Emerging Topical Onychomycosis Therapies – Quo Vadis?

Introduction: Onychomycosis, a common chronic fungal infection affecting fingernails and toenails, globally may affect 10 – 30% of the population. This chronic disease is difficult to eradicate. The goal of developing a highly effective and safe topical treatment has not yet been reached as it depends on the type of onychomycosis and the variety of invaders.

Areas covered: Topical drug delivery to the nail is highly desirable in treating nail disorders. However, efficacy of topical therapies is low due to their limited permeability across the nail plate. Advances have especially been made by the development of new therapeutic options including new drug entities, new formulations and reformulations. This overview updates emerging topical treatments for onychomycosis, research progress and future perspectives.

Expert opinion: Development of novel effective noninvasive topical therapy for treating onychomycosis and other nail diseases such as psoriasis is long overdue. Previously there was a lack of basic knowledge about nail and its barrier properties, but with the recent increased interest in this field both from industry and academia, we hope extensive research will continue in this field to bring about successful and safe treatments for such chronic diseases.     

Section 1 Occupation as a modifying factor in the diagnosis and treatment of rheumatic diseases

Summary

In the U.K., rheumatic diseases account for 30 million man days lost to industry every year. The author reviews the evidence from surveys of the part played by occupational factors in the aetiology of rheumatic diseases, and comments on the problems associated with the early diagnosis in theoretically vulnerable workers. The importance of rehabilitation in treatment is stressed, as is the need for closer liason between industry and the health services, and some of the attempts to achieve a more coordinated and comprehensive approach are discussed.     

Pediatric dermatology in practice: spectrum of skin diseases and approach to patients at a Turkish pediatric dermatology center

Purpose: The aim of this study was to determine the real spectrum of skin diseases in Turkish children and how they were managed.

Methods: Data on a total of 6000 consecutive patients aged 0–18 years attending the pediatric dermatology clinic were analyzed for diagnosis, disease group, diagnostic pattern, treatment modality, and referral and hospitalization frequency.

Results: Allergic skin diseases (49.9%) were the leading group of dermatoses, which were followed by infectious diseases (20.5%), and disorders of skin appendages (10.2%). Atopic dermatitis was the most common dermatose, which was followed by papular urticaria and unclassified eczema. Most of the patients (92.0%) had diagnosis on clinical basis, whereas skin biopsy was performed in 3.7% and laboratory investigation in 4.4% of the patients. The hospitalization rate was 0.3%, and Henoch–Schönlein purpura was the most frequent dermatose for which hospitalization was required. Local treatment was prescribed in 56.0% of the patients, local treatment and systemic treatment together in 26.4%, and systemic treatment in 6.2%. Viral warts followed by viral exanthems caused by enteroviruses and acquired melanocytic nevi were the most frequently referred skin problems. Further investigation and treatment for systemic or related diseases was the most common reason for referrals (2.1%), and pediatrics was the department to which most of the referrals were made (1.8%).

Conclusion: This study provided important data on the spectrum of skin diseases encountered in the pediatric age groups and general approach to patients in a pediatric dermatology clinic in Turkey.     

The impact of a worksite migraine intervention program on work productivity,productivity costs,and non-workplace impairment among Spanish postal service employees from an employer perspective

SUMMARY

Background: Migraine is associated with a significant productivity loss to employers, who may benefit from making a migraine intervention available to their employees.

Objective: To evaluate changes in migraine-related productivity and non-workplace impairment associated with a migraine intervention program from the employer perspective.

Methods: This was a pre-test post-test study of Spanish Postal Service employees with migraine. The intervention consisted of counseling from occupational health physicians and rizatriptan 10?mg for symptomatic treatment of two subsequent migraine headaches. Physicians also prescribed additional medications for migraine prophylaxis, treatment of tension headaches, and rescue medications. Migraine-related work loss and non-workplace impairment (interference with daily and social activities) were self-reported at baseline (pre-intervention) and separately following each migraine headache (post-intervention) with the aid of a diary. Migraine-related work loss was reported as work loss due to absenteeism, reduced productivity while at work, and the sum of the two (total lost work day equivalents [LWDE]). An employer perspective was taken for the cost analysis, and thus productivity costs were the only costs considered.

Results: A total of 436 patients comprised the population for analysis. The number of migraine-related LWDE per migraine attack were 0.48 days per migraine headache in the month before the intervention, decreasing to 0.20 days and 0.07 days per migraine headache during the first and second migraine headaches following the intervention (^?p?<?0.0001 vs. baseline). Total migraine-related productivity costs per migraine headache were €34/patient before the intervention, decreasing to €14/patient and €5/patient during the first and second headaches following the intervention (?p < 0.0001).

Non-workplace activity impairment was also significantly reduced (?p < 0.0001) following the intervention. The main limitations of the study were the lack of a parallel control group and the potential for differential recall bias between the usual care and the intervention periods. In addition, the results may not be generalizable to other employers or other countries.

Conclusion: This study documents the value of a workplace migraine intervention program, which focused on migraine prevention and rizatriptan-based symptomatic treatment. It also highlights the important role occupational health clinics can play in helping employers and employees reduce the burden of migraine.     

Costs of needlestick injuries and subsequent hepatitis and HIV infection

ABSTRACT

Background: Physicians, nurses and other healthcare workers (HCWs) are at risk of bloodborne pathogens infection from needlestick injuries, but costs of needlesticks are little studied.

Methods: We used the cost-of-illness and incidence approaches. We used the perspective of the medical provider (medical costs) and the individual (lost product­ivity). Data on needlesticks, infections from hepatitis B and C (HBV, HCV) and human immune-deficiency (HIV) among HCWs, as well as data on per-unit costs were culled from research literature, Centers for Disease Control and Prevention reports, and Bureau of Labor Statistics reports. We also generated estimates based upon industry employment and scenarios for source-patients. These data and estimates were combined with assumptions to produce a model that generated base-case estimates as well as one-way and multi-way probabilistic sensitivity analyses. Future costs were discounted by 3%.

Results: We estimated 644?963 needlesticks in the healthcare industry for 2004 of which 49% generated costs. Medical costs were $107.3 million of which 96% resulted from testing and prophylaxis and 4% from treating long-term infections (34 persons with chronic HBV, 143 with chronic HCV, and 1 with HIV). Lost-work productivity generated $81.2 million, for which 59% involved testing and prophylaxis and 41% involved long-term infections. Combined medical and work productivity costs summed to $188.5 million. Multi-way sensitivity analysis suggested a range on combined costs from $100.7 million to $405.9 million.

Conclusion: Detailed methodology was developed to estimate costs of needlesticks and subsequent infections for hospital-based and non-hospital-based health care workers. The combined medical and lost productivity costs comprised roughly 0.1% of all occupational injury and illness costs for all jobs in the economy. We did not account for lost home production or pain and suffering costs, however, nor did we estimate benefit/cost ratios of specific interventions to reduce needlesticks.     

Capturing Data in Rare Disease Registries to Support Regulatory Decision Making: A Survey Study Among Industry and Other Stakeholders

Introduction

In rare diseases, registry-based studies can be used to provide natural history data pre-approval and complement drug efficacy and/or safety knowledge post-approval.

Objective

The objective of this study was to investigate the opinion of stakeholders about key aspects of rare disease registries that are used to support regulatory decision making and to compare the responses of employees from industry to other stakeholders.

Methods

A web-based survey was used to gauge the importance of (1) common data elements (including safety outcomes), (2) data quality and (3) governance aspects that are generic across different rare diseases. The survey included 47 questions. The data were collected in the period April-October 2019.

Results

Seventy-three respondents completed ≥ 80% of the survey. Most of the respondents were from the industry (n = 42, 57%). For safety data, 31 (42%) respondents were in favour of collecting all adverse events. For data quality, the respondents found a level of 30% reasonable for source data verification. For missing data, a level of 20% was considered acceptable. Compared to responders from industry, the other stakeholders found it less relevant to share data with industry and found it less acceptable if the registry is financed by industry.

Conclusions

This study showed that the opinion towards data and governance is well aligned across parties, and issues of data and governance on their own should not pose a barrier to collaboration. This finding is supportive of the European Medicines Agency’s efforts to encourage stakeholders to work with existing registries when collecting data to support regulatory decision making.

     

Economic impact of multiple sclerosis disease-modifying drugs in an employed population: direct and indirect costs*

ABSTRACT

Objective: The study objective is to compare the annual total medical and indirect costs of newly treated and untreated employees with multiple sclerosis (MS).

Research design and methods: A retrospective database analysis of employer medical, drug, and disability claims database (Ingenix Employer database, 1999–2005; 17 large US companies) was conducted for employees 18–64 years of age with ≥1 MS diagnosis after January 1, 2002. Employees with ≥1 MS disease-modifying drug (DMD) claim comprised the newly treated group; employees with MS but no DMD at any time comprised the untreated, comparison group. Index date was the day after the most recent claim (treated, DMD claim; untreated, MS claim) meeting the following requirements: continuous health coverage for 3 months before (baseline period) and 12 months after the index date (study period) and actively employed during baseline.

Main outcome measures: Total medical costs and indirect (work loss) costs over the 1-year study period (2006 $US) were compared for DMD-treated and untreated MS employees, adjusting for baseline characteristics, including comorbidities.

Results: During the baseline, MS employees who became treated (n?=?258) were younger (40.9 vs. 44.4 years, p?<?0.0001) and had a higher proportion of women (72 vs. 62%, p?=?0.007) than the untreated group of MS employees who never received DMD treatment (n?=?322). The 3-month baseline MS-related medical costs were higher among treated MS employees ($2520 vs. $1012, p?<?0.0001). There was a nonsignificant trend toward higher baseline non-MS-related medical costs in untreated versus treated MS employees. Risk-adjusted total annual medical costs ($4393 vs. $6187, p?<?0.0001) and indirect costs ($2252 vs. $3053, p?<?0.0001) were significantly lower for treated MS employees than for untreated MS employees.

Conclusions: Initiation of MS disease-modifying drugs was associated with substantial significant medical and indirect savings for employees with MS. Study findings should be considered in the context of the study limitations (e.g., analytic focus on employees with at least 12-month follow-up; lack of clinical detail on MS severity).     

A questionnaire-based survey of dry eye disease among leather tannery workers in Kanpur,India: a case-control study

Context: Kanpur is a major leather processing center in India, where a large number of tanneries are situated. During tanning process, workers are constantly exposed to heat, leather dust produced in buffering operations and a wide range of chemicals. All these factors are known to cause dry eye. Being ophthalmologists of a tertiary health care center in Kanpur, we used to notice over a period of time that a considerable number of patients with dry eye symptoms, attending our out-patient department, were related to leather tanning industries. But, no published data is available on the prevalence of and risk factors for dry eye disorders among tannery worker.

Objective: To estimate the prevalence of dry eye problem and its severity among the workers of leather tanneries in the industrial belt of Kanpur and to evaluate various risk factors related to it.

Methods: In this cross-sectional case–control study, Ocular Surface Disease Index (OSDI) Questionnaire was presented to randomly selected tannery workers and control group. OSDI score was calculated based on subjects’ response, and was evaluated with OSDI chart to assess the magnitude of dry eye symptoms and to grade its severity. Results were analyzed statistically to evaluate the significance level.

Results: A total of 800 workers were selected by simple random sampling, out of which 72 workers were excluded from the study. Thus the questionnaire was presented to a total of 728 workers, while control group included 260 individuals. All the workers as well as controls were male with age ranging from 20 to 59 years. The mean age for tannery workers was 34.05?±?8.96 years and that for control group was 32.97?±?10.59 years (p?=?0.14). The tannery workers had mean duration of work at tanneries for 6.99?±?4.86 years. The prevalence of dry eye symptoms among tannery workers was 33.79% (95% CI: 30.35–37.24), while that in control group was 15.77% (95% CI: 11.31–20.23) (p?p?p?=?0.036 and <0.0001, respectively).

Conclusion: Dry eye is a significantly prevalent occupational hazard among tannery workers, severity of which increases with the age and the duration of work in tannery. Chemical exposure in hot and dusty working environment of a tannery may have a causative role. Tannery workers should be motivated to use various preventive measures to reduce chemical and dust exposure such as wearing protective glasses, and their ocular health should be monitored periodically for adequate and timely treatment, if required.     

Alcohol Use and Psychosocial Stressors in the Norwegian Workforce

Background: Although alcohol use can have detrimental effects for employees, little is known about the prevalence, distribution, and correlates in the Norwegian workforce. Aims: To determine the overall and the work-related prevalence of weekly alcohol use, and to establish associations between psychosocial work stressors and alcohol use among Norwegian employees. Methods: Data were from a 2015 national probability sample of 1,608 Norwegian employees (response rate 32%). Job demands, lack of job control, role expectations, workplace bullying, and leadership were examined as correlates of several dimensions of alcohol use. Results: Average weekly alcohol consumption was 4.28 units (SD = 7.91). Male workers reported significantly higher consumption than female workers. Also, 2.6% of male and 2.0% of female workers reported problematic alcohol use. Only 0.1% of workers reported weekly alcohol use before the workday, 0.4% reported weekly use during the workday, 20.1% reported weekly use after ending the work day, and 80% reported use during weekends/days off. Alcohol intake increased with age, but was not related to marital status, educational level, work schedule, or leadership position. Problematic alcohol use was related to job demands and workplace bullying. Alcohol use after work was positively related to lack of job control and role ambiguity and negatively related to bullying. Conclusions/importance: Weekly alcohol use before and during the workday is not prevalent among Norwegian workers. Interventions to reduce job demands and workplace bullying may reduce problematic alcohol intake, whereas increasing job control and reducing role ambiguity may reduce after work use.     

Hazards associated with the boat building industry in New Zealand: an OSH audit.

AIM: To randomly audit the boat building industry in New Zealand to assess the occupational health status and level of knowledge of employees. METHODS: A survey was conducted using a nurse and inspector administered questionnaire. 151 workers from 120 randomly selected firms participated in the survey. RESULTS: 31.5% respondents thought they had had some sort of work related health problem since working in that job. 22% reported wheezing during the last twelve months. 14-16% met criteria for occupational causation, and 4% met a measure of severe wheezing related to work. 25.6% of workers had dermatitis. Only a quarter of these met criteria for occupational causation. No respondents reported symptoms suggestive of chronic solvent neurotoxicity. Solvents and epoxy resins comprised the majority of chemicals with which there was contact. Observation suggested little use of Material Safety Data Sheets as a source of knowledge about toxicity of the chemicals used. Although 94.3% reported wearing gloves, this did not correlate with numbers reporting dermatitis suggesting non-compliance or glove failure. CONCLUSION: New Zealand boat builders and their employees remain at risk for occupational health problems by virtue of their employment.     

Occupational risk factors for relapse-free survival in bladder cancer patients

ABSTRACT

The influence of occupational risk factors on bladder cancer development is well investigated. However, studies on the influence on bladder cancer prognosis are rare. Therefore, it was of interest to investigate the time to first relapse in the follow-ups of three case-control series from Dortmund, Neuss, and Lutherstadt Wittenberg, Germany. Relapse-free survival of in total 794 urinary bladder cancer patients (Dortmund 174, Neuss 407, Lutherstadt Wittenberg 213) was derived from medical records. Cox regression models were used to determine the impact of profession and exposure to bladder carcinogens if the risk factor was present in at least four cases. One or several relapses were observed in 416 cases (52%). Median time to first relapse was 0.94 yr. Ten professions were observed in at least 4 patients. No significant associations were found. However, workers in the leather industry (n = 4), printing industry (n = 4), transportation (n = 43), and chemical industry (n = 40) and locksmiths/mechanics (n = 44) showed shorter relapse-free times. No trend to shorter relapse-free time was observed for miners (n = 42), agriculturists (n = 18), painters/lacquerers (n = 21), colorant production and processing workers (n = 7), foundry workers (n = 5), and persons exposed to aromatic amines (n = 45). Although the follow-up comprised nearly 800 cases, data on occupations and exposures of interest were not sufficient to obtain significant results. However, first results indicated potential associations that are worth further investigations.     

A cross-sectional study of changes in markers of immunological effects and lung health due to exposure to multi-walled carbon nanotubes

Background: Multi-wall carbon nanotubes (MWCNTs) are manufactured nanomaterials to which workers and the general population will be increasingly exposed in coming years. Little is known about potential human health effects of exposure to MWCNTs, but effects on the lung and the immune system have been reported in animal and mechanistic studies.

Objectives: We conducted a cross-sectional study to assess the association between occupational exposure to MWCNTs and effects on lung health and the immune system.

Methods: We assessed 51 immune markers and three pneumoproteins in serum, complete blood cell counts (CBC), fractional exhaled nitric oxide (FENO), and lung function among 22 workers of a MWCNT producing facility and 39 age- and gender-matched, unexposed controls. Measurements were repeated four months later among 16 workers also included in the first phase of the study. Regression analyses were adjusted for potentially confounding parameters age, body mass index, smoking, and sex, and we explored potential confounding by other factors in sensitivity analyses.

Results: We observed significant upward trends for immune markers C-C motif ligand 20 (p?=?.005), basic fibroblast growth factor (p?=?.05), and soluble IL-1 receptor II (p?=?.0004) with increasing exposure to MWCNT. These effects were replicated in the second phase of the study and were robust to sensitivity analyses. We also observed differences in FENO and several CBC parameters between exposed and non-exposed, but no difference in lung function or the pneumoproteins.

Conclusions: We observed indications of early effects of occupational exposure to MWCNTs on lung health and the immune system.     

The role of healthcare communications agencies in maintaining compliance when working with the pharmaceutical industry and healthcare professionals

ABSTRACT

Background: Relationships between the pharmaceutical industry and healthcare professionals continue to drive discussion about the potential for conflicts of interest. Despite greater regulation and oversight, there are still calls for increased transparency and further restrictions on these relationships. Regulatory authorities, the pharmaceutical industry, professional societies, and other interested parties have responded by developing robust guidelines for interactions between the pharmaceutical industry and healthcare professionals. This, in turn, is driving change in the way that healthcare communications agencies work, increasing the need for them to visibly demonstrate processes that ensure their employees comply with relevant laws, regulations, and guidelines.

Exposition: In our group of healthcare communications agencies we have established an internal compliance program and developed a policy that reflects the services we provide, and we recommend that other agencies adopt a similar program. Compliance training, implemented by a nominated compliance team, can be enforced by including compulsory tests for employees who interact with the pharmaceutical industry and healthcare professionals, with annual reassessment. The compliance team also has an important role to play in ensuring ongoing communication and staff education, including awareness of new legal and best practice developments. Management of the compliance program is essential, with clear mechanisms for auditing and evaluation, and the inclusion of compliance adherence in staff performance objectives. A visible framework for handling potential compliance issues should also be developed, with clear definitions of different levels of noncompliance and potential associated consequences. Compliance programs may also include other elements, such as terminology and documentation guidance, so that the program becomes an integral tool used by employees on a daily basis.

Conclusion: With a robust internal compliance program, healthcare communication agencies can play a significant role in helping maintain appropriate pharmaceutical industry–healthcare professional relationships in an increasingly regulated and scrutinized environment.     

Novel nail penetration enhancer containing vesicles “nPEVs” for treatment of onychomycosis

Context: The systemic treatment of onychomycosis has been hampered by the reported side effects of antifungals in addition to the limited blood circulation to the affected nails. Topical ungual treatment would circumvent the limitations of systemic onychomycosis treatment.

Objective: Preparation and characterization of nail penetration enhancer containing nanovesicles (nPEVs) loaded with sertaconazole for topical treatment of onychomycosis.

Materials and methods: nPEVs were prepared using different nail penetration enhancers (N-acetyl-L-cysteine, thioglycolic acid, thiourea and ethanol) by the thin film hydration method, and characterized for their particle size, zeta potential, entrapment efficiency (EE%), elasticity, viscosity, physical stability and morphology. The selected nPEVs formula and the marketed Dermofix® cream were compared in terms of nail hydration, transungual drug uptake and antifungal activity against Trichophyton rubrum.

Results: N-acetyl-l-cysteine was the optimum nail penetration enhancer for incorporation within vesicles. nPEVs showed high EE% of sertaconazole ranging from 77 to 95%, a size ranging from 38–538?nm and a zeta potential ranging from +48 to +72?mV. The selected nPEVs formula displayed spherical morphology and good storage stability. Compared to the conventional marketed cream, the selected nPEVs formula showed 1.4-folds higher hydration and drug uptake enhancement into nail clippings. Furthermore, it showed significantly higher zone of inhibition for Trichophyton rubrum (20.9?±?0.25?mm) than the marketed cream (11.6?±?0.44?mm).

Conclusion: Nail penetration enhancer containing nanovesicles (nPEVs) present a very promising option, worthy of clinical experimentation on onychomycotic patients.     

The evaluation of nail heath conditions with skin ultrasound

Background/purpose: Skin ultrasound is a non-invasive technique widely used in the dermatological fields. Previous studies have indicated that ultrasound was able to measure nails depth. The use of ultrasound is particularly appropriate for the study of nail morphology because of the differences in tissue density. The objective of this present study was to understand the characteristics and changes of adult nail texture associated with mild irritation.

Methods: The skin ultrasound measurement and clinical grading scales were used to evaluate nail texture and other important objective parameters relating to nail health in subjects with and without mild irritant hand eczema (IHE).

Results: There was no difference in the objective parameters between the left and right hands of subjects within each group (P?>?0.05). There were significant differences between the groups for the objective parameters (P?<?0.05), and the left hand was more obviously damaged than the right one.

Conclusions: The surface texture of nails with IHE was different from the normal group. The nails of the IHE group were much more uneven and thicker, although there was no noticeable change in density.