The effect of prescription patterns on the performance of the pharmacy department of a Regional Referral Hospital, Uganda.

Background: Poor drug prescription patterns (PP) result in irrational medicine use, avoidable stock outs and drug expiries. Objective: This study primarily assessed the effects of PP on the performance of the pharmacy department (PD) of Mbarara Regional Referral Hospital (MRRH) Uganda. Methods: This was a mixed method cross-sectional study conducted in the outpatient department (OPD) of MRRH, questionnaires were administered to 86 prescribers and 300 patient prescriptions were reviewed. Ethical clearance was granted and informed consent of patients. Data were analysed, presented in the form of graphs, tables. Results: The overall prescription fill rate was 60.5%, being higher among dental officers and lower among those who did not adhere to generic prescribing and EML. Medical officers made most prescriptions at 69.3%. Prescriptions with four (47.1%) and six (17.5%) medicines respectively were made by clinical officers. Of the 300 prescriptions, 76% adhered to the Essential Medicines List (EML), 62% used generic name including 87.3% from dental officers and 52.9% by clinical officersThe overall prescription fill rate was 60.5%, being higher among dental officers and lower among those who did not adhere to generic prescribing and EML. Medical officers made most prescriptions at 69.3%. Prescriptions with four (47.1%) and six (17.5%) medicines respectively were made by clinical officers. Of the 300 prescriptions, 76% adhered to the Essential Medicines List (EML), 62% used generic name including 87.3% from dental officers and 52.9% by clinical officers. Conclusion: Prescription pattern affected the performance of the PD of MRRH, calling for its continued monitoring to ensure that guidelines are upheld, EML and UCG are availed and utilized.

Prevalence and factors associated with sputum smear non-conversion after two months of tuberculosis treatment among smear-positive pulmonary tuberculosis patients in Rwanda: a cross-sectional study.

BACKGROUND: Non-conversion of sputum smear prolongs the infectivity of pulmonary tuberculosis patients and has been associated with unfavorable tuberculosis (TB) treatment outcomes. Nevertheless, there is a limited evidence on predictors of sputum smear non-conversion among smear-positive PTB (SPPTB) patients in Rwanda. Therefore, this study aimed to determine the factors associated with sputum smear non-conversion after two months of treatment among SPPTB patients in Rwanda. METHODS: A cross-sectional study was conducted among SPPTB patients registered in the national electronic TB reporting system by all health facilities countrywide (Rwanda) from July 2019 to June 2021. Eligible patients who had completed the first two months of anti-TB treatment and with smear results at the end of the second month of treatment were included in the study. Bivariate and multivariate logistic regression analyses were done using STATA version 16 to determine the factors associated with sputum smear non-conversion. Adjusted odds ratio (OR), 95% confidence interval (CI), and p-value < 0.05 was considered statistically significant. RESULTS: This study included 7,211 patients. Of them, 632 (9%) patients had sputum smear non-conversion at the end of the second month of treatment. In multivariate logistic regression analysis, age groups of 20-39 years (AOR = 1.7, 95% CI: 1.0-2.8) and 40-59 years (AOR:2, 95% CI: 1.1-3.3), history of first-line TB treatment failure (AOR = 2, 95% CI: 1.1-3.6), follow-up by community health workers(CHWs) (AOR = 1.2, 95% CI: 1.0-1.5), BMI < 18.5 at TB treatment initiation (AOR = 1.5, 95% CI: 1.2-1.8), and living in Northern Province of Rwanda (AOR = 1.4, 95% CI: 1.0-2.0), were found to be significantly associated with sputum smear non-conversion after two months of treatment. CONCLUSION: Sputum smear non-conversion among SPPTB patients remains low in Rwanda compared to countries of similar health care setting. Identified risk factors for sputum smear non-conversion among SPPTB patients in Rwanda were age (20-39 years, 40-59 years), history of first-line TB treatment failure, follow up by CHWs, BMI < 18.5 at TB treatment initiation and residence (Northern province).

Implementation of a Brazilian Cardioprotective Nutritional (BALANCE) Program for improvement on quality of diet and secondary prevention of cardiovascular events: A randomized, multicenter trial

Background Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized. Objectives This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PRE dicting bleeding Complications in patients undergoing stent Implantation and Sub sequent Dual Anti Platelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting. Methods Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT. Results Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: −3.86%; 95% confidence interval: −7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: −1.14%; 95% confidence interval: −2.26 to −0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity. Conclusions Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT. (AU)

Use of an online medical database for clinical decision-making processes: assessment of knowledge, attitude, and practice of oral health care providers.

Purpose: This study was conducted to determine the level of knowledge, attitude, and practice of oral health care providers toward the use of online medical databases for clinical decision-making processes. Subjects and methods: The study population included all the licensed oral health care providers living in Rwanda, registered either with the Rwanda Allied Health Professional Council (RAHPC) or Rwanda Medical and Dental Council (RMDC). A self-administered questionnaire was used to collect demographic data as well as data regarding knowledge, attitude, and practice of oral health care providers regarding the use of online medical databases for making clinical decisions. A pilot study with 12 oral health care providers was done before the main study to pretest the questionnaire. Results: The study results show that among the 201 respondents, 80% (N=160) reported using internet-based resources to support their clinical decisions, while 20% (N=41) of oral health care providers do not use online resources when making their clinical decisions. In general, there was a positive attitude towards internet-based resources among the participants, as 92% (N=184) respondents believe that internet-based resources are helpful in clinical decision-making processes. Of clinical importance, 68% respondents (N=136) believe that by using current internet-based information, better clinical care can be offered to their patients. Conclusion: Educating oral health care providers on the useful and appropriate online resources available for supporting clinical decision-making processes might increase the efficiency of patient care.

Successful Steroid Therapy for Lipoid Pneumonia Developing After Allogeneic Hematopoietic Stem Cell Transplant: A Case Report.

Lipoid pneumonia is an uncommon noninfectious inflammatory lung disease characterized by lipid deposition in the alveoli, and its etiology and treatment have not been elucidated. We report the case of a 32-year-old woman who developed lipoid pneumonia 9 months after allogeneic hematopoietic stem cell transplant for chronic myelogenous leukemia in lymphoid blast crisis. She complained of progressive cough and dyspnea shortly after discontinuation of immunosuppressive therapy given for graft-vs-host disease. Computed tomography demonstrated diffuse ground-glass opacities in the lungs, and pulmonary function test revealed restrictive impairment. Bronchoalveolar lavage fluid showed milky appearance, and transbronchial lung biopsy specimen revealed foamy macrophages infiltrating the alveoli. Based on these findings, she was diagnosed as having lipoid pneumonia. Prednisolone (1 mg/kg/d) promptly improved the symptoms, pulmonary shadows, and pulmonary function. The findings and clinical course of this case suggest that lipoid pneumonia should be recognized as one of the pulmonary complications of allogeneic hematopoietic stem cell transplantation.

Seroprevalence of Brucellosis among Patients Attending a District Hospital in Rwanda.

Studies on human brucellosis in Rwanda are scarce, and the incidence is likely to be higher than official estimates. In a recent study using Rose Bengal Test (RBT) on women who had aborted or had still births in Huye district, 25% were Brucella seroprevalent. Thus, purpose of the present study was to investigate the Brucella seroprevalence in patients presenting with the key signs and symptoms of brucellosis. Cross-sectional study was done in Nyagatare District in the Eastern Province of Rwanda. A total of 198 patients were recruited from Nyagatare District Hospital, blood samples were collected, and sera analyzed with RBT. A questionnaire was used to explore the risk factors. A total of 12 patients (6.1%; 95% confidence interval [CI] = 0.662-7.820) were Brucella seropositive. Infection was significantly associated with drinking unboiled milk (odds ratio [OR] = 8.3; 95% CI = 2.4-29.2) and having had recurrent fever (OR = 5.6; 95% CI = 1.5-21.3). Drinking unboiled milk is a risk factor for Brucella infection. Provision of adequate resources and trainings to staff in brucellosis diagnosis is needed to reduce recurrence of fevers probably because of misdiagnosis. Public awareness creation on transmission routes of brucellosis is to be intensified.

Plasma levels of natriuretic peptides and year-by-year blood pressure variability: a population-based study.

Augmented blood pressure (BP) variability over various time periods has been recognized as a risk factor for cardiovascular diseases. Both atrial and B-type natriuretic peptides (ANP and BNP) are secreted in response to volume or pressure overload to the heart, exerting natriuretic and vasodilator actions. In this study, we examined the relationships between year-by-year BP variability and plasma levels of ANP and BNP in the general population. Study subjects were local residents receiving an annual heath checkup, who had an estimated glomerular filtration rate of >30 ml min-1 per 1.73 m2 and no history of heart disease. Of those, we selected 314 subjects that received checkups at least five times over the past 6 years. BP variability year-by-year was retrospectively evaluated by s.d., coefficient of variation, average real variability and variation independent of the mean of BP values of 6 or 7 time points. The four parameters of BP variability were each found to significantly correlate with logarithmically transformed ANP and BNP levels by simple regression. When classified by quartiles of s.d. of systolic BP, the highest quartile group showed significantly higher levels of the natriuretic peptides compared with other groups. Multivariate analyses revealed that BP variability was an independent determinant for the ANP and BNP levels. In conclusion, augmented year-by-year BP variability over the past 6 years was associated with elevation of plasma levels of ANP and BNP, suggesting a possible relationship between the BP variability and cardiac load, in the general population.

Nosocomial BK Polyomavirus Infection Causing Hemorrhagic Cystitis Among Patients With Hematological Malignancies After Hematopoietic Stem Cell Transplantation.

BK polyomavirus (BKPyV) is recognized as a pathogen that causes diseases such as hemorrhagic cystitis and nephritis after allogeneic hematopoietic stem cell transplantation (HSCT) or renal transplantation. BKPyV-associated disease is thought to occur through reactivation under immunosuppression. However, the possibility of its nosocomial transmission and the clinical significance of such transmission have not been elucidated. During a 6-month period, nine adult patients (median age: 47 years) who had hematological disorders and who were treated with HSCT (n = 7) or chemotherapy (n = 2) in a single hematology department developed hemorrhagic cystitis due to BKPyV infection. The polymerase chain reaction products of BKPyV DNA obtained from each patient were sequenced. Of the nine patients, six had subtype I, 2 had subtype IV, and 1 had subtype II or III. In the alignment of sequences, four and two of the six subtype I strains were completely homologous (100%). These results strongly suggest that BKPyV has the potential to cause nosocomial infection within a medical facility, especially among recipients of HSCT. Further studies are clearly warranted to elucidate the route(s) of BKPyV transmission in order to establish optimal infection control.

Life-Long Wheel Running Attenuates Age-Related Fiber Loss in the Plantaris Muscle of Mice: a Pilot Study.

The purpose of this study was to investigate whether long-term wheel running would attenuate age-related loss of muscle fiber. Male ICR mice were divided into young (Y, n=12, aged 3 months), old-sedentary (OS, n=5, aged 24 months), and old-exercise (OE, n=6, aged 24 months) groups. The OE group started spontaneous wheel running at 3 months and continued until 24 months of age. Soleus and plantaris muscles were fixed in 4% paraformaldehyde buffer. The fixed muscle was digested in a 50% NaOH solution to isolate single fiber and then fiber number was quantified. The masses of the soleus and plantaris muscles were significantly lower at 24 months than at 3 months of age, and this age-related difference was attenuated by wheel running (P<0.05). Soleus muscle fiber number did not differ among the groups. In the plantaris muscle, the fiber number in the OS group (1 288±92 fibers) was significantly lower than in the Y group (1 874±93 fibers), and this decrease was attenuated in the OE group (1 591±80 fibers) (P<0.05). These results suggest that age-related fiber loss occurs only in the fast-twitch fiber-rich muscle of mice, and that life-long wheel running exercise can prevent this fiber loss.

A randomized controlled trial of cyclosporine and tacrolimus with strict control of blood concentrations after unrelated bone marrow transplantation.

Previous studies have suggested that tacrolimus (TAC) is more potent than cyclosporine (CSA) for prophylaxis against acute GVHD after allogeneic hematopoietic stem cell transplantation (HSCT). However, the target blood concentrations of these drugs in these studies were not consistent with the current recommendations. Therefore, we performed a randomized controlled trial to compare CSA and TAC with target blood concentrations of 500 and 15 ng/ml, respectively, to prevent acute GVHD after unrelated HSCT. A total of 107 patients were randomized into a CSA group (n=53) or a TAC group (n=54). During the first 4 weeks after HSCT, more than 90% of the patients achieved a mean blood concentration of between 80 and 120% of the target concentration. The incidences of grade II-IV and grade III-IV acute GVHD were 39.6 and 7.5% for the CSA group and 33.3 and 9.4% for the TAC group, respectively (P=0.41 and P=0.76). Other clinical outcomes, including overall survival, disease-free survival and the incidences of relapse, non-relapse mortality, and organ toxicities, were also equivalent. We concluded that the combinations of CSA and TAC with strict dose adjustment showed similar efficacies and toxicities as prophylaxis against acute GVHD after unrelated HSCT.

Post-transplant lymphoproliferative disorder of the adrenal gland after allogeneic hematopoietic stem cell transplantation: report of two cases and literature review.

Post-transplant lymphoproliferative disorder (PTLD) is one of the life-threatening complications after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT), and it is associated almost exclusively with Epstein-Barr virus (EBV). We herein report 2 cases of EBV-associated PTLD after allogeneic HSCT localized in the adrenal gland. Both patients developed adrenal tumor within 3 months after HSCT and were successfully treated with rituximab or tapering immunosuppressive agents. Both remained alive without recurrence. A literature review revealed 12 reported cases of PTLD involving the adrenal gland, but the adrenal gland was involved as one of the lesions of advanced-stage PTLD after SOT. To the best of our knowledge, this is the first report to show cases of isolated EBV-associated adrenal PTLD after HSCT. PTLD should be recognized as one of the causes of isolated adrenal tumor after HSCT.

Favorable survival after allogeneic stem cell transplantation with reduced-intensity conditioning regimens for relapsed/refractory follicular lymphoma.

Allogeneic stem cell transplantation (allo-SCT) is a curative option for patients with relapsed follicular lymphoma (FL). Prospective studies of reduced-intensity conditioning (RIC) have revealed that chemosensitivity at allo-SCT is the most reliable predictor of outcome; however, limited data are available for progressive/refractory disease. We report here a retrospective analysis of RIC allo-SCT for patients with FL. The purpose of this study was to elucidate the role of allo-SCT for patients with relapsed/refractory FL. We analyzed 46 patients-11 (24%) transplanted in CR, 6 (13%) transplanted in PR and 29 (63%) with progressive/refractory disease. The estimated 5-year overall survival rate was 71.6% (95% confidence interval (CI), 51.5-84.5%). According to the disease status at transplantation, the 5-year survival rate was 80.7% (95% CI, 37.7-95.4%) in the patients with CR or PR and 66.1% (95% CI, 41.5-82.3%) in those with progressive/refractory disease (P=0.29). There were no differences in relapse/progression and non-relapse mortality between the patients with chemosensitive disease and progressive/refractory disease. Allo-SCT may be a valuable treatment option, even for patients with progressive/refractory FL.

Mutations of the functional ARH1 allele in tumors from ARH1 heterozygous mice and cells affect ARH1 catalytic activity, cell proliferation and tumorigenesis.

ADP-ribosylation results from transfer of the ADP-ribose moiety of nicotinamide adenine dinucleotide (NAD) to an acceptor with ADP-ribose-acceptor content determined by the activities of ADP-ribosyltransferases, which modify the acceptor, and ADP-ribose-acceptor hydrolase (ARH), which cleave the ADP-ribose-acceptor bond. ARH1 was discovered as an ADP-ribose(arginine)protein hydrolase. Previously, we showed that ARH1-knockout and ARH1 heterozygous mice spontaneously developed tumors. Further, ARH1-knockout and ARH1 heterozygous mouse embryonic fibroblasts (MEFs) produced tumors when injected into nude mice. In tumors arising in ARH1 heterozygous mice and MEFs, we found both loss of heterozygosity (LOH) of the ARH1 gene and ARH1 gene mutations. In the present report, we found that these mutant ARH1 genes encode proteins with reduced ARH1 enzymatic activity. Moreover, MEFs transformed with ARH1 mutant genes exhibiting different levels of ARH1 activity showed altered rates of proliferation, anchorage-independent colony growth in soft agar, and tumorigenesis in nude mice. MEFs transformed with the wild-type (WT) gene, but expressing low levels of hydrolase activity were also tumorigenic. However, transformation with the WT gene was less likely to yield tumors than transformation with a mutant gene exhibiting similar hydrolase activity. Thus, control of protein-ADP-ribosylation by ARH1 is critical for tumorigenesis. In the human cancer database, LOH and mutations of the ARH1 gene were observed. Further, ARH1 gene mutations were located in exons 3 and 4, comparable to exons 2 and 3 of the murine ARH1 gene, which comprise the catalytic site. Thus, human ARH1 gene mutations similar to their murine counterparts may be involved in human cancers.

Clinical significance of pretransplant serum ferritin on the outcome of allogeneic hematopoietic SCT: a prospective cohort study by the Kanto Study Group for Cell Therapy.

This prospective study aimed to investigate the influence of pretransplant serum ferritin levels on the outcomes of allogeneic hematopoietic SCT (HSCT). In total, 190 patients with acute leukemia or myelodysplastic syndrome were consecutively enrolled. The patients were divided into two groups: low-ferritin group (<1000 ng/mL) and high-ferritin group (⩾1000 ng/mL). The primary end point was the cumulative incidence of infection within 100 days after HSCT, which was similar between the two groups: bloodstream infection, 35 vs 38%, P=0.65; bacterial infection, 44 vs 41%, P=0.68; and fungal infection, 6 vs 8%, P=0.71. The 1-year adjusted probability of OS of the high-ferritin group was significantly lower than that of the low-ferritin group (76 vs 63%, P=0.017). Using receiver operating characteristic curve, the threshold of pretransplant serum ferritin levels for bloodstream infection was 1400 ng/mL; the threshold for OS, EFS and non-relapse mortality was 1349 ng/mL. In conclusion, pretransplant serum ferritin levels of ⩾1000 ng/mL did not influence the incidence of infection but adversely affected OS after HSCT. A higher threshold of pretransplant serum ferritin levels may predict HSCT outcomes.

Osteoprotegerin is secreted into the coronary circulation: a possible association with the renin-angiotensin system and cardiac hypertrophy.

The circulating osteoprotegerin (OPG) level reflects a series of cardiovascular diseases; however, the source(s) of circulating OPG remain(s) to be determined. This study explored whether OPG is released in the coronary circulation and whether it is associated with cardiac structure and function. Fifty-six patients (67±10 years old, male 57%, hypertension 73%, coronary artery disease 50%) were enrolled, and blood samples were collected simultaneously from the orifice of the left coronary artery (CA) and the coronary sinus (CS) after angiography. The concentration of OPG was higher in the CS than in the CA (7.7±4.1 vs. 6.7±3.6 pmol/l, p<0.001). The trans-cardiac OPG concentration was significantly (p=0.019) decreased in patients who have been prescribed either an angiotensin converting enzyme inhibitor or an angiotensin II type 1 receptor blocker (ACEI/ARB). In patients subgroup who did not take an ACEI/ARB (n=27), the trans-cardiac OPG level was positively correlated with age (r=0.396, p=0.041) and relative wall thickness of left ventricle (r=0.534, p=0.004). In multivariate linear regression analysis, relative wall thickness remained to be the independent variable for the trans-cardiac OPG level (p=0.004). Moreover, trans-cardiac OPG was significantly (p=0.021) increased in patients with relative wall thickness greater than 0.45 but it did not differ if the left ventricular mass index was increased (≥116 for males, or ≥ 104 for females, g/m(2)) or not (p=0.627). This study suggests that OPG is secreted into the coronary circulation and is associated with concentric remodeling/hypertrophy of LV, possibly in interactions with the renin-angiotensin system.