Patient Recruitment and Study Design
The study was initiated after obtaining ethics committee approval (2019/1455) from the ethics committee of Istanbul University, Istanbul Faculty of Medicine. Patients were recruited from all adult patient clinics in Istanbul Faculty of Medicine Hospital which is the biggest tertiary university hospital in Istanbul, following approval from heads of departments. A simple application of computation which automatically subtracts serum albumin from serum total protein level was integrated to the hospital computer operating system. It computes the CG value in all patients whose serum total protein and albumin levels were measured due to any reason in the central biochemistry laboratory. Technicians working in the biochemistry laboratory informed the Immunology and Allergic Diseases Division daily about all the patients with a CG value between 1.5-2.5 g/dL for further evaluation. The patients were given detailed information about the study by phone and asked if they wished to become a study participant. Patients who agreed to participate in the study and signed the written informed consent forms were invited to the Immunology and Allergic Diseases outpatient clinic to provide further clinical information. Inpatients who gave consent to participate in the study were visited on the wards. Patients who did not give informed consent, those on intravenous fluids replacement and those under the age of 18 were excluded from the study. Further analyses of IgG, IgM, IgA levels and protein electrophoresis were performed on the study participants’ remaining serum samples which were kept in the biochemistry laboratory. If there were no remaining suitable serum samples for further analysis, patients were asked for donation of venous blood samples. The patients who did not have remaining suitable serum samples and did not want to donate serum samples were excluded from the study.
Fifty patients were planned to be included for each level of CG at 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4 and 2.5 g/dL. Therefore, in order to reach 550 volunteers, 686 patients were interviewed. Since 82 of these patients did not give informed consent after receiving detailed study information, they were excluded. Fifty-four patients were also excluded from the study since their blood samples were unsuitable for laboratory tests (Figure 1).
Age, gender and clinical features, comprising of clinics which follow-up the patients, current diseases, drugs used, frequency of antibiotic use, need for parenteral antibiotics, infections in the medical history and infection frequency of the total 550 patients were recorded in the assessment forms.