Trends in hospital admissions for adverse drug reactions in England: analysis of national hospital episode statistics 1998

1472-6904-7-9 1472-6904 Research article Trends in hospital admissions for adverse drug reactions in England: analysis of national hospital episode statistics 1998–2005 Patel Hitesh dochiteshpatel@hotmail.com Bell Derek d.bell@imperial.ac.uk Molokhia Mariam mariam.molokhia@lshtm.ac.uk Srishanmuganathan Janakan sjanakan@hotmail.com Patel Mitesh mitesh.patel@doctors.net Car Josip josip.car@imperial.ac.uk Majeed Azeem a.majeed@imperial.ac.uk

Charing Cross Hospital, London W6 8RF, UK

Chelsea and Westminster Hospital, London SW10 9NH, UK

Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, WC1E 7HT, UK

St Mary's Hospital, London W2 1NY, UK

Department of Primary Care and Social Medicine, Imperial College, London W6 8RF, UK

BMC Clinical Pharmacology 1472-6904 2007 7 1 9 http://www.biomedcentral.com/1472-6904/7/9 17894876 10.1186/1472-6904-7-9 28 11 2006 25 9 2007 25 9 2007 2007 Patel et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Adverse drug reactions (ADRs) are a frequent cause of mortality and morbidity to patients worldwide, with great associated costs to the healthcare providers including the NHS in England. We examined trends in hospital admissions associated with adverse drug reaction in English hospitals and the accuracy of national reporting.

Methods

Data from the Hospital Episode Statistics database (collected by the Department of Health) was obtained and analysed for all English hospital episodes (1998–2005) using ICD-10 codes with a primary (codes including the words ('drug-induced' or 'due to') or secondary diagnosis of ADR (Y40–59). More detailed analysis was performed for the year 2004–2005

Results

Between 1998 and 2005 there were 447 071 ADRs representing 0.50% of total hospital episodes and over this period the number of ADRs increased by 45%. All ADRs with an external code increased over this period. In 2005 the total number of episodes (all age groups) was 13,706,765 of which 76,692 (0.56%) were drug related. Systemic agents, which include anti-neoplastic drugs, were the most implicated class (15.7%), followed by analgesics (11.7%) and cardiovascular drugs (10.1%). There has been a 6 fold increase in nephropathy secondary to drugs and a 65% decline in drug induced extra-pyramidal side effects. 59% of cases involving adverse drug reactions involved patients above 60 years of age.

Conclusion

ADRs have major public health and economic implications. Our data suggest that national Hospital Episode Statistics in England have recognised limitations and that consequently, admissions associated with adverse drug reactions continue to be under-recorded. External causes of ADR have increased at a greater rate than the increase in total hospital admissions. Improved and more detailed reporting combined with educational interventions to improve the recording of ADRs are needed to accurately monitor the morbidity caused by ADRs and to meaningfully evaluate national initiatives to reduce adverse drug reactions.

Background

Adverse drug reactions cause considerable morbidity and mortality world-wide 1 and in many cases are avoidable. Pirmohamed and colleagues estimated that in England, adverse drug reactions were responsible for around 6.5% of all acute hospital admissions and at least 5,000 deaths per year 2. In the USA, adverse drug reactions are one of the leading causes of death in the population 3. Hence, adverse drug reactions have a major impact on public health, reducing patients' quality of life and imposing a considerable financial burden on the health care systems at a time when many health care systems are under considerable financial strain.

Drug reactions can be typically described in two groups. Type A reactions "intrinsic" (which are often dose-dependent) are relatively common. Type B reactions are usually more serious: idiosyncratic reactions that are not necessarily dose-dependent. We expect the majority of ADR admissions to be Type A reactions. Notification to pharmacovigilance agencies (e.g. the Medicines and Healthcare products Regulatory Agency yellow card in the UK) is designed to capture new ADRs not known at the marketing stage, i.e. usually but not exclusively, Type B reactions.

Adverse drug reactions are commonest amongst the elderly 2 This is not surprising as the elderly generally have the highest prevalence of long-term diseases 4. Poly-pharmacotherapy, combined with a poorer physiological reserve, puts the elderly particularly at risk of adverse drug reactions 5. Poly-pharmacotherapy amongst elderly patients is likely to increase still further through the implementation of 'pay for performance' schemes, such as the new contract for NHS general practitioners in the UK. This rewards tighter meeting of 'treatment targets' for specific long-term diseases, such as high blood pressure or high cholesterol, which commonly results in prescribing of higher doses of medication or poly-pharmacotherapy with higher number of different medications than in the past.

More evidence-based prescribing for long-term diseases will benefit patients, but may also increase the number of adverse drug reactions in the population merely because of the potential for increased drug reactions. The number of older people in the population of developed countries is also increasing rapidly. For example, in the United Kingdom, the number of people aged 65 years and over is predicted to increase by around 53% between 2001 and 2031 6. This increase in the elderly population combined with increased prescribing for long-term diseases is likely to result in an increase in the number of people at risk of suffering from adverse drug reactions.

Despite the importance of adverse drug reactions, methods for monitoring them are limited. Some adverse drug reactions are identified during clinical trials during drug development and testing, however, rare reactions may fail to be detected. Once a drug is marketed, detection of adverse drug reactions generally depends on notifications to regulatory authorities, such as the Medicines and Healthcare products Regulatory Agency, which runs the yellow card scheme in the United Kingdom. However, even for serious and well-recognized ADRs notification of adverse drug reactions from such spontaneous reporting schemes is low, often less than 10% and even lower where the association between the drug and the adverse event is unknown 7.

Hence, many adverse drug reactions do not become apparent until a drug has been in widespread use for several years. Consequently, current systems for the detection of ADRs have serious limitations. For example, the associations between COX-2 inhibitors and increased risk for myocardial infarction and stroke were only highlighted and reviewed after these drugs had been used for several years by hundreds of thousands of patients, although initial concerns were identified from trial data 8.

Other information on adverse drug reactions comes from ad-hoc studies. However, with a few exceptions, such as the study by Pirmohamed and colleagues in North-West England, 2 these previous studies have tended to be small (although with similar results; often based in one hospital) and many are now very old 1.

Hospital Episode Statistics (HES) are collected by the Department of Health and contain details of all admissions to NHS hospitals in England 9. HES data includes private patients treated in NHS hospitals, patients who were resident outside of England and care delivered by treatment centres (including those in the independent sector) but funded by the NHS. HES were established in 1987 following a report on the collection and use of hospital activity information published by a steering group chaired by Dame Edith Körner 10. Before 1987, only a 10 per cent sample of admitted patient records were collected nationally whereas HES collect a detailed record for each 'consultant episode' of admitted patient care delivered by NHS hospitals in England.

HES data are available for every financial year from 1989–90 onwards but the dataset has been modified over time to reflect changing administrative requirements and the introduction of new clinical classifications. For example, in 1995, the recording of diagnoses changed from the 9th to the 10th revision of the International Classification of Diseases (ICD) 9. In the 2004–05 financial year, there were about 12.1 million hospital admissions, resulting in nearly 14 million consultant episodes, in England.

Waller and colleagues 11, studied HES data from 1996–2000, looking at 258, 222 episodes associated with confirmed ADRs and concluded that HES grossly underestimates the burden of ADRs. As part of preparatory work for projects on the epidemiology of adverse drug reactions, and educational interventions to improve recording of these reactions, we wished to examine the contribution of recorded adverse drug reactions to acute hospital admissions nationally. We aimed to examine the current epidemiology of hospital admission for adverse drug reactions, the age distribution of these admissions, and their impact on hospital activity. We also aimed to compare estimates of hospital admissions due to adverse drug reactions to those from previous studies to determine how well adverse drug reactions were being recorded in current practice and how much scope there was to improve recording.

Methods

We obtained for the period 1998–2005 from the Department of Health, HES-records in which there was an ICD10 code containing the words 'drug-induced' or which indicated that a diagnosis was 'due to' a drug. We also studied codes in the range Y40 – Y59 ("correct drug properly administered in therapeutic or prophylactic dosage as the cause of any adverse effect"), otherwise known as 'external cause' (Table 1). This excludes accidental or intentional poisoning due to drugs. We studied codes that explicitly stated that the episode was caused by a drug. Thus, we did not include conditions like toxic epidermal necrolysis, which is invariably drug induced but does have other known causes.

Table 1

ICD-10 codes (Y40–Y59) for drugs, medicaments and biological substances causing adverse effects in therapeutic use

ICD-10

External cause mortality/morbidity by:

Y40

Systemic antibiotics: Penicillins, cefalosporins and other beta-lactam antibiotics, chloramphenicol, macrolides, tetracyclines, aminoglycosides, rifamycins, antifungals, others

Y41

Other systemic anti-infectives and antiparasitics: Sulphonamides, other anti-mycobacterial, anti-malarials, anti-protozoal, anti-helminthics, anti-virals

Y42

Hormones and substitutes: Glucocorticoids, thyroid hormones, anti-thyroids, insulin, oral hypoglycaemics, oral contraceptives, oestrogen and progestogen, anti-gonadotrophins, anti-oestrogens, anti-progestogens, androgens

Y43

Systemic agents: Anti-allergic and anti-emetic drugs, anti-neoplastic and immunosuppressive drugs, acidifying/alkalising agents

Y44

Agents affecting blood constituents: Iron preparations, anti-megaloblastic-anaemia preparations, anticoagulants, anticoagulant antagonists, antithrombotic drugs, thrombolytic drugs, blood products, plasma substitutes

Y45

Analgesics, anti-pyretics and anti-inflammatory drugs: Opioids and related analgesics, salicylates, propionic acid derivatives, nonsteroidal anti-inflammatory drugs, antirheumatics, 4-aminophenol derivatives

Y46

Anti-epileptics and anti-parkinsonism drugs: Succinimides, oxazolidinediones, hydantoin derivatives, deoxybarbiturates, iminostilbenes, valproic acid, anti-parkinsonism drugs, anti-spasticity drugs

Y47

Sedatives, hypnotics and anti-anxiety drugs: Barbiturates, benzodiazepines, cloral derivatives, paraldehyde, bromine compounds, sedative, hypnotic and antianxiety drug, unspecified

Y48

Anaesthetics and therapeutic gases: Inhaled/parenteral anaesthetics, local anaesthetics, therapeutic gases

Y49

Psychotropic drugs: Tricyclic and tetracyclic antidepressants, monoamine-oxidase-inhibitor, phenothiazine antipsychotics and neuroleptics, butyrophenone and thioxanthene neuroleptics, other antidepressants, antipsychotics and neuroleptics

Y50

Central nervous system stimulants: Analeptics, opioid receptor antagonists, methylxanthines, other central nervous system stimulants

Y51

Drugs primarily affecting the autonomic nervous system: Anticholinesterase agents, cholinergics, ganglionic blocking drugs, anticholinergics, antimuscarinics, spasmolytics, alpha-adrenoreceptor agonists/antagonists, beta-adrenoreceptor agonists/antagonists, centrally acting and adrenergic-neuron-blocking agents

Y52

Agents affecting the cardiovascular system: Cardiac-stimulant glycosides, calcium-channel blockers, other anti-dysrhythmic drugs, other coronary vasodilators, angiotensin-converting-enzyme inhibitors, other anti-hypertensives, anti-hyperlipidaemic and anti-arteriosclerotic drugs, peripheral vasodilators, anti-varicose drugs

Y53

Agents affecting the gastrointestinal system: Antacids, anti-gastric-secretion drugs, laxatives, anti-diarrhoeal, emetics

Y54

Agents affecting water-balance and mineral and uric acid metabolism: Mineralocorticoids, mineralocorticoid antagonists, carbonic-anhydrase inhibitors, benzothiadiazine derivatives, other diuretics, electrolytic, caloric and water-balance agents, agents affecting calcification, agents affecting uric acid metabolism

Y55

Agents acting on smooth and skeletal muscles and the respiratory system: Oxytocic drugs, skeletal muscle relaxants, anti-tussives, expectorants, anti-common-cold drugs, anti-asthmatics

Y56

Topical agents primarily affecting skin and mucous membrane: Local anti-fungal, anti-infective, anti-inflammatory drugs, anti-pruritics, local detergents, emollients, keratolytics, ophthalmological drugs, otorhinolaryngological drugs, dental drugs

Y57

Other and unspecified drugs: Appetite depressants, lipotropic drugs, antidotes and chelating agents, alcohol deterrents, x-ray contrast media, vitamins

Y58

Bacterial vaccines

Y59

Other vaccines: Viral/rickettsial/protozoal vaccines, immunoglobulin

Includes: Correct drug properly administered in therapeutic or prophylactic dosage as the cause of any adverse effect Excludes: Accidental overdose of drug or wrong drug given or taken in error (X40–X44); accidents in the technique of administration of drugs, medicaments and biological substances in medical and surgical procedures (Y60–Y69)

HES records contain a main diagnosis field and up to 13 secondary diagnosis fields (seven before 2002/3). We examined the number of episodes per year and for the most recent year for which data was available (2004/05); we also examined several other measures, including the number of admissions by age and the total bed days used by patients with diagnoses of adverse drug reactions. An episode is defined as the time a patient spends under the care of one consultant. Most admissions result in just one episode of care and hence episodes are a reasonably good proxy for admissions.

HES data is collected in financial year from 1 April to 31 March the following year. Our data is presented in this format. HES data is collected comprehensively and undergoes extensive processing and validation to maintain quality. This process is detailed on their official website 9. Some of the data presented changed classification during the time period and it became dubious whether the episode was related exclusively to an ADR. These data were not included and are marked as U/C (unclassified) in the tables.

Results

Overall burden of hospital admissions for ADRs

Table 2 summarises the total number of episodes and the total number of episodes associated with ADRs. In our seven year study period, there were 88,822,005 total hospital episodes and 447,041 episodes with a diagnostic code indicative of ADRs (0.5%). Of these 68,971 (0.08%) were primary diagnoses and 378,070 (0.4%) were of 'external cause'.

Table 2

Total number of Hospital Episode Statsitics for which there was a primary diagnosis or 'external cause' of ADR 1998–2005

1998–9

1999–00

2000–1

2001–2

2002–3

2003–4

2004–5

% Change 1998–2005

Total No. of Episodes

11,983,893

12,167,574

12,674,277

12,357,360

12,757,656

13,174,480

13,706,765

14.4

No. with 'drug induced' codes

10506

10105

9823

9442

9246

9453

10396

-1.0

No. with external cause codes

42,555

47,385

50,113

52,160

56,943

62,618

66,296

55.8

Total Adverse Drug Reactions

53,061

57,490

59,936

61,602

66,189

72,071

76,692

44.5

Change in burden

Between 1998–2005, the total number of hospital episodes increased by 14% but the total number of reported episodes linked with ADRs increased by 45% (largely due to an increase in external cause codes). Table 3 and 4 highlight the burden of ADRs according to ICD-10 code. Drug induced haemolytic anaemia (927%), nephropathy (590%), adrenocortical failure (146%), cardiomyopathy (144%) and aplastic anaemia (139%) were the five fastest growing ADRs as a primary diagnosis (Table 3). In contrast, the top five fastest growing ADRs as external causes were drugs relating to: water balance (164%), autonomic system (108%), central nervous system stimulants (102%), cardiovascular system (92%) and biologicals/vaccines (77%). Primary diagnosis of ADRs decreased by 1% during this study. Reported rates under the categories of 'drug-induced extra-pyramidal side effects' (-65%) and 'malignant hyperpyrexia' (-33%) showed the largest declines (Table 3).

Table 3

Annual number of Hospital Episode Statistics finished consultant episodes with a primary diagnosis for an ADR (ICD-10 code)

ICD-10

1998–9

1999–00

2000–1

2001–2

2002–3

2003–4

2004–5

% Change 1998–2005

D59.0/2

Drug induced haemolytic anaemia

154

926.7

D61.1

Drug induced aplastic anaemia

101

116

114

186

182

162

241

138.6

E03.2

Hypothyroidism due to medicaments

13.0

E27.3

Drug induced adrenocortical failure

145.8

F11

Mental disorders due to opioids

4360

4287

4398

4187

3916

3690

3746

-14.1

F13

Mental disorders due to sedatives/hypnotics

223

247

239

232

206

189

-15.2

F19

Mental disorders due to multiple psychoactive drugs

3513

3137

2725

2643

2601

2690

2775

-21.0

G21.0

Malignant neuroleptic syndrome

101

106

121

108

102

128

26.7

G21.1

Drug induced Parkinsonism

145

115

124

133

112

108

149

2.8

G24.0

Drug induced dystonia

149

130

145

130

115

152

109

-26.8

G25.1/4/6

Drug induced extrapyramidal syndrome/chorea/tics

136

146

110

125

-64.7

G72.0

Drug induced myopathy

17.0

H91.0

Ototoxic hearing loss

U/C¹

U/C

I42.7

Drug induced cardiomyopathy

144.0

J70.2/3/4

Drug induced interstitial lung disorders

74.1

K71

Drug induced liver disease

406

318

372

351

459

437

448

10.3

L56.0/1

Drug induced phototoxicity

25.0

M10.2

Drug induced gout

13.3

M32.0

Drug induced systemic lupus erythematosus

52.9

M34.2

Drug induced systemic sclerosis

U/C

N14

Drug induced nephropathy

100

318

414

590.0

T88.3

Malignant hyperthermia due to anaesthesia

-33.3

T88.6

Drug induced anaphylaxis

366

435

399

384

375

469

563

53.8

T88.7

Unspecified adverse drug effect

696

737

721

602

664

748

1068

53.4

Total

10506

10105

9823

9442

9246

9453

10396

-1.0

¹U/C – unclassified: data not available due to a coding change

Table 4

Annual number of HES finished consultant episodes with an 'external code' for an adverse drug reaction

ICD-10

1998–9

1999–00

2000–1

2001–2

2002–3

2003–4

2004–5

% Change 1998–2005

Y40

Systemic antibiotics

4,206

4,212

4,533

4,341

4,697

5,624

6,449

53.3

Y41

Other systemic anti-infectives/anti-parasitics

829

816

1,017

945

1,195

1,134

1,453

75.3

Y42

Hormones (including synthetic, antagonists)

4,547

5,088

4,934

5,113

5,803

5,461

5,319

Y43

Primarily systemic agents

7,501

8,271

9,078

9,877

10,766

11,226

12,054

60.7

Y44

Agents primarily affecting blood constituents

4,062

4,483

4,723

4,797

5,230

5,995

4,272

5.2

Y45

Analgesics/antipyretics/anti-inflammatory

5,951

6,726

6,787

6,819

7,540

8,079

9,004

51.3

Y46

Antiepileptics/antiParkinsonism drugs

1,230

1,267

1,224

1,340

1,401

1,501

1,628

32.4

Y47

Sedatives, hypnotics, anti-anxiety drugs

370

400

450

430

480

586

560

51.4

Y48

Anaesthetics, therapeutic gases

414

538

502

440

505

521

531

28.3

Y49

Psychotropic drugs

1,653

1,678

2,008

1,992

1,953

2,364

2,544

53.9

Y50

Central nervous system stimulants

102.2

Y51

Drugs affecting autonomic nervous system

1,702

2,056

2,277

2,470

2,686

3,239

3,532

107.5

Y52

Agents primarily affecting cardiovascular system

4,044

4,752

5,376

5,667

6,234

6,836

7,768

92.1

Y53

Agents primarily affecting gastrointestinal system

398

410

486

416

461

579

656

64.8

Y54

Agents affecting water/mineral balance/uric acid

2,136

2,617

2,945

3,526

4,151

5,118

5,638

164

Y55

Agents affecting muscle/respiratory system

312

299

342

321

323

430

422

35.3

Y56

Topical agents affecting skin/ENT, dental

1,138

1,236

983

1,202

1,065

1,079

1,224

7.6

Y57

Other and unspecified medicaments

1,524

1,715

1,780

1,907

1,906

2,014

2,398

57.3

Y58

Bacterial vaccines

226

347

255

182

197

356

281

24.3

Y59

Other vaccines/biologicals

266

407

338

299

281

405

470

76.7

Total

42,555

47,385

50,113

52,160

56,943

62,618

66,296

55.8

Detailed overview for 2004–5

In 2004, there were 10,396 (0.08%) ADR admissions associated with a primary diagnosis and 66,296 (0.5%) ADRs as a secondary cause. Combined, they account for 0.56% of hospital episodes. The three commonest classes of adverse drug reaction, classified as an external cause (Table 4) resulting in hospital admission were systemic agents (Y43); analgesics, antipyretics and anti-inflammatory drugs (Y45); and systemic antibiotics (Y40). 'Mental disorders' secondary to opioids and psychoactive drugs reflected 63% of all the primary diagnoses of ADR (Table 3).

Most hospital episodes associated with adverse drug reactions occurred in the elderly. In 2004–5, 59% of hospital episodes in which there was an external ICD10 code for an adverse drug reaction occurred in people aged 60 years and over. The mean age of ADRs was 60 (Table 5, 6). Younger patients tended to have ADRs from vaccines and psychoactive drugs.

Table 5

Number of HES finished consultant episodes with a primary diagnosis of an ADR in 2004/05: mean age of admissions, age & gender distribution of episodes and total bed days

ICD-10

Male %

Mean age

Age 0–14 (%)

Age 15–59 (%)

Age 60–74 (%)

Age 75+ (%)

Total Bed days

D59.0/2

Drug induced haemolytic anaemia

0 (0.0)

52 (0.5)

75 (0.8)

27 (0.3)

160

D61.1

Drug induced aplastic anaemia

2 (0.0)

89 (0.9)

74 (0.7)

73 (0.7)

604

E03.2

Hypothyroidism due to medicaments

0 (0.0)

6 (0.1)

3 (0.0)

17 (0.2)

191

E27.3

Drug induced adrenocortical failure

11 (0.1)

22 (0.2)

12 (0.1)

14 (0.1)

584

F11

Mental disorders due to opioids

14 (0.1)

3681 (36.9)

33 (0.3)

14 (0.1)

47390

F13

Mental disorders due to sedatives/hypnotics

6 (0.1)

123 (1.2)

33 (0.3)

27 (0.3)

4922

F19

Mental disorders due to multiple psychoactive drugs

14 (0.1)

2734 (27.4)

17 (0.2)

10 (0.1)

64152

G21.0

Malignant neuroleptic syndrome

0 (0.0)

88 (0.9)

28 (0.3)

12 (0.1)

2,315

G21.1

Drug induced Parkinsonism

1 0.0)

11 (0.1)

44 (0.4)

93 (0.9)

1,964

G24.0

Drug induced dystonia

10 (0.1)

65 (0.7)

16 (0.2)

18 (0.2)

550

G25.1/4/6

Drug induced extrapyramidal syndrome/chorea/tics

2 (0.0)

15 (0.2)

18 (0.2)

13 (0.1)

407

G72.0

Drug induced myopathy

1 (0.0)

12 (0.1)

20 (0.2)

22 (0.2)

517

H91.0

Ototoxic hearing loss

U/C

I42.7

Drug induced cardiomyopathy

7 (0.1)

42 (0.4)

7 (0.1)

5 (0.1)

376

J70.2/3/4

Drug induced interstitial lung disorders

3 (0.0)

24 (0.2)

40 (0.4)

27 (0.3)

858

K71

Drug induced liver disease

12 (0.1)

315 (3.2)

50 (0.5)

71 (0.7)

3408

L56.0/1

Drug induced phototoxicity

1 (0.0)

2 (0.0)

0 (0.0)

M10.2

Drug induced gout

0 (0.0)

4 (0.0)

9 (0.1)

21 (0.2)

237

M32.0

Drug induced systemic lupus erythematosus

0 (0.0)

19 (0.2)

2 (0.0)

5 (0.1)

M34.2

Drug induced systemic sclerosis

U/C

N14

Drug induced nephropathy

0 (0.0)

3 (0.0)

5 (0.1)

3 (0.0)

111

T88.3

Malignant hyperthermia due to anaesthesia

2 (0.0)

0 (0.0)

T88.6

Drug induced anaphylaxis

19 (0.2)

326 (3.3)

130 (1.3)

87 (0.9)

883

T88.7

Unspecified adverse drug effect

80 (0.8)

565 (5.7)

203 (2.0)

217 (2.2)

2,471

Total

185 (1.9)

8200 (82.1)

821 (8.2)

776 (7.8)

132194

Table 6

Number of HES finished consultant episodes with an external ICD10 cause for an adverse drug reaction in 2004/05: mean age of admissions, age & gender distribution of episodes and total bed days

ICD-10

Male %

Mean age

Age 0–14 (%)

Age 15–59 (%)

Age 60–74 (%)

Age 75+ (%)

Total bed days

Y40

Antibiotics

467 (0.7)

2468 (3.7)

1433 (2.2)

2064 (3.1)

48,868

Y41

Other anti-infectives

48 (0.1)

776 (1.2)

245 (0.4)

362 (0.5)

9,280

Y42

Hormones

173 (0.3)