Prevalence and clinical characteristics of people with HIV with limited treatment options in Japan: A Japanese claims data analysis.

INTRODUCTION: Long-term medication leads some people with HIV (PWH) to limited treatment options (LTO) due to multiple factors. The present study investigated the prevalence of PWH with LTO in Japan and their clinical characteristics, persistence, and adherence. METHODS: PWH who received antiretroviral therapy (ART) between 2017 and 2022 were identified in the Medical Data Vision (MDV) Japanese claims database. PWH with LTO were defined as: 1) receiving regimens indicative for LTO or 2) having a complex treatment history (≥4 different core agents, ≥11 ART agents). Prevalence by calendar year, clinical characteristics, persistence, and adherence measured by the proportion of days covered (PDC) of ART were investigated. RESULTS: A total of 5740 PWH were included, and 207 (3.6 %) were identified as LTO. Mean (SD) age was 50.3 (11.8) years, 148 (71.5 %) had evidence of AIDS-defining condition, and 25 (12.1 %) had hemophilia. The prevalence of PWH with LTO increased from 2.58 % in 2017 to 3.55 % in 2022. Persistence at 1 year was estimated as 70.3 % and mean PDC through 1 year was 96.7 %. CONCLUSION: Between the years 2017-2022, 3.6 % (approximately 200) Japanese PWH were identified as having LTO. The results of this analysis found clinical characteristics of PWH with LTO as older age and higher percentages with an AIDS-defining condition and hemophilia than the general HIV population. Low persistence indicates that treatment optimization is required in this population. These results will help health care providers to understand the clinical characteristics of PWH with LTO and may contribute to the establishment of appropriate treatment strategies.

The safety and effectiveness of remdesivir in a postmarketing surveillance study in Japan.

BACKGROUND: To evaluate the occurrence of adverse drug reactions (ADRs) and to assess mortality and health status in participants receiving remdesivir in real-world settings in Japan. METHODS: This postmarketing surveillance study used an all-case surveillance method for enrollment. Participants with SARS-CoV-2 infection administered remdesivir from July 2020 to November 2021 in Japan were eligible for inclusion. The observation period was from remdesivir treatment initiation to 4 weeks after the end of treatment or treatment discontinuation. Clinical status and outcomes were analyzed by Kaplan-Meier plots and compared across subgroups at baseline, Day 14, Day 28, and the final observation point. RESULTS: The analysis included 2128 participants (mean age, 67 years; 71.4 % male; 84.1 % with current comorbidities). ADRs and serious adverse drug reactions (SADRs) were reported among 10.4 % and 1.2 % participants, respectively. Overall, 191/2127 participants died (mortality rate [95 % confidence interval], 11.10 [9.66-12.75] per 100 person-months), 1511/2127 showed clinical improvement (117.8 [112.0-123.9] per 100 person-months), 1392/2127 recovered (103.9 [98.6-110.0] per 100 person-months), and 216/324 were extubated (107.0 [93.6-122.3] per 100 person-months). CONCLUSIONS: The incidence of ADRs and SADRs was low, and no new safety concerns were identified. Observed mortality and clinical improvement results were consistent with prior studies, confirming remdesivir's benefits in real-world settings in Japan.

Abdominal pregnancy implanted on surface of pedunculated subserosal uterine leiomyoma: A case report.

Abdominal pregnancy is a rare form of ectopic pregnancy. Various sites of implantation in abdominal pregnancy have been reported. Uterine serosa is an extremely rare implantation site, with only a few cases reported to date. No case of abdominal pregnancy implanted on the surface of a subserosal uterine leiomyoma has been reported. We herein report the case of a 40-year-old primigravida woman who was diagnosed with abdominal pregnancy implanted on the surface of a pedunculated subserosal uterine leiomyoma. The uterine leiomyoma with gestational tissue was resected laparoscopically and the postoperative course was uneventful. It is necessary to remember the possibility of unexpected implantation sites and that laparoscopic surgery may be more difficult in such cases than that for fallopian tube pregnancy.

Ovarian abscess caused by Helicobacter cinaedi in a patient with endometriosis.

Helicobacter cinaedi is a rarely encountered pathogen that easily induces bacteremia. Various foci of H. cinaedi infection have been reported; however, no case of adnexal abscess caused by H. cinaedi has been reported in the English literature. We herein report a case of ovarian abscess caused by H. cinaedi. A 38-year-old nulligravid Japanese woman was admitted to our hospital with an adnexal abscess. Clinical findings included fever, leukocytosis, and elevated C-reactive protein. Laparoscopic right partial oophorectomy with abdominal lavage was performed. H. cinaedi was isolated from cultures of blood and ovarian abscess fluid after surgery. Intravenous ampicillin/sulbactam was administered for 2 weeks, followed by oral amoxicillin for an additional 2 weeks. The postoperative course was uneventful and clinical findings improved. There was no evidence of relapse. H. cinaedi can cause ovarian abscess and is likely an under-recognized pathogen.

Resolution of dopamine agonist-resistant hyperprolactinemia by hysterectomy: a case report.

Prolactin-producing uterine leiomyomas are very rare. Although hyperprolactinemia rapidly improves after removal of such leiomyomas, no preoperative diagnostic test has been established for prolactin-producing uterine leiomyomas. A 45-year-old Japanese woman, gravida 3 para 3, was referred to our hospital for further examination of hyperprolactinemia resistant to a dopamine agonist. A pituitary prolactinoma was undetectable by brain magnetic resonance imaging. A bromocriptine loading test revealed an increased serum prolactin concentration after loading. Examination for the detection of an ectopic prolactinoma revealed a 9.0 cm diameter uterine leiomyoma that had measured 6.6 cm in diameter about six months before the first visit to our hospital. The hyperprolactinemia rapidly improved after hysterectomy. A prolactin-producing uterine leiomyoma should be considered as a possible cause of hyperprolactinemia resistant to dopamine agonists. Responsiveness to dopamine agonists; deterioration of hyperprolactinemia may be diagnostic for prolactin-producing uterine leiomyomas, although further research is required.

Steroid Pulse Therapy for De Novo Minimal Change Disease During Pregnancy.

BACKGROUND Nephrotic syndrome occurs very rarely, in only about 0.01%-0.02% of all pregnancies, and de novo minimal change disease during pregnancy is especially rare. Nephrotic syndrome and, especially, minimal change disease are highly responsive to steroids, and preterm labor may be avoidable if the maternal condition is improved with steroid therapy. Therefore, prompt diagnosis and proper management are critical to maternal and fetal outcome when severe proteinuria occurs during pregnancy. CASE REPORT A 30-year-old pregnant Japanese woman presented with systemic edema, oliguria, and severe proteinuria and hypoalbuminemia at 25 weeks of gestation, although she was normotensive. The patient had high urinary protein selectivity. Her illness was diagnosed as de novo nephrotic syndrome with high steroid responsiveness rather than pre-eclampsia. She began steroid pulse therapy the day after admission. Complete remission was confirmed after 3 weeks. The patient did not relapse during pregnancy and delivered a healthy male baby at 37 weeks of gestation. A renal biopsy at a relapse after delivery confirmed minimal change disease. CONCLUSIONS In pregnant women with de novo minimal change disease, serious maternal and/or fetal complications may occur if severe proteinuria and hypoalbuminemia are unabated for an extended time. Evaluation of urinary protein selectivity is noninvasive and useful for prediction of steroid responsiveness. Results of urinary protein selectivity can be obtained earlier than results of renal biopsy. Renal biopsy during pregnancy is not always necessary for initiation of steroid therapy. Rapid initiation of steroid pulse therapy may enable quicker achievement of remission and prevent serious perinatal complications.

Association of molecular markers in Plasmodium falciparum crt and mdr1 with in vitro chloroquine resistance: a Philippine study.

Specific mutations in the pfcrt and pfmdr1 genes have been reported to be associated with chloroquine-resistant falciparum malaria parasites worldwide. These genetic markers are considered to be useful tools for the elucidation of several aspects of the epidemiology of drug resistant malaria. In this study, Plasmodium falciparum isolates from three distinct areas of the Philippines were analyzed for drug-resistance-associated genetic mutations, and their association with the in vitro chloroquine (CQ) response. Two novel pfcrt 72-76 allelic types, CVMDT and SVMDT, were detected. The frequency of the pfcrt K76T mutation in the isolates that were successfully tested for in vitro CQ susceptibility was found to be 100% in Kalinga, 80% in Palawan, and 87% in Mindanao. The frequency of the pfmdr1 N86Y mutation was 39% in Kalinga, 35% in Palawan, and 93% in Mindanao isolates. No mutations were found at positions 1042 and 1246 of pfmdr1. However, there were no significant associations found between polymorphisms in these genes and in vitro CQ susceptibility. The results of this study indicate that mutations in pfcrt and pfmdr1 are not predictive of in vitro CQ resistance in Philippine isolates and may therefore not be suitable as molecular markers for surveillance.

Plasmodium falciparum: the fungal metabolite gliotoxin inhibits proteasome proteolytic activity and exerts a plasmodicidal effect on P. falciparum.

The in vitro antimalarial activity of the fungal metabolite gliotoxin (GTX) was evaluated, and its mechanism of action was studied. GTX showed plasmodicidal activity against both Plasmodium falciparum chloroquine-resistant strain K-1 and chloroquine-susceptible strain FCR-3. GTX cytotoxicity was significantly lower against a normal liver cell line (Chang Liver cells). The intracellular reduced glutathione level of parasitized and of normal red blood cells was not affected by GTX treatment. However, GTX decreased the chymotrypsin-like activity of parasite proteasomes in a time-dependent manner. The results of this study indicate that GTX possesses plasmodicidal activity and that this effect is due to inhibition of parasite proteasome activity, suggesting that GTX may constitute a useful antimalarial therapy.

Potent plasmodicidal activity of a heat-induced reformulation of deoxycholate-amphotericin B (Fungizone) against Plasmodium falciparum.

The emergence and spread of drug-resistant Plasmodium falciparum continue to pose problems in malaria chemotherapy. Therefore, it is necessary to identify new antimalarial drugs and therapeutic strategies. In the present study, the activity of a heat-treated form of amphotericin B (HT-AMB) against P. falciparum was evaluated. The efficacy and toxicity of HT-AMB were also compared with those of the standard formulation (AMB). HT-AMB showed significant activity against a chloroquine-resistant strain (strain K-1) and a chloroquine-susceptible strain (strain FCR-3) in vitro. The 50% inhibitory concentrations of HT-AMB were 0.32 +/- 0.03 mug/ml for strain K-1 and 0.33 +/- 0.03 mug/ml for strain FCR-3. In the presence of 1.0 mug of HT-AMB per ml, only pyknotic parasites were observed after 24 h of incubation of early trophozoites (ring forms). However, when late trophozoites and schizonts were cultured with 1.0 mug of HT-AMB per ml, those forms multiplied to ring forms but the number of infected erythrocytes did not increase. These results indicate that HT-AMB possesses potent antiplasmodial activity and that the drug is more effective against the ring-form stage than against the late trophozoite and schizont stages. HT-AMB was observed to have little cytotoxic effect against a human liver cell line (Chang liver cells). In conclusion, the results suggest that HT-AMB has promising properties and merits further in vivo investigations as a treatment for falciparum malaria.

Pyrimethamine-sulfadoxine treatment of uncomplicated Plasmodium falciparum malaria in Lao PDR.

A 28-day in vivo treatment trial to evaluate the efficacy of pyrimethamine/sulfadoxine (Fansidar, PS) was conducted in 21 Lao patients with uncomplicated Plasmodium falciparum malaria. Sixteen patients (76%) were completely cured with PS without any reappearance of asexual stage parasitemia during the follow-up examination. On the other hand, 5 patients (24%) failed to respond to this trial medication, resulting in recrudescence of asexual stage P. falciparum malaria. PS resistance resulted in higher prevalence of post-treatment gametocytemia, 25% gametocyte carriers among PS sensitive cases versus 75% of the resistant cases. These findings suggest that although the level of PS resistance is still valid for treatment of malaria in the study area of Lao PDR, post-treatment induction of gametocytemia among resistant cases may result an increase in transmission rate of PS resistant falciparum malaria.

Plasmodium falciparum: selenium-induced cytotoxicity to P. falciparum.

The in vitro antimalarial activity of sodium selenite (NaSe) was investigated and the mechanism of its action was studied. NaSe had antimalarial activity against both the chloroquine-susceptible strain FCR-3 and chloroquine-resistant strain K-1 of Plasmodium falciparum. The shrunken cytoplasm of the parasite was observed in a smear 12 h after treatment with NaSe. Co-treatment with copper sulfate (CuSO(4)) in culture did not affect the antimalarial activity of NaSe, but NaSe cytotoxicity against the mammalian cell line Alexander was decreased significantly. The intracellular reduced glutathione level of parasitized red blood cells was decreased significantly by treatment with NaSe, and the decrease was consistent with their mortality. Treatment with NaSe had a strong inhibitory effect on plasmodial development, and NaSe cytotoxicity to human cells was decreased by co-treatment with CuSO(4). These results suggest that co-treatment with NaSe and CuSO(4) may be useful as a new antimalarial therapy.