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Abstract Background A law making all indoor workplaces including bars and restaurants smokefree became operational in New Zealand in December 2004. New Zealand has a national free-phone Quitline Service which has been operational since 1999. Previous work has shown that the number of calls to the Quitline are influenced by marketing of the service through media campaigns. We set out to investigate if the smokefree law increased calls to the Quitline. Methods For 24 months prior to the law, and 12 months after the law, data were collected on: (i) Quitline caller registrations and the issuing of nicotine replacement therapy (NRT) vouchers by the Quitline Service; (ii) expenditure on Quitline-related television advertising; (iii) expenditure on other smokefree television advertising; and (iv) print media coverage of smoking in major New Zealand newspapers. These data were inputs to a time series analysis using a Box-Jenkins transfer function model. This used the law change as the intervention variable, with the response series being the monthly Quitline caller rates and monthly first time NRT voucher issue rates. Results The monthly rates of Quitline caller registrations and NRT voucher issues were observed to increase in the months after the law change. The increase in both these outcomes was even greater when considered in terms of per level of Quitline advertising expenditure (though these patterns may have partly reflected marked reductions in advertising expenditure at the time of the law change and hence are of limited validity). In the more robust time series analyses, the law change (intervention variable) had a significant effect (p = 0.025) on increasing the monthly caller registration rate in December 2004. This was after adjusting for the possible effects of Quitline advertising expenditure, print media coverage, and other smoking-related advertising expenditure. Conclusion The new national smokefree law resulted in increased quitting-related behaviour. This would suggest there is an extra opportunity for health agencies to promote quitting at such times.

In the event of an influenza pandemic, the most probable way in which the virus would be introduced to an isolated geographical area is by an infected traveller. We use a mathematical model, structured on the location at which infection occurs and based on published parameters for influenza, to describe an epidemic in a community of one million people. The model is then modified to reflect a variety of control strategies based on social distancing measures, targeted antiviral treatment and antiviral prophylaxis and home quarantine, and the effectiveness of the strategies is compared. The results suggest that the only single strategy that would be successful in preventing an epidemic (with R0=2.0) is targeted antiviral treatment and prophylaxis, and that closing schools combined with either closing work places or home quarantine would only prevent such an epidemic if these strategies were combined with a modest level of antiviral coverage.

Aim: To estimate the key transmission parameters associated with an outbreak of pandemic influenza in an institutional setting (New Zealand 1918)., Methods: Historical morbidity and mortality data were obtained from the report of the medical officer for a large military camp. A susceptible-exposed-infectious-recovered epidemiological model was solved numerically to find a range of best-fit estimates for key epidemic parameters and an incidence curve. Mortality data were subsequently modelled by performing a convolution of incidence distribution with a best-fit incidence-mortality lag distribution., Results: Basic reproduction number (R0) values for three possible scenarios ranged between 1.3, and 3.1, and corresponding average latent period and infectious period estimates ranged between 0.7 and 1.3 days, and 0.2 and 0.3 days respectively. The mean and median best-estimate incidence-mortality lag periods were 6.9 and 6.6 days respectively. This delay is consistent with secondary bacterial pneumonia being a relatively important cause of death in this predominantly young male population., Conclusion: These R0 estimates are broadly consistent with others made for the 1918 influenza pandemic and are not particularly large relative to some other infectious diseases. This finding suggests that if a novel influenza strain of similar virulence emerged then it could potentially be controlled through the prompt use of major public health measures.

The poorly water-soluble drug GWX was co-precipitated with hydroxypropyl methylcellulose phthalate (HPMCP) using a solvent change method. The two co-precipitate formulations made, with drug-HPMCP ratios of 2:8 and 5:5, were analysed using modulated temperature differential scanning calorimetry. They were found to consist of completely amorphous solid solution and a mixture of amorphous solid solution, crystalline drug and amorphous drug, respectively. Stability with respect to crystallization of the two co-precipitates and pure amorphous drug made by quench cooling was compared by storing preparations at 25 degrees C and 40 degrees C, under vacuum over P(2)O(5), and at 75% relative humidity (r.h.). Humidity (75% r.h. compared with dry) had a larger influence on crystallization of the amorphous drug than temperature (25 degrees C compared with 40 degrees C). The solid solution phase in co-precipitates had a relatively higher stability than amorphous drug alone, with respect to crystallization, in presence of the plasticizer water, and crystalline drug. These findings were partly explained by evidence of decreased molecular mobility in the amorphous solid solution with respect to amorphous drug alone, using enthalpy relaxation measurements. At an ageing temperature of 65 degrees C, the calculated half-life for enthalpy relaxation of the 2:8 drug-HPMCP ratio coprecipitate was about 6 orders of magnitude greater than that of amorphous drug alone, indicating a large difference in relative molecular mobility.

Drug-hydroxypropyl methylcellulose phthalate (HPMCP) mixtures were completely dissolved in acetone, and the resulting solution was added drop-wise into HCl(aq). Resulting co-precipitates were filtered, and then dried under vacuum at 45 degrees C, -800 mbar for 24 h. Modulated differential scanning calorimetry, thermogravimetric analysis, X-ray powder diffraction and HPLC were used to detect and quantify different phases present in co-precipitates. A 1/8 factorial study followed by a circumscribed central composite (CCC) study of significant factors, were used to detect and quantify respectively, the effects that processing factors had on the percentage of drug present in co-precipitates which was incorporated into solid solution (the response). Robustness of the model obtained from the CCC study was tested. Statistically significant factors were found to be the percentage of drug added into solvent, stirrer speed, and antisolvent pH. The statistically significant mathematical model obtained from the CCC study predicted that the dominant factor influencing the response is the percentage of drug added into solvent. The effect of stirrer speed on the response includes a local maximum at stirrer speed approximately 700 rpm. Both stirrer speed and antisolvent pH showed interactions with the percentage of drug added into solvent. The model obtained from this study indicated the possibility of two opposing phenomena influencing the response: crystallization inhibition by HPMCP, and solvent-antisolvent plasticization. Testing of this model using eight experimentally determined points showed reasonable robustness, with six out of eight points lying inside 95% prediction intervals.

Research compound GWX belongs to biopharmaceutical classification system type II, and hence shows dissolution-rate-limited absorption. To improve its dissolution performance, GWX was formulated as a co-precipitate with hydroxypropyl methylcellulose phthalate (HPMCP). Co-precipitates with various drug-HPMCP ratios were prepared and characterised using modulated differential scanning calorimetry (MDSC), X-ray powder diffraction, HPLC and dissolution testing. Co-precipitates with 1:9 and 2:8 drug-HPMCP ratios showed the highest extent of dissolution after both 5 and 90 min, followed by 3:7, 4:6, and 5:5 drug-HPMCP co-precipitates, in respective order. Co-precipitates with drug-HPMCP ratios of 6:4 and greater showed no significant improvement in dissolution over crystalline drug alone. The amounts of crystalline and amorphous drug in co-precipitates, as determined by MDSC, and HPLC quantification of the total amount of drug in co-precipitates were used to determine the amount of drug incorporated into solid solution. It was found that dissolution rate and extent was correlated to the amount of drug incorporated into amorphous solid solution for the 1:9 to 5:5 drug-HPMCP ratio co-precipitates. Amorphous drug alone and physical mixtures of drug and HPMCP showed very little and no significant improvement in dissolution rate or extent, respectively, above crystalline drug alone. Amorphous drug alone re-crystallized to a large extent within 1 min of contact with the dissolution medium, whereas 4:6 drug-HPMCP co-precipitate showed a lower degree of re-crystallization and 2:8 drug-HPMCP co-precipitate showed very little re-crystallization. It was concluded that the likely mechanisms of improved dissolution of low drug-HPMCP ratio co-precipitates were improved wetting or increased surface area for mass transfer, thermodynamically enhanced dissolution of a higher energy amorphous form and inhibition of re-crystallization, when drug was incorporated into solid solution.