A cluster randomized trial to measure the impact on nonsteroidal anti-inflammatory drug and proton pump inhibitor prescribing in Italy of distributing cost-free paracetamol to osteoarthritic patients.

BACKGROUND: Paracetamol is recommended as first-line treatment for pain control in osteoarthritis because it has fewer side effects than do other therapeutic options, including nonsteroidal anti-inflammatory drugs (NSAIDs). Prescribing proton pump inhibitors (PPIs) as gastric bleeding prophylaxis in chronic NSAID users is also common, although not recommended. In Italy, paracetamol is not reimbursed by the National Health System. The aim of this trial was to test whether the availability to osteoarthritis patients of free paracetamol would decrease their use of NSAIDs and, as a secondary objective, whether opioid and PPI consumption would also decrease. METHODS: Eight general practitioners (GPs) (59 patients) were randomized to usual care and 8 (58 patients) to the experimental arm, where prescribed paracetamol was directly distributed for free by the local hospital. After 6 months, paracetamol was also available for free in the control arm. The main outcome was the pre/post difference in average NSAID and PPI consumption. Differences between experimental and control arms in pre/post differences are reported, as registered by the drug prescription information system. RESULTS: Average NSAID consumption decreased non-significantly, from 6.79 to 2.16 defined daily dose (DDD) in the experimental arm and from 3.19 to 2.97 DDD in the control group (p = 0.067). No changes were observed for PPIs (from 11.27 to 14.65 DDD and from 9.74 to 12.58 DDD in experimental and control arms, respectively, p = 0.788) or opioids (from 1.61 to 1.14 DDD and from 1.41 to 1.56 DDD in experimental and control arms, respectively, p = 0.419). When the intervention was extended to the control arm, no decrease in NSAID consumption was observed (from 2.46 to 2.43 DDD, p = 0.521). CONCLUSIONS: Removing small economic barriers had small or no effect on the appropriateness of opioid or PPI prescribing to patients with osteoarthritis; a reduction in NSAID consumption cannot be ruled out. TRIAL REGISTRATION NUMBER: NCT02691754 (Approved February 24, 2016).

Availability of drug at convenient stores is not associated with an increased incidence of their poisoning.

PURPOSE: In late 2012, South Korea revised the Pharmaceutical Affairs Act to make selected medications including acetaminophen, ibuprofen, and cold medications available in nonpharmacy outlets, including the 24-hour convenient stores (CVS). The objective of this study was to identify whether the characteristics and trend of self-poisonings associated with these medications were altered after the legislative change. METHODS: A retrospective study was performed using national data from the Emergency Department (ED)-based Injury In-depth Surveillance database. The patients diagnosed with poisoning were sorted from 2011 to 2016 and included in the study. As the Act was implemented from 2013, the demographic characteristics and clinical outcomes were compared before and after January 2013. A piecewise regression analysis was performed to determine the association between the monthly use of acetaminophen, medication for cold, and nonsteroidal anti-inflammatory drugs (NSAIDs) and the incidence of total poisonings before and after the January 2013. RESULTS: Among 1 536 277 patients included in the database, 17 523 patients diagnosed with poisoning were enrolled. After the legislative change, the etiology of poisoning did not change, although the frequency of hospitalization from ED was significantly increased. The monthly trend for poisoning due to acetaminophen, cold medications, and NSAIDs showed no significant slope change between before and after the legislative change. The proportional use of acetaminophen and cold medications was significantly decreased, while that of NSAIDs was unchanged before and after the legislative change. CONCLUSIONS: The change in the Pharmaceutical Affairs Act was not associated with any change in the monthly frequency of medication-related poisoning.

Availability of Paracetamol Sold Over the Counter in Europe: A Descriptive Cross-Sectional International Survey of Pack Size Restriction.

Due to the risk of hepatotoxicity when excessive amounts of paracetamol are consumed, Poisons Information Centers (PICs) frequently receive paracetamol-related enquiries. This study examined how widely pack size restrictions of paracetamol sold over the counter have been implemented in Europe and also availability of paracetamol through non-pharmacy outlets and their possible associations with frequency of poisoning enquiries. A cross-sectional European multi-centre questionnaire study was performed using a questionnaire to identify the extent and nature of paracetamol pack size restrictions, non-pharmacy outlet sales and the frequency of paracetamol-related enquiries to PICs. In total, 21 European countries participated. All PICs provided telephone hotline services. In 14 (67%) countries, pack size restrictions had been implemented in pharmacies (range: 8-30 g). No significant difference (median difference 0.7%, p-value = 0.36) was found when comparing median frequencies of paracetamol-related enquiries in countries with pack size restriction to countries without restrictions. A significantly lower median frequency of paracetamol-related enquiries was found in countries without non-pharmacy outlet sales compared to those with such sales (median difference 2.2%, p = 0.02). Pack size restrictions on pharmacy sales of paracetamol have been implemented in two-thirds of examined countries. There was no difference in the proportion of paracetamol-related enquiries to PICs among countries with and without pack size restrictions. However, a lower rate of paracetamol-related enquiries was noted in countries where paracetamol was not available in non-pharmacy outlets.

Increased availability of paracetamol in Sweden and incidence of paracetamol poisoning: using laboratory data to increase validity of a population-based registry study.

PURPOSE: To estimate the incidence trend and outcome of paracetamol poisoning, in relation to increased availability of paracetamol from non-pharmacy outlets in 2009. METHOD: Patients' serum paracetamol results over 14 years (2000-2013) from 20 (out of 21) regions in Sweden were linked to national registers of hospital care, cause of death, and prescriptions. Paracetamol poisonings were defined by serum paracetamol levels, hospital diagnoses, or cause of death. The change in incidence of poisonings following increased availability of paracetamol was analysed by using segmental regression of time series. RESULTS: Of the 12 068 paracetamol poisonings, 85% were classified as intentional self-harm. Following increased availability from non-pharmacy outlets, there was a 40.5% increase in the incidence of paracetamol poisoning, from 11.5/100 000 in 2009 to 16.2/100 000 in 2013. Regression analyses indicated a change in the trend (p < 0.0001) but not an immediate jump in the incidence (p = 0.5991) following the increased availability. Adjusting for trends in hospital episodes for self-harm, suicides, and the sales volume of paracetamol did not influence the result. All-cause mortality at 30 days (3.2%) did not change over time. CONCLUSIONS: The incidence of paracetamol poisoning in Sweden has increased since 2009, contrasting the decreased incidence in the period of 2007-2009. The change in trend was temporally associated with the introduction of availability of paracetamol from non-pharmacy outlets but did not appear to be related to sales volume of paracetamol or general trends in self-harm or suicides. © 2017 Commonwealth of Australia. Pharmacoepidemiology and Drug Safety © 2017 John Wiley & Sons, Ltd.

How well are national guidelines relating to the general sales of aspirin and paracetamol, adhered to by retail stores: a mystery shopper study.

OBJECTIVE: To determine whether non-pharmaceutical retail outlets are aboding to the current Medicines and Healthcare products Regulatory Agency (MHRA) national guidelines for over-the-counter (OTC) sales of aspirin and paracetamol. METHODS: Stages 1 and 2 of the study deployed eight and four medical students, respectively, to undertake a mystery shopper style investigation. Stage 1: eight medical students attempted to buy ≥ 96 tablets/capsules aspirin or paracetamol in one transaction in 62 shops. Stage 2: four medical students attempted to purchase 32 paracetamol 500 mg along with a 'flu remedy preparation also containing paracetamol, in 54 shops. RESULTS: Stage 1 data revealed that 58% and 57% retailers sold more than the MHRA guidelines recommended for paracetamol and aspirin, respectively. We observed that 23% and 28% retailers were willing to sell ≥ 96 tablets of paracetamol or aspirin with no questions asked. Stage 2 results showed that 57% retailers sold 32 × 500 mg paracetamol in conjunction with a paracetamol-containing 'flu preparation; while 98% shops sold 16 × paracetamol 500 mg along with a paracetamol-containing 'flu remedy, with no questions asked of the shopper or advice given. DISCUSSION: MHRA national guidelines for OTC medicines sales appear to be poorly adhered to in non-pharmacy shops. Sales of aspirin and paracetamol OTC must be better regulated in the UK to ultimately reduce morbidity and mortality rates of deliberate and accidental overdoses.

Care versus convenience: Examining paracetamol overdose in New Zealand and harm reduction strategies through sale and supply.

AIM: To examine statistics on paracetamol overdose in New Zealand and investigate options to reduce paracetamol overdose rates, through supply reduction strategies. METHOD: Data was gathered from the Ministry of Health's National Minimum Dataset and Wellington Hospital Emergency Department attendances. Twenty articles on supply reduction strategies were sourced through article database searches. A survey on paracetamol availability from online pharmacies within New Zealand was conducted by searching for New Zealand online pharmacies through Google. RESULTS: A five-year audit of data (2007-2012) from the Wellington Hospital Emergency Department revealed that paracetamol was the most common medication used for overdose (23%). National data on aminophenol derivatives accounted for 22.4% of poisonings in New Zealand's public hospitals. An online search found that 25 out of 27 online pharmacies sold packets containing 50 grams of paracetamol. However, the literature supported restricting packets to the minimum threshold for an acute exposure (10 g). CONCLUSION: Paracetamol poisoning is the most common form of drug overdose in many developed countries. Tightening restrictions on the quantity of paracetamol sold per packet, in all outlets in New Zealand, may be an effective strategy to reduce overdose rates. This includes online pharmacies where large quantities of paracetamol per packet are available for sale.

Internet survey of home storage of paracetamol by individuals in the UK.

AIM: Paracetamol (acetaminophen) is a common cause of liver failure due to overdose. Legislation introduced in the UK in 1998 to limit pack sizes of paracetamol has had limited impact on the overall number and severity of paracetamol overdoses. This may be because people have large amounts of paracetamol stored at home, but no previous studies have explored this question. METHODS: Individuals who regularly take part in market research surveys were invited to take part in an Internet survey. They were asked to supply demographic details, the frequency with which they use paracetamol and ibuprofen, and details of the amount and location of these drugs that they possessed. RESULTS: The mean age of respondents was 43.3 years (standard deviation 14.5 years), and 49.9% were female. People with both ibuprofen and paracetamol tended to have more packs and tablets of paracetamol (P < 0.001) and over a third had 32 or more paracetamol tablets. The most common pack size was 16 tablet packs (44.8% of all packs), which accounted for 39.4% of tablets. The most common site of paracetamol storage in the home was the kitchen (63.8% of people, 95% confidence interval 60.7, 66.7). CONCLUSION: This study suggests that pack size legislation in the UK has had limited effect on the amount of paracetamol that individuals have access to in the home. This may explain, at least in part, the limited impact of the pack size legislation on paracetamol overdoses in the UK.

What can be done to reduce mortality from paracetamol overdoses? A patient interview study.

BACKGROUND: Paracetamol (acetaminophen) is the most common self-poisoning agent in the UK and a leading cause of fatal hepatotoxicity. Following legislation in 1998 to limit pack sizes, beneficial effects on paracetamol-related mortality and morbidity were reported in England. However, there are still over 100 deaths a year and evidence of breaches of sales guidelines. AIM: To investigate characteristics of people taking larger paracetamol overdoses and compliance with sales guidelines, to inform possible further initiatives to reduce paracetamol fatalities. DESIGN AND METHODS: Interview study of 60 general hospital patients who took overdoses of over 16 paracetamol tablets (8 g). RESULTS: Half of all paracetamol overdoses involved over 16 tablets. Patients were predominantly young (three-quarters aged 16-40 years) and female (58.3%); over half (53.3%) had taken a previous paracetamol overdose. Three-quarters said they wanted to die. Half took the overdose within an hour of first thinking of it, half (53.3%) took tablets already in the home and 58.3% bought tablets specifically for the overdose. Ten people tried to buy more than 32 tablets in one transaction; four succeeded. Most knew that a paracetamol overdose could cause death or permanent damage (88.3%) and harm the liver (80.0%) but 70.0% thought they would lose consciousness. Warnings on packs had little deterrent effect. Media and internet influences were identified. Patients chose paracetamol because it was cheap and easily available. CONCLUSIONS: Further measures to reduce breaches of sales guidelines and the dangers of paracetamol overdose are required. Media and internet site producers should follow guidelines on reporting suicide.

Paracetamol availability in pharmacy and non-pharmacy outlets in Dublin, Ireland.

INTRODUCTION: In 2004, there were 11,092 presentations to Irish hospitals with deliberate self-harm, including 7,933 cases of drug overdose, of which 31% involved paracetamol. Limiting the availability of paracetamol reduces morbidity and mortality associated with paracetamol overdose. AIM: The present study aimed to determine the level of compliance with statutory regulations governing the sale of paracetamol in Ireland. METHODS: Researchers visited pharmacy (n = 20) and non-pharmacy outlets (newsagents, mini-markets and supermarkets) (n = 50) in Dublin city and attempted to purchase amounts of paracetamol that exceeded the statutory limits for a single transaction. RESULTS: Amounts of paracetamol in excess of statutory limits for a single transaction were purchased in 50.0% of pharmacies, 81.8% of newsagents/mini-markets and 20.0% of supermarkets. One year later, we again visited pharmacy (n = 20) and non-pharmacy outlets (n = 50) in Dublin city and purchased amounts of paracetamol in excess of statutory limits in 50.0% of pharmacies, 52.3% of newsagents/mini-markets and 10.0% of supermarkets. CONCLUSION: We recommend that (a) notwithstanding the improvement in compliance rates in newsagents/mini-markets, the sale of paracetamol in these outlets should be discontinued; (b) the sale of paracetamol in supermarkets should continue, although automated checkout tills should be appropriately re-programmed; and (c) there should be greater efforts to ensure compliance with statutory regulations in pharmacies.

Paracetamol (acetaminophen) pack size restrictions and poisoning severity: time trends in enquiries to a UK poisons centre.

BACKGROUND AND OBJECTIVE: In September 1998, legislation was introduced in the United Kingdom to limit paracetamol pack sizes to 16 tablets of 500 mg at general sales outlets and 32 tablets of 500 mg at pharmacies. The effect of the regulations on severity of paracetamol poisoning is unclear. The aim of this study was to describe trends in the severity of paracetamol poisoning and to assess the impact of the 1998 Regulations on the enquiries to a UK poisons centre. METHODS: We extracted data about the age, sex and number of tablets or capsules of paracetamol ingested by patients notified to Guy's and St Thomas' Poisons Unit (London, UK) between 1996 and 2004. RESULTS AND DISCUSSION: During the study period, there were approximately 140 000 patients with suspected paracetamol poisoning, accounting for around 11% of all patients reported to the poisons unit. The median number of tablets fell from 25 to 20 for males and 20 to 16 for females after 1998. There was also a reduction in the proportion of patients who ingested 17-32 tablets (from 36% to 30%) and 33-100 tablets (from 25% to 19%). CONCLUSION: Following the 1998 Regulations there was a decline in the severity, but not frequency, of paracetamol poisoning cases reported to Guy's and St Thomas' Poisons Unit. It is unclear whether the decline in severity was a direct consequence of the regulations.

Impact of restricting paracetamol pack sizes on paracetamol poisoning in the United Kingdom: a review of the literature.

Paracetamol (acetaminophen) is the most common drug taken in overdose in the UK, accounting for 48% of poisoning admissions to hospital and being involved in an estimated 100-200 deaths per year. In 1998, the UK government introduced legislation that reduced the maximum pack size of all non-effervescent tablets and capsules containing aspirin (acetylsalicylic acid) or paracetamol that can be sold or supplied from outlets other than registered pharmacies from 25 to 16 tablets or capsules. This article reviews the literature to determine the effectiveness of the legislation, focusing specifically on paracetamol poisoning. Seventeen studies on this subject were identified. Three studies found reductions in mortality rates; one study found an increase in mortality rates, while one found an initial reduction followed by an eventual increase; three found no significant difference in mortality rates before and after introduction of the legislation. Five studies found reductions in admissions to liver units, three of these finding a reduction in liver transplantation rates; two further studies found no change in liver function tests and rates of paracetamol-induced acute liver injury or failure. Four studies found a sustained decrease in hospital admissions, while two found an initial decrease followed by an eventual increase. One study found a decline in admissions for paracetamol poisoning and an increase in admissions for non-paracetamol poisoning. Sales data are conflicting, with two studies finding no significant difference in paracetamol sales before and after the introduction of the legislation and one reporting a decline. The severity of overdose appears to have decreased since the maximum permitted packet size was reduced, with five studies reporting a reduction in the number of severe overdoses (measured by numbers of tablets ingested, serum paracetamol concentrations and usage of antidotes). Only two studies reported an increase in the number of severe overdoses.Paracetamol-associated mortality rates, admissions to liver units/liver transplants, hospital admissions and the severity of paracetamol overdose appear to have been decreasing since 1998. However, one study showed that the reductions in mortality and hospital admissions began in 1997; therefore, the contribution of the 1998 legislation to the observed changes is unclear. Most of the studies are based on short-term follow-up so it is difficult to draw any conclusions regarding long-term trends. Many of the studies were also restricted to relatively small areas of the UK; this, combined with a variety of outcome measures, makes it difficult to distinguish any conclusive trends. The studies also suffer from a lack of comparison and control groups. Some studies do not clearly differentiate between the paracetamol preparations covered by the legislation and those not. The limited number of studies to date, combined with a variety of outcome measures, make it difficult to determine with accuracy whether or not the legislation has been a success. More long-term studies are needed to fully assess the impact of the legislation.

How has legislation restricting paracetamol pack size affected patterns of deprivation related inequalities in self-harm in Scotland?

OBJECTIVE: To describe how changes in legislation to control sales and thus restrict the general availability of paracetamol have affected deprivation-related inequalities in deliberate self-harm associated with the drug in Scotland. DESIGN AND SETTING: A descriptive analysis of routine death and hospital discharge data for the entire Scottish population between 1995 and 2002. PARTICIPANTS: Patients in Scotland admitted to hospital with a diagnosis of poisoning and deaths in Scotland due to poisoning 1995-2002. OUTCOME MEASURES: Changes in mortality and overdose rates by deprivation quintile, and case fatality rates due to poisoning involving paracetamol. RESULTS: Rates of overdose involving paracetamol, while much higher in disadvantaged quintiles, fell in each deprivation quintile following the 1998 legislation. They then returned to levels similar, or above those in the mid 1990s. All quintiles were affected to a similar extent with the relationship between them remaining constant over time. Case fatality rates were significantly higher in more disadvantaged quintiles. CONCLUSIONS: Marked inequalities exist in paracetamol related harm in Scotland. The most disadvantaged groups (both male and female) have higher overdose and death rates, as well as higher case fatality rates. Following the restrictions all social groups saw similar reductions in paracetamol related harm. This effect has been short-lived and rates have returned to pre-legislation levels. Legislation has not permanently affected overall use of paracetamol in overdose in Scotland or reduced the proportion of patients taking paracetamol as a component of the overdose in the longer term. An important public health policy has failed to achieve its objective and it is not clear why. We need a better understanding of why this measure had only short-term benefits if its full potential is to be achieved.

Decreased availability of antimalarials in the private sector following the policy change from chloroquine to sulphadoxine-pyrimethamine in the Kilombero Valley, Tanzania.

BACKGROUND: Malaria control strategies emphasize the need for prompt and effective treatment of malaria episodes. To increase treatment efficacy, Tanzania changed its first-line treatment from chloroquine to sulphadoxine-pyrimethamine (SP) in 2001. The effect of this policy change on the availability of antimalarials was studied in rural south-eastern Tanzania. METHODS: In 2001 and 2004, the study area was searched for commercial outlets selling drugs and their stocks were recorded. Household information was obtained from the local Demographic Surveillance System. RESULTS: From 2001 to 2004, the number of general shops stocking drugs increased by 15% and the number of drug stores nearly doubled. However, the proportion of general shops stocking antimalarials dropped markedly, resulting in an almost 50% decrease of antimalarial selling outlets. This led to more households being located farther from a treatment source. In 2004, five out of 25 studied villages with a total population of 13,506 (18%) had neither a health facility, nor a shop as source of malaria treatment. CONCLUSION: While the change to SP resulted in a higher treatment efficacy, it also led to a decreased antimalarial availability in the study area. Although there was no apparent impact on overall antimalarial use, the decline in access may have disproportionately affected the poorest and most remote groups. In view of the imminent policy change to artemisinin-based combination therapy these issues need to be addressed urgently if the benefits of this new class of antimalarials are to be extended to the whole population.

Legislation restricting paracetamol sales and patterns of self-harm and death from paracetamol-containing preparations in Scotland.

AIMS: To describe how changes in legislation to restrict paracetamol sales have affected overdose discharges and death associated with the drug in Scotland. METHODS: A descriptive analysis of routine death and hospital discharge data for the entire Scottish population between 1995 and 2004. Patients in Scotland participated who were discharged from hospital with a diagnosis of poisoning; deaths in Scotland from diagnosis of poisoning 1995-2003 were also analysed. Outcome measures were changes in mortality and overdose due to poisoning involving paracetamol. A comparison was made of in-hospital and out-of-hospital mortality in fatalities involving paracetamol. RESULTS: The majority of paracetamol-associated deaths were due to co-proxamol. Deaths associated with paracetamol alone or with ethanol occurred principally in hospital and were a minority of deaths overall. The proportion of in-hospital deaths attributed to paracetamol increased (post/pre ratio 1.347; 95% confidence interval 1.076, 1.639; P = 0.013). Overall numbers of cases discharged with poisoning fell. The proportion of these involving paracetamol in any form increased significantly in all groups except young men aged 10 to <20 years. CONCLUSIONS: Legislation has not reduced mortality or proportional use of paracetamol in overdose, both of which appear to have increased in Scotland since pack-size limitations. Other approaches are necessary to reduce the death rate from overdoses involving paracetamol.

Impact of paracetamol pack size restrictions on poisoning from paracetamol in England and Wales: an observational study.

BACKGROUND: About 500 drug poisoning deaths involving paracetamol (acetaminophen) occur every year in England and Wales. To reduce the number of deaths, regulations were introduced in 1998 to restrict the sale of paracetamol. In this paper, we evaluate the impact of these regulations. METHODS: Mortality data for England and Wales were provided by the Office for National Statistics. Deaths were defined as due to compound paracetamol (paracetamol in combination with another analgesic, a low dose opioid or other ingredients) or paracetamol only, with or without alcohol or other drugs. The Department of Health provided data on all hospital admissions with a primary diagnosis of paracetamol poisoning. RESULTS: Mortality rates for paracetamol only were similar for males and females, and decreased from about 4.5 to 2.8 per million between 1997 and 1999 and again from about 3.1 to 2.2 per million between 2001 and 2002. These falls may be attributable to random variation in the rates. Deaths involving compound paracetamol, which were not subject to the 1998 regulations, remained relatively constant over the study period. There was evidence of a decreasing trend in paracetamol only mortality rates and this followed overall trends for other drug poisoning excluding opioids and drugs of misuse. Hospital admissions due to paracetamol poisoning increased from about 27 000 to 33 000 between 1995/1996 and 1997/1998 and then decreased to 25 000 in 2001/2002. There were almost 50 per cent more admissions for females than males, with the highest admission rates amongst females aged 15-24 years old. CONCLUSIONS: Between 1993 and 2002, mortality rates and hospital admissions due to paracetamol poisoning declined. However, the contribution of the 1998 regulations to this decline is not clear. Paracetamol poisoning continues to be an important public health issue in England and Wales and represents significant workload for the NHS in England.

Restricting paracetamol in the United Kingdom to reduce poisoning: a systematic review.

BACKGROUND: Paracetamol poisoning is implicated in about 150-200 poisoning deaths per year in England and Wales. We review previous studies assessing the effectiveness of regulations introduced in 1998 to restrict sales of paracetamol and reduce paracetamol poisoning. METHODS: We searched the following electronic databases: MEDLINE, EMBASE, CINHAL, HIMIC, COCH, APC, CENTRAL and DARE. English language publications between 1998 and 2003 were included. Studies were included if they took place in the United Kingdom and assessed changes in any aspect of paracetamol poisoning following the introduction of the 1998 regulations. RESULTS: Twelve studies were identified, which examined several different outcomes. Three studies examined admissions to liver transplant units; all reported reductions. Eight studies evaluated severity of paracetamol poisoning; three reported reductions but five did not. Five out of six studies reported reductions in hospital admissions. One study reported reduced mortality in England and Wales after 1 year while another found no difference in Scotland 2 years after the regulations were introduced. Two studies observed a significant reduction in over-the-counter sales. Studies suffered from several limitations including short follow-up periods, no case definition for paracetamol poisoning and lack of comparison groups. CONCLUSIONS: The limitations of these studies makes it difficult to draw firm conclusions. They do, however, suggest that the 1998 regulations may have been associated with reduced admissions to liver units and liver transplants, reduced hospital attendance due to paracetamol poisoning and reduced sales of paracetamol. Further research is needed to fully evaluate the impact of the 1998 regulations. In the future, formal evaluation of the impact of similar interventions should be an integral part of policy formation.