American Geriatrics Society-Beers Criteria and adverse drug reactions: a comparative cross-sectional study of Nigerian and South African older inpatients

Figures & data

Figure 1 Flowchart depicting the selection process of the included older persons.

Abbreviation: ICU, intensive care unit.

Table 1 Characteristics of the older persons investigated in the study

Variable	Grouping	Nigeria, n (%)	South Africa, n (%)	P-value
Age (mean ± SD)		70.53±8.22 years	69.49±7.64 years	0.10
Age classification	60–69 years	135 (50.4)	196 (57.8)
	70–79 years	93 (34.7)	102 (30.1)	0.29
	80–89 years	31 (11.6)	34 (10.0)
	≥90 years	9 (3.3)	7 (2.1)
Gender	Female	122 (45.5)	188 (55.5)
	Male	146 (54.5)	151 (44.5)	0.02
Marital status	Single	109 (40.7)	190 (56.0)
	Married	159 (59.3)	149 (44.0)	<0.001
Comorbidity index (mean ± SD)		3.82±1.21	4.68±2.14	<0.001
Patients’ comorbidity index	<4.0	104 (38.8)	115 (33.9)
	≥4.0	164 (61.2)	224 (66.1)	0.21
Comorbidity	Circulatory system	111 (41.4)	64 (18.5)
	Endocrine system	10 (3.7)	47 (13.8)
	Musculoskeletal system	23 (8.6)	32 (9.4)	0.93
	Neoplasm	24 (9.0)	74 (21.8)
	Genitourinary system	22 (8.2)	28 (8.3)
	Digestive system	18 (6.7)	16 (4.7)
	Infectious diseases	23 (8.6)	17 (5.0)
	Othersa	37 (13.8)	61 (18.0)
Mean duration of hospital stay (mean ± SD)		11.47±13.31 days	7.30±6.5 days	<0.001
Duration of hospital stay	2–9 days	179 (66.8)	245 (72.3)
	10–19 days	55 (20.5)	78 (23.0)
	20–29 days	18 (6.7)	13 (3.8)	0.005
	≥30 days	16 (6.0)	3 (0.9)

Note:

a Other systems include skin, respiratory, nervous, mental, and behavioral, eye diseases and diseases affecting more than 1 system.

Table 2 The classification of PIM received by the older persons in Nigeria and South Africa

Pharmacological classification	ATC classification	Nigeria, n (%)	South Africa, n (%)
Antidepressants	N06A	8 (9.3)	10 (9.8)
Opioids	N02A	10 (11.6)	1 (1.0)
Antidiabetics	A10	4 (4.7)	27 (26.5)
Antihistamine (systemic use)	R06A	1 (1.2)	8 (7.8)
Anti-inflammatory, antirheumatic, NSAIDs	M01A	19 (22.1)	24 (23.5)
Psychoanaleptics	N06CA01	2 (2.3)	0 (0.0)
Psycholeptics	N05	6 (7.0)	6 (5.9)
Cardiovascular agents	C	34 (39.5)	11 (10.7)
Drugs for gastrointestinal disorders	A03	2 (2.3)	15 (14.7)
Total		86 (100.0)	102 (100.0)

Abbreviations: ATC, Anatomical Therapeutic Chemical; PIM, potentially inappropriate medicine.

Table 3 The triggers for identifying suspected ADRs

Trigger	Nigeria, n (%)	South Africa, n (%)
Decreased glucose level <50 mg/dL	6 (2.2)	11 (3.2)
Serum creatinine rising twice over baseline	3 (1.1)	6 (1.8)
Use of antiemetics	18 (6.7)	26 (7.7)
Over sedation	4 (1.5)	12 (3.5)
Abrupt stoppage of medication	18 (6.7)	12 (3.5)
Potassium level below 2.5 mmol/L	7 (2.6)	11 (3.2)
Potassium above 5.1 mmol/L	6 (2.2)	2 (0.6)
Sodium level below 135 mmol/L	1 (0.4)	4 (1.2)
Othersa	4 (1.5)	2 (0.6)
No trigger found	201 (75.0)	253 (74.6)
Total	268 (100.0)	339 (100.0)

Note:

a Not all triggers identified are true ADRs.

Abbreviation: ADRs, adverse drug reactions.

Table 4 The ADRs and the offending medications among older persons

Systems affected by the ADRs	Nigeria, n (%)	Offending medication	South Africa, n (%)	Offending medications
Digestive system	22 (51.2)		9 (24.3)
Constipation	7	Chlorpromazine (1), tramadol (3), diclofenac (2), amitriptyline (1)	1	Metoclopramide (1)
Vomiting	5	Tramadol (1), pentazocine (2), atorvastatin (1), digoxin (1)	2	Ciprofloxacin (1), tramadol (1)
Diarrhea	5	Ceftriaxone (2), isoniazid (1), lisinopril (1), diclofenac (1)	–	–
GIT bleeding	5	Diclofenac (4), aspirin (1)	5	Ibuprofen (5)
Hepatitis	–	–	1	Rifafour (1)
Vascular system	10 (23.3)		8 (21.6)
Hyperkalemia	5	Lisinopril (3), digoxin (2)	1	Furosemide (1)
Hypotension	3	Methyldopa (2), nifedipine (1)	3	Amiodarone (1), morphine (1), prazosin (1)
Epistaxis	1	Warfarin	1	Warfarin (1)
Thrombocytosis	1	Heparin	–	–
High blood pressure	–	–	1	Pantoprazole (1)
Hypokalemia	–	–	1	Hydrochlorothiazide (1)
Hyponatremia	–	–	1	Enalapril (1)
Endocrine system	3 (7.0)		4 (10.8)
Hypoglycemia	3	Insulin (3)	3	Insulin (2), insulin sliding scale (1)
Metabolic change	–	–		Metformin (1)
Genitourinary system	2 (4.7)		1 (2.7)
AKI	1	Diclofenac	1	Herbal medicine (1)
Urinary retention	1	Timolol	–	–
Nervous system	5 (11.6)		9 (24.3)
Encephalopathy	1	Furosemide	–	–
Fall	1	Tramadol	–	–
Gait impairment	1	Amitriptyline	–	–
Complex partial seizure	1	Chlorpromazine	–	–
Sedation	1	Bromazepam	3	Midazolam + fentanyl (1), lorazepam (1), dormicum (1)
Confusion	–	–	6	Haloperidol (1), morphine (1), adrenaline (1), risperidone (2), tramadol (1)
Cutaneous (skin)	1 (2.3)		0 (0.0)
Stephen Johnson syndrome	1	Spironolactone	–	–
Total	43 (100.0)		31 (100.0)

Abbreviations: ADRs, adverse drug reactions; AKI, acute kidney injury; GIT, gastrointestinal tract.

Table 5 The univariate and multivariate analysis of independent variables and ADRs in Nigeria and South Africa

Location	Variable	Grouping	No ADR	ADR	Univariate analysis		Multivariate analysis
					Crude OR (95% CI)	P-value	Adjusted OR (95% CI)	P-value
Nigeria	Age group	60–79 years	195 (72.8)	33 (12.3)
		≥80 years	36 (13.4)	4 (1.5)	0.66 (0.22–1.97)	0.45	–	–
	Gender	Female	104 (38.8)	18 (6.7)
		Male	127 (47.4)	19 (7.1)	0.86 (0.43–1.73)	0.68	–	–
	Age-comorbidity index	<4.0	85 (31.7)	19 (7.1)
		≥4.0	146 (54.5)	18 (6.7)	0.55 (0.27–1.11)	0.09	–	–
	Chronic diseases	Nonurinary	217 (81.0)	35 (13.1)
		Urinary	14 (5.2)	2 (0.7)	0.89 (0.19–4.07)	1.00	–	–
		Nonmusculoskeletal	218 (81.3)	27 (10.1)
		Musculoskeletal	13 (4.9)	10 (3.7)	6.21 (2.48–15.50)	<0.001*	5.45 (2.13–13.95)	<0.001**
	Medicine utilization	No PIM	160 (59.7)	22 (8.2)
		PIM	71 (26.5)	15 (5.6)	1.54 (0.75–3.14)	0.24	1.48 (0.70–3.17)	0.31
		Nonpsychoanaleptic	225 (84.0)	33 (12.3)
		Psychoanaleptics (N06CA01)	6 (2.2)	4 (1.5)	4.54 (1.22–16.96)	0.04*	2.85 (0.60–13.47)	0.19
		Non-NSAIDs	216 (80.6)	33 (12.3)
		NSAIDs (M01A)	15 (5.6)	4 (1.5)	1.75 (0.55–5.56)	0.49	–	–
	Duration of hospital stay	<12 days	157 (58.6)	19 (7.1)
		≥12 days	74 (27.6)	18 (6.7)	2.01 (1.00–4.05)	0.048*	1.76 (0.84–3.68)	0.13
South Africa	Age	60–79 years	270 (79.6)	28 (8.3)
		≥80 years	38 (11.2)	3 (0.9)	0.76 (0.22–2.63)	0.66	–	–
	Gender	Female	166 (49.0)	22 (6.5)
		Male	142 (41.9)	9 (2.6)	0.48 (0.21–1.07)	0.07	–	–
	Age-comorbidity index	<4.0	105 (31.0)	10 (2.9)
		≥4.0	203 (59.9)	21 (6.2)	1.09 (0.49–2.39)	0.84	–	–
	Chronic diseases	Nonurinary	278 (82.0)	29 (8.6)
		Urinary	30 (8.9)	2 (0.6)	0.64 (0.15–2.81)	0.75	–	–
		Nonmusculoskeletal	277 (81.7)	30 (8.9)
		Musculoskeletal	31 (9.1)	1 (0.3)	0.30 (0.04–2.26)	0.21	0.30 (0.04–2.27)	0.24
	Medicine utilization	No PIM	216 (63.7)	21 (6.2)
		PIM	92 (27.1)	10 (2.9)	1.12 (0.51–2.47)	0.78	1.09 (0.48–2.49)	0.83
	Drug classification	Nonpsychoanaleptics	299 (88.2)	30 (8.8)
		Psychoanaleptics (N06CA01)	9 (2.7)	1 (0.3)	1.11 (0.14–9.04)	1.00	1.05 (0.12–9.23)	0.97
		Non-NSAIDs	286 (84.4)	29 (8.5)
		NSAIDs (M01A)	22 (6.5)	2 (0.6)	0.90 (0.20–4.00)	0.89	–	–
	Duration of hospital stay	<12 days	238 (70.2)	24 (7.1)
		≥12 days	70 (20.6)	7 (2.1)	0.99 (0.41–2.40)	0.98	1.01 (0.42–2.46)	0.98

Notes:

* Significant P-value estimated by Chi-squared test.

** Significant value estimated by logistic regression Hosmer-Lemeshow test for goodness of fit. χ²=0.87, df=3, P=0.83 (Nigeria), χ²=0.83, df=3, P=0.84 (South Africa).

Abbreviations: ADR, adverse drug reaction; PIM, potentially inappropriate medicine.

Table S1 PIM utilization among participants in Nigeria and South Africa

PIM	Nigeria, n (%)	South Africa, n (%)
Digoxin	16 (18.6)	9 (2.7)
Amitriptyline	8 (9.3)	10 (2.9)
Pentazocine	7 (8.1)	1 (0.3)
Glibenclamide	4 (4.6)	3 (0.9)
Chlorpheniramine	1 (1.2)	7 (2.1)
Ibuprofen	1 (1.2)	22 (6.5)
Diclofenac	17 (19.8)	0 (0.0)
Diazepam	3 (3.5)	0 (0.0)
Bromazepam	2 (2.3)	0 (0.0)
Dextropropoxyphene	1 (1.2)	0 (0.0)
Methyldopa	7 (8.1)	0 (0.0)
Metoclopramide	1 (1.2)	0 (0.0)
Amiodarone	0 (0.0)	1 (0.3)
Hyoscine	0 (0.0)	15 (4.4)
Risperidone	0 (0.0)	6 (1.8)
Insulin sliding scale	0 (0.0)	21 (6.2)
Amiodarone and digoxin	1 (1.2)	1 (0.3)
Chlorpromazine and metoclopramide	1 (1.2)	0 (0.0)
Diclofenac and pentazocine	1 (1.2)	0 (0.0)
Digoxin and bromazepam	1 (1.2)	0 (0.0)
Amitriptyline and insulin sliding scale	0 (0.0)	1 (0.3)
Ibuprofen and promethazine	0 (0.0)	1 (0.3)
Insulin sliding scale and glibenclamide	0 (0.0)	1 (0.3)
Insulin sliding scale, digoxin, and amiodarone	0 (0.0)	1 (0.3)
Digoxin, amiodarone, and methyldopa	1 (1.2)	0 (0.0)
PIM due to disease condition
Tramadol (history of fall without fracture)	1 (1.2)	0 (0.0)
PIM based on kidney function
Spironolactone (Crcl <30 m L/min)	1 (1.2)	0 (0.0)
PIM due to DDI
Lisinopril + Amiloride	8 (1.2)	0 (0.0)
Amitriptyline + Chlorpromazine	2 (1.2)	0 (0.0)
Hyoscine + Chlorpheniramine	0 (0.0)	1 (0.3)
NSAIDs + Prednisolone	1 (1.2)	1 (0.3)
Total	86 (100.0)	102 (100.0)

Abbreviations: DDI, drug-drug interaction; Crcl, creatinine clearance; PIM, potentially inappropriate medicine.

Table S2 Potential inappropriate medicines that resulted in ADRs among study participants

PIM in Nigeria	n (%)	PIM in South Africa	n (%)
Diclofenac	3 (20.0)	Ibuprofen	2 (20.0)
Tramadol	1 (6.7)	Tramadol	2 (20.0)
Pentazocine	2 (13.3)	Insulin sliding scale	4 (10.0)
Steroid + Tramadol + Aspirin (>325 mg)	1 (6.7)	Prazosin	1 (10.0)
Amitryptiline	2 (13.3)	Lorazepam	1 (10.0)
Chlorpromazine	2 (13.3)	–	–
Methyldopa (antihypertensive)	2 (13.3)	–	–
Digoxin	1 (6.7)	–	–
Bromazepam	1 (6.7)	–	–
Total	15 (100.0)	Total	10 (100.0)

Abbreviations: ADRs, adverse drug reactions; PIM, potentially inappropriate medicine.