Study Design and Site
This study is based on data of SCD patients registered at MSC. The cohort was established in the year 2004 by the Muhimbili National Hospital (MNH) in collaboration with Muhimbili University of Health and Allied Sciences (MUHAS), the oldest and largest biomedical university in Tanzania. The MSC was established to provide a clinical spectrum of sickle cell disease, identify causes of morbidity and mortality and to develop strategies for appropriate interventions.
Study population
Muhimbili National Hospital has an existing health service with dedicated SCD clinics for children and adults. In 2004, this framework was used to develop a platform for the integrated approach called Muhimbili Sickle Cell Cohort (MSC). Between March 2004 and March 2016, a total of 8484 individuals were seen and given unique demographic identity numbers. Screening for SCD was done by the sickling test, which uses sodium metabisulphite. A total of 5476 (64%) individuals were confirmed HbSS, 2121 (25%) with sickle cell trait (HbAS) and 897 (11%) had normal hemoglobin pattern (HbAA). Apart from a few patients with S/β-thalassemia, more than 99% of patients have homozygous (SS) SCD. Individuals who were confirmed to have SCD were enrolled in the MSC. The registered patients were assigned a unique SCD identification number.
Cohort Description
From the inception of MSC (2004) up to 2016 around 5476 (figure 1), sickle cell patients were enrolled at Muhimbili sickle cell cohort (MSC). Out of the total registered patients, 2797 (51.08%) were males while females were 2679 (48.92%) as shown in Table 1. The minimum age at registration was less than 1 year 402(7.34%) while the majority of registered patients were children between 5 to 17 years old (45.38%). Regarding the place of birth, most of the enrolled patients were born in the Coastal regions (72.92) which include Dar es Salaam. Out of 366 reported deaths (figure 1), children under five years were 36.34%while those between 5-17 years were 45.35%.
Table 1: Demographics Characteristics of SCD patients who were enrolled at Muhimbili Sickle Cohort
|
Total
|
All SCD
|
5476
|
Age groups
|
|
0-4
|
2294(41.89%)
|
5-17
|
2485 (45.38%)
|
18+
|
680 (12.42%)
|
Gender
|
|
Female
|
2679 (48.92%)
|
Male
|
2797 (51.08%)
|
Place of Birth
|
|
Coastal Regions
|
3993(72.92%)
|
Others
|
1476 (26.95%)
|
Missing
|
7 (0.13%)
|
Fig.2 shows the annual trend of enrollment and loss to follow-up patterns from 2004 to 2016. The highest number of registration was done at the beginning of the study (2004) while loss to follow up events appears to be increasing as time goes with a maximum peak in 2015. During this year, SCD patients were referred to government hospitals to attend SCD clinics away from the MSC at MNH. In our analysis, we considered visits up to 2014 since people who are referred to other hospitals cannot be categorized as loss to follow-up. The number shown at the top of the blue bars present the total number of lost to follow-up events at each respective year. The line on the top of the bar plot represents a cumulative enrollment of SCD patients from 2004 to 2016.
Sampling
A total of 5476 patients were confirmed of their HbSS status and were enrolled at MSC between 2004 to 2016. Three sets of data were collected; one on visit dates and demographic information, clinical results (patient's routine checks) and test results (hematological parameters). The three datasets were merged based on the unique demographic id, visit id and visit date.
It should be noted that clinical and hematological information was not taken at every clinic visit, some visits only recorded basic information. Hence during data merge, we found missing values that were taken care with missing values techniques. Patients were divided into two groups; active (not missing clinics more than nine-month between consecutive clinics) and inactive (miss clinics more than months between consecutive clinics and did not attend clinic for the last 9 months with reference to 30/12/2016). As shown in Fig.1, a total of 3183 (58.13%) were actively participating in the clinic while 2293 were inactive due to reasons like they are deceased or dropping out of the study. From the inactive group, 366 (6.68%) were identified as deceased and 1925 (35.19%) classified as LTFU.
Study Outcome and exposure
The primary outcome was loss to follow-up (LTFU) event, which was defined as no clinic attendance for at least nine months with reference to the patient's previous clinic attendance date. This was decided based on a practice of 3-6 months between clinic appointments.
Data management and analysis
Data from the MSC collected between the years 2004-2016 was used in this analysis. The investigation was done using R Studio 1.2.5033 and Microsoft Excel spreadsheets. Survival analysis techniques, both non-parametric methods (Kaplan-Meier estimator and Log-rank test) and semi-parametric method (Cox’s proportional hazard model) were used. A P-value cutoff of 0.05 was used to ascertain the statistical significance of the obtained results.
Analysis assumptions
The following analysis assumptions were used in our study. SCD patient who did not attend clinic for more than nine months with reference to the previous clinic attendance date was classified as LTFU. Time in the study was taken as a difference between the first clinic attendance date and the last day. For the analysis we have used an event record that is close to the last attendance date for the patient while age was calculated twice at registration and at the time of LTFU event which was used for the analysis. Furthermore, patients who were reported dead and those who were present in the last window of nine-month (a reference to 30/12/2016) were censored. All survival times were assumed independent and censoring occurred at the right censor.