Acquired rifamycin resistance among patients with tuberculosis and HIV in new York City, 2001-2023.

Introduction: Acquired rifamycin resistance (ARR) in tuberculosis (TB) has been associated with HIV infection and can necessitate complicated TB treatment regimens, particularly in people living with HIV (PLWH). This work examines clinical characteristics and treatment outcomes of PLWH who developed ARR from 2001 to 2023 in New York City (NYC) to inform best practices for treating these patients. Methods: PLWH who developed ARR 2001-2023 were identified from the NYC TB registry. Results: Sixteen PLWH developed ARR; 15 were diagnosed 2001-2009 and the 16th was diagnosed in 2017. Median CD4 count was 48/mm3. On initial presentation, 14 had positive sputum cultures; of these, 12 culture-converted prior to developing ARR. Ten patients completed a course of TB treatment but subsequently relapsed; in six of these cases, ARR was discovered upon relapse, triggering treatment with a non-rifamycin-containing regimen, while in the other four, ARR was discovered during a second round of rifamycin-containing treatment. Three patients were lost to follow-up during their initial course of TB treatment and later returned to care; after being restarted on a rifamycin-containing regimen, ARR was discovered. Finally, three patients culture-converted during their first course of treatment but subsequently had cultures that grew rifamycin-resistant Mycobacterium tuberculosis prior to treatment completion, leading to changes in their treatment regimens. Among the 16 patients, eight died before being cured of TB, seven successfully completed treatment, and one was lost to follow-up. Conclusions: PLWH should be monitored closely for the development of ARR during treatment for TB, and sputum culture conversion should be interpreted cautiously in this group. Collecting a final sputum sample may be especially important for PLWH, as treatment failure and relapse were common in this population. The decrease in the number of cases of ARR among PLWH during the study period may reflect the decrease in the total number of PLWH diagnosed with TB in NYC in recent years, improved immune status of PLWH due to increased uptake of antiretroviral drugs, and improvements in the way anti-TB regimens are designed for PLWH (such as recommending daily rather than intermittent rifamycin dosing).

Tracking Declines in Mercury Exposure in the New York City Adult Population, 2004-2014.

Mercury is a toxic metal that can be measured in human blood and urine. Population-based biomonitoring from 2004 guided New York City (NYC) Department of Health and Mental Hygiene (DOHMH) efforts to reduce exposures by educating the public about risks and benefits of fish consumption-a predominant source of exposure in the general population-and removing mercury-containing skin-lightening creams and other consumer products from the marketplace. We describe changes in exposures over the past decade in relation to these local public health actions and in the context of national changes by comparing mercury concentrations measured in blood (1201 specimens) and urine (1408 specimens) from the NYC Health and Nutrition Examination Survey (NYC HANES) 2013-2014 with measurements from NYC HANES 2004 and National Health and Nutrition Examination Surveys (NHANES) 2003-2004 and 2013-2014. We found that NYC adult blood and urine geometric mean mercury concentrations decreased 46% and 45%, respectively. Adult New Yorkers with blood mercury concentration ≥ 5 µg/L (the New York State reportable level) declined from 24.8% (95% CL = 22.2%, 27.7%) to 12.0% (95% CL = 10.1%, 14.3%). The decline in blood mercury in NYC was greater than the national decline, while the decline in urine mercury was similar. As in 2004, Asian New Yorkers had higher blood mercury concentrations than other racial/ethnic groups. Foreign-born adults of East or Southeast Asian origin had the highest prevalence of reportable levels (29.7%; 95% CL = 21.0%, 40.1%) across sociodemographic groups, and Asians generally were the most frequent fish consumers, eating on average 11 fish meals in the past month compared with 7 among other groups (p < 0.001). Fish consumption patterns were similar over time, and fish continues to be consumed more frequently in NYC than nationwide (24.7% of NYC adults ate fish ten or more times in the past 30 days vs. 14.7% nationally, p < 0.001). The findings are consistent with the hypothesis that blood mercury levels have declined in part because of local and national efforts to promote consumption of lower mercury fish. Local NYC efforts may have accelerated the reduction in exposure. Having "silver-colored fillings" on five or more teeth was associated with the highest 95th percentile for urine mercury (4.06 µg/L; 95% CL = 3.1, 5.9). An estimated 5.5% of the adult population (95% CL = 4.3%, 7.0%) reported using a skin-lightening cream in the past 30 days, but there was little evidence that use was associated with elevated urine mercury in 2013-14.

Increasing Ketamine Use for Refractory Status Epilepticus in US Pediatric Hospitals.

Ketamine is an emerging therapy for pediatric refractory status epilepticus. The circumstances of its use, however, are understudied. The authors described pediatric refractory status epilepticus treated with ketamine from 2010 to 2014 at 45 centers using the Pediatric Hospital Inpatient System database. For comparison, they described children treated with pentobarbital. The authors estimated that 48 children received ketamine and pentobarbital for refractory status epilepticus, and 630 pentobarbital without ketamine. Those receiving only pentobarbital were median age 3 [interquartile range 0-10], and spent 30 [18-52] days in-hospital, including 17 [9-28] intensive care unit (ICU) days; 17% died. Median cost was $148 000 [81 000-241 000]. The pentobarbital-ketamine group was older (7 [2-11]) with longer hospital stays (51 [30-93]) and more ICU days (29 [20-56]); 29% died. Median cost was $298 000 [176 000-607 000]. For 71%, ketamine was given ≥1 day after pentobarbital. Ketamine cases per half-year increased from 2 to 9 ( P < .05). Ketamine is increasingly used for severe pediatric refractory status epilepticus, typically after pentobarbital. Research on its effectiveness is indicated.

Death After Jail Release.

The period immediately after release from prison or jail carries increased mortality risk. This study sought to better understand postrelease death by matching electronic health records from those incarcerated in New York City jails between 2011 and 2012 with vital statistics records. The in-jail and 6-week postrelease mortality rates were estimated to be 1.39 and 5.89 per 1,000 person-years, respectively. Of 59 deaths occurring within 6 weeks of release from jail, the causes included opioid overdose (37.3%), other drugs (8.5%), chronic disease (25.4%), assaultive trauma (20.3%), and other trauma (8.5%). These data confirm that overdose death accounts for the most frequent cause of postrelease death. Matching between correctional health systems and vital statistics can inform quality improvement efforts in jail health care delivery.

A survey of patient expectations regarding sexual function following radical prostatectomy.

OBJECTIVE: To assess the understanding of patients, who had previously undergone radical prostatectomy (RP), about their postoperative sexual function, as clinical experience suggests that some RP patients have unrealistic expectations about their long-term sexual function. PATIENTS AND METHODS: Patients presenting within 3 months of their open RP or robot-assisted laparoscopic prostatectomy (RALP) were questioned about the sexual function information that they had received preoperatively. Patients were questioned about erectile function (EF), postoperative ejaculatory status, orgasm, and postoperative penile morphology changes. Statistical analyses were performed to assess for differences between patients who underwent open RP vs RALP. RESULTS: In all, 336 consecutive patients (from nine surgeons) with a mean (SD) age of 64 (11) years had the survey instrument administered (216 underwent open RP and 120 underwent RALP). There were no significant differences in patient age or comorbidity profiles between the two groups. Only 38% of men had an accurate recollection of their nerve-sparing status. The mean (SD) elapsed time after RP at the time of postoperative assessment was 3 (2) months. RALP patients expected a shorter EF recovery time (6 vs 12 months, P = 0.02), a higher likelihood of recovery back to baseline EF (75% vs 50%, P = 0.01), and a lower potential need for intracavernosal injection therapy (4% vs 20%, P = 0.01). Almost half of all patients were unaware that they were rendered anejaculatory by their surgery. None of the RALP patients and only 10% of open RP patients recalled being informed of the potential for penile length loss (P < 0.01) and none were aware of the association between RP and Peyronie's disease. CONCLUSIONS: Patients who have undergone RP have largely unrealistic expectations about their postoperative sexual function.

Deformity stabilization and improvement in men with untreated Peyronie's disease.

OBJECTIVE: To define predictors of the deformity stabilisation and improvement in men with untreated Peyronie's disease (PD). PATIENTS AND METHODS: The study population consisted of patients with PD-associated uniplanar curvature, who opted for no treatment and were followed for at least 12 months. All patients had deformity assessment (DA) performed on initial presentation and at follow-up. Stabilisation of PD was defined as no change between DAs (±10°), while improvement and progression were defined as ≥10° change. Patients were subdivided into different groups based on time to presentation: ≤6 months (A), 7-12 months (B), and 13-18 months (C). Multivariable analysis was used to define predictors of stabilisation and improvement. RESULTS: In all, 176 men met the inclusion criteria. The mean age was 54 years, with a mean (sd) PD duration of 9 (12) months and mean curvature of 42 (27)°. In all, 67% of the entire population had no change in deformity over time, 12% improved with a mean (sd) change of 27 (14)°, and 21% worsened with a mean (sd) change of 22 (11)°. On multivariate analysis, predictors of stabilisation included: time to presentation of >6 months (odds ratio [OR] 2.4, P < 0.01), per decade increase in age (OR 1.5, P < 0.05), and age (r = 0.32, P < 0.05). Predictors of improvement included: time to presentation of ≤6 months (OR 4.1, P < 0.001), and per decade decrease in age (OR 2.1, P < 0.01). CONCLUSIONS: In men with uniplanar curvature, PD stabilisation and improvement rates change with time-to-presentation and patient age. These data may aid in counselling patients with PD.

Peyronie's disease in teenagers.

INTRODUCTION: Peyronie's disease (PD) is commonly seen in middle-aged men, and little is known about this condition in teenagers. AIM: To investigate the characteristics of PD in teenagers. METHODS: The findings were compared between patients with the disease who were teenagers with those over 40 years of age. Statistical analyses were conducted to define differentiating features between these two groups. MAIN OUTCOME MEASURES: The demographics, clinical features, and associated comorbidities of patients with PD were reviewed. RESULTS: Thirty-two teenaged males were evaluated for PD in a single institution over a 10-year period. The median age for our cohort was 18 (15-19) years. Forty-five percent of patients had already been seen by another urologist, and 28% had been told they did not have PD. The mean duration of PD before seeking medical care in our cohort was 3 ± 1 months. Sixteen percent of patients reported antecedent penile trauma, half of which happened during coitus or masturbation, and 18% of patients had hemoglobin (Hb) A1c levels > 5%. Dupuytren's contracture was not seen in this population. Twenty-two percent of patients presented with penile pain. Subsequent ED was seen in 37% of patients. Multiple noncontiguous plaques were seen in 37% of patients. Twelve percent were previously treated with vitamin E, while another 12% had previous intralesional verapamil. High distress was reported by 94% of patients. Thirty-four percent sought medical attention for anxiety/mood disorder, and 28% had a negative encounter with a sexual partner related to PD. All of the 32 patients had penile curvature with a mean of 32 ± 12 degrees. Seventy-two percent of the patients had dorsal curvature while 22% had an associated deformity. Using duplex Doppler ultrasound, 12% had a calcified plaque, while none of the patients had abnormal hemodynamics. When compared with PD in adults, teenagers had greater than seven times the prevalence of multiple noncontiguous plaques (37% vs. 5%). Also, the prevalence of HbA1c level > 5% was higher in the teenagers as well (18% vs. 5%). CONCLUSIONS: PD does occur in teenagers often causing high distress levels. Compared to older adults, teenagers often present earlier, and more commonly have elevated HbA1c level and increased number of plaques at presentation.

Defining predictors of response to intralesional verapamil injection therapy for Peyronie's disease.

OBJECTIVE: • To assess factors that predict penile curvature responses to intralesional verapamil (ILV) injection therapy for men with Peyronie's disease (PD). PATIENTS AND METHODS: • Men with PD for <1 year were assessed at baseline and after 3 months of bi-monthly ILV-injection therapy. Curvature was assessed at the time of maximum penile rigidity. • Univariate relationships were tested with correlation or chi-square analyses. • Multivariate analyses included logistic and linear regression. • We analysed curvature improvement, defined as a decrease of ≥10 ° from baseline. Additionally, the relationship between curvature outcomes and patient age and degree of baseline penile curvature were assessed. RESULTS: • Data from 131 men were included and the rates of penile curvature change were:26% improved, 12% worsened, and 62% stable. • Age (r=-0.24, P < 0.01) and larger baseline penile curvature (r= 0.33, P < 0.01) were associated with improved curvature on univariate analysis. • On multivariate analysis (logistic regression), both age [odds ratio (OR) 0.93, P < 0.01, 95%CI 0.89-0.97] and larger baseline penile curvature (OR 1.07, P < 0.01, 95%CI 1.04-1.11) were associated with improvements in curvature after ILV-injection therapy. • Improvements in curvature were associated with age (≤40 years vs >40 years; OR 0.27, P < 0.05, 95%CI 0.10-0.75) and degree of penile curvature at baseline (≤30 ° vs >30 °; OR 9.12, P < 0.01, 95%CI 1.94-42.84) when dichotomized as indicated. CONCLUSION: • Younger age and larger baseline penile curvature were predictive of favourable curvature outcomes. • Analysis of dichotomized variables suggests that age and baseline curvature thresholds may be important to consider when deciding on ILV as a therapeutic strategy for PD.

Erectile dysfunction after plaque incision and grafting: short-term assessment of incidence and predictors.

INTRODUCTION: Plaque incision and grafting (PIG) surgery for Peyronie's disease (PD) is a recognized management strategy. One of the recognized complications of PIG surgery is the development of postoperative erectile dysfunction (ED). AIM: To determine the incidence of ED after PIG surgery and attempt to define predictors of ED development. METHODS: All patients underwent preoperative cavernosometry. Grafting was performed with either cadaveric pericardium (Tutoplast) or intestinal submucosa (Surgisis). Prior to 2006, the procedure used an H-type incision, whereas after this date, the Egydio approach has been used. MAIN OUTCOME MEASURES: Men undergoing PIG completed preoperative and 6-month postoperative International Index of Erectile Function (IIEF) questionnaires. RESULTS: 56 patients were analyzed. Mean patient and partner ages were 57 ± 22 and 54 ± 18 years, respectively. Mean duration of PD at the time of PIG was 22 ± 9 months. Seventy-five percent had curvature alone, 11% had hourglass/indentation deformity, and the remainder had combined curvature/indentation. Mean preoperative curvature was 52 ± 23°. Fifty-two had grafting with Tutoplast, while four had grafting with Surgisis. All men at baseline were capable of generating a penetration rigidity erection. Preoperatively, 50% of men had cavernosal insufficiency and 21% had venous leak (baseline and postoperative erectile function [EF] domain scores were 23 ± 4 and 17 ± 9, respectively [P < 0.01]). Forty-six percent of men experienced a ≥6-point decrease in EF domain score after PIG. The predictors of a ≥6-point reduction in IIEF-EF domain score on multivariable analysis were degree of preoperative curvature, type of plaque incision, patient age, and baseline venous leak. Conclusions. Almost one-half of men had significant reduction in their erectile rigidity after PIG. Reduction was predicted by larger baseline curvature, the Egydio plaque incision technique, older patient age, and the presence of venous leak at baseline. Based on these data, we discourage older men, those with venous leak, and those with profound curvature from considering PIG surgery.

Predicting delay in presentation in men with Peyronie's disease.

INTRODUCTION: Many men with Peyronie's disease (PD) delay presentation to a urologist. The reasons for this are unclear. AIM: To define the differences in men who present early compared to those presenting in a delayed fashion and to determine predictors of delayed presentation. METHODS: A retrospective analysis of all patients presenting for the first medical evaluation of PD. All patients underwent a standard history and physical examination and had a standardized deformity assessment. Demographic and PD parameters were recorded. MAIN OUTCOME MEASURES: Statistical comparison was used to define factors that were different between early and delayed presenters and multivariable analysis was used to define predictors of presentation >12 months. RESULTS: 482 patients were analyzed, 61% presenting ≤12 months, 39% >12 months. Mean patient age was 52 ± 13 years and mean duration of PD was 17 ± 30 months. Mean measured curvature was 42° ± 19°. Multivariable analysis revealed that delayed presentation patients were significantly more likely to be older (odds ratio [OR] = 4.0), to be in long-term relationships (OR = 3.6), to have dorsal curvature (OR = 2.5), to have curvature <45° (OR = 3.3), to be heterosexual (OR = 2.0), and to have simple deformity (OR = 1.5). CONCLUSIONS: One-third of men with PD presented in a delayed fashion and they tended to be older, to be in long-term relationships, to have dorsal curvature, or to have simple deformity.

Integrin beta6 mediates phospholipid and collectin homeostasis by activation of latent TGF-beta1.

Surfactant lines the alveolar surface and prevents alveolar collapse. Derangements of surfactant cause respiratory failure and interstitial lung diseases. The collectins, surfactant proteins A and D, are also important in innate host defense. However, surfactant regulation in the postnatal lung is poorly understood. We found that the epithelial integrin, alphavbeta6, regulates surfactant homeostasis in vivo by activating latent transforming growth factor (TGF)-beta. Adult mice lacking the beta-subunit of alphavbeta6 (Itgb6-/-) developed increased bronchoalveolar lavage phospholipids and surfactant proteins A and D, and demonstrated abnormal-appearing alveolar macrophages, reminiscent of the human disease pulmonary alveolar proteinosis. Using lung-specific expression of constitutively active TGF-beta1 in Itgb6-/- mice, we found that TGF-beta1 was sufficient to normalize these abnormalities. Tgfbeta1-deficient mice also demonstrated increased phospholipids and surfactant proteins A and D, but mice lacking the key TGF-beta signaling molecule, SMAD3, did not. Therefore, integrin-mediated activation of latent TGF-beta1 regulates surfactant constituents independent of intracellular SMAD3. In vivo increases in surfactant protein A and D were not associated with increases in mRNA for these proteins in alveolar tissue from Itgb6-/- mice. On the other hand, isolated alveolar macrophages from Itgb6-/- mice were defective in processing phospholipids in vitro, suggesting that reduced surfactant clearance contributes to altered surfactant homeostasis in these mice in vivo. These findings show that alphavbeta6 and TGF-beta1 regulate homeostasis of phospholipids and collectins in adult mouse lungs and may have implications for anti-fibrotic therapeutics that inhibit active TGF-beta in the lung.