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Mar 2026 DOI 10.14302/issn.2994-6743.ijstd-26-6060
Objective To describe the clinical features and real-world treatment of people living with human immunodeficiency virus (PLHIV) using fixed-dose or free combinations of 2-drug regimens (2DR) of antiretroviral therapy (ART). Design Italian retrospective cohort study. Methods Data were extracted from PLHIV who initiated or switched to 2DR: Group 1 (fixed dose), Group 2 (free combination). Results Group 1 was younger and more predominantly male, and had shorter time from AIDS-defining diagnosis to 2DR-ART and from diagnosis to baseline, a lower prevalence of resistance, and fewer comorbidities than Group 2. Median baseline viral load was <50 copies/mL in both groups, but Group 1 had a higher mean due to outliers. The most common ART classes before switching to 2DR were Integrase Strand Transfer Inhibitor (INSTI)-based (48.97%), Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-based (22.73%), and Protease Inhibitor (PI)-based (16.53%). Distribution varied: Group 1: INSTI-based (53.13%), NNRTI-based (24.31%), and PI-based (15.04%); Group 2: INSTI-based (29.41%), PI-based (23.53%), and NNRTI-based (15.29%). After switching, Group 1 was on dolutegravir/lamivudine (79,33%) and dolutegravir/rilpivirine (20,67%); Group 2 mostly on INSTI-PI (52.81%), followed by NNRTI combinations, mainly with doravirine (19.10%). Duration of ART after switching was shorter in Group 1. Conclusion Italian PLHIV on 2DR fixed-dose combinations were younger, virologically suppressed individuals at baseline, with a shorter lead time from diagnosis, lower prevalence of resistance and lower comorbidity rate compared to those on free combinations. These findings underscore an unmet need for 2DR fixed-dose combinations, as the free combinations were predominantly utilized for more challenging populations.
Dec 2023 DOI 10.14302/issn.2324-7339.jcrhap-23-4634
Introduction Human Immunodeficiency Virus (HIV) remains a persistent global public health challenge. In 2020, approximately 37.9 million individuals were living with HIV globally, including 1.7 million children <15 years old, with a global HIV prevalence of 0.8% among adults. A larger portion of people living with HIV are found in low-and middle-income countries, and Sub-Saharan Africa (SSA) is home to about 68% of people living with HIV in the world. Strikingly, with increased uptakes in PMTCT, challenges in ART programs, and high viremia among children and adolescents in SSA, the success rate of ART might be quickly compromised, with possible HIVDR emergence, particularly after years of paediatric ART exposure. Therefore, monitoring ART response in children and adolescents in terms of HIVDR patterns and other socio-economic determinants of disease progression might help achieve better treatment outcomes at individual levels. At a programmatic level, this can guide further optimization of treatment options for SSA especially Zimbabwean rural where there is paucity of information on HIVDR prevalence in children and adolescents. Methods We enrolled 89 children and adolescents experiencing virologic failure from Chidamoyo Christian Hospital in Hurungwe. We managed to amplify all the 89 using nested PCR and 32.5% (29) had resistance to at least one ART drug and analysis was done using the 29 samples. Results Among the 89 participants with virologic failure,29 were resistant to at least one of their ART drugs. 39.2% of males and 23.07% of females had HIV-1 with resistance to at least one medication. Among 29 participants with HIVDR mutations, the prevalence of at least one HIVDR mutation to protease inhibitors (PIs), Nucleotide Reverse Transcriptase Inhibitors (NRTI), and Non-Nucleotide Reverse Transcriptase Inhibitors (NNRTI) were 6.47% ,46.76% and 46.76% respectively. Of the 29 participants who had HIVDR 19 (65.5%) had resistance to a drug they were currently taking and they needed to be switched to a better effective ART regimen Conclusion Use of HIVDR testing in guiding and monitoring development of HIVDR at the start of ART or at 1st failure can be very important in treatment options and patient management.
Sep 2023 DOI 10.14302/issn.2576-9383.jhhr-23-4713
A global increase in incidence of chronic liver disease (CLD) indicated the necessity of dietary and lifestyle modification. Low glycemic index (GI) diet was reported to have a significant role in controlling diabetes caused by liver dysfunction. The International Standards Organisation (ISO) has standardized the determination of GI of a food in healthy individuals. This study aimed to estimate GI value of a high protein, energy dense liver nutritional supplement. This cross-over randomized controlled study randomly allotted 15 participants to consume either reference food 27.5 gm glucose (glucose monohydrate) or 77 gm nutritional supplement (equivalent to 25 gm of available carbohydrates); switching to another arm was done after 3 days wash-out period. After overnight fast, blood samples were collected at 15, 30, 45 and 60 minutes post-consumption of s upplement or reference food. The GI was calculated from the incremental area under the blood glucose response elicited by the nutritional supplement as a percentage of the response after consumption of 27.5 gm of glucose (glucose monohydrate) by the same participant using a standard formula. Mean GI of the nutritional supplementwas estimated as 11.4 ± 2.4.With the consumption of this nutritional supplement, the blood glucose levels were reduced at all postprandial time points, compared to the reference food. The liver nutritional supplement tested has a low GI, and comparatively slower and more sustained blood glucose response. Therefore, it can be used in patients with CLD to prevent CLD-associated metabolic complications and improve health outcomes and quality of life.
Apr 2022 DOI 10.14302/issn.2372-6601.jhor-22-4133
Background Monoclonal gammopathy of undetermined significance (MGUS) and chronic myeloid leukemia (CML) are diseases of different lineages. The diagnosis of both MGUS and CML in the same patient is a rare occurrence and has not been reported in much literature. Case Presentation We describe a 56-year-old man with a history of rheumatoid arthritis incidentally found to have an increase in IgA paraprotein. With less than 10% monoclonal plasma cells on the bone marrow biopsy and absence of hypercalcemia, renal failure, anemia and bone lesions, MGUS was diagnosed. The conventional cytogenetics at the time showed the presence of the Philadelphia chromosome in 30% of metaphases. However, there was no morphologic evidence of CML in the peripheral blood or bone marrow. Patient received no treatment and lost follow-up until 3 years later when a routine CBC showed leukocytosis and thrombocytosis. CML, chronic phase was diagnosed following a bone marrow aspiration and biopsy with Philadelphia chromosome observed in 100% of metaphases. Patient was treated with imatinib and later switched to dasatinib and complete molecular remission was continued to be achieved. Discussion and Conclusion Here we report a case of pre-leukemic CML as an incidental finding during the diagnosis of MGUS. The possible underlying mechanisms of the association are discussed although the exact cause of the coexistence is unclear.
Dec 2020 DOI 10.14302/issn.2998-4785.ijne-20-3617
Background Overuse and abuse of antibiotics resulted in emergence of multidrug-resistant organisms (MDRO), increased rates of invasive candidiasis, prolonged hospital stay, NEC (Necrotizing enterocolitis), LOS (Late onset sepsis) or death. Restriction of the prescription, switching to a narrower spectrum and stopping antibiotics when not needed are some of the major approaches to antibiotic stewardship. Methods We identified restricted antimicrobials and devised an antimicrobial justification form. Clinicians needed to fill the form before prescribing restricted antimicrobials thereby comparing the antimicrobial usage pattern before and after the introduction of form. Babies enrolled before the introduction of the justification form were labelled as Group 1, and as Group 2 after justification form. The HIC (hospital infection control) staff nurse paid daily visits to NICU to monitor number of babies started on restricted antibiotics and whether the forms were duly filled or not. Any lag would be intimated to the Head HIC team for rectification. Any change of antibiotic within the restricted group also warranted justification. Culture report notified within 48 – 72 hrs so as to facilitate the stoppage of antibiotics in case of negative culture. Results There was a statistically significant reduction in the usage of restricted antimicrobials in the Group B as compared to Group A 150 (40.54%) vs 190 (49.35%) (p = 0.01). There was a statistically significant increase in the % of babies de-escalated from high end antimicrobials in Group B as compared to Group A 90 (60%) vs 56 (29.47%) (p = <0.0001). Duration of restricted antimicrobials reduced from 13.78 ± 2.7 days in Group A to 9.9 ±1.8 days in Group B (p = <0.0001). No difference in the number of babies started on any antibiotic between both the groups (p = 0.1). Conclusion Introduction of the antibiotic justification form as a part of antimicrobial stewardship program resulted in an overall reduced usage of restricted antimicrobials along with rapid de-escalation.
Nov 2019 DOI 10.14302/issn.2691-5014.jphn-19-3067
This study evaluated the impact of switching exclusively formula-fed infants with caregiver-perceived formula intolerance to a reduced lactose, partially hydrolyzed 100% whey-based formula (PHF-W) with Lactobacillus reuteri and 2-fucosyllactose. Infants identified as ‘very’ or ‘extremely’ fussy by caregivers were eligible for this single-arm, single-blind study. Subjects switched their current formula to study formula for three weeks. Gastrointestinal tolerance was assessed by the Infant Gastrointestinal Symptom Questionnaire (IGSQ) at baseline and end of the study. Caregivers ranked their infants’ fussiness (not at all, slightly, moderately, very, extremely) after the first three feedings of study formula and 24 hours after enrollment. A paired t-test was used to compare the change in IGSQ score, and a paired t-test and Wilcoxon signed rank test were used to compare post-feeding fussiness scores to baseline. Fifty infants (mean±std age 28.9±14.5 days) were enrolled; 41 completed the study per protocol. Mean (±std) baseline IGSQ score was 34.9±10.0, dropping to 22.1±7.5 after three weeks (p < 0.001). 48/50 (96%) caregivers stated their infants’ fussiness improved after 24 hours, and 2 (4%) remained the same. 42/46 (91%) caregivers stated their infants’ fussiness improved after the first feeding, and 4 (9%) remained the same. Caregiver-ranked fussiness significantly improved after the first, second, and third feedings and after 24 hours as compared to baseline (p < 0.001 for all). IGSQ scores significantly improved after three weeks of feeding with PHF-W containing Lactobacillus reuteri and 2-fucosyllactose in infants with caregiver-perceived intolerance, and improvements in fussiness were noted as quickly as after the first feeding.
Oct 2019 DOI 10.14302/issn.2372-6601.jhor-19-2986
With the definition of four gene classes, all differences between tumor cells and normal cells can be explained. Proliferative mutations induce a shortcut, forcing the cell to divide. They allow replication without control, induce somatic pairing defects of chromosomes and genome instability. Intact Tumor Supressors or mutant Switch Functions can inhibit this process. Oncogene mutations optimize the growth of the cells.
Oct 2019 DOI 10.14302/issn.2642-3146.jec-19-3049
As a result of mathematical modeling it has been shown that any closed electrical line can be interpreted as a ring waveguide where the Fermi-Pasta-Ulam recurrences of the electron and phonon currents interact with each other on the transversal and longitudinal periodical structures of the line conductor’s crystalline lattice as well as on the structures of the wire insulation. An electronic circuit simulating the mathematical model through the dynamics of magnons and phonons in a closed ferrite core with two different coils switched into the shoulders of a multivibrator has been developed. It has been demonstrated that the interacting ferromagnetic and ferroacoustic resonances excited simultaneously in a ferrite core qualitatively correspond to the dynamics of the electron and phonon currents interaction process in a closed electrical line.
Mar 2018 DOI 10.14302/issn.2575-1212.jvhc-18-2013
Lipopolysaccharide (LPS) is a component of the outer membrane of gram negative bacteria. LPS challenging allows switching transcription of proinflammatory cytokines on via over stimulation of Toll-like receptors (TLRs) signaling pathway with subsequent pathogenic inflammatory response. We investigated the possible reproductive toxicity of LPS in male Wister albino rats. Oxidative stress markers, antioxidant status and caspase-3 activity were analyzed in testicular tissues of rats exposed to either saline or LPS (4 mg/kg BW, ip; 0.18 of the LD50). The samples were collected at 6 h and 72 h after injection of LPS. A significant reduction in testicular reduced glutathione (GSH), glutathione-S-transferase (GST) and superoxide dismutase (SOD) was observed at 72 h compared to control group. Total antioxidant capacity was decreased at 6 h with additional significant reduction at 72 h. Catalase activity was reduced significantly at both 6 and 72 h. Malondialdehyde (MDA) was increased (P ≤ 0.05) in LPS injected rats without variation between 6 and 72 h. A significant increase in nitric oxide (NO) was observed at 72 h after injection. A time-dependent increase in LPS-treated groups was observed in the concentration of caspase-3.Histopathological analysis revealed degenerative changes and necrosis of seminiferous tubules after 6 h with further accumulation of eosinophilic edematous transudate in its lumen after 72 h. In conclusion, by increasing time of exposure, LPS induced lipid peroxidation, oxidative stress, reduced testicular antioxidant capacity and encouraged testicular apoptosis which could be possible mechanisms for impairment of testicular function.
Nov 2017 DOI 10.14302/issn.2372-6601.jhor-17-1761
With the introduction of tyrosine kinase inhibitors (TKI), patients with chronic myeloid leukemia (CML) have obtained survival rates close to normal. It may appear paradoxical, then, that medication adherence is suboptimal in some health care settings. As the first of its kind, this study aimed to explore drivers and barriers to TKI treatment adherence in Danish CML patients. A literature study informed the design of qualitative interviews with 20 patients, individually and in focus groups, focusing on their disease perceptions of CML, their health-related quality of life (QoL) and medication adherence. The study showed that many participants had previously switched treatment due to lacking efficacy or intolerance but most felt their current disease burden was tolerable. Anxiety might, however, resurface if treatment stopped working or with the occurrence of infections or side effects, creating a state of ‘fragile peace’. To these patients, their role functioning – as professionals, spouses, parents and grandparents – was crucial to uphold a positive self-image and meaningful life. Whether treatment enabled or hindered this was thus decisive to their QoL and medication adherence. Our participants expressed high adherence rates with only one having intentionally non-adhered due to side effects and poor QoL. Most participants felt well-informed about CML and treatment and privileged to receive specialised personal care from the public health care system acting to motivate their medication adherence. As a novel finding, this study indicates that the prospect of treatment-free remission may positively affect ‘adherence’ suggest this should be explored in future studies.