Changes in patient-reported satisfaction and quality-of-life 6 months after rhinoplasty.

BACKGROUND: Rhinoplasty is a challenging and demanding procedure in plastic surgery. Surgical success, patient satisfaction, and improved quality-of-life are important outcomes. OBJECTIVES: This study aimed to evaluate patient-reported satisfaction with appearance, treatment, and decision outcomes as well as quality-of-life after rhinoplasty using validated questionnaires. The role of patient demographics on outcomes was also studied. METHODS: Patients who underwent a primary rhinoplasty were selected for this cohort study. Patient-reported satisfaction with appearance, treatment, and decision as well as quality-of-life were evaluated with the Utrecht Questionnaire and FACE-Q at intake and 6 months postoperatively. RESULTS: Overall, 380 patients were included. Patients reported a more positive subjective perception of nasal appearance (VAS score) at 6 months post-surgery compared with preoperative scores (7.9 ± 1.6 vs 3.2 ± 1.4, p < 0.05). Furthermore, higher quality-of-life and body image scores were observed at 6 months postoperatively compared with preoperative scores (7.7 ± 3.5 vs 15.2 ± 4.4, p < 0.05). Patients reported high satisfaction with treatment outcome (70.3 ± 23.4) as well as with their decision to undergo surgery (75.9 ± 23.4) on a scale of 0-100 at 6 months postoperatively. Patients reached similar postoperative scores regardless of their intake scores. Patients ≥30 years and patients with a history of cosmetic surgery were less satisfied postoperatively. CONCLUSION: Despite differences in appearance satisfaction at intake, most patients showed greater satisfaction with appearance, treatment, and decision outcomes as well as quality-of-life 6 months postoperatively. However, older age and a history of cosmetic surgery influenced these outcomes negatively. These factors should be considered during preoperative management of outcome expectations.

Spatial Analysis of Drug-Susceptible and Multidrug-Resistant Cases of Tuberculosis, Ho Chi Minh City, Vietnam, 2020-2023.

We characterized the spatial distribution of drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB) cases in Ho Chi Minh City, Vietnam, a major metropolis in southeastern Asia, and explored demographic and socioeconomic factors associated with local TB burden. Hot spots of DS and MDR TB incidence were observed in the central parts of Ho Chi Minh City, and substantial heterogeneity was observed across wards. Positive spatial autocorrelation was observed for both DS TB and MDR TB. Ward-level TB incidence was associated with HIV prevalence and the male proportion of the population. No ward-level demographic and socioeconomic indicators were associated with MDR TB case count relative to total TB case count. Our findings might inform spatially targeted TB control strategies and provide insights for generating hypotheses about the nature of the relationship between DS and MDR TB in Ho Chi Minh City and the wider southeastern region of Asia.

Fate of thiamethoxam from treated seeds in mesocosms and response of aquatic invertebrate communities.

Thiamethoxam is a neonicotinoid insecticide widely applied in the Canadian Prairies. It has been detected in surface waters of agro-ecosystems, including wetlands, but the potential effects on non-target invertebrate communities in these wetlands have not been well characterized. In an effort to understand better the fate of thiamethoxam in wetlands and the response of invertebrates (zooplankton and emergent insects), model systems were used to mimic wetland flooding into planted fields. Outdoor mesocosms were treated with a single application of thiamethoxam-treated canola seeds at three treatment levels based on a recommended seeding rate (i.e., 6 kg/ha; 1×, 10×, and 100× seeding rate) and monitored over ten weeks. The mean half-life of thiamethoxam in the water column was 6.2 d. There was no ecologically meaningful impact on zooplankton abundances or community structure among treatments. Statistically significant differences were observed in aquatic insect abundance between control mesocosms and the two greatest thiamethoxam treatments (10× and 100× seeding rate). The observed results indicate exposure to thiamethoxam at environmentally relevant concentrations likely does not represent a significant ecological risk to abundance and community structure of wetland zooplankton and emergent insects.

Clinical targeting of HIV capsid protein with a long-acting small molecule.

Oral antiretroviral agents provide life-saving treatments for millions of people living with HIV, and can prevent new infections via pre-exposure prophylaxis1-5. However, some people living with HIV who are heavily treatment-experienced have limited or no treatment options, owing to multidrug resistance6. In addition, suboptimal adherence to oral daily regimens can negatively affect the outcome of treatment-which contributes to virologic failure, resistance generation and viral transmission-as well as of pre-exposure prophylaxis, leading to new infections1,2,4,7-9. Long-acting agents from new antiretroviral classes can provide much-needed treatment options for people living with HIV who are heavily treatment-experienced, and additionally can improve adherence10. Here we describe GS-6207, a small molecule that disrupts the functions of HIV capsid protein and is amenable to long-acting therapy owing to its high potency, low in vivo systemic clearance and slow release kinetics from the subcutaneous injection site. Drawing on X-ray crystallographic information, we designed GS-6207 to bind tightly at a conserved interface between capsid protein monomers, where it interferes with capsid-protein-mediated interactions between proteins that are essential for multiple phases of the viral replication cycle. GS-6207 exhibits antiviral activity at picomolar concentrations against all subtypes of HIV-1 that we tested, and shows high synergy and no cross-resistance with approved antiretroviral drugs. In phase-1 clinical studies, monotherapy with a single subcutaneous dose of GS-6207 (450 mg) resulted in a mean log10-transformed reduction of plasma viral load of 2.2 after 9 days, and showed sustained plasma exposure at antivirally active concentrations for more than 6 months. These results provide clinical validation for therapies that target the functions of HIV capsid protein, and demonstrate the potential of GS-6207 as a long-acting agent to treat or prevent infection with HIV.

Evaluation of cold-weather wastewater nitrification technology for removal of polar chemicals of emerging concern from rural Manitoba wastewaters.

Aerated lagoons, typically used by small communities, often provide limited removal of wastewater nutrients. Given increasingly stringent wastewater standards, it is imperative that effective, but economical and easy-to-operate, treatment technologies be developed. The Submerged Attached Growth Reactor (SAGR®) is a treatment process developed to perform nitrification near freezing temperatures. Previous tests on full-scale installations have shown that SAGR could consistently remove ammonia to below current Canadian standards and provide additional total suspended solids and biochemical oxygen demand removal. In this study, we evaluated removal of polar chemicals of emerging concern (CECs), including pharmaceuticals, personal care products, and pesticides, at SAGR installations in two Manitoba First Nations communities (MCN and LPFN) under cold winter conditions. Both showed some removal of diclofenac, naproxen, clarithromycin, metoprolol, and trimethoprim, likely by biotransformation. Average naproxen removal was 21% (2.53 × 103 ng L-1) in MCN and 64% (1.58 × 103 ng L-1) in LPFN. Atenolol was well-removed by SAGR, by 80% on average (range of 64%-94%). Clarithromycin, metoprolol, and trimethoprim removal was similar within and between systems, ranging from 54% to 76% (30.8-3.07 × 102 ng L-1 removed). Carbamazepine was detected in nearly all samples, but was not well-removed, consistent with other treatment studies. Overall, results showed that SAGR technology could moderately remove CECs, while providing the designed treatment performance for other parameters. This work will help to improve our understanding of wastewater treatment in small and/or remote communities with limited infrastructure and challenging cold-weather conditions.

Fate of thiamethoxam in mesocosms and response of the zooplankton community.

Thiamethoxam is a neonicotinoid insecticide that can reach wetlands in agro-ecosystems through runoff. The fate and effects of thiamethoxam on non-target organisms in shallow wetland ecosystems have not been well characterized. To this end, a mesocosm study was conducted with a focus on characterizing zooplankton community responses. A single pulse application of thiamethoxam (0, 25, 50, 100, 250, and 500 µg/L; n = 3) was applied to experimental systems and monitored for 8 weeks. The mean half-life of thiamethoxam among the different treatments was 3.7 days in the water column with concentrations of <0.8 µg/L in the majority of mesocosms by 56 days. Principal response curve analysis did not show any significant concentration-dependent differences in the zooplankton community among treatments over the course of the study. The minimum detectable difference (MDD%) values for abundance of potentially sensitive arthropod taxa (nauplius larvae, cyclopoid copepods) allowed the detections from controls as low as 42 and 59% effect, respectively. The MDD% values for total abundance of zooplankton (including the potentially less sensitive taxonomic group of Rotifera) allowed the detection from controls as low as 41% effect. There were no statistically significant differences in zooplankton abundance or diversity between control and treated mesocosms at the end of the study. There were also no statistically significant differences for individual taxa that were sustained between sampling points, or manifested as a concentration-response. We conclude that acute exposure to thiamethoxam at environmentally relevant concentrations (typically ng/L) likely does not represent a significant adverse ecological risk to wetland zooplankton community abundance and structure.

Structure-activity relationships of diamine inhibitors of cytochrome P450 (CYP) 3A as novel pharmacoenhancers. Part II: P2/P3 region and discovery of cobicistat (GS-9350).

The HIV protease inhibitor (PI) ritonavir (RTV) has been widely used as a pharmacoenhancer for other PIs, which are substrates of cytochrome P450 3A (CYP3A). However the potent anti-HIV activity of ritonavir may limit its use as a pharmacoenhancer with other classes of anti-HIV agents. Ritonavir is also associated with limitations such as poor physicochemical properties. To address these issues a series of compounds with replacements at the P2 and/or P3 region was designed and evaluated as novel CYP3A inhibitors. Through these efforts, a potent and selective inhibitor of CYP3A, GS-9350 (cobicistat) with improved physiochemical properties was discovered.

Structure-activity relationships of diamine inhibitors of cytochrome P450 (CYP) 3A as novel pharmacoenhancers, part I: core region.

Ritonavir (RTV), an HIV-1 protease inhibitor (PI), is also a potent mechanism-based inhibitor of human cytochrome P450 3A (CYP3A) and has been widely prescribed as a pharmacoenhancer. As a boosting agent for marketed PIs, it reduces pill burden, and improves compliance. Removal of the hydroxyl group from RTV reduces, but does not eliminate HIV PI activity and does not affect CYP3A inhibition. Herein we report the discovery of a novel series of CYP3A inhibitors that are devoid of antiviral activity. The synthesis and evaluation of analogs with extensive modifications of the 1,4-diamine core along with the structure activity relationships with respect to anti-HIV activity, CYP3A inhibitory activity, selectivity against other CYP enzymes and the human pregnane X receptor (PXR) will be discussed.

Cobicistat (GS-9350): A Potent and Selective Inhibitor of Human CYP3A as a Novel Pharmacoenhancer.

Cobicistat (3, GS-9350) is a newly discovered, potent, and selective inhibitor of human cytochrome P450 3A (CYP3A) enzymes. In contrast to ritonavir, 3 is devoid of anti-HIV activity and is thus more suitable for use in boosting anti-HIV drugs without risking selection of potential drug-resistant HIV variants. Compound 3 shows reduced liability for drug interactions and may have potential improvements in tolerability over ritonavir. In addition, 3 has high aqueous solubility and can be readily coformulated with other agents.

Normocalcemic hyperparathyroidism in Vietnamese immigrants living in southern California.

OBJECTIVE: To characterize the normocalcemic hyperparathyroidism in Vietnamese immigrants living in southern California. METHODS: Of 14 Vietnamese patients with primary hyperparathyroidism who were observed between 1991 and 1996, 50% (7 patients; 2 men and 5 women) had normal and/or fluctuating levels of serum total calcium. When the serum calcium was corrected for the albumin, the "corrected" calcium was lower than the measured serum total calcium. Their mean age was 56.4 +/- 11.4 years. All patients had normal serum levels of albumin and serum phosphate. RESULTS: Women were affected more often than men by a ratio of 5:2. The serum-ionized calcium as well as intact PTH were increased in all patients. Five patients underwent surgery with confirmation of parathyroid adenomas. Two patients refused surgery. They did not have osteitis fibrosa cystica by radiological examination. One patient had low plasma levels of 25-hydroxyvitamin D. Five of 7 normocalcemic patients (70%) were born in the month of December compared with 2 of seven hypercalcemic patients (30%). CONCLUSION: The blood ionized calcium and intact parathyroid hormone are necessary for confirmation of normocalcemic hyperparathyroidism. Most of our normocalcemic hyperparathyroid patients (70%) were born in the month of December. We postulate that a combination of exposure to solar ultraviolet light during the formation of the fetal parathyroid glands and stimulation from low vitamin D levels in the wintertime may be related to the development of hyperparathyroidism. However, it is difficult to prove a definite correlation between normocalcemic hyperparathyroidism and their month of birth (December), especially when these observations were seen in a small group of patients.

Hyperthyroidism and asthma.

Two patients presented with new onset of thyrotoxicosis and they then developed episodic wheezing a few months afterward. The asthmatic attacks improved when the patients were rendered in a euthyroid state with treatment. The present paper discusses the relationship between two diseases, hyperthyroidism and asthma, and the underlying factors potentially contributing to their conditions. The present findings suggest that asthma may develop in a susceptible individual with hyperthyroidism and it is possible that the reactive oxygen species may be a contributory factor in exacerbating wheezing in our hyperthyroid patients.

Folate and vitamin B12-deficiency anemias in Vietnamese immigrants living in Southern California.

BACKGROUND: Although the occurrence of iron deficiency anemia and hemoglobinopathies in Vietnamese immigrants has been reported, folate and vitamin B12 deficiencies have not. Proper diagnosis and effective treatment is necessary to achieve a complete correction of anemia. METHODS: We retrospectively analyzed the records of Vietnamese immigrants seen in our medical clinic from 1991 to 1993. Fifty-nine anemic patients (48 females and 11 males) had low levels of red blood cell (RBC) folate and/or serum vitamin B12. RESULTS: The patients' mean age was 37.7+/-17 years. Mean hemoglobin and hematocrit values were 11.4+/-0.7 g/dL and 34.4%+/-2.2%, respectively. Mean corpuscular volume (MCV) was normal in 40 patients (68%) (mean, 89.1+/-5 fL) and low in 19 patients (32%) (mean, 69.7+/-6 fL). Forty-four patients had low RBC folate levels (mean, 157.7+/-41.7 ng/mL). Twenty patients had low serum vitamin B12 levels (mean, 165.6+/-47 pg/mL). Fourteen patients had ferritin levels of <20%. CONCLUSIONS: Concomitant folate, vitamin B12, and iron deficiencies or hemoglobinopathies might have been responsible for either normal or low MCV in some of our anemic patients. In this ethnic group, RBC folate and serum vitamin B12 levels should be determined in all anemic patients.

Headache and complement C'1-esterase inhibitor deficiency in Vietnamese immigrants living in southern California.

The objective was to measure complement C'1-esterase inhibitor (C1INH) in a group of Vietnamese outpatients with headache. All 51 patients (7 males and 44 females), with either migraine or chronic tension-type headache, were evaluated during 1994 and 1995. Their ages ranged from 15 to 69 years old (mean age, 37.5 years). They were found to have low levels of C1INH (mean, 11 +/- 2 mg/dL versus control subjects, 15 +/- 2 mg/dL with p < 0.0001). Twenty patients (5 males and 15 females) were treated with a low dose of danazol, 200 mg daily for 1-2 months. The improvement of the headache coincided with the return to normal levels of C1INH in all of our patients (pretreatment, 11 +/- 2 mg/dL versus post-treatment, 16 +/- 2 mg/dL with p < 0.001). The levels of C1q and C4d/C4 ratios did not change as a result of treatment with danazol. Our patients may represent a form of androgen-responsive headache, which is associated with low levels of C1INH, normal levels of C1q and normal C4d/C4. It differentiated them from angioedema (hereditary or acquired form); they had no known precipitating factors or a family history of angioedema.

Organic arsenic intoxication from bird's nest soup.

OBJECTIVE: To present a case of organic arsenic intoxication after consumption of bird's nest soup in a Vietnamese patient. METHOD: We have described the clinical picture of a patient with organic arsenic intoxication, and high levels of urine arsenic after consumption of bird's nest soup. RESULT: Withdrawal of bird's nest soup coincided with a decrease in urinary arsenic levels and the disappearance of peripheral neuropathy. CONCLUSION: This case illustrates the environmental contamination of bird's nest soup with organic arsenic. A prompt removal of the source from the diet resulted in clinical improvement.

Aquagenic urticaria: report of a case and review of the literature.

OBJECTIVE: To present a case of aquagenic urticaria and to review the literature regarding this very rare physical urticaria. METHOD: We described the clinical history of a patient with aquagenic urticaria. A water challenge test was performed, with plasma histamine levels measured before and after the challenge. RESULT: Our patient presented with a history of severe itching and wheals within five minutes of contact with water, regardless of its temperature or source (sea or tap water). A water challenge produced hives but serum histamine levels did not change. Prophylaxis with antihistamine or anticholinergic medications was not effective. CONCLUSION: Exposure to water can cause urticaria in susceptible patients and antihistamine and anticholinergic medication may not prevent the reaction. The mechanism of this phenomenon remains poorly understood.

An antineutrophil cytoplasmic autoantibody associated with a propylthiouracil-induced adult respiratory distress-like syndrome: report of a case and review of the literature.

OBJECTIVE: To report the first case of propylthiouracil-induced adult respiratory distress-like syndrome associated with the presence of an antineutrophil cytoplasmic autoantibody. METHODS: We describe the initial manifestations, laboratory findings, and clinical course in a patient and discuss underlying factors potentially contributing to her condition. RESULTS: A 57-year-old woman with hyperthyroidism had an influenza-like illness and vasculitis during propylthiouracil therapy. Three days after she was admitted to the hospital, an adult respiratory distress-like syndrome developed. Results of perinuclear antineutrophil cytoplasmic antibody (pANCA) and antimyeloperoxidase antibody studies were positive. Her condition improved after the introduction of glucocorticoid therapy and the withdrawal of propylthiouracil treatment. The pANCA level, however, remained unchanged 3 months after her dismissal from the hospital. CONCLUSION: The propylthiouracil-induced adult respiratory distress-like syndrome may be a hypersensitivity phenomenon, and the presence of the pANCA could be a marker of a common mechanism of injury that stimulates its production rather than a pathogenic factor responsible for vascular injury in our patient.

Complement abnormalities with lower extremities discomfort in Vietnamese immigrants.

The objective was to measure complement C'l esterase inhibitor (CIINH) in a group of Vietnamese outpatients with lower extremities discomfort of undetermined etiology. All 25 female patients were followed between 1992 and 1995. Their age ranged from 24 to 82 years old (mean age, 46.68 +/- 13.77). They presented with unexplained lower extremities discomfort. They were found to have low levels of CIINH (mean, 11.36 +/- 1.44 mg/dL versus control subjects, 15.64 +/- 2.22 mg/dL). Twenty-one patients were treated with oral Danazol 200 mg daily for 1-2 months. The improvement of the symptoms in our patients coincided with increased CIINH level in all of our patients (pretreatment, 11.33 +/- 1.46 mg/dL versus posttreatment, 16.82 +/- 2.98 mg/dL with p < 0.001) and the return to normal functional activity of CIINH associated with and without Danazol treatment. These patients may represent a form of androgen-responsive limited to the lower extremity's discomfort associated with low levels of CIINH, normal levels of Clq and normal ratio of C4d/C4 that differentiated them from angioedema (hereditary or acquired form), having no known precipitating factors or a family history of hereditary angioedema.