Prevalence of Missed Medication Doses and Outcomes of Hospitalized Patients Living with HIV in Uganda

Abstract

Background

Missed Medication Doses (MMD) are a common but preventable form of medication error that compromise treatment outcomes. Evidence on the burden and consequences of MMD among hospitalized people living with HIV (PLHIV) in Uganda remains limited.

Methods

We conducted a cross-sectional study at KNRH, Kampala, Uganda, reviewing medical records of PLHIV admitted to the infectious diseases unit between January 2022 and December 2023. Eligible files included treatment charts documenting prescribed and administered parenteral medications. Descriptive statistics summarized patient characteristics and prevalence of MMD. Associations between patient factors and MMD were assessed using chi-square tests and multivariable logistic regression. Outcomes examined included length of hospital stay, in-hospital mortality, and readmission.

Results

Of 814 records screened, 462 met the inclusion criteria. Patients were predominantly female (61.0%), with a mean age of 25.8 years (SD 14.4). Overall, 403 patients (87.2%; 95% CI: 84.1–90.0) experienced at least one MMD. Missed doses were common across nearly all medications, with omission rates exceeding 80% for ceftriaxone, paracetamol, metronidazole, omeprazole, metoclopramide, and levofloxacin, and approaching 100% for furosemide, co-amoxiclav, ondansetron, enoxaparin, albumin, and artesunate. Lower odds of MMD were independently associated with Luo ethnicity (aOR = 0.15, 95% CI: 0.03–0.59), separated marital status (aOR = 0.16, 95% CI: 0.03–0.73), and Muslim faith (aOR = 0.21, 95% CI: 0.07–0.61). Older age was associated with a modest increase in risk (aOR = 1.02 per year, p = 0.032). Length of hospital stay did not differ significantly between patients with and without MMD. Overall in-hospital mortality was high (69.0%) and was lower among patients with documented MMD compared to those without (p < 0.001).

Conclusion

Missed parenteral medication doses are highly prevalent among hospitalized PLHIV in Uganda. Strengthening medication administration and documentation systems is urgently needed to improve patient safety and outcomes.

Introduction

Globally, Missed Medication Doses (MMD) represent a major health challenge that reduces treatment effectiveness and worsens patient outcomes. The World Health Organization (WHO) recognizes the severe impact of medication errors, including missed medication doses, which cause substantial avoidable harm and cost billions of dollars annually.1 An MMD is a dose of medication that is overdue, meaning it was prescribed but not given to the patient as scheduled.2 In the United States, medication errors are a leading cause of death, ranking third behind heart disease and cancer, contributing to an estimated 1.3 million injuries annually.3 A recent report by the Institute of Medicine suggests that as many as 98,000 Americans die each year in hospitals due to missed medications, with most of these errors being preventable.4 This highlights the urgent need for improved medication safety measures.

Previous studies have demonstrated the prevalence and consequences of MMD. A study in England revealed that out of 18,664 scheduled medication doses for 444 inpatients across 27 wards over six data collection days, 14.6% (95% CI 14.1–15.1) were missed.5 Alarmingly, the rate of missed ‘time-critical’ medications reached 19.3% (95% CI 16.3–22.6%), and over a third (34.5%) of all omissions were deemed potentially preventable, emphasizing the need for interventions to improve medication administration processes. Parenteral medication errors, including missed doses, pose a significant risk to inpatients, particularly in resource-limited settings where corrective measures are often scarce.6 Research in Uganda has indicated that a significant proportion (25%) of inpatients diagnosed with malaria experience delays in receiving their initial doses of antimalarial medication,7 which has been associated with a substantial increase in the mean length of hospital stay by 95%. Missed medication doses can occur due to forgetfulness by healthcare providers, difficulties in administering medications, or drug unavailability, and they may result in increased hospital stay, morbidity, and mortality.8

Despite these findings, there is limited data on MMD among people living with HIV in Uganda, who often require multiple medications for comorbidities and opportunistic infections. This study aimed to assess the burden of missed medication doses and outcomes among inpatients living with HIV who experienced MMDs at Kiruddu National Referral Hospital (KNRH), thereby contributing to the body of literature on medication safety and patient outcomes in Uganda.

Materials and Methods

Study Design and Setting

The study employed a cross-sectional review of retrospective data to assess the outcomes of inpatients living with HIV with MMDs at KNRH. KNRH is located on Buziga Hill, in Makindye division along Salaama-Munyonyo road, one of the five administrative units of the Kampala Capital City Authority. KNRH is approximately 10 kilometers (6 mi) southeast of the central business district of the city. The KNRH HIV clinic has over 2,500 PLWH, and monthly, nearly 150 PLHIV are admitted with various conditions on the infectious disease unit.

Study Population

The study population comprised all records of PLHIV who were admitted to the Infectious Disease Unit at KNRH between January 2022 and December 2023.

Inclusion Criteria

All files of PLHIV admitted to the Infectious Disease Unit during the study period that contained complete treatment charts were eligible for inclusion.

Exclusion Criteria

Patient files of inpatients who were HIV positive but lacked a treatment chart and/or documented treatment outcomes were excluded from the study.

Sample Size Determination and Sampling Technique

A census of all eligible patient files was conducted. Out of 814 patient files initially reviewed, 462 met the inclusion criteria and were consecutively selected and enrolled in the study. This approach ensured that all eligible records were included, providing a complete sample for analysis.

Data Collection

The data for this retrospective study were collected by reviewing the medical records of all patients admitted to the Infectious Disease Unit at KNRH between January 2022 and December 2023. A pretested data abstraction tool was used to obtain the patient information and parenteral drug prescription and administration records from the files.

Study Outcomes

In this study, an MMD referred to any prescribed parenteral medication that was not administered or whose administration was not documented in the treatment records.

Not Missed

A dose was considered given if it was administered and documentation (signature, date, and time) was completed in the patient chart.

Missed

A dose was considered missed if it was prescribed, but there was no documentation of administration (signature, date, and time) in the patient records, regardless of whether the drug was actually given or not.

Treatment Outcomes

For this study, treatment outcome is categorized based on the patient’s status at the end of hospitalization:

1. Discharged – Patient completed admission and was discharged alive from the facility.

2. Death – Patient died during hospitalization.

3. Length of hospital stay – In this instance, this was the duration from the date of admission to discharge or death.

Data Analysis and Sample Size Estimation

Univariate Analysis

Data was cleaned, coded, and categorized according to the specific objectives and manually entered into Epidata software. Descriptive statistics were computed STATA to summarize each variable. Appropriate graphs and charts were generated for better interpretation of the findings.

Bivariate Analysis

Bivariate analysis was conducted to examine the association between the independent variables (patient-related factors associated with MMD) and the dependent variable (MMD). For categorical variables, the chi-square test (χ2) was used to assess the level of association. Cross-tabulations were generated to visualize these relationships. The statistical significance of the values was determined by the p-value at a 95% level of confidence, where a P-value equal to or less than 0.05 (P ≤ 0.05) was regarded as significant, indicating an association between the variables.

Multivariable Analysis

Multivariable analysis was performed to identify independent predictors of treatment outcomes (discharge or death), with MMD as the outcome variable, while controlling for potential confounding factors. Variables that demonstrated a statistically significant association at the bivariate level (p ≤ 0.05) were entered into a logistic regression model. Adjusted odds ratios (AOR) with their corresponding 95% confidence intervals (CI) were calculated to determine the strength and direction of associations. Statistical significance was considered at p ≤ 0.05.

Ethics Approval and Consent

Prior to the study, ethical approval was obtained from the Mildmay Uganda Research and Ethics Committee (MUREC) (Reference No. MUREC-2023-314). The study was conducted in accordance with the principles of the Declaration of Helsinki. Due to the minimal risk associated with the use of retrospective, anonymized data, a waiver of informed consent was granted by the ethics committee. Administrative approval for accessing and using patient records was also obtained from Kiruddu National Referral Hospital.

Results

Out of 814 patient files initially reviewed, 462 met the inclusion criteria for analysis. The exclusion of 356 files was mainly due to missing treatment charts or undocumented patient outcomes (discharge or death).

Characteristics of Study Participants

Of the 462 included, majority were female (61%, n = 280), with a mean age of 25.8 (SD of 14.4) years. Most patients were of Bantu ethnicity (n = 373, 81%), married (n = 125, 27%), Christian (n = 219, 47%), and informally employed (n = 173, 37%) (Table 1).

Table 1.

Characteristics of Study Participants

Variable	Category	Total (n)	Missed Medication Dose, n (%)	Did Not Miss Medication Dose, n (%)	p-value
Sex	Male	182	159 (87)	23 (13)	0.857
	Female	280	243 (86)	37 (14)
Tribe	Bantu	373	329 (88)	44 (12)	0.012
	Luo	19	13 (68)	6 (32)
Region	Rural	229	201 (88)	28 (12)	0.483
	Urban	214	183 (85)	31 (15)
Marital status	Married	125	110 (88)	15 (12)	0.023
	Separated	16	10 (63)	6 (37)
	Single	49	39 (80)	10 (20)
Religion	Christian	219	190 (87)	29 (13)	0.026
	Muslim	55	41 (74)	14 (26)
Level of education	Primary	4	3 (75)	1 (25)	0.376
	Secondary	24	22 (92)	2 (8)
	Tertiary	53	42 (80)	11 (20)
Employment	Formal	39	30 (76)	9 (24)	0.341
	Informal	173	149 (86)	24 (14)
	Unemployed	39	32 (82)	7 (18)
Age (Mean, SD)	—	462	25.8 ± 14.4	24.6 ± 13.0	0.345

Prevalence of Missed Medication Doses

Overall, 403 patients (87.2%) {95% CI: 84.1–90} had at least one missed medication dose, while 59 (12.8%) had no missed doses. Patients of Bantu ethnicity had a much higher proportion of missed doses (88%) compared to Luo patients (68%), p = 0.012 (Table 1). Similarly, separated patients had the lowest proportion of missed doses (63%), compared to 88% among married and 80% among single patients, p = 0.023. Further, missed doses were less common among Muslim patients (74%) compared to Christians (87%), p = 0.026.

Missed Doses by Drug Category

Ceftriaxone (total prescribed (n) = 272) and paracetamol (n = 180), two of the most frequently prescribed drugs, were missed in 89% and 90% of cases, respectively (Figure 1). Similarly, high omission rates were observed for other commonly used agents, including metronidazole (n = 146, 84%), omeprazole (n = 51, 94%), metoclopramide (n = 49, 88%), and levofloxacin (n = 49, 92%) Figure 1.

Figure 1.

Proportion of drug doses missed for specific medicines. n stands for number of doses prescribed.

Patient-Sociodemographic Factors Associated with Missed Medication Doses Among Inpatients Living with HIV at Kiruddu National Referral Hospital

At multivaribale analysis, tribe showed a strong independent association with missed medication. Compared to patients of Bantu origin, those from the Luo tribe had significantly lower odds of missing doses (adjusted OR = 0.15, 95% CI: 0.03–0.59, p = 0.007). Additionally, separated patients were less likely to miss doses compared to married patients (adjusted OR = 0.16, 95% CI: 0.03–0.73, p = 0.018). Religion emerged as another significant predictor. Muslim patients were less likely to experience missed doses than Christians (adjusted OR = 0.21, 95% CI: 0.07–0.61, p = 0.004). Finally, age was also a significant predictor: for every one-year increase in age, the odds of missing a dose increased by approximately 2% (OR = 1.02, 95% CI: 0.97–1.07, p = 0.032) (Table 2).

Table 2.

Showing the Patient-Sociodemographic Factors Associated with Missed Medication Doses Among Inpatients Living with HIV

Variable	Unadjusted Results		Adjusted Results
	95% CI	P-value	95% CI	P-value
Sex
Female	1		1
Male	1.05 (0.61 1.83)	0.857	1.33(0.48 3.69)	0.576
Tribe
Bantu	1		1
Luo	0.28 (0.11 0.81)	0.017	0.15(0.03 0.59)	0.007
Region
Rural	1
Urban	0.82 (0.47 1.42)	0.485
Marital Status
Married	1		1
Separated	0.22 (0.07 0.71)	0.011	0.16(0.03 0.73)	0.018
Single	0.53 (0.22 1.28)	0.159	1.11 (0.29 4.15)	0.872
Religion
Christian	1		1
Moslem	0.45(0.21 0.92)	0.029	0.21(0.07 0.61)	0.004
Level of education
Primary	1
Secondary	3.66 (0.25 53.83)	0.343
Tertiary	1.27(0.12 13.46)	0.841
Days of hospital stay	1.00 (0.98 1.02)	0.699
Employment
Formal	1
Informal	1.86(0.78 4.40)	0.157
Unemployed	1.37(0.45 4.14)	0.576
Age	1.00(0.98 1.02)	0.560	1.02(0.97 1.07)	0.032

Outcomes of Inpatients Living with HIV with Missed Medication Doses

The mean duration of hospital stay was comparable between patients with missed doses (9.9 ± 20.9 days) and those without (8.7 ± 9.0 days), with no statistically significant difference (p = 0.685). Overall, 301 (69.0%) patients died during admission. Mortality was lower among those with MMD (61.9%, number who died, n = 249) compared to those who did not miss medication (85.2%, n = 52), p < 0.001. There was no difference in the rates of readmission among those with MMD (6.5%, 26/402) and without MMD (1.7%, 1/60), p = 0.154.

Discussion

The most striking finding of this study was the very high prevalence of MMD, with approximately 87.0% of hospitalized people living with HIV experiencing at least one missed parenteral dose. This figure suggests a significant challenge in medication administration and documentation by nurses within this inpatient population. Such a high rate of missed doses can have serious clinical implications, potentially leading to treatment failure, drug resistance, increased viral load, disease progression, and a greater risk of opportunistic infections9. However, given the reliance on paper-based medication charts during the study period, we consider incomplete or inconsistent documentation to be a major contributor to the apparent burden of MMD. Similar to our results, Kiguba et al conducted a prospective cohort at Mulago National Referral Hospital and similarly reported extensive antibiotic use, but with frequent under-administration and missed-dose days (44%),10 particularly for ceftriaxone, metronidazole, and ciprofloxacin.10

Together with our results, these data underscore the systemic challenges in Uganda’s tertiary hospitals, including drug stock-outs, high medication costs, inadequate documentation, and heavy reliance on parenteral formulations, which compound the risk of missed or delayed therapy.11,12

The multivariable analysis identified several socio-demographic factors significantly associated with the likelihood of missed parenteral medication doses. Individuals from the Luo tribe were significantly less likely to miss medication doses compared to those from the Bantu tribe. This suggests that tribal affiliation is an independent factor influencing medication administration among HIV positive inpatients but the reasons are unclear. Nevertheless, ethnicity is known to increase risk of MMD through implicit bias, language and cultural barriers as well as differences in socioeconomic position between tribes.13 Importantly, medications in this setting are administered by hospital staff, and the data did not capture caregiver involvement, socioeconomic status, or other behavioural modifiers. As such, these findings should not be interpreted as evidence of differential treatment but rather as associations that may reflect unmeasured structural or contextual factors such as communication barriers, implicit bias, or documentation practices.

It was also determined that separated individuals were significantly less likely to miss medication doses compared to married individuals (Odds Ratio = 0.16, P = 0.018). This finding warrants further exploration, as it deviates from common assumptions that single or separated individuals might have less support. It could indicate a higher degree of personal agency or different coping mechanisms in managing their health within the hospital environment. Muslims were significantly less likely to miss medication doses compared to Christians (Odds Ratio = 0.21, P = 0.004). Similar to tribal affiliation, religious practices or community structures might provide a supportive framework that indirectly contributes to more consistent medication administration. A previous study at our study site showed that Muslims have significantly varied antibiotic medication practices compared to non-Muslims.11 Conversely, older age was significantly associated with higher odds of missing medication doses (Odds Ratio = 1.02, P = 0.0318), indicating that with each increasing year of age, there is a slight increase in the odds of missing medication doses. This is a common finding in healthcare, often attributed to age-related cognitive decline, polypharmacy, increased dependency on nursing staff, or communication barriers that may hinder effective medication administration.14

The above findings are consistent with a study done in Canada where age, and the marital status of patients including the number of medication they were receiving was found to contribute to the patients risk of missing medication doses.15 This findings suggest the need for further qualitative or observational research to better understand these findings.

At first glance, the lower mortality among patients with missed doses appears counterintuitive. The counterintuitive finding of lower mortality among patients with documented missed medication doses is most plausibly explained by methodological rather than biological factors.16 First, confounding by severity may have occurred: critically ill patients are often prioritized for prompt administration of medicines, appearing in the “no-missed” group but nevertheless experiencing higher mortality due to their underlying condition. Second, a reversed form of the healthy-adherer (or healthy-user) bias may be operating, whereby more stable patients who inherently have a better prognosis are more likely to accumulate missed or undocumented doses without adverse consequences. Third, misclassification and documentation bias is highly likely in our paper-based system, as doses may have been administered but not signed off, artificially inflating the “missed dose” category among survivors. Fourth, immortal time (survivor) bias could occur because patients must survive long enough to accumulate missed-dose events; those who die early are automatically classified as having no omissions, inflating mortality in the “not-missed” group.

Furthermore, some frequently missed medications, such as paracetamol, may have been prescribed on a PRN basis or perceived as less critical to immediate survival, although prescription indications were not captured in the dataset. Meanwhile, certain drugs are more frequently missed because they are not always readily available in the hospital, requiring patients to purchase them, which may not be affordable. Additionally, medications that are less commonly prescribed may show higher percentages of missed doses when they are omitted, even though the absolute number of missed doses is small. These factors underscore the need for cautious interpretation of mortality findings.

Revised Study Limitations

Our results should be interpreted in the context of some limitations. First, its retrospective, chart-review design relied on paper-based medication records, making it difficult to distinguish true missed doses from undocumented administrations and thus introducing potential misclassification bias. Second, incomplete documentation led to the exclusion of a substantial proportion of reviewed files, which may have resulted in underestimation of the true burden of missed medication doses. Thirdly, because indicators of disease severity at admission were not documented, residual confounding by severity may explain some associations, particularly the lower mortality observed among patients with missed doses. Forth, the single-centre design at Kiruddu National Referral Hospital limits generalisability to other facilities, especially those with different staffing levels, drug supply chains, or electronic medication systems. However, the results seem to be comparable to findings from another national referral hospital in Uganda7 - indicating generalizability to the Ugandan context. Fifth, our analysis focused only on parenteral medications, so the effect of missed oral or non-parenteral therapies on patient outcomes was not assessed but potentially relevant. Finally, as a cross-sectional review of routinely collected data, we could not establish temporal or causal relationships between missed doses and outcomes such as mortality or readmission.

Conclusion

This study demonstrates an alarmingly high prevalence of missed parenteral medication doses among hospitalized PLWH at a national referral hospital in Uganda, affecting both critical and supportive therapies. Although we observed a paradoxically lower mortality among patients with documented missed doses, this likely reflects confounding, documentation bias, and survivor effects rather than a true protective impact. Importantly, several patient-associated factors were independently linked to missed doses: lower odds among Luo ethnicity, separated marital status, and Muslim faith, and a small increase in risk with advancing age. Taken together with prior Ugandan evidence on antibiotic under administration, our findings underscore that missed or undocumented doses are a pervasive system-level challenge. Addressing the root causes such as inadequate documentation, drug stock outs, heavy nursing workloads, and delayed parenteral to oral switches will be essential to improving medication safety, reducing preventable harm, and strengthening quality of care for PLWH.

Funding Statement

This work was supported by Government of Uganda through Kiruddu National Referral Hospital Seed Grant Scheme. The findings and conclusions in this manuscript are those of the author(s) and do not necessarily represent the official position of the funding agencies.

Abbreviations

MMD, Missed medication doses; PLWHIV, People Living With HIV; KNRH, Kiruddu National Referral Hospital; WHO, World Health Organisation.

Data Sharing Statement

Datasets used in this analysis are available from the corresponding author upon reasonable request.

Disclosure

The authors do not have any conflict of interest to declare for this work.