Training pharmacists and pharmacy assistants in the stage-of-change model of smoking cessation: a randomised controlled trial in Scotland.

OBJECTIVE: To evaluate a training workshop for community pharmacy personnel to improve their counselling in smoking cessation based on the stage-of-change model. DESIGN: A randomised controlled trial of community pharmacies and pharmacy customers. SETTING: All 76 non-city community pharmacies registered in Grampian, Scotland, were invited to participate. Sixty-two pharmacies (82%) were recruited. SUBJECTS: All the intervention pharmacy personnel were invited to attend the training; 40 pharmacists and 54 assistants attended. A total of 492 customers who smoked (224 intervention, 268 controls) were recruited during the 12-month recruitment period (overall recruitment rate 63%). MAIN OUTCOME MEASURES: The perceptions of customers and pharmacy personnel of the pharmacy support and self-reported smoking cessation rates for the two groups of customers at one, four, and nine months. RESULTS: The intervention customer respondents were significantly more likely to have discussed stopping smoking with pharmacy personnel, 85% (113) compared with 62% (99) of the controls (p < 0.001). The former also rated their discussion more highly; 34% (45) of the intervention customers compared with 16% (25) of the controls rated it as "very useful" (p = 0.048). Assuming non-responders had lapsed, one-month point prevalence of abstinence was claimed by 30% of intervention customers and 24% of controls (p = 0.12); four months' continuous abstinence was claimed by 16% of intervention customers and 11% of controls (p = 0.094); and nine months' continuous abstinence was claimed by 12% of intervention customers and 7% of controls (p = 0.089). These trends in outcome were not affected by potential confounders (sex, age, socioeconomic status, nicotine dependence, and type of nicotine replacement product used) or adjustment for clustering. CONCLUSIONS: The intervention was associated with increased and more highly rated counselling, and a trend toward higher smoking cessation rates, indicating that community pharmacy personnel have the potential to make a significant contribution to national smoking cessation targets.

A virtual laboratory notebook for simulation models.

In this paper we describe how we have adopted the laboratory notebook as a metaphor for interacting with computer simulation models. This 'virtual' notebook stores the simulation output and meta-data (which is used to record the scientist's interactions with the simulation). The meta-data stored consists of annotations (equivalent to marginal notes in a laboratory notebook), a history tree and a log of user interactions. The history tree structure records when in 'simulation' time, and from what starting point in the tree changes are made to the parameters by the user. Typically these changes define a new run of the simulation model (which is represented as a new branch of the history tree). The tree shows the structure of the changes made to the simulation and the log is required to keep the order in which the changes occurred. Together they form a record which you would normally find in a laboratory notebook. The history tree is plotted in simulation parameter space. This shows the scientist's interactions with the simulation visually and allows direct manipulation of the parameter information presented, which in turn is used to control directly the state of the simulation. The interactions with the system are graphical and usually involve directly selecting or dragging data markers and other graphical control devices around in parameter space. If the graphical manipulators do not provide precise enough control then textual manipulation is still available which allows numerical values to be entered by hand. The Virtual Laboratory Notebook, by providing interesting interactions with the visual view of the history tree, provides a mechanism for giving the user complex and novel ways of interacting with biological computer simulation models.

Immunomodulation of psoriasis with a topical cyclosporin A formulation.

Topical cyclosporin A (CyA; Sandimmun) in a formulation incorporating the penetration enhancers (PE) propylene glycol (18%) and azone (2%) was tested for efficacy in a double-blind, vehicle-controlled trial in 5 chronic plaque psoriatic patients. On each patient, two similar plaques were treated daily, under occlusion, for 4 weeks with either 8% (w/v) CyA, containing PE, or with vehicle comprising olive oil with PE. All sites improved significantly, but there was no significant difference between those receiving active and control preparations. Cryostat sections of biopsies performed after 4 weeks' treatment showed significant reductions in CyA compared with vehicle-treated sites in the number of cells, positive for CD3 and CD25 in the epidermis and CD25 and HLA-DR in the dermis. These results suggest that amounts of CyA adequate to affect the lymphocytic infiltrate penetrated the epidermis but that only partial suppression occurred in the dermis, as indicated by the reduction in lymphocyte activation status.

Enhanced percutaneous absorption of a novel topical cyclosporin A formulation and assessment of its immunosuppressive activity.

No clinically successful topical cyclosporin A (CyA) formulation has been produced, mainly due to the apparent lack of drug penetration. This study has produced the first in vitro kinetic data on CyA penetration across human cadaver stratum corneum and has shown that addition of the penetration enhancers (PE) Azone and propylene glycol to the CyA vehicle significantly enhanced drug permeation across the skin barrier. Using flow-through permeability cells with 5% w/v CyA (Sandimmun) alone (CyA) or with PE (CyA + PE) in olive oil in the donor chamber, the penetration rate (mean +/- SD microgram/cm2/h) into receptor fluid was 53 +/- 43 (n = 13) for CyA and 660 +/- 175 (n = 7) for CyA + PE. The in vivo efficacy of this formulation was assessed in guinea-pigs undergoing delayed-type hypersensitivity (DTH) reactions to dinitrofluorobenzene (DNFB). CyA was applied topically at the time of challenge and twice daily thereafter. At 24 h, skin reactions revealed that compared with appropriate drug vehicles, concentrations of 0.25, 0.5 and 5% CyA +/- PE had a significant inhibitory effect upon the erythema response and this corresponded with significant reductions in T-cell infiltrates (0.5 and 5% CyA). No statistically significant reductions in erythema were demonstrated with 0.05% CyA +/- PE, but there was a reduction in the number of infiltrating lymphocytes in sites receiving 0.05% CyA + PE compared with vehicle-treated sites (P less than 0.01). This suggests that PE permitted some penetration of an otherwise non-immunosuppressive concentration of CyA through the skin.

A study of the causes of non-compliance by patients prescribed eyedrops.

An investigation into the causes of non-compliance by patients using eyedrops has been undertaken by questionnaire, ability tests, and by tests on eyedrop bottles. The results indicate a high prevalence of non-compliance, compounded by an inability adequately to instill a drop into the eye. About half the patients had difficulty aiming the drop, and other problems including squeezing the bottle, blinking, and seeing the tip of the bottle. Ability tests included a measurement of the grip strength of patients to complement measurement of the force required to expel a drop from a bottle. Some patients, particularly those with arthritis, could not generate enough force to squeeze a bottle. These same patients also had difficulty with the other movements required to administer drops. While some attempts have been made to produce devices to assist with eyedrops which can improve the aim of the patient, none give assistance in expelling a drop. An additional problem found was the reluctance of patients to admit to medical staff that they experienced any difficulty with their drops.

Effect of dimethylsulfoxide concentration on the permeability of neonatal rat stratum corneum to alkanols.

The effect of dimethylsulfoxide (DMSO) concentration on the permeability of neonatal rat stratum corneum to 14C labeled propan-1-ol and hexan-1-ol was studied in vitro. The permeability coefficients were determined from a range of DMSO-water systems. After soaking in water overnight, the same stratum corneum was used with water as both delivery and recipient phases for the alkanols. Concentrations below 70% DMSO reduced the penetration rate as a result of the solvent effect of DMSO and the formation of a DMSO-alkanol complex. Above 70% DMSO permeability increased, with a permeability coefficient greater than that from water being achieved at concentrations in excess of 80% DMSO. The second run, with water as delivery phase, showed that the effect was reversible below 70% DMSO, but that at higher concentrations DMSO had produced an irreversible change in the permeability of stratum corneum. We hypothesize a hydrogen bond-mediated mechanism for the increased permeability.

Effect of preheating on the permeability of neonatal rat stratum corneum to alkanols.

We heated flat sheets of neonatal rat stratum corneum for various times at temperatures between 40 and 90 degrees C before determining the permeability coefficient (Kp) of propanol and/or hexanol from water. Below 70 degrees C, Kp remained constant; at 75 degrees C, Kp increased linearly with exposure time; at 80 degrees C and above, there was a large increase in under 2 h, with no further increase on longer heating. There was a 15-fold increase in 6-h Kp between 70 degrees C and 80 degrees C, values being constant above 80 degrees C but at a figure less than for lipid-extracted stratum corneum. Thermal analysis showed that the increase in Kp corresponds to changes in the 80 degrees C lipid endotherm, suggesting that the increased Kp is due to a disordering of the lipid structures. The effect of treating preheated stratum corneum with dimethylsulfoxide (DMSO) vapor for 16 h was also studied. Below 70 degrees C, Kp was increased five-fold, but between 70 and 80 degrees C this difference was eliminated, so that above 80 degrees C the Kp was the same as with heat treatment alone. We concluded that both heat and DMSO affect the lipid structures of stratum corneum. DMSO produced a small, reversible structural change, while the effect of heat is irreversible and produces a greater degree of disorder in the lipid structures, but the lipid still contributed to the barrier effect of stratum corneum.