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In Baringo County, Kenya, trachoma remains endemic despite repeated mass drug administration (MDA) efforts, with coverage in one of the wards consistently falling short of world health organization (WHO) targets. The disease is endemic in 12 out of the 47 counties in Kenya. Baringo county is a pastoral conflict, hard to reach area where eight rounds of mass drug administration (MDA) for trachoma have been implemented. In Loyamorok ward, treatment coverage has been below 68% against the WHO recommended threshold of 80%. Community engagements that promote participatory approaches are key to MDA success. In this study, we describe community-based participatory approaches qualitatively developed and implemented during the intervention phase of a study that involved a pre-intervention, intervention and post intervention phases and aimed to address barriers of community participation and access to trachoma MDA. Interviews and focus group discussions were used to identify barriers to community participation in MDA, that included power and gender dynamics, rampant insecurity, community myths and misconceptions, migration in search of water and pastures, vastness and terrain and ineffective teams which resulted to unsupervised swallowing of drugs during MDA campaigns. Stakeholders in trachoma were identified through meetings with national, county and sub-county health management teams. The stakeholders, community members and the research team used the identified barriers to formulate MDA strategies including effective stakeholder engagement, enhanced social mobilization, community awareness creation on trachoma, effective planning and execution of MDA and implementation monitoring of the MDA campaign, all aimed at increasing MDA coverage. Overall MDA coverage in the area increased from 67.6% in 2021 to 87% in 2023 thus meeting the WHO threshold of 80%. The use of community-based, participatory approaches in the development and implementation of data driven strategies has the potential to positively influence MDA coverage for trachoma, and other neglected tropical diseases. Author summary: Trachoma is a disease of the eye and a leading infectious cause of blindness in sub-Saharan Africa. It is caused by a bacterium called Chlamydia trachomatis. It is transmitted by directly or indirectly transferring of eye and nose discharges from people who already have the disease mostly by flies. The disease in controlled by among other things provision of drugs to communities where the disease is endemic through mass drug administration (MDA). For the MDA to be effective, more than 80% of the community members should be reached. In areas where communities record very low access to MDA, there is need to identify barriers and develop strategies to mitigate the same. In this study we describe community-based participatory approaches employed to develop and test implementation strategies aimed at increasing access to trachoma MDA in Loyamorok ward of Baringo county. The results showed an increase in community participation in the subsequent MDA, which could be attributed to the implemented strategies. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this work was to summarize the incidence of herpes zoster (HZ) complications in different populations. Methods: Systematic literature review of PubMed, Embase, and Virtual Health Library records between January 1, 2002 and October 20, 2022 using search strings for HZ, complications, and frequency measurements. Results: The review included 124 studies, most conducted in the general population (n = 93) and on individuals with comorbidities (n = 41) ≥ 18 years of age. Most studies were conducted in Europe (n = 44), Asia (n = 40), and North America (n = 36). Postherpetic neuralgia (PHN) was the most studied neurological complication. Variable relative PHN incidence was found in the general population (2.6–46.7%) or based on diagnosis: immunocompromised (3.9–33.8%), depression (0–50%), and human immunodeficiency virus (HIV) (6.1–40.2%). High incidence rates were observed in hematological malignancies (HM) and solid organ malignancies (132.5 and 93.7 per 1000 person-years, respectively). Ocular complications were frequently reported with herpes zoster ophthalmicus (HZO). The relative incidence (incidence rate) of HZO in the general population was reported as 1.4–15.9% (0.31–0.35 per 1000 person-years). High relative incidence was observed in HIV (up to 10.1%) and HM (3.2–11.3%). Disseminated HZ was the most frequently reported cutaneous complication. The relative incidence of disseminated HZ was 0.3–8.2% in the general population, 0–0.5% in the immunocompetent, and 0–20.6% in patients with comorbidities. High relative incidence was reported in HM and solid organ transplant (up to 19.3% and 14.8%, respectively). Discussion: Most reported complications were neurological (n = 110), ocular (n = 48), and cutaneous (n = 38). Few studies stratified complications by age or gender (or both). Incidence appeared higher in select immunocompromised populations. Higher incidence was associated with older age in several studies; the general association with gender was unclear. Conclusions: Variable incidence of HZ complications was reported by population subgroup. Further research is required to quantitatively analyze incidence by age, gender, and location. [ABSTRACT FROM AUTHOR]

Background The objective of this study was to estimate the annual incidence rates of herpes zoster (HZ) and postherpetic neuralgia (PHN) among individuals aged ≥19 years and the proportion who received HZ vaccination among those aged ≥50 years. Methods This observational cohort study was conducted with administrative claims data from HealthVerity and included insured individuals across the US. Crude and US age- and sex-standardized incidence rates of HZ and PHN were calculated from 1 January 2019 to 31 May 2022 by calendar year in persons aged ≥19 years. Outcomes were defined as ≥1 ICD-10 diagnosis code for HZ or PHN. Analyses were stratified by age, sex, and immunocompromised status. Among those aged ≥50 years, the proportion who received 1 or 2 doses of recombinant zoster vaccine (Shingrix) or 1 dose of Zostavax was calculated. Results Standardized annual incidence rates from 2019 to 2021 were 542 to 685 per 100 000 person-years for HZ and 35 to 38 per 100 000 person-years for PHN. Rates were highest among females, older adults, and individuals who were immunocompromised. From 1 January 2019 to 31 May 2022, 4.3% and 9.0% of persons aged ≥50 years received 1 and 2 doses of Shingrix, respectively, and 0.2% received 1 dose of Zostavax. Conclusions In this US claims database analysis, HZ and PHN were more frequent among older adults, females, and individuals who were immunocompromised. Between 1 January 2019 and 31 May 2022, 9% of persons aged ≥50 years received 2 doses of the Shingrix vaccine. Greater efforts are needed to increase vaccine uptake against HZ, especially for those at highest risk. [ABSTRACT FROM AUTHOR]

Experience with mycophenolate in uveitis due to Behçet syndrome (BS) is limited. Twelve patients with panuveitis or posterior uveitis who were started mycophenolate were included. Data on demographic characteristics, therapies, ocular attacks, and adverse events were extracted from patient charts. Seven patients with BS uveitis were prescribed mycophenolate for remission induction, of which 6 were refractory/intolerant to conventional immunosuppressives. Mycophenolate was combined with anti-TNFs in 3 patients, resulting in no further ocular attacks. Mycophenolate had to be stopped in the fourth patient due to adverse events. The remaining 3 patients continued to have ocular attacks and were switched to other agents without any drop in visual acuity. Among the 5 patients who were prescribed mycophenolate for maintenance, 2 were relapse free, but 3 experienced ocular attacks. One patient had an exacerbation of mucocutaneous lesions, and 2 experienced adverse events. Mycophenolate monotherapy may not be adequate for remission induction of refractory BS uveitis, but it can be a safe and effective alternative when combined with a biologic agent. It may also be an option for maintenance therapy. [ABSTRACT FROM AUTHOR]

Purpose: To enable the practical application of a novel transdermal therapeutic system (TTS) that combines the achievement of supersaturation by the pH-shift method and user activated system (UAS), for more than 24 h for the expected period of TTS utilization, we investigated the supersaturation achievement conditions for permeation enhancement. Methods: Supersaturation was achieved using the pH-shift method. After achieving supersaturation, the skin permeation-enhancing properties of flurbiprofen (FP) and ketoconazole (KCZ) with different crystallization properties were evaluated by in vitro permeation test using excised skin. Additionally, we investigated the conditions for achieving supersaturation of KCZ through a 54-h in vitro permeation test using a silicone membrane, which showed a reliable enhancement in permeation for more than 24 h. Results: Compared to FP, the skin permeability of KCZ, which exhibits slow crystallization, was significantly increased at 50 µg/mL supersaturation. Furthermore, hydroxypropyl methylcellulose (HPMC), an anti-nucleant polymer, was added to maintain the most stable kinetic solubility increase of KCZ for approximately 54 h with supersaturation at 500 μg/mL. This result could be explained by the strong crystal growth inhibition effect of HPMC on KCZ. Conclusion: KCZ, which has a slow crystallization rate, increases skin permeability by achieving supersaturation. The combination of KCZ and HPMC provides stable supersaturation and permeation enhancement for approximately 54 h after achieving supersaturation via the pH-shift method. In addition, this combination can be expected to be used as the novel TTS that combines the achievement of supersaturation by the pH-shift method and UAS. [ABSTRACT FROM AUTHOR]

Background: More than 1.7 billion people are affected by neglected tropical diseases (NTDs) worldwide. Forty percent of the NTD-affected people live in Africa with the poorest, most vulnerable, and hard to reach geographical areas. The NTDs cause significant social and economic burden and deepen marginalization and stigmatization. The World Health Organization's current roadmap for NTD aims to prevent, control, eliminate, or eradicate 20 tropical diseases. Ethiopia experiences a high burden of these diseases, but current access to diagnostics, medicine, and/or care has been little explored to inform the country's NTD strategic plan. The overall purpose of the scoping review was to map and characterize the burden of NTDs and challenges in access to diagnostics, medicine, and/or care in Ethiopia. Methods: A systematic search of evidence was conducted in PubMed, Cochrane Library, and Google Scholar from January 2000 until May 2022, without restrictions of language or study design. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review was followed for screening of studies. Key findings were extracted and narrated qualitatively. Results: The search resulted in 4532 articles, of which 105 met the inclusion criteria and were included in the scoping review under three themes: burden of NTDs, access to diagnostics, medicine and/or care, and key barriers. Although gains have been made in the prevention and control of NTDs in Ethiopia, the burden remains high, and progress in access to diagnostics, medicine/drugs, and/or care is very slow. Poverty, poor quality of life, and underfunding of NTD programs decelerate the process of NTD elimination program in the country. Conclusions: The scoping review identified a considerable number of studies on the burden of NTDs in Ethiopia and strategies for diagnosis, treatment, and/or care; however, there is a paucity of evidence on the suitability and potential benefits of novel diagnostic technologies and medicines in the country. A regular review and analysis of such country-level evidence is important to inform the country NTDs roadmap and local implementation strategies. [ABSTRACT FROM AUTHOR]

Introduction: Herpes zoster (HZ), or shingles, is caused by the reactivation of varicella zoster virus (VZV) and typically presents as an acute, painful dermatomal rash, but can lead to long-term, distressing complications such as postherpetic neuralgia (PHN). Increasing trends in HZ cases are evident globally among the aging population; however, reviews investigating the epidemiology and clinical management of HZ in Turkey are lacking. Therefore, a literature review of local studies in Turkey was conducted to identify the data available and identify gaps in the literature. Methods: Literature searches were carried out in PubMed and local journals to retrieve published articles that reported surveillance data, seroepidemiology, patient outcomes, or clinical management related to HZ or VZV in Turkey until April 30, 2022. Studies included primary data reports, case studies, secondary data reviews, and epidemiological studies in healthy or at-risk populations; HZ was the primary focus of the review. Results: No studies reported VZV or HZ epidemiological data at a national level. One large retrospective study in Istanbul reported that HZ incidence rates significantly increased in adults 18–44 years of age between 2011 and 2019. Four single-center studies reported the proportion of dermatological patients with HZ at 0.43–1.56%. PHN was the most common reported complication, occurring in 8–58.9% of patients with HZ. However, out of 39 identified case reports, HZ ophthalmicus was the most frequently reported complication. Two studies highlighted poor disease awareness and risk perception of HZ among Turkish citizens. Conclusion: Overall, there were limited comprehensive epidemiological data on HZ in Turkey. However, the abundance of case studies on HZ complications indicates a strong disease presence and diverse clinical management in Turkey. Further research will be important to understand the impact of HZ, increase disease awareness, and support the introduction of new preventative strategies. [ABSTRACT FROM AUTHOR]

Uveitis in childhood poses a distinct challenge, mainly because of the insidious onset and chronic course of intraocular inflammation in most cases, which may result in permanent visual loss due to delayed diagnosis and treatment. Although anterior uveitis, frequently associated with juvenile idiopathic arthritis, is the most common form of ocular involvement, idiopathic intermediate uveitis (pars planitis) is also a common uveitic entity in childhood. Posterior or panuveitis of a variety of noninfectious or infectious etiologies may be seen as well. Pediatric uveitis needs to be closely monitored since serious ocular complications such as intraocular pressure elevation, cataract, and macular edema may rapidly develop due to inadequately controlled inflammation and/or the use of corticosteroids. Methotrexate is generally the firstline corticosteroid-sparing agent, and adalimumab is the first-line biologic in refractory cases of noninfectious uveitis. A multidisciplinary approach is essential to monitor systemic disease associations, treatment response, and adverse events in children with uveitis. [ABSTRACT FROM AUTHOR]

Childhood uveitis is a sight-threatening condition, because if not properly recognized and treated can lead to several ocular complications and blindness. It represents a real challenge not only from an etiologic/diagnostic point of view, but also for management and therapy In this review we will discuss the main etiologies, the diagnostic approach, risk factors associated to childhood noninfectious uveitis (cNIU), and the difficulties in eye examination in childhood. Moreover, we will discuss the treatment of cNIU in terms of therapeutic choice, timing of initiation, and withdrawal. Identification of specific diagnosis is mandatory to prevent severe complications, thus a thorough differential diagnosis is essential. Pediatric eye examination may be extremely challenging due to the scarce collaboration, but novel techniques and biomarkers will help in identifying low grade of inflammation, eventually modifying long-term outcomes. Once identified the appropriate diagnosis, recognition of children who may benefit of a systemic treatment is crucial. What, When, and how long are the key questions to address in this field. Current evidence and future results of ongoing clinical trials will help in driving treatment. A proper ocular screening, not only in the context of systemic disease, should be discussed by experts. [ABSTRACT FROM AUTHOR]

Background: Herpes zoster (HZ) is a skin disease that can also cause virus-infectious peripheral neuropathies. Despite this, there is limited information on patient preferences for seeking medical attention for HZ and zoster-associated pain (ZAP). Our study aimed to evaluate how frequently patients with ZAP choose to visit neurologists for their symptoms. Methods: This study conducted a retrospective review of electronic health records in three general hospitals from January 2017 to June 2022. Using association rule mining, the study analyzed referral behaviors. Results: We identified 33,633 patients with 111,488 outpatient visits over 5.5 years. The study found that the majority of patients (74.77– 91.22%) visited dermatologists during their first outpatient visit, while only a small percentage (0.86– 1.47%) preferred to consult a neurologist. The proportion of patients referred to a specialist during their medical visit varied significantly between different specialties within the same hospital (p < 0.05) and even within the same specialty (p< 0.05). There was a weak association (Lift:1.00– 1.17) of referral behaviors between dermatology and neurology. Across the three hospitals, the average number of visits to a neurologist for ZAP was 1.42– 2.49, with an average electronic health record duration of 11– 15 days per patient. After consulting with a neurologist, some patients were referred to other specialists. Conclusion: It was observed that patients with HZ and ZAP tended to visit a variety of specialists, with only a small number seeking the assistance of neurologists. However, from the perspective of neuroprotection, it is the duty of neurologists to provide more means. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and pain fluctuations of methylcobalamin in combination with lidocaine local injection treatment for subacute herpetic neuralgia (SHN). Methods: Seventy-nine women (60.4 ± 2.7 years) with thoracic SHN were enrolled and randomized to receive a combination of methylcobalamin and lidocaine local injection (MI, N=40), or a combination of lidocaine patch 5% and oral methylcobalamin (PO, N=39) for four weeks. Repeated-measures analyses of variance were used to evaluate the effect on pain levels. Generalized estimation equations were used to analyze the cause-effect relationship between pain fluctuations and influencing factors. Results: At the treatment endpoint, the group, treatment time, and group interacted with treatment time effects of the pain scores and area were statistically significant (P< 0.001), The pain scores were 2.9 ± 0.9 (MI) and 4.3 ± 1.5 (PO). 80.00% (MI) or 28.21% (PO) of patients had pain scores ≤  3, the odds ratio was 2.84 (95% CI: 1.68 to 4.79). The incidence of postherpetic neuralgia was 5.0% (2/40) at 3 months. Pain fluctuated repeatedly during treatment. The pain fluctuation increased from 8.75 log folds in the afternoon, to 79.85 log folds at night. With the ADLs level increasing from 1 to 3, the pain fluctuated from 4.28 to 17.70 log folds. Allodynia, itching, sleep quality, and ADLs were the significant influencing factors (P< 0.05). Conclusion: This study validated the efficacy of methylcobalamin combined with lidocaine for SHN, and confirmed that pain levels in patients with SHN had an obvious circadian rhythm. ADLs were an important cause of pain fluctuations. [ABSTRACT FROM AUTHOR]

Postherpetic neuralgia (PHN) is a devastating disease with extraordinarily poor treatment outcomes. Both pulsed radiofrequency (PRF) and ozone have good effects on the treatment of the disease. However, whether PRF and ozone have a synergistic effect on PHN remains unclear. Therefore, this study aimed to assess the therapeutic effects of ozone alone and in combination with PRF in the treatment of PHN. Ninety-one patients with PHN were assigned into two groups: PRF combined with ozone (PRF + ozone group, n = 44) and ozone therapy alone (ozone group, n = 47). In PRF + ozone group, the high-voltage, long-duration PRF was applied to the target dorsal root ganglions. Then ozonated water (11.5 µg/mL) was injected through the inner cannula. In the ozone group, all other processes were the same as those in the PRF + ozone group apart from the electrical stimulation. The therapeutic efficacy was evaluated by visual analog scale and tactile sensation at pre-treatment and post-treatment 3, 6, and 12 months. Compared with pre-treatment data, the visual analog scale score was significantly decreased in both groups after treatment. Compared with the ozone group, the visual analog scale score was significantly decreased in the PRF + ozone group at 3, 6, and 12 months. Similarly, the tactile sensation was also significantly decreased at post-treatment when compared to pre-treatment. However, there were no statistical differences between the two groups. Regression analysis results showed that the history of diabetes mellitus and age had significant negative and positive effects, respectively, on the treatment results. To conclude, the administration of PRF + ozone and ozone therapy alone could both improve pain symptoms. Moreover, treatment effects and total efficacy rates tended to be higher for the combination of PRF and ozone than ozone alone. This conclusion was especially true for long-term therapeutic effects. [ABSTRACT FROM AUTHOR]

Background: Effective mass drug administration (MDA) is the cornerstone in the elimination of lymphatic filariasis (LF) and a critical component in combatting all neglected tropical diseases for which preventative chemotherapy is recommended (PC-NTDs). Despite its importance, MDA coverage, however defined, is rarely investigated systematically across time and geography. Most commonly, investigations into coverage react to unsatisfactory outcomes and tend to focus on a single year and health district. Such investigations omit more macro-level influences including sociological, environmental, and programmatic factors. The USAID NTD database contains measures of performance from thousands of district-level LF MDA campaigns across 14 years and 10 West African countries. Specifically, performance was measured as an MDA's epidemiological coverage, calculated as persons treated divided by persons at risk. This analysis aims to explain MDA coverage across time and geography in West Africa using sociological, environmental, and programmatic factors. Methodology: The analysis links epidemiological coverage data from 3,880 LF MDAs with contextual, non-NTD data via location (each MDA was specific to a health district) and time (MDA month, year). Contextual data included rainfall, temperature, violence or social unrest, COVID-19, the 2014 Ebola outbreak, road access/isolation, population density, observance of Ramadan, and the number of previously completed MDAs. Principal findings: We fit a hierarchical linear regression model with coverage as the dependent variable and performed sensitivity analyses to confirm the selection of the explanatory factors. Above average rainfall, COVID-19, Ebola, violence and social unrest were all significantly associated with lower coverage. Years of prior experience in a district and above average temperature were significantly associated with higher coverage. Conclusions/Significance: These generalized and context-focused findings supplement current literature on coverage dynamics and MDA performance. Findings may be used to quantify typically anecdotal considerations in MDA planning. The model and methodology are offered as a tool for further investigation. Author summary: Elimination of lymphatic filariasis, and of certain other neglected tropical diseases, depends critically on the successful treatment of the population through a series of typically annual mass drug administration (MDA) campaigns. When an MDA falls short of expectations in terms of population treated, organizers can learn and adapt the next round of MDA to improve performance. Because this learning is often based on anecdotal evidence or surveys specific to a narrow geography, there is an opportunity in the literature to augment our understanding of what impacts MDA performance, particularly in terms of more contextual factors and trends or patterns that reach across multiple years and regions. In this analysis we linked a performance measure from 3,880 MDA campaigns across 10 West African countries to contextual factors such as rainfall, temperature, violence or social unrest, COVID-19, the 2014 Ebola outbreak, road access/isolation, population density, observance of Ramadan, and the number of previously completed MDAs. We hope the findings themselves will better equip MDA organizers in decision-making and offer this mixed-level model as an approach to better understanding coverage dynamics in West Africa and elsewhere. [ABSTRACT FROM AUTHOR]

Background As countries reach the trachoma elimination threshold and cases of trachomatous inflammation follicular (TF) become rare, it becomes difficult to train survey graders to recognize clinical signs. We assess the use of photography as a grading tool, the efficiency of an in-country grading center and the comparability of field and photographic grading. Methods During January–February 2017 surveys in Amhara, Ethiopia, field graders assessed TF, trachomatous inflammation intense (TI) and trachomatous scarring (TS). Photographs were taken from each conjunctiva and later graded at the Gondar Grading Center (GGC) at the University of Gondar in Amhara. Two trained ophthalmology residents graded each set of photographs and a third grader provided an adjudicating grade when needed. Results A total of 4953 photographs of 2477 conjunctivae from 1241 participants in 10 communities were graded over 5 d at the GGC. Six examined participants were not photographed. Agreement between field and photographic grades were for TF: percent agreement (PA) 96.7%, κ=0.70 (95% confidence interval [CI] 0.64 to 0.77; for TI: PA 94.7%, κ=0.32 (95% CI 0.20 to 0.43); and for TS: PA 83.5%, κ=0.22 (95% CI 0.15 to 0.29). Conclusions Conjunctival photography may be a solution for programs near the elimination threshold where there are few available community cases for training field graders. [ABSTRACT FROM AUTHOR]

Introduction: The reactivation of varicella zoster virus (VZV) in previously infected individuals can cause herpes zoster (HZ), which is characterized by a localized, painful dermatomal rash. While there is a global trend of increasing HZ cases, there is a lack of research examining the epidemiology of HZ within the Gulf Cooperation Council (GCC) countries. Therefore, we aimed to critically appraise evidence on VZV and HZ epidemiology in the GCC countries and identify gaps in the current literature. Methods: A literature review was conducted via a comprehensive appraisal of the literature. PubMed and local-language journals were searched to identify articles related to HZ and VZV published up until 31 January 2022, with a sole focus on the GCC countries. Included studies reported on surveillance data, seroepidemiology, and patient outcomes for HZ and VZV, and comprised primary data reports, case series, case reports, narrative and systematic literature reviews, studies reporting HZ incidence or prevalence, and Ministry of Health reports. Results: Thirteen studies were found that reported on VZV seroprevalence in Saudi Arabia, the United Arab Emirates (UAE), and Qatar, ranging from 15.0% to 92.2%, while no data were identified for Bahrain, Kuwait, or Oman. There was very limited country-wide information on the incidence of HZ in GCC countries, and three identified studies reported HZ prevalence as seen in a single clinic, ranging from 0.62% to 2.3%. A single study from Saudi Arabia and government surveillance data reported on the impact of VZV vaccination on VZV infection, though there was no evidence on the impact of VZV vaccination on HZ. Conclusion: There is a clear gap in the literature regarding the incidence of HZ infection, and the impacts of HZ and VZV vaccinations in the GCC countries. Further research into the epidemiology of HZ is necessary to inform the implementation of vaccination programs in the GCC countries. [ABSTRACT FROM AUTHOR]

Intoduction Postherpetic neuralgia (PHN), a chronic and debilitating pain condition, is caused by acute herpes zoster lesions. It affects the patient's daily activities, sleep, social well-being, and quality of life (QoL). The mainstays of its treatment are systemic medications such as tricyclic antidepressants and antiepileptics. Objective To determine the effectiveness of carbamazepine and amitriptyline in the management of PHN. Methods In this study, amitriptyline and carbamazepine were given to PHN patients who met the inclusion criteria at Khyber Teaching Hospital in Peshawar. Patients were separated into two groups after written informed consent, a physical examination, and relevant investigations. Group A received 25mg amitriptyline at night time and Group B received 200 mg carbamazepine two times daily for eight weeks. The severity of the pain and the effectiveness of the therapy was assessed using a visual analogue scale (VAS score). SPSS 23 was used to analyzed the data. Results There was no significant difference statistically in the age of patients (p=0.41), gender (p=0.40), duration of PHN (P=0.40), and pre-treatment VAS score (p=0.11). The effectiveness (good to excellent) of amitriptyline and carbamazepine was 86% and 80% respectively (p=0.66). Upon intragroup comparison, amitriptyline (p<0.001) and carbamazepine (p<0.02) were statistically significant in the reduction in PHN. Conclusion Amitriptyline and carbamazepine reduce PHN-associated pain and discomfort. Both medications improve PHN patients' QoL, well-being, and physical functioning. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) has been reported as a potential risk factor for developing herpes zoster (HZ). We aimed at comparing incidence rates of HZ between people with versus without COPD in the US. This retrospective cohort study used data from Optum's de‐identified Clinformatics Data Mart database from 1/1/2013 through 12/31/2018. We identified two cohorts of people ≥40 years without prior HZ, HZ vaccination, postherpetic neuralgia (PHN) or HZ ophthalmicus: those with (COPD+) and those without (COPD−) a COPD diagnosis. Adjusted incidence rate ratios (aIRRs) of HZ and PHN were calculated using generalized linear models, controlling for the propensity score of being diagnosed with COPD and relevant demographic and clinical characteristics. People in the COPD+ cohort (n = 161 970) were considerably older, had more comorbidities and were more likely to use corticosteroids than those in the COPD− cohort (n = 9 643 522). The incidence rate of HZ was 5.7‐fold higher in the COPD+ versus COPD− cohorts (13.0 vs. 2.3 per 1000 person‐years [PY]; aIRR, 2.77; 95% confidence interval [CI], 2.69 to 2.85; P < 0.001). The unadjusted incidence rate of PHN was 1.7‐fold higher in the COPD+/HZ+ versus COPD−/HZ+ cohort (64.8 vs. 37.1 per 1000 PY), but not after adjustment (aIRR, 1.07; 95% CI, 0.79 to 1.45). HZ and PHN incidence rates increased with age. After adjustment, COPD+ adults had a 2.8‐fold increased risk of developing HZ. These results may help to increase awareness about potential risk factors for HZ and highlight the need for vaccination among those at increased risk. [ABSTRACT FROM AUTHOR]

Background Biannual azithromycin distribution to children 1–59 months old reduced all-cause mortality by 18% [incidence rate ratio (IRR) 0.82, 95% confidence interval (CI): 0.74, 0.90] in an intention-to-treat analysis of a randomized controlled trial in Niger. Estimation of the effect in compliance-related subgroups can support decision making around implementation of this intervention in programmatic settings. Methods The cluster-randomized, placebo-controlled design of the original trial enabled unbiased estimation of the effect of azithromycin on mortality rates in two subgroups: (i) treated children (complier average causal effect analysis); and (ii) untreated children (spillover effect analysis), using negative binomial regression. Results In Niger, 594 eligible communities were randomized to biannual azithromycin or placebo distribution and were followed from December 2014 to August 2017, with a mean treatment coverage of 90% [standard deviation (SD) 10%] in both arms. Subgroup analyses included 2581 deaths among treated children and 245 deaths among untreated children. Among treated children, the incidence rate ratio comparing mortality in azithromycin communities to placebo communities was 0.80 (95% CI: 0.72, 0.88), with mortality rates (deaths per 1000 person-years at risk) of 16.6 in azithromycin communities and 20.9 in placebo communities. Among untreated children, the incidence rate ratio was 0.91 (95% CI: 0.69, 1.21), with rates of 33.6 in azithromycin communities and 34.4 in placebo communities. Conclusions As expected, this analysis suggested similar efficacy among treated children compared with the intention-to-treat analysis. Though the results were consistent with a small spillover benefit to untreated children, this trial was underpowered to detect spillovers. [ABSTRACT FROM AUTHOR]

Background: The reactivation of herpes zoster (HZ) is associated with disease stress. However, the relationship between chondromalacia patella (CMP) and HZ remains poorly understood. This study investigated the relationship between CMP and the risk of developing HZ.Methods: Data were collected from the Taiwan's National Health Insurance Research Database. Patients with CMP diagnosed between 2000 and 2017 were assigned to the case group; patients without CMP were randomly selected from the same database and paired with controls matched by age and sex. The primary outcome was a diagnosis of HZ. All patients were followed until their diagnosis of HZ, their withdrawal from the NHI program, their death, or the end of 2017, whichever was earliest. The risk of developing HZ was compared between the case and control groups.Results: In total, 22,710 patients with CMP and 90,840 matched controls were enrolled. The overall incidence rates of HZ in the CMP and control cohorts were 7.94 and 7.35 per 1,000 person-years, respectively. After potential confounders were controlled for, the case group exhibited a higher risk of HZ than did the control group [adjusted hazard ratio (aHR) = 1.06, p < 0.05]. In a stratification analysis by age, patients over 65 years old in the CMP group exhibited a higher risk of HZ than did those in the control group (aHR = 1.22, p < 0.01). In a stratification analysis by sex, women with CMP were at greater risk of developing HZ than women without CMP (aHR = 1.18, p < 0.01).Conclusion: Patients with CMP, especially elder adults and women, exhibited a higher risk of HZ. The HZ risk of patients with CMP should thus be assessed, and the necessity of HZ vaccination should be informed. [ABSTRACT FROM AUTHOR]

Objective: Data on the real-world burden of herpes zoster (HZ) in adults with type 2 diabetes (T2D) in the U.S. are limited. We assessed HZ in patients with and without T2D and measured the impact of HZ on health care resource use (HCRU) and costs.Research Design and Methods: This retrospective cohort analysis used U.S. commercial claims data (sourced from claims incurred between 1 January 2012 and 31 July 2018). HZ incidence rates/1,000 person-years (PYs) were calculated in patients with and without T2D. HZ risk was evaluated using Poisson regression to generate adjusted incidence rate ratios (aIRRs). Patients with T2D with HZ were propensity score matched to patients with T2D only and to patients with HZ without T2D. HCRU and costs were compared across cohorts during a 1-year follow-up period. Cox proportional hazards analyses evaluated factors associated with HZ-related complications.Results: Crude HZ incidence rates in patients with and without T2D were 9.8/1,000 PY and 2.6/1,000 PY, respectively. T2D patients were almost twice as likely to be diagnosed with HZ (aIRR 1.84; 95% CI 1.82-1.85). HZ was associated with increased HCRU and health care costs. At 12 months, unadjusted incremental all-cause health care costs for patients with T2D with HZ versus patients with T2D without HZ were $5,216. The unadjusted incremental HZ-related health care costs for patients with T2D with HZ versus patients with HZ without T2D were $2,726. Age was the most important predictor for HZ-related complications.Conclusions: Given the increased risk of HZ and HCRU and cost burden in patients with T2D, HZ prevention in patients with T2D may be beneficial. [ABSTRACT FROM AUTHOR]

Currently, national governments of onchocerciasis endemic African countries are working towards the elimination of the disease using mass drug administration (MDA) with ivermectin as a primary strategy. Attainment of this goal requires implementation of prolonged high MDA coverage in all endemic areas, and vigilant monitoring and evaluation of the program. This study was thus conducted with the purpose of i) providing estimate of ivermectin coverage, ii) validating the MDA coverage reported through community drug distributors (CDDs), iii) determining the factors associated with MDA coverage, and iv) estimating the difference between MDA program reach and survey coverage rates following MDA campaign carried out in May 2017 in Asosa and Yeki districts in Ethiopia. A community-based cross-sectional study was conducted among 2,824 study participants in Asosa and Yeki districts. A total of 50 kebeles (smallest administrative units) were randomly selected from the two districts. A systematic sampling was employed to select study households from the 50 kebeles. Then, a household member was randomly selected for the interview. Univariate and multivariate logistic regression analysis were used to determine the odds ratio and to observe the associations between the MDA survey coverage and the variables used. Eighty-seven percent (2458/2824) of the respondents from both districts responded that they were offered ivermectin during the May 2017 MDA campaign. At the district level, 1182 individuals from Yeki and 1276 from Asosa, received the drug, that indicate 88.5% and 85.8% MDA program reach in Yeki and Assosa districts, respectively. Whereas, a total of 366 individuals were not offered ivermectin in both study districts. Of these, 47(12.8%), 143(39.1%), and 176(48.1%) did not receive the drug because of program implementation-related reasons, ineligibility criteria, and personal issues, respectively. Of the 1488 and 1336 respondents in Asosa and Yeki, 1272 and 1182 participants took the drug, resulting in survey coverage rate of 85.5% (95% CI: 83.6–87.2%) and 88.5% (95% CI: 86.7–90.1%), respectively. Multivariable logistic regression analysis revealed significantly low survey coverage rate in females (AOR = 0.5, 95%CI: 0.3–0.6; p<0.001) and in those whose age ranges between 15–24 years (AOR = 0.5, 95%CI: 0.3–0.8; p = 0.007) and 25–34 years (AOR = 0.5, 95%CI: 0.3–0.9; p = 0.021) in Asosa. The researchers believe that the current study generated operational evidence on MDA program reach and coverage rates in two study districts in Ethiopia. The survey coverages were lower than the recommended 90% minimum threshold for success. Only Yeki district reached the 90% threshold survey coverage. Both districts had reported higher coverages than the survey estimates (even outside the 95% CI), thus, were not validated. The majority (60.9%) of the reasons for not receiving the drug were related to program implementation and recipients'personal issues. Efforts must therefore be directed to enhance MDA coverage in future rounds via proper MDA planning and implementation, such as allocating adequate time to the MDA activities, health education, and mobilizing of all segments of the population, including adolescents and the youth. The researchers also recommend such studies to be extended to other MDA programs for other neglected tropical diseases (NTDs). [ABSTRACT FROM AUTHOR]

The two major problems in the development of new drugs are low aqueous solubility and low oral bioavailability. Although, drug delivery via oral route is most preferred for years but it also has some drawbacks. Various techniques for improving the solubility have been developed, however the success of these techniques depends on the physical and chemical properties of the drug under development. In recent years, mucoadhesive drug delivery gained high popularity in comparison to other routes of drug delivery as it can circumvent the drawbacks of conventional delivery system such as first pass metabolism, enzymatic degradation, GI toxicity of some drugs, instability in acidic or alkaline environment and poor bioavailability. Various mucoadhesive dosage forms have been developed recently including tablets, patches, films, ointments, gels etc. The objective of current review is to provide a comprehensive overview of mucoadhesive drug delivery including the mechanism and theories behind mucoadhesion, factors affecting mucoadhesion, different dosage forms, polymers used in mucoadhesive formulations, characterization techniques, marketed products and current scenario & future challenges. [ABSTRACT FROM AUTHOR]

Background: Globally, although effective prevention strategies and treatment are available, trachoma remains the major cause of infectious loss of sight. Trachoma is a predominant neglected disease in Ethiopia, and there is a 40.4% prevalence of active trachoma in the Goro district, Southeast Ethiopia. World Health Organization (WHO) recommends azithromycin mass treatment of at least 80% coverage to eliminate trachoma, even though the coverage of azithromycin mass treatment has not been studied yet in depth. Thus, this study aimed to assess the coverage and factors influencing azithromycin mass treatment uptake among adults in Goro district, Southeast Ethiopia. Methods: A community-based cross-sectional study was conducted from April 1st to April 30th, 2021 among all adults aged 15 years old and above. The multistage sampling technique was used to select 593 study respondents. A structured interviewer-administered questionnaire was used. Data were entered into Epi-Data version 3.1 and analyzed using SPSS version 23.0 software. Descriptive analysis and binary logistic regression analysis were used to analyze the data. Adjusted odds ratios (AOR) along with a 95% confidence interval (CI) and p-value < 0.05 were used to declare the strength and the significance of association, respectively. Results/Principal findings: Five hundred and seventy eight study participants with a 97% response rate were included. The proportion of azithromycin mass drug administration coverage was found to be 75.80%; 95% CI: (72%-79%) in this study. Having better knowledge about trachoma (AOR = 2.36; 95% CI: 1.19–4.70), having better knowledge about azithromycin mass treatment (AOR = 4.19; 95% CI: 2.19–7.98), being educated (AOR = 7.20; 95% CI: 1.02–51.09), a campaign conducted at the quiet time (off-harvesting/planting season) (AOR = 6.23; 95% CI: 3.23–11.98), heard about the serious adverse effect from others (AOR = 0.25; 95% CI: 0.10–0.59) and being a volunteer to take azithromycin in the next campaign (AOR = 5.46; 95% CI: 2.76–10.79) were significantly associated with azithromycin mass drug administration coverage. Conclusions/Significance: The proportion of azithromycin mass treatment coverage of this study was lower than the WHO minimum target coverage. Thus, strengthening awareness, enhancing azithromycin mass trachoma treatment messages, and conducting campaigns off-season outside of harvesting and planting time should be prioritized in the future to meet the 2030 Sustainable Development Goal (SDG) target. Author summary: Trachoma is the leading cause of infectious loss of sight worldwide. The mass treatment with azithromycin has been used in the prevention and treatment of chlamydia trachomatis and is recognized as a potentially vital and important public health strategy for the control of trachoma disease and other co-infections. Oral azithromycin is easy to administer and offers a better resolution for controlling blinding trachoma for long periods. The proportion of azithromycin mass treatment coverage in the Goro district was lower than the WHO minimum target. Having better knowledge about the trachoma and azithromycin mass treatment and being educated were some of the factors positively affecting the uptake of the azithromycin mass treatment. Hearing serious adverse effects of the drug from other people and campaigns conducted during harvesting or seeding time were some factors negatively affecting the coverage of azithromycin mass treatment in the current study. [ABSTRACT FROM AUTHOR]

Background: Herpes zoster (commonly called shingles) is caused by the reactivation of varicella zoster virus, and results in substantial morbidity. While the risk of zoster increases significantly with age and immunosuppression, relatively little is known about other risk factors for zoster. Moreover, much evidence to date stems from electronic healthcare or administrative data. Hence, the aim of this study was to explore potential risk factors for herpes zoster using survey data from a nationally-representative sample of the general community-dwelling population in England.Methods: Data were extracted from the 2015 Health Survey for England, an annual cross-sectional representative survey of households in England. The lifetime prevalence of self-reported herpes zoster was described by age, gender and other socio-demographic factors, health behaviours (physical activity levels, body mass index, smoking status and alcohol consumption) and clinical conditions, including; diabetes, respiratory, digestive and genito-urinary system and mental health disorders. Logistic regression models were then used to identify possible factors associated with shingles, and results were presented as odds ratios with 95% confidence intervals.Results: The lifetime prevalence of shingles among the sample was 11.5% (12.6% among women, 10.3% among men), which increased with age. After adjusting for a range of covariates, increased age, female gender (odds ratio: 1.21; 95%CI: 1.03, 1.43), White ethnic backgrounds (odds ratio: 2.00; 95%CI: 1.40, 2.88), moderate physical activity 7 days per week (odds ratio: 1.29; 95%CI: 1.01, 1.66) and digestive disorders (odds ratio: 1.51; 95%CI: 1.13, 1.51) were each associated with increased odds of having had herpes zoster.Conclusions: Age, gender, ethnicity and digestive disorders may be risk factors for herpes zoster among a nationally representative sample of adults in England. These potential risk factors and possible mechanisms should be further explored using longitudinal studies. [ABSTRACT FROM AUTHOR]

Background: The epidemiology of trachoma in several Pacific Islands differs from other endemic settings, in that there is a high prevalence of clinical signs of trachoma, particularly trachomatous inflammation—follicular (TF), but few cases of trichiasis and limited evidence of ocular chlamydial infection. This so-called "Pacific enigma" has led to uncertainty regarding the appropriate public health response. In 2019 alongside Nauru's national trachoma population survey, we performed bacteriological and serological assessments of children to better understand the typology of trachoma and to determine whether there is a need for trachoma interventions. Methods: We used two-stage cluster sampling, examining residents aged ≥1 year and collecting household-level water, sanitation, and hygiene (WASH) variables. Children aged 1–9 years provided conjunctival swabs and finger-prick dried blood spots to investigate the presence of Chlamydia trachomatis nucleic acid and anti-Pgp3 antibodies, respectively. Principal Findings: In 818 participants aged 1–9 years, the age-adjusted TF prevalence was 21.8% (95% CI 15.2–26.2%); ocular C. trachomatis prevalence was 34.5% (95% CI 30.6–38.9), and anti-Pgp3 antibody prevalence was 32.1% (95% CI 28.4%–36.3%). The age- and gender-adjusted prevalence of trichiasis in ≥15-year-olds was 0.3% (95% CI 0.00–0.85), but no individual with trichiasis had trachomatous scarring (TS). Multivariable analysis showed an association between age and both TF (OR per year of age 1.3 [95% CI 1.2–1.4]) and anti-Pgp3 positivity (OR 1.2 [95% CI 1.2–1.3]). There were high rates of access to water and sanitation and no WASH variable was associated with the presence of TF. Conclusions: TF, nucleic acid, and age-specific antibody prevalence collectively indicate that high levels of C. trachomatis transmission among children present a high risk of ocular damage due to trachoma. The absence of trichiasis with trachomatous scarring suggest a relatively recent increase in transmission intensity. Author summary: In contrast to several neighbouring Pacific Island nations, Nauruan children are heavily affected by active trachoma and the cause is ocular infection with C. trachomatis. Comprehensive public health intervention to control trachoma in Nauru is required. The use of laboratory markers for current and previous C. trachomatis infection should be considered in baseline trachoma prevalence surveys as we approach global elimination of trachoma, and in settings with inconsistent findings during previous screening exercises. [ABSTRACT FROM AUTHOR]

Percutaneous occupational exposure to industrial toxicants can be assessed in vitro on excised human or animal skins. Numerous factors can significantly influence skin permeation of chemicals and the flux determination. Among them, the vehicle used to solubilize the solid substances is a tricky key step. A "realistic surrogate" that closely matches the exposure scenario is recommended in first intention. When direct transposition of occupational exposure conditions to in vitro experiments is impossible, it is recommended that the vehicle used does not affect the skin barrier (in particular in terms of structural integrity, composition, or enzymatic activity). Indeed, any such effect could alter the percutaneous absorption of substances in a number of ways, as we will see. Potential effects are described for five monophasic vehicles, including the three most frequently used: water, ethanol, acetone; and two that are more rarely used, but are realistic: artificial sebum and artificial sweat. Finally, we discuss a number of criteria to be verified and the associated tests that should be performed when choosing the most appropriate vehicle, keeping in mind that, in the context of occupational exposure, the scientific quality of the percutaneous absorption data provided, and how they are interpreted, may have long-range consequences. From the narrative review presented, we also identify and discuss important factors to consider in future updates of the OECD guidelines for in vitro skin absorption experiments. [ABSTRACT FROM AUTHOR]

Background: To eliminate trachoma as a public health problem, the World Health Organization recommends the SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) strategy. As part of the SAFE strategy in the Amhara Region, Ethiopia, the Trachoma Control Program distributed >124 million doses of antibiotics between 2007 and 2015. Despite this, trachoma remained hyperendemic in many districts and a considerable level of Chlamydia trachomatis (Ct) infection was evident.Methods: We utilized residual material from Abbott m2000 Ct diagnostic tests to sequence 99 ocular Ct samples from Amhara and investigated the role of Ct genomic variation in continued transmission of Ct.Results: Sequences were typical of ocular Ct at the whole-genome level and in tissue tropism-associated genes. There was no evidence of macrolide resistance in this population. Polymorphism around the ompA gene was associated with village-level trachomatous inflammation-follicular prevalence. Greater ompA diversity at the district level was associated with increased Ct infection prevalence.Conclusions: We found no evidence for Ct genomic variation contributing to continued transmission of Ct after treatment, adding to evidence that azithromycin does not drive acquisition of macrolide resistance in Ct. Increased Ct infection in areas with more ompA variants requires longitudinal investigation to understand what impact this may have on treatment success and host immunity. [ABSTRACT FROM AUTHOR]

Background: Postherpetic neuralgia (PHN) is one of the most common and serious complications of herpes zoster. PHN of the first branch of the trigeminal nerve is painful and difficult to treat, as no definitive effective treatment is available. The aim of this retrospective study was to observe the efficacy and safety of treatment of PHN of the first branch of the trigeminal nerve with high-voltage pulsed radiofrequency (PRF) of the supraorbital nerve. Methods: Fifty-two patients diagnosed with the PHN of the first branch of the trigeminal nerve at the Department of Pain Management, Shengjing Hospital, China Medical University, between April 2017 and October 2020 were selected. The PRF treatment of the supraorbital nerve was used. The patients were divided into two groups according to the treatment received: group C, conventional PRF group; and group H, high-voltage PRF group. The basic conditions, pain scores, and SF-36 scores of patients before treatment were recorded. Also, intraoperative and postoperative adverse events, visual analog scale (VAS) scores, 36-Item Short Form Health Survey (SF-36) scores at 1 week, 1 month, 3 months, and 6 months of follow-up were recorded. Furthermore, treatment efficiency was followed up at 6 months after treatment. Results: The VAS scores of patients in both groups were significantly lower at all time points after treatment compared with presurgery. VAS scores in group H were lower than those in group C 1, 3, and 6 months after treatment. SF36 scores of patients in group H were better than those in group C 1, 3, and 6 months after treatment. The treatment efficiency at 6 months after treatment was higher in group H than in group C. No serious adverse events occurred in both groups. Conclusion: The efficacy of the high-voltage PRF of the supraorbital nerve in treating the PHN of the first branch of the trigeminal nerve was superior to that of conventional PRF. It was a safe and effective treatment method. [ABSTRACT FROM AUTHOR]

Background The recombinant zoster vaccine had over 90% efficacy in preventing herpes zoster in clinical trials. However, its effectiveness outside of a clinical trial setting has not been investigated. This study aimed to assess the effectiveness of the recombinant zoster vaccine in general practice. Methods A de-identified administrative claims database, the OptumLabs Data Warehouse, was used to conduct this retrospective cohort study to assess the effectiveness of the recombinant zoster vaccine against herpes zoster in nonimmunocompromised, vaccine age–eligible individuals enrolled in the database for ≥365 days. Results A total of 4 769 819 adults were included in this study, with 173 745 (3.6%) adults receiving 2 valid doses of the recombinant zoster vaccine. The incidence rate of herpes zoster was 258.8 (95% confidence interval [CI], 230.0–289.4) cases per 100 000 person-years in vaccinated persons compared with 893.1 (95% CI, 886.2–900.0) in unvaccinated persons. Recombinant zoster vaccine effectiveness was 85.5% (95% CI, 83.5–87.3%) overall, with an effectiveness of 86.8% (95% CI, 84.6–88.7%) in individuals 50 to 79 years old compared with 80.3% (95% CI, 75.1–84.3%) in individuals aged 80 and older. In patients with a history of live zoster vaccine within 5 years of study inclusion, vaccine effectiveness was 84.8% (95% CI, 75.3–90.7%). Conclusions Recombinant zoster vaccine effectiveness against herpes zoster was high in a real-world setting. Given the low vaccine coverage and high effectiveness, a major public health effort is needed to identify and address barriers to vaccination and increase immunization rates. [ABSTRACT FROM AUTHOR]

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Introduction: Noninfectious uveitis (NIU) is one of the leading causes of blindness worldwide. In adult patients, anterior NIU is usually managed with topical corticosteroids. In intermediate, posterior uveitis. and panuveitis, systemic corticosteroids are used especially in case of bilaterality or association with systemic disease. Biotherapies are recommended in case of inefficacy or intolerance to corticosteroids or conventional immunosuppressive drugs. Anti-TNF-α agents are by far the most widely used biotherapies. In case of failure or poor tolerance to anti-TNF-α, new targeted therapies can be proposed. Areas covered: We present and discuss an updated overview on biologics and biotherapies in NIU. Expert opinion: In case of dependency to systemic or intravitreal steroids, sight-threatening disease, and/or failure of conventional immunosuppressive drugs, anti-TNF-α are used as first-line biologics to achieve quiescence of inflammation. Anti-interleukin-6 is another option that may be proposed as first-line biologic or in case of poor efficacy of anti-TNF-α. Interferon can be directly proposed in specific indications (e.g. refractory macular edema, sight-threatening Behçet's uveitis). In the rare cases that remain unresponsive to traditional biotherapies, novel molecules, such as Janus-associated-kinase and anti-phosphodiesterase-4-inhibitors can be used. Therapeutic response must always be evaluated by clinical and appropriate ancillary investigations. [ABSTRACT FROM AUTHOR]

The article discusses research on relapse and remission in children with chronic noninfectious uveitis (NIU) treated with methotrexate (MTX). It enumerates the patient inclusion criteria for the study and the conditions described to determine relapse of uveitis. Data shows the demographic characteristics of children with uveitis treated with MTX. Results reveal MTX tapering/discontinuation in a number of patients and those with sustained remission after MTX discontinuation.

Introduction: Adalimumab is established as an effective treatment for pediatric noninfectious uveitis refractory to methotrexate. However current use of the medication is empiric, according to fixed-dosing regimens and a significant proportion of patients will be nonresponsive or suboptimally responsive to adalimumab. Areas covered: There remains considerable scope to improve outcomes through tailoring treatment according to individual patient responsiveness. Monitoring of anti-drug antibodies and serum drug trough levels may assist in predicting which patients are likely to have a poor response to adalimumab and enable tailoring of regimens to individual patients. Expert opinion: We propose use of these biomarkers to individualize therapy in suboptimally responding patients, and present an algorithm of treatment escalation for pediatric noninfectious uveitis. [ABSTRACT FROM AUTHOR]

Oxidative stress occurs in extrinsic skin aging processes and diseases when the enhanced production of free radicals exceeds the homeostatic antioxidant capacity of the skin. The spin probe, 3-(carboxy)-2,2,5,5-tetramethylpyrrolidin-1-oxyl (PCA), is frequently used to study the cutaneous radical production by electron paramagnetic resonance (EPR) spectroscopy. This approach requires delivering PCA into the skin, yet solvent effects on the skin penetration and spatial distribution of PCA have not been thoroughly investigated. Three solvents of ethanol, phosphate-buffered saline (PBS) and ethanol-PBS (1:1) were studied. For both human and porcine skin ex vivo, the amount of PCA in the stratum corneum (SC) was the lowest when using ethanol and very similar for PBS and ethanol-PBS. The highest amount of PCA in the viable skin layers was detected for ethanol-PBS, yet it only took up less than 5% of the total amount. The majority of PCA was localized in the SC, among which PCA with high mobility was predominantly distributed in the hydrophilic microenvironment of corneocytes and PCA with lower mobility was mainly in the less hydrophilic microenvironment of intercellular skin lipids. A higher ethanol concentration in the solvent could improve the distribution of PCA in the hydrophilic microenvironments of the SC. The results suggest that ethanol-PBS (1:1) is best-suited for delivering most PCA deep into the skin. This work enhances the understanding of solvent effects on the skin penetration and distribution of PCA and supports the utilization of PCA in studying cutaneous radical production. [ABSTRACT FROM AUTHOR]

Background: After approximately 5 years of SAFE (surgery, antibiotics, facial cleanliness, environmental improvement) interventions for trachoma, hyperendemic (trachomatous inflammation-follicular (TF) ≥30%) districts remained in Amhara, Ethiopia. This study's aim was to characterize the epidemiology of Chlamydia trachomatis (Ct) infection and load among pre-school aged children living under the SAFE strategy. Methods: Conjunctival swabs from a population-based sample of children aged 1–5 years collected between 2011 and 2015 were assayed to provide Ct infection data from 4 endemic zones (comprised of 58 districts). Ct load was determined using a calibration curve. Children were graded for TF and trachomatous inflammation-intense (TI). Results: 7,441 children were swabbed in 4 zones. TF and TI prevalence were 39.9% (95% confidence Interval [CI]: 37.5%, 42.4%), and 9.2% (95% CI: 8.1%, 10.3%) respectively. Ct infection prevalence was 6.0% (95% CI: 5.0%, 7.2%). Infection was highest among children aged 2 to 4 years (6.6%-7.0%). Approximately 10% of infection occurred among children aged 1 year. Ct load decreased with age (P = 0.002), with the highest loads observed in children aged 1 year (P = 0.01) vs. aged 5 years. Participants with TF (P = 0.20) and TI (P<0.01) had loads greater than individuals without active trachoma. Conclusions: In this hyperendemic setting, it appears that the youngest children may contribute in meaningful ways towards persistent active trachoma. Author summary: Current World Health Organization recommendations for the treatment of trachoma state that hyperendemic districts, districts with a 30% or greater prevalence of the clinical sign trachomatous inflammation-follicular, should receive 5 years of annual mass drug administration with antibiotic to target Chlamydia trachomatis as part of the surgery, antibiotic, facial cleanliness, and environmental improvement (SAFE) strategy. After approximately 5 years of SAFE in Amhara region, Ethiopia, however, many districts remained hyperendemic as measured by observed clinical signs. Given the persistent nature of trachoma in Amhara, a better understanding of the nature of actual Chlamydia trachomatis infection, including the distribution of infectious load within children, would be helpful for Amhara and for programs serving other hyperendemic regions. From 2011 to 2015 nearly 7,500 ocular swabs from 4 endemic zones were collected to monitor Chlamydia trachomatis following 5 years of SAFE among children aged 1 to 5 years, the group most at risk for infection. It was determined that pre-school age children still harbored considerable infection. The youngest children had the highest infection prevalence and highest infectious load burden, and therefore likely contributed in meaningful ways towards the persistent active trachoma observed in some districts. Treatment regimens focused on the youngest children or children harboring the highest infectious loads should be explored to help countries experiencing persistent trachoma reach elimination as a public health problem faster. [ABSTRACT FROM AUTHOR]

The article focuses on the biomaterials and biomechanics behind oral and maxillofacial implants. It states that the U.S. Food and Drug Administration has a listing of over 50 companies involved in the manufacture, distribution, and marketing of dental implants. It comments on titanium and titanium alloy implants with different intrinsic strength properties. It mentions the need for better understanding of the effects biomaterials have on bone and bone cells and on events at the interface between the biomaterial and bone. It talks about the ultrastructure of the area between bone and implant surface and on the effect dental cement has on mineralized tissue.

Background/Aims: The mechanisms by which permeation enhancers increase human skin permeation of caffeine and naproxen were assessed in vitro. Methods: Active compound solubility in the vehicles and in the stratum corneum (SC), active compound flux across epidermal membranes and uptake of active and vehicle components into the SC were measured. The effect of vehicle pH on the permeation of caffeine and naproxen was also determined. Results: Oleic acid and eucalyptol significantly enhanced the skin penetration of caffeine and naproxen, compared to aqueous controls. Naproxen permeation was increased from vehicles with pH presenting more ionized naproxen. Caffeine maximum flux enhancement was associated with an increase in caffeine SC solubility and skin diffusivity, whereas for naproxen a penetration enhancer/vehicle-induced increase in solubility in the SC correlated with an increase in maximum flux. SC solubility was related to experimentally determined active uptake, which was in turn predicted by vehicle uptake and active compound solubility in the vehicle. Conclusion: A permeation enhancer-induced alteration in diffusivity, rather than effects on SC solubility, was the main driving force behind increases in permeation flux of the hydrophilic molecule caffeine. For the more the lipophilic molecule naproxen, increased SC solubility drove the increases in permeation flux. [ABSTRACT FROM AUTHOR]

Background and Objective: The aim of this study was to test the hypothesis that tincture of benzoin (TOB) facilitates immediate transmucosal nicotine absorption while simultaneously promoting a safe and sustained delivery of the nicotine. Methods: In combination with TOB, nicotine toxicity and diffusion across human mucosal cells were measured using a 3-D human mucosal tissue model. Results: Nicotine was delivered 2.1 times more quickly in combination with TOB than in combination with saline ( p < 0.05). Despite the increased diffusion, nicotine in combination with TOB significantly increased mucosal cell survival ( p < 0.05) by reducing the release of mitochondrial cytochrome c into the cytoplasm when compared with nicotine without TOB. The average percentage distribution of cytochrome c in the cytosolic fraction over time of nicotine + 79% ethyl alcohol (ETOH) versus nicotine plus TOB (79% ETOH) was significantly different over 120 min (60.0 ± 29.9% cytosol, 16.1 ± 9.4% cytosol, p = 0.03). Related to the reduction of cytochrome c release into the cytoplasm, TOB suppressed caspase-3 and -9 activity, thereby preventing intrinsic apoptosis and providing cytoprotection of the mucosal cells (ETOH + nicotine vs ETOH + nicotine + TOB: p = 0.008 for caspase 3, p < 0.001 for caspase 9). Conclusion: Two hours of TOB (17-24% benzoin, 79% ETOH) plus nicotine promotes diffusion of nicotine across human mucosal cells and simultaneously prevents human mucosal cell toxicity by inhibiting cytochrome c release into the cytosol, thereby preventing caspase 3 and 9 activity and subsequent intrinsic apoptosis. [ABSTRACT FROM AUTHOR]

Purpose: Recurrent aphthous stomatitis (RAS) is the most common painful ulcerative disease of oral mucosa happening in ∼20% of people. Aimed to develop Myrtus communis L. (Myrtle) containing oral patches, we applied box-behnken design to evaluate the effect of polymers such as Polyvinyl pyrrolidone (PVP), Gelatin, Methylcellulose (MC) and Pectin. Methods: The patches properties such as tensile strength, folding endurance, swelling index, thickness, mucoadhesive strength and the pattern of myrtle release were evaluated as dependent variables. Then, the model was adjusted according to the best fitted equation with box behnken design. Results: The results indicated that preparation of myrtle patch with hydrophilic polymers showed the disintegration time up to 24h and more. Using of polyvinyl pyrrolidone as a water soluble polymer and a pore-former polymer led to faster release of soluble materials from the patch to 29 (min-1). Also it decreases swelling index by increasing the patch disintegration. Gelatin and Pectin, with rigid matrix and water interaction properties, decreased the swelling ratio. Pectin increased the tensile strength, but gelatin produced an opposite effect. Thinner Myrtle patch (about 28μm) was obtained by formulation of methyl cellulose with equal ratio with polyvinyl pyrrolidone or gelatin. Conclusion: Altogether, the analysis showed that the optimal formulation was achieved with of 35.04 mg of Gelatin, 7.22 mg of Pectin, 7.20 mg of polyvinyl pyrrolidone, 50.52 mg of methyl cellulose and 20 mg of Myrtle extract. [ABSTRACT FROM AUTHOR]

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. [ABSTRACT FROM AUTHOR]

The article explores a well-designed study documenting the continued overall increase in incidences of herpes zoster (HZ) from 1994–2018, despite a decrease in the rates since 2007 in persons ≤20 years old or >60 years old. The recent decrease in incidence rates in age groups during the time when vaccination against varicella or herpes zoster has been recommended supports the conclusion that current vaccination recommendations should be reconsidered.

Immobilization of heparin to surfaces has been used for decades to reduce the thrombogenicity of blood contacting devices. This study evaluates how the mode of covalent heparin bonding affects the hemocompatibility and uptake of antithrombin on surfaces in whole blood. End-point attached (EPA) heparin, using the proprietary Carmeda® Bioactive Surface (CBAS® Surface), was compared with other methods of covalent heparin bonding that typically yield multiple covalent linkages (using reductive amination of periodate oxidized native heparin or EDC coupling of native heparin). All heparin surfaces were immobilized on flexible polyvinyl chloride tubing and exposed to fresh non-anticoagulated blood in an in vitro recirculating Chandler loop blood model. After exposure, biomarkers for coagulation and platelet activation were analyzed in the solution phase, and adsorbed plasma proteins were eluted from the heparin surfaces and measured for surface concentration of antithrombin and total adsorbed protein. Only the EPA-heparin surface conferred thromboresistance, as observed by the absence of clotting. Attachment and activation of platelets as well as activation of the clotting cascade was significantly lower on the EPA-heparin surface when compared with the other heparin surfaces. In addition, antithrombin constituted ∼40% of the total adsorbed plasma protein concentration on the EPA-heparin surfaces. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1817-1824, 2014. [ABSTRACT FROM AUTHOR]

Aim: To uptake and release hydrophilic model drugs and insulin in a novel conductive polymer (CP) nanotube transdermal patch. Materials & methods: The externally controlled transdermal delivery of model drugs and insulin were tested ex vivo and results were compared with CP films. The unique intrinsic properties of CPs provide electrostatic interaction between the model drugs and polymer backbone. Results & discussion: When a pulsed potential was applied, the drug delivery release profile mimics that of injection delivery. With a constant potential applied, the release rate constants of the patch system were up to three-times faster than the control (0 V) and released approximately 80% more drug molecules over 24 h. Conclusion: The CP nanotube transdermal patch represents a new and promising drug method, specifically for hydrophilic molecules, which have been a large obstacle for conventional transdermal drug delivery systems. Original submitted: 7 March 2013; Revised submitted: 1 August 2013 [ABSTRACT FROM AUTHOR]