Topically Applied Therapies for the Treatment of Skin Disease: Past, Present, and Future.

The purpose of this review is to summarize essential biological, pharmaceutical, and clinical aspects in the field of topically applied medicines that may help scientists when trying to develop new topical medicines. After a brief history of topical drug delivery, a review of the structure and function of the skin and routes of drug absorption and their limitations is provided. The most prevalent diseases and current topical treatment approaches are then detailed, the organization of which reflects the key disease categories of autoimmune and inflammatory diseases, microbial infections, skin cancers, and genetic skin diseases. The complexity of topical product development through to large-scale manufacturing along with recommended risk mitigation approaches are then highlighted. As such topical treatments are applied externally, patient preferences along with the challenges they invoke are then described, and finally the future of this field of drug delivery is discussed, with an emphasis on areas that are more likely to yield significant improvements over the topical medicines in current use or would expand the range of medicines and diseases treatable by this route of administration. SIGNIFICANCE STATEMENT: This review of the key aspects of the skin and its associated diseases and current treatments along with the intricacies of topical formulation development should be helpful in making judicious decisions about the development of new or improved topical medicines. These aspects include the choices of the active ingredients, formulations, the target patient population's preferences, limitations, and the future with regard to new skin diseases and topical medicine approaches.

The Swallowing Characteristics of Thickeners, Jellies and Yoghurt Observed Using an In Vitro Model.

Drinks and foods may be thickened to improve swallowing safety for dysphagia patients, but the resultant consistencies are not always palatable. Characterising alternative appetising foods is an important task. The study aims to characterise the in vitro swallowing behaviour of specifically formulated thickened dysphagia fluids containing xanthan gum and/or starch with standard jellies and yoghurt using a validated mechanical model, the "Cambridge Throat". Observing from the side, the model throat can follow an experimental oral transit time (in vitro-OTT) and a bolus length (BL) at the juncture of the pharynx and larynx, to assess the velocity and cohesion of bolus flow. Our results showed that higher thickener concentration produced longer in vitro-OTT and shorter BL. At high concentration (spoon-thick), fluids thickened with starch-based thickener showed significantly longer in vitro-OTT than when xanthan gum-based thickener was used (84.5 s ± 34.5 s and 5.5 s ± 1.6 s, respectively, p < 0.05). In contrast, at low concentration (nectar-like), fluids containing xanthan gum-based thickener demonstrated shorter BL than those of starch-based thickener (6.4 mm ± 0.5 mm and 8.2 mm ± 0.8 mm, respectively, p < 0.05). The jellies and yoghurt had comparable in vitro-OTT and BL to thickeners at high concentrations (honey-like and spoon-thick), indicating similar swallowing characteristics. The in vitro results showed correlation with published in vivo data though the limitations of applying the in vitro swallowing test for dysphagia studies were noted. These findings contribute useful information for designing new thickening agents and selecting alternative and palatable safe-to-swallow foods.

Heat Enhanced Follicular Delivery of Isotretinoin to the Skin.

PURPOSE: The aim of this work was to evaluate the use of short durations of externally applied heat with chemical penetration enhancers to improve delivery of isotretinoin to the skin and in particular via the follicular route. METHODS: A range of chemical penetration enhancers were screened for their ability to improve isotretinoin delivery into human skin with heat using infinite dose, Franz cell experiments conducted in a water bath at a higher temperature to simulate heated conditions. Following this a prototype external heating system was developed that provided short durations of heat and its ability to improve delivery of finite doses into the skin and hair follicles was assessed. RESULTS: The magnitude of the effect of heat on drug delivery was influenced by the choice of vehicle with changes in isotretinoin flux across skin ranging from not statistically significant to 25 fold increases with heat in the infinite dose studies. The prototype heating system provided significant increases in the total delivery of isotretinoin into the skin from an optimised vehicle. Drug distribution in the skin revealed significant increases in isotretinoin delivery to the hair follicles, and deeper skin layers, but not to the stratum corneum, providing strong evidence that the enhancement in delivery occurred mainly via the hair follicles. CONCLUSION: These data indicate that the use of short durations of heat combined with chemical penetration enhancers offers a valuable strategy for improving the delivery of drugs such as isotretinoin to the skin via the hair follicles. Graphical Abstract Schematic illustration of the sodium thiosulphate heating system on a Franz diffusion cell and the subsequent impact of a short burst of heat on the delivery of isotretinoin into human skin.

Moisture uptake of polyoxyethylene glycol glycerides used as matrices for drug delivery: kinetic modelling and practical implications.

PURPOSE: Gelucire 50/13, a polyoxyethylene glycol glyceride mixture, has been widely used in drug delivery, but its moisture uptake behaviour is still poorly understood. In this study, the effects of relative humidity, temperature, and drug incorporation on the moisture uptake of Gelucire are reported in relation to their practical implications for preparation of solid dispersions using this material. METHODS: DVS combined with kinetics modelling was used as the main experimental method to study the moisture uptake behaviour of Gelucire. Thermal and microscopic methods were employed to investigate the effect of moisture uptake on the physical properties of the material and drug loaded solid dispersions. RESULTS: The moisture uptake by Gelucire 50/13 is temperature and relative humidity dependent. At low temperatures and low relative humidities, moisture sorption follows a GAB model. The model fitting indicated that at high relative humidities the sorption is a complex process, potentially involving PEG being dissolved and the PEG solution acting as solvent to dissolve other components. CONCLUSION: Careful control of the storage and processing environmental conditions are required when using Gelucire 50/13. The incorporation of model drugs not only influences the moisture uptake capacity of Gelucire 50/13 but also the solidification behaviour.

Skin permeation and penetration of mometasone furoate in the presence of emollients: An ex vivo evaluation of clinical application protocols.

Background: Topical corticosteroids (TCS) and emollients are developed independently by the pharmaceutical industry but are often used together in practice. There is potential for the TCS and emollient formulations to interact on the skin surface affecting TCS absorption into the skin. Clinical guidelines acknowledge this issue but lack an evidence base and differ in their recommendations. There is a current clinical need to establish whether the application protocol employed for TCS and emollient products can impact delivery of TCS to the skin. Objectives: To investigate whether the sequence of application of a TCS and emollient and the time between their application can affect TCS skin absorption. Methods: The delivery of mometasone furoate (MF) to ex vivo human skin was evaluated following the application of Elocon cream either 5 or 30 min, before and after three different emollients. Mechanistic explanation of the changes in drug absorption was provided by modelling the skin permeation data and Raman microscopy of mixed Elocon cream and emollient formulations. Results: A circa fivefold difference in MF absorption was observed depending on the emollient and application protocol. Applying Elocon cream at short intervals in relation to Hydromol intensive significantly increased MF absorption regardless of the application protocol. In contrast, applying Elocon cream after Diprobase cream or ointment significantly reduced MF absorption relative to Elocon cream alone or when Elocon cream was applied before these emollients. The changes in drug absorption observed were attributed to the presence of emollients altering Elocon cream formulation performance through different mechanisms, including introduction of penetration enhancing excipients and inducing drug crystallization in the mixed TCS emollient layer on the skin surface. Conclusions: Emollients can affect MF absorption in different ways depending on the emollient and sequence of administration. Using a 30 min gap between product applications may not be sufficient to mitigate emollient effects on TCS absorption.

Polymer Architecture Effects on Poly(N,N-Diethyl Acrylamide)-b-Poly(Ethylene Glycol)-b-Poly(N,N-Diethyl Acrylamide) Thermoreversible Gels and Their Evaluation as a Healthcare Material.

Thermoreversible gels which transition between liquid-like and solid-like states when warmed have enabled significant novel healthcare technologies. Poly(N,N-diethyl acrylamide) (PDEA) is a thermoresponsive polymer which can be used as a trigger to form thermoreversible gels, however its use in these materials is limited and crucial design principles are unknown. Herein ABA copolymers with the structure PDEA-b-poly(ethylene glycol) (PEG)-b-PDEA are synthesized to give four block copolymers with varied molecular weight of PDEA and PEG blocks. Rheometry on solutions of the block copolymers reveals that high molecular weight PEG blocks are required to form thermoreversible gels with predominantly solid-like behavior. Furthermore, small-angle X-ray scattering elucidates clear differences in the nanostructure of the copolymer library which can be linked to distinct rheological behaviors. A thermoreversible gel formulation based on PDEA (20 kDa)-b-PEG (10 kDa)-b-PDEA (20 kDa) is designed by optimizing the polymer concentration and ionic strength. It is found that the gel is mucoadhesive, stable, and non-toxic, as well as giving controlled release of a hydrophobic drug. Overall, this study provides insight into the effect of polymer architecture on the nanostructure and rheology of PDEA-b-PEG-b-PDEA and presents the development of a highly functional thermoreversible gel with high promise for healthcare applications.

The use of polymer blends to improve stability and performance of electrospun solid dispersions: The role of miscibility and phase separation.

Solid dispersion-based nanofiber formulations of poorly soluble drugs prepared by electrospinning (ES) with a water-soluble polymer, can offer significant improvements in drug dissolution for oral drug administration. However, when hygroscopic polymers, such as polyvinylpyrrolidone (PVP) are used, environmental moisture sorption can lead to poor physical stability on storage. This study investigated the use of polymer blends to modify PVP-based ES formulations of a model poorly soluble drug, fenofibrate (FF), to improve its physical stability without compromising dissolution enhancement. FF-PVP ES dispersions demonstrated clear dissolution enhancement, but poor storage stability against high humidity. Polymer blends of PVP with Eudragit E, Soluplus and hypromellose acetate succinate (HPMCAS), were selected because of the low intrinsic moisture sorption of these polymers. The drug-polymer and polymer-polymer miscibility study revealed that FF was more miscible with Eudragit E and Soluplus than with PVP and HPMCAS, and that PVP was more miscible with HPMCAS than Eudragit E and Soluplus. This led to different configurations of phase separation in the placebo and drug-loaded fibres. The in vitro drug release data confirmed that the use of PVP-Eudragit E retained the dissolution enhancement of the PVP formulation, whereas PVP-Soluplus reduced the drug release rate in comparison to FF-PVP formulations. The moisture sorption results confirmed that moisture uptake by the polymer blends was reduced, but formulation deformation occurred to phase-separated blend formulations. The data revealed the importance of miscibility and phase separation in understanding the physical stability of the ES fibre mats. The findings provide insight into the design of formulations that can provide dissolution enhancement balanced with improved storage stability.

Easy to Swallow "Instant" Jelly Formulations for Sustained Release Gliclazide Delivery.

It is a challenge to safely administer sustained release medicines to patients with dysphagia. Sustained release tablets must not be crushed and multiparticulates with large particle sizes cause gritiness reducing patient acceptability. The aim of this study was to develop "instant" jellies as delivery vehicles incorporating sustained release microparticles for patients with dysphagia. Dry powder mixtures containing gelling agents such as sodium alginate and calcium ions were hydrated in 20 mL of water and formed a jelly texture within 10 min. The "instant" jellies demonstrated comparable properites to commercial "read-to-eat" jellies in appearance, rheological/textural properties and in vitro swallowing performance in an artificial throat model. Gliclazide sustained release microparticles were produced by fluidized bed coating using Eudragit® NM 30 D and achieved 99% production yield and final coated particle size (D50) of 198 ± 4.3 µm. Sustained gliclazide release was achieved over 15 h and the incorporation of the particles into the jellies significantly decreased the drug release rate. This novel drug delivery system offers a patient-centric solution to the long-standing challenge of administering sustained release medicines to patients with dysphagia and can potentially be used for paediatric patients.

Home health care agency staffing patterns before and after the Balanced Budget Act of 1997, by rural and urban location.

CONTEXT: The Balanced Budget Act (BBA) of 1997 and other recent policies have led to reduced Medicare funding for home health agencies (HHAs) and visits per beneficiary. PURPOSE: We examine the staffing characteristics of stable Medicare-certified HHAs across rural and urban counties from 1996 to 2002, a period encompassing the changes associated with the BBA and related policies. METHODS: Data were drawn from Medicare Provider of Service files and the Area Resource File. The unit of analysis was the 3,126 counties in the United States, grouped into 5 categories: metropolitan, nonmetropolitan adjacent, and 3 nonmetropolitan nonadjacent groups identified by largest town size. Only relatively stable HHAs were included. We generated summary HHA staff statistics for each county group and year. FINDINGS: All staff categories, other than therapists, declined from 1997 to 2002 across the metropolitan and nonmetropolitan county groupings. There were substantial population-adjusted decreases in stable HHA-based home health aides in all counties, including remote counties. CONCLUSIONS: The limited presence of stable HHA staff in certain nonmetropolitan county types has been exacerbated since implementation of the BBA, especially in the most rural counties. The loss of aides in more rural counties may limit the availability of home-based long-term care in these locations, where the need for long-term care is considerable. Future research should examine the degree to which the presence of HHA staff influences actual access and whether other paid and unpaid sources of care substitute for Medicare home health care in counties with limited supplies of HHA staff.

Advance directives for health care among older community residents.

Advance directives (ADs) for healthcare are useful planning tools for older people. In addition, the utilization of ADs is important for health and human services planners, administrators, and policy makers to understand because whether or not people have an AD, and what types of ADs they have can dramatically influence the treatment trajectories and the well-being of older people who can longer make decisions for themselves. Using telephone survey data with a random sample of Oklahoma residents age 60 and older, we examined the prevalence of four measures of AD use. Prior to the implementation of this survey in 2002, the Oklahoma Aging Services Division was very active in promoting two types of AD---the living will and the durable power of attorney for healthcare. More than half of those interviewed had a living will, two-fifths had a durable power of attorney for healthcare, and one-third had both ADs. Older age and higher levels of education were consistently associated with having ADs.

Agency ownership, patient payment source, and length of service in home care, 1992 2000.

PURPOSE: Little is known about whether an association exists between agency ownership and length of service among home care patients with different payment sources. This study investigated how for-profit and not-for-profit agencies responded to policy changes in the 1990s with respect to length of service. DESIGN AND METHODS: We examined length of service among 37,364 home care patients using the 1992, 1994, 1996, 1998, and 2000 National Home and Hospice Care Surveys. We used Kaplan-Meier methods and Cox regression models. RESULTS: After we adjusted for patient and agency characteristics, our results revealed that agency ownership was not associated with length of service for patients with private insurance, Medicare, Medicaid, Medicare plus Medicaid, or Medicare plus private insurance. This finding was consistent from 1992 through 2000. Length of service among patients with Medicare decreased significantly from 1998 through 2000, but length of service among patients with Medicaid did not change significantly from 1992 through 2000. IMPLICATIONS: Agency ownership is not associated with patient length of service in home care. Regardless of the policy changes in the home care arena in the 1990s, for-profit and not-for-profit home health agencies behaved similarly with regard to length of service among patients within differently structured payment systems.

Factors associated with medication hassles experienced by family caregivers of older adults.

OBJECTIVE: We wished to identify potential factors associated with medication administration hassles, daily irritants, among informal caregivers who provide long-term medication assistance to persons aged 55 or older. METHODS: A sample of 156 informal caregivers were recruited from seven states and several types of settings. The dependent variable was scores on the Family Caregiver Medication Administration Hassles Scale (FCMAHS). Independent variables included in the analyses were medication complexity; caregiver's gender, ethnicity, relationship to recipient, length of time in caregiving, education, and employment outside the home; care recipient's physical capacity and mental capacity; and whether the caregiver and care recipient live together. After preliminary analysis to reduce the number of independent variables, the remaining variables were included in a linear model (GLM procedure). Possible interactions and residuals were considered. RESULTS: Whites and Hispanics experience greater medication administration hassles than other groups, and perceived hassle intensity increases with medication complexity. Medication administration hassle scores increase with increasing education levels up to a high school degree, after which they remain consistently high. Caregivers whose care recipients have moderate levels of cognitive functioning have higher medication administration hassles scores than those whose care recipients have very high or very low cognitive functioning. CONCLUSION: The preliminary set of significant variables can be used to identify caregivers who may be at risk of experiencing medication administration hassles, increased stress, and potentially harmful events for their care recipients. PRACTICE IMPLICATIONS: Family caregivers are accepting complex caregiving responsibility for family members while receiving little or no support or assistance with caregiving hassles associated with this duty. The FCMAHS offers the means to monitor how caregivers are handling the daily irritants involved with medication administration so that educational interventions can be provided before hassles lead to more serious stress and strain.

Length of hospice care among U.S. adults: 1992-2000.

This study examined length of service use among U.S. adult hospice patients based on data from the 1992-2000 National Home and Hospice Care Surveys. With the Kaplan-Meier method, we estimated length of service use of current and discharged hospice patients simultaneously. Using a multivariate Cox proportional hazards model, we examined trends in patients' service use during the 1990s. Findings show that length of service use decreased significantly among adult patients who had Medicare as their only payment source. Although overall length of service use declined significantly in 1996, 1998, and 2000 compared to 1992, it was similar between 1996 and 2000.

Effect of transdermal magnesium cream on serum and urinary magnesium levels in humans: A pilot study.

BACKGROUND: Oral magnesium supplementation is commonly used to support a low magnesium diet. This investigation set out to determine whether magnesium in a cream could be absorbed transdermally in humans to improve magnesium status. METHODS AND FINDINGS: In this single blind, parallel designed pilot study, n = 25 participants (aged 34.3+/-14.8y, height 171.5+/-11cm, weight 75.9 +/-14 Kg) were randomly assigned to either a 56mg/day magnesium cream or placebo cream group for two weeks. Magnesium serum and 24hour urinary excretion were measured at baseline and at 14 days intervention. Food diaries were recorded for 8 days during this period. Mg test and placebo groups' serum and urinary Mg did not differ at baseline. After the Mg2+ cream intervention there was a clinically relevant increase in serum magnesium (0.82 to 0.89 mmol/l,p = 0.29) that was not seen in the placebo group (0.77 to 0.79 mmol/L), but was only statistically significant (p = 0.02)) in a subgroup of non-athletes. Magnesium urinary excretion increased from baseline slightly in the Mg2+ group but with no statistical significance (p = 0.48). The Mg2+ group showed an 8.54% increase in serum Mg2+ and a 9.1% increase in urinary Mg2+ while these figures for the placebo group were smaller, i.e. +2.6% for serum Mg2+ and -32% for urinary Mg2+. In the placebo group, both serum and urine concentrations showed no statistically significant change after the application of the placebo cream. CONCLUSION: No previous studies have looked at transdermal absorbency of Mg2+ in human subjects. In this pilot study, transdermal delivery of 56 mg Mg/day (a low dose compared with commercial transdermal Mg2+ products available) showed a larger percentage rise in both serum and urinary markers from pre to post intervention compared with subjects using the placebo cream, but statistical significance was achieved only for serum Mg2+ in a subgroup of non-athletes. Future studies should look at higher dosage of magnesium cream for longer durations. TRIAL REGISTRATION: ISRCTN registry ID No. ISRTN15136969.

Recent trends in advance directives at nursing home admission and one year after admission.

PURPOSE: Advance directives are important planning and decision-making tools for individuals in nursing homes. DESIGN AND METHODS: By using the nursing facility Minimum Data Set, we examined the prevalence of advance directives at admission and 12 months post-admission. RESULTS: The prevalence of having any advance directive at admission declined slightly from 2000 to 2004, whereas the prevalence of having any advanced directive at 12 months after admission increased slightly during the same period. Compared with admissions, residents at 12 months post-admission were more likely to have their decisions made by family members and to have advance directives of any type. IMPLICATIONS: The results suggest that greater use of advance directives in nursing homes may depend on additional information and support from nursing facility personnel and the health and social services professionals who are in contact with individuals moving toward nursing home admission, as well as those who remain in facilities over time.

Environmental contexts of ultimate decisions: why White nursing home residents are twice as likely as African American residents to have an advance directive.

OBJECTIVES: The purpose of this study was to determine the extent to which observed differences between White and African American nursing home residents in having an advance directive are attributable to differences between the groups in personal characteristics, the organizational environment of the nursing home, and the geographical environment of the counties in which the nursing homes are located. METHODS: By using the Medical Expenditure Panel Survey Nursing Home Component matched with county-level measures from the Area Resource File, we modeled the probability of having an advance directive as a function of nursing home resident, facility, and county characteristics for African American and White residents. RESULTS: The probability of having an advance directive was 27.0% for African American residents and 63.6% for White residents. Nearly half of this 36.6 percentage point gap could be explained by group differences in personal, facility, and county characteristics. DISCUSSION: County characteristics play a more prominent role than do personal or facility measures in explaining the observed ethnic gap in the prevalence of advance directives. Additional studies should focus further on geographic, health status, and attitudinal variations among nursing home residents that may account for the remaining ethnic difference in the prevalence of advance directives among nursing home residents.

Disc-shaped polyoxyethylene glycol glycerides gel nanoparticles as novel protein delivery vehicles.

Disc-shaped nanoparticles with high aspect ratios have been reported to show preferential cellular uptake in vitro by mammalian cells. However, engineering and producing such disc-shaped nanoparticles are often complex. This study reports for the first time the use of a single, approved pharmaceutical excipient to prepare stable disc-shaped nanoparticles with a high aspect ratio via a simple, organic solvent free process. These disc-shaped nanoparticles were formed by fragmentation of stearoyl macrogol-32 glycerides (Gelucire 50/13) hydrogels. The nanoparticles showed good physical stability as a result of their outer coating of polyethylene glycol (PEG) that is a part of Gelucire composition. Using lysozyme as a model hydrophilic protein, these nanoparticles demonstrated a good loading capacity for hydrophilic macromolecules, mainly via surface adsorption. As a result of the higher hydrophobicity of the core of the nano-discs, the loading efficiency of hydrophobic model components, such as Coumarin-6, was significantly increased in comparison to the model hydrophilic compound. These Gelucire nano-discs exhibited no cytotoxicity at the tested level of 600µg/ml for Caco-2 cells. Rapid in vitro cellular uptake of the disc-shaped nanoparticles by Caco-2 cells was observed. This rapid internalisation was attributed to the high aspect ratio of the disc-shape nanoparticles which provides a high contact surface area between the particles and cells and may lower the strain energy required for membrane deformation during uptake. The results of this study demonstrate the promising potential of Gelucire nano-discs as effective nanocarriers for drug delivery and which can be manufactured using a simple solvent-free process.

An evaluation of a low-intensity intervention to introduce medical students to healthy older people.

This is a report of a controlled, prospective, longitudinal trial of an intervention to affect medical students' attitudes toward aging. Members of the Class of 2002 at the University of Oklahoma College of Medicine were assigned a senior mentor (a community-dwelling older person) upon matriculation into medical school. Students were required to perform a structured interview with the mentor once per semester for the first 2 preclinical years and to discuss these interviews in small groups mediated by geriatrics faculty. Members of the Class of 2001 were controls. Attitudes toward aging were determined using the Aging Semantic Differential (ASD) attitude scale in August 1998 and again at the end of the second year of medical school. Initial mean ASD scores were not significantly different for the two groups. Although both classes experienced improvements in their ASD scores from Time 0 to Time 1, the improvement for the class of 2002 was significantly greater than that for the class of 2001 (2001 class mean = 0.17, 2002 class mean = 0.40, t = -3.09, degrees of freedom (df) = 219, P =.002). This difference held up under controls for sex, age, prior visits to a nursing home, prior work/volunteering in an old-age environment, and a prior course on aging (Model F = 3.00, df = 6/214, P =.008; class F = 9.70, df = 1, P =.002). It was concluded that a low-intensity intervention to introduce entering medical students to healthy older people might have a positive effect on attitudes toward aging.

The influence of rural location on utilization of formal home care: the role of Medicaid.

PURPOSE: This research examines the impact of rural-urban residence on formal home-care utilization among older people and determines whether and how Medicaid coverage influences the association between rural-urban location and risk of formal home-care use. DESIGN AND METHODS: We combined data from the 1998 consolidated file of the Medical Expenditure Panel Survey Household Component with data from the Area Resource File to generate the analytical data set. We established two measures of formal home-care utilization: home care reimbursed through any source, and Medicare-reimbursed home health care. Our measures of rural-urban residence included metropolitan counties, nonmetropolitan counties having towns of at least 10,000 people, and nonmetropolitan counties with no towns of 10,000 people. We used logistic regression analyses to examine main effects and interaction effects of Medicaid coverage and residence on the two types of formal home care under controls for person-level characteristics and state fixed effects. RESULTS: The unadjusted logistic analyses demonstrate that older people who reside in the most rural counties (nonmetropolitan counties having no town of 10,000) are significantly more likely than metropolitan residents to use any formal home care and Medicare home health care. The fully adjusted logistic analysis results point to an interplay between residential status and Medicaid coverage with regard to formal home-care use. In comparison with metropolitan residents covered by Medicaid, the adjusted relative risk of any formal home-care use is significantly higher for Medicaid enrollees residing in nonmetropolitan counties having no town of 10,000 people. Use of Medicare home health care is significantly greater for residents of the most rural counties, irrespective of their Medicaid coverage, as well as Medicaid-covered residents of nonmetropolitan counties having a town of at least 10,000 people. IMPLICATIONS: In nonmetropolitan areas, Medicaid may be an important mechanism for linking older individuals with formal home care, especially Medicare home health care, and with the services that generate formal home care. Formal home care, including Medicare home health care, may substitute for less available forms of care in the most rural of nonmetropolitan areas. Therefore, policies that limit access to formal home care could lead to increased service-related vulnerabilities among older rural residents.

Development of the family caregiver medication administration hassles scale.

PURPOSE: "Medication administration hassles" are the minor daily irritants that family caregivers experience when they assist a dependent family member with medication regimens. This study was designed to develop and test a multidimensional measure of the hassles in family caregiver medication administration. DESIGN AND METHOD: The authors employed a multiphase process (caregiver focus groups, instrument development, pilot testing, and field testing). Approximately 180 family caregivers representing diverse socioeconomic circumstances and racial or ethnic backgrounds participated in the study. The final version of the instrument consists of 24 items and four subscales: Information Seeking/Information Sharing (9 items, alpha =.92), Safety Issues (5 items, alpha =.83), Scheduling Logistics (7 items, alpha =.90), and Polypharmacy (3 items, alpha =.80). Overall scale reliability is.95, and test-retest reliability at 2 weeks is.84. IMPLICATIONS: Caregiver medication administration hassles represent a complex, multidimensional construct that warrants consideration in studies of contemporary family caregiver stress, strain, and burden.