus standard therapy met the primary efficacy end point, generating a significantly greater SRI response at week 52 compared with placebo (43.2% versus 33.5%; P = 0.017). The rate with 1 mg/kg belimumab was 40.6% (P = 0.089). Response rates at week 76 were 32.4%, 39.1%, and 38.5% with placebo, 1 mg/kg belimumab, and 10 mg/kg belimumab, respectively. In post hoc sensitivity analyses evaluating higher SELENA-SLEDAI score thresholds, 10 mg/kg belimumab achieved better discrimination at weeks 52 and 76. Risk of severe flares over 76 weeks (based on the modified SLE Flare Index) was reduced with 1 mg/kg belimumab (34%) (P = 0.023) and 10 mg/kg belimumab (23%) (P = 0.13). Serious and severe adverse events, including infections, laboratory abnormalities, malignancies, and deaths, were comparable across groups. CONCLUSION: Belimumab plus standard therapy significantly improved SRI response rate, reduced SLE disease activity and severe flares, and was generally well tolerated in SLE.