The impact of regional disparities on the availability of meningococcal vaccines in the US.

BACKGROUND: In the United States (US), three types of vaccines are available to prevent invasive meningococcal disease (IMD), a severe and potentially fatal infection: quadrivalent conjugate vaccines against serogroups A, C, W, Y (MenACWY), and monovalent vaccines against serogroup B (MenB) as well as a newly licensed pentavalent vaccine (MenABCWY) protecting against serogroup A, B, C, W, and Y. The CDC's Advisory Committee on Immunization Practices (ACIP) routinely recommends MenACWY vaccine for all 11- to 12-year-olds with a booster dose at 16 years. MenB vaccination is recommended based on shared clinical decision-making (SCDM) for 16- to 23-year-olds. Recently, the pentavalent meningococcal vaccine (MenABCWY) was recommended by the ACIP. Meningococcal vaccine uptake is suboptimal across the country, particularly among individuals with lower socioeconomic status (SES), despite these recommendations. The objective of the spatial analyses was to assess the relationship between stocking of MenACWY and MenB vaccines, area-level SES, and state-level policies. METHODS: The number of MenACWY and MenB doses stocked by vaccinators was obtained from IQVIA and the CDC's Vaccine for Children (VFC) program and compiled into a county-level dataset from 2016 to 2019. SES, as measured using the CDC's Social Vulnerability Index (SVI), state-level school recommendations, and universal purchasing programs were among the main county-level covariates included to control for factors likely influencing stocking. Data were stratified by public and private market. Bayesian spatial regression models were developed to quantify the variations in rates of stocking and the relative rates of stocking of both vaccines. RESULTS: After accounting for county-level characteristics, lower SES counties tended to have fewer doses of MenB relative to MenACWY on both public and private markets. Lower SES counties tended to have more supply of public vs. private doses. Universal purchasing programs had a strong effect on the markets for both vaccines shifting nearly all doses to the public market. School vaccination strategy was key for improving stocking rates. CONCLUSIONS: Overall, the results show that MenACWY has greater stock relative to MenB across the US. This difference is exacerbated in vulnerable areas without school entry requirements for vaccination and results in inequity of vaccine availability. Beyond state-level policy and SES differences, SCDM recommendations may be a contributing factor, although this was not directly assessed by our model.

Repeated sprint training in hypoxia induces specific skeletal muscle adaptations through S100A protein signaling.

Athletes increasingly engage in repeated sprint training consisting in repeated short all-out efforts interspersed by short recoveries. When performed in hypoxia (RSH), it may lead to greater training effects than in normoxia (RSN); however, the underlying molecular mechanisms remain unclear. This study aimed at elucidating the effects of RSH on skeletal muscle metabolic adaptations as compared to RSN. Sixteen healthy young men performed nine repeated sprint training sessions in either normoxia (FIO2 = 0.209, RSN, n = 7) or normobaric hypoxia (FIO2 = 0.136, RSH, n = 9). Before and after the training period, exercise performance was assessed by using repeated sprint ability (RSA) and Wingate tests. Vastus lateralis muscle biopsies were performed to investigate muscle metabolic adaptations using proteomics combined with western blot analysis. Similar improvements were observed in RSA and Wingate tests in both RSN and RSH groups. At the muscle level, RSN and RSH reduced oxidative phosphorylation protein content but triggered an increase in mitochondrial biogenesis proteins. Proteomics showed an increase in several S100A family proteins in the RSH group, among which S100A13 most strongly. We confirmed a significant increase in S100A13 protein by western blot in RSH, which was associated with increased Akt phosphorylation and its downstream targets regulating protein synthesis. Altogether our data indicate that RSH may activate an S100A/Akt pathway to trigger specific adaptations as compared to RSN.

Validation of Claims-Based Algorithm for Lyme Disease, Massachusetts, USA.

Compared with notifiable disease surveillance, claims-based algorithms estimate higher Lyme disease incidence, but their accuracy is unknown. We applied a previously developed Lyme disease algorithm (diagnosis code plus antimicrobial drug prescription dispensing within 30 days) to an administrative claims database in Massachusetts, USA, to identify a Lyme disease cohort during July 2000-June 2019. Clinicians reviewed and adjudicated medical charts from a cohort subset by using national surveillance case definitions. We calculated positive predictive values (PPVs). We identified 12,229 Lyme disease episodes in the claims database and reviewed and adjudicated 128 medical charts. The algorithm's PPV for confirmed, probable, or suspected cases was 93.8% (95% CI 88.1%-97.3%); the PPV was 66.4% (95% CI 57.5%-74.5%) for confirmed and probable cases only. In a high incidence setting, a claims-based algorithm identified cases with a high PPV, suggesting it can be used to assess Lyme disease burden and supplement traditional surveillance data.

Syndromic Surveillance for COVID-19, Massachusetts, February 2020-November 2022: The Impact of Fever and Severity on Algorithm Performance.

OBJECTIVES: Syndromic surveillance can help identify the onset, location, affected populations, and trends in infectious diseases quickly and efficiently. We developed an electronic medical record-based surveillance algorithm for COVID-19-like illness (CLI) and assessed its performance in 5 Massachusetts medical practice groups compared with statewide counts of confirmed cases. MATERIALS AND METHODS: Using data from February 2020 through November 2022, the CLI algorithm was implemented in sites that provide ambulatory and inpatient care for about 25% of the state. The initial algorithm for CLI was modeled on influenza-like illness: an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis code for COVID-19 and an ICD-10-CM diagnosis code suggesting severe lower respiratory tract infection or ≥1 ICD-10-CM diagnosis code for upper or lower respiratory tract infection plus fever. We generated weekly counts of CLI cases and patients with ≥1 clinical encounter and visually compared trends with those of statewide laboratory-confirmed cases. RESULTS: The initial algorithm tracked well with the spring 2020 wave of COVID-19, but the components that required fever did not clearly detect the November 2020-January 2021 surge and identified <1% of weekly encounters as CLI. We revised the algorithm by adding more mild symptoms and removing the fever requirement; this revision improved alignment with statewide confirmed cases through spring 2022 and increased the proportion of encounters identified as CLI to about 2% to 6% weekly. Alignment between CLI trends and confirmed COVID-19 case counts diverged again in fall 2022, likely because of decreased COVID-19 testing and increases in other respiratory viruses. PRACTICE IMPLICATIONS: Our work highlights the importance of using a broad definition for COVID-19 syndromic surveillance and the need for surveillance systems that are flexible and adaptable to changing trends and patterns in disease or care.

Hypoxia Does Not Change Performance and Psychophysiological Responses During Repeated Cycling Sprints to Exhaustion With Short Exercise-to-Rest Ratio.

PURPOSE: To compare the acute performance and psychophysiological responses of repeated cycling sprints to exhaustion with a short exercise-to-rest ratio (1:6), between different effort durations and inspired oxygen fractions. METHODS: On separate visits, 10 active participants completed 6 repeated cycling sprint exercises to exhaustion with 3 different effort durations (5, 10, and 20 s) and 2 conditions of inspired oxygen (20.9% and 13.6%). Exercise-to-rest ratio was 1:6 for all trials (ie, 5:30, 10:60, and 20:120). Vastus lateralis muscle oxygenation (near-infrared spectroscopy), blood lactate concentration, and lower-limb and breathing discomfort, using ratings of perceived exertion, were measured. RESULTS: Number of sprints and peak power output decreased while blood lactate increased (all P < .001) during 5:30 compared with 10:60 or 20:120. No condition or interaction effects were reported for blood lactate and exercise-related sensation. Muscle deoxyhemoglobin increased (P < .001) and total hemoglobin decreased (P = .002) during sprint with increasing sprint duration (no condition or interaction). CONCLUSION: During repeated-sprint exercise to exhaustion with a short exercise-to-rest ratio, the psychophysiological responses did not differ between normoxia and moderate hypoxia, probably due to an extended recovery period. It means that hypoxia did not modify repeated-sprint exercise performance with a short exercise-to-rest ratio. The sprint duration was the primary underlying factor of the observed differences in performance and muscle oxygenation reported between the repeated-sprint exercise sessions.

The Oxidative-Glycolytic Balance Influenced by Sprint Duration Is Key during Repeated Sprint in Hypoxia.

PURPOSE: This study investigates the effects of normobaric hypoxia on repeated sprint exercise (RSE) with different balance between oxidative (phosphocreatine and oxidative pathway) and glycolytic contributions. Therefore, performance and psychophysiological responses were compared during RSE to exhaustion with the same exercise-to-rest ratio (1:2) but different sprint durations (5, 10, or 20 s) either in normoxic (RSN) or hypoxic (RSH; F io2 = 0.13) conditions. METHODS: On separate visits, 10 active participants completed in random order three cycling RSN (5:10; 10:20 and 20:40) and three similar RSH sessions to exhaustion. Vastus lateralis muscle oxygenation was recorded by near-infrared spectroscopy. Blood lactate concentration, limb and breathing discomfort, and ratings of perceived exertion were measured. RESULTS: Total sprint number was smaller in hypoxia than in normoxia for 5:10 (20.8 ± 8.6 vs 14.7 ± 3.4; P = 0.014) and 10:20 (13.7 ± 6.3 vs 8.8 ± 2.5; P = 0.018) but not 20:40 (5.6 ± 1.9 vs 5.6 ± 2.5). The fatigue index was larger in hypoxia only for 5:10 (-43.5%, P < 0.001). Irrespective of condition, blood lactate concentration increased with the sprint duration with higher values for 20:40 than 5:10 (13.1 ± 2.7 vs 11.5 ± 2.2 mmoL·L -1 ; P = 0.027). Limb and breathing discomfort and ratings of perceived exertion did not differ in all RSE. Muscle oxygenation was mainly impacted by sprint duration (i.e., main effect of sprint duration on [HHb] min, [tHb] max, Δ[HHb], and Δ[tHb]) but not by hypoxia. The normoxia-to-hypoxia percentage decrease for total sprint number for 5:10 was correlated with the highest power output over 5 s ( R2 = 0.55; P = 0.013) and 10 s ( R2 = 0.53; P = 0.016). CONCLUSIONS: Hypoxia impairs repeated sprint ability when the oxidative but not the glycolytic contribution is substantial. The oxidative-glycolytic balance, influenced partly by sprint duration, is key during repeated sprint in hypoxia.

Healthcare claims-based Lyme disease case-finding algorithms in the United States: A systematic literature review.

BACKGROUND AND OBJECTIVE: Lyme disease (LD) is the fifth most commonly reported notifiable infectious disease in the United States (US) with approximately 35,000 cases reported in 2019 via public health surveillance. However, healthcare claims-based studies estimate that the number of LD cases is >10 times larger than reported through surveillance. To assess the burden of LD using healthcare claims data and the effectiveness of interventions for LD prevention and treatment, it is important to use validated well-performing LD case-finding algorithms ("LD algorithms"). We conducted a systematic literature review to identify LD algorithms used with US healthcare claims data and their validation status. METHODS: We searched PubMed and Embase for articles published in English since January 1, 2000 (search date: February 20, 2021), using the following search terms: (1) "Lyme disease"; and (2) "claim*" or "administrative* data"; and (3) "United States" or "the US*". We then reviewed the titles, abstracts, full texts, and bibliographies of the articles to select eligible articles, i.e., those describing LD algorithms used with US healthcare claims data. RESULTS: We identified 15 eligible articles. Of these, seven studies used LD algorithms with LD diagnosis codes only, four studies used LD diagnosis codes and antibiotic dispensing records, and the remaining four studies used serologic test order codes in combination with LD diagnosis codes and antibiotics records. Only one of the studies that provided data on algorithm performance: sensitivity 50% and positive predictive value 5%, and this was based on Lyme disease diagnosis code only. CONCLUSIONS: US claims-based LD case-finding algorithms have used diverse strategies. Only one algorithm was validated, and its performance was poor. Further studies are warranted to assess performance for different algorithm designs and inform efforts to better assess the true burden of LD.

Differences in the limb blood flow between two types of blood flow restriction cuffs: A pilot study.

Introduction: The determination of the optimal occlusion level is a key parameter in blood flow restriction (BFR). This study aimed to compare the effects of elastic (BStrong) vs. nylon (Hokanson) BFR cuffs on blood flow in the lower and upper limbs. Methods: Eleven healthy participants undertook several BFR sessions with 2 different cuffs of similar width on their lower and upper limbs at different pressures [200, 250, 300, 350, and 400 mmHg for BStrong and 0, 40, and 60% of the arterial occlusion pressure (AOP) for Hokanson]. Doppler ultrasound recorded blood flows through the brachial and femoral artery at rest. Results: With BStrong, only 350 and 400 mmHg pressures were significantly different from resting values (0% AOP). With Hokanson, both 40% and 60% of the AOP were significantly different from resting values (p < 0.05). Discussion: While both cuffs elicited BFR, they failed to accurately modulate blood flow. Hokanson is appropriate for research settings while BStrong appears to be a convenient tool for practitioners due to its safety (i.e., the impossibility of completely occluding arteries) and the possibility of exercising freely detached from the pump.

Impact of an Electronic Medical Record Best Practice Alert on Expedited Partner Therapy for Chlamydia Infection and Reinfection.

BACKGROUND: Atrius Health implemented a best practice alert (BPA) to encourage clinicians to provide expedited partner therapy (EPT) in October 2014. We assessed (1) the impact of the BPA on EPT provision and chlamydial reinfection and (2) the impact of EPT on testing for chlamydia reinfection and reinfection rates. METHODS: We included patients ≥15 years with ≥1 positive chlamydia test between January 2013 and March 2019. Tests-of-reinfection were defined as chlamydia tests 28-120 days after initial infection, and corresponding positive results were considered evidence of reinfection. We used interrupted time series analyses to identify changes in (1) frequency of EPT, (2) tests-of-reinfection, and (3) reinfections after the BPA was released. Log-binomial regression models, with generalized estimating equation methods, assessed associations between (1) EPT and tests-of-reinfection and (2) EPT and reinfection. RESULTS: Among 7267 chlamydia infections, EPT was given to 1475 (20%) patients. Expedited partner therapy frequency increased from 15% to 22% of infections between January 2013 and September 2014 (ß = 0.003, P = .03). After the BPA was released, EPT frequency declined to 19% of infections by March 2019 (ß = -0.004, P = .008). On average, 35% of chlamydia infections received a test-of-reinfection and 7% were reinfected; there were no significant changes in these percentages after BPA implementation. Patients given EPT were more likely to receive tests-of-reinfection (prevalence ratio [PR] 1.09; 95% confidence interval [CI], 1.01-1.16) but without change in reinfections (PR 0.88; 95% CI, 0.66-1.17). CONCLUSIONS: Best practice alerts in electronic medical record systems may not be effective at increasing EPT prescribing and decreasing chlamydial reinfection. However, patients given EPT were more likely to receive a test of chlamydia reinfection.

Effects of Active Preconditioning With Local and Systemic Hypoxia on Submaximal Cycling.

PURPOSE: The authors compared the effects of active preconditioning with local and systemic hypoxia during submaximal cycling. METHODS: On separate visits, 14 active participants completed 4 trials. Each visit was composed of 1 preconditioning phase followed, after 40 minutes of rest, by 3 × 6-minute cycling bouts (intensity = 85% of critical power; rest = 6 min). The preconditioning phase consisted of 4 × 5-minute cycling bouts at 1.5 W·kg-1 (rest = 5 min) in 4 conditions: control (no occlusion and normoxia), blood flow restriction (60% of total occlusion), HYP (systemic hypoxia; inspired fraction of oxygen = 13.6%), and blood flow restriction + HYP (local and systemic hypoxia combined). RESULTS: During the preconditioning phase, there were main effects of both systemic (all P < .014) and local hypoxia (all P ≤ .001) on heart rate, arterial oxygen saturation, leg discomfort, difficulty of breathing, and blood lactate concentration. Cardiorespiratory variables, gross efficiency, energy cost, and energy expenditure during the last minute of 6-minute cycling bouts did not differ between conditions (all P > .105). CONCLUSION: Local and systemic hypoxic stimuli, or a combination of both, during active preconditioning did not improve physiological responses such as cycling efficiency during subsequent submaximal cycling.

Post-exercise accumulation of interstitial lung water is greater in hypobaric than normobaric hypoxia in adults born prematurely.

We aimed to gauge the interstitial lung water accumulation following moderate-intensity exercise under normobaric and hypobaric hypoxic conditions in a group of preterm born but otherwise healthy young adults. Sixteen pre-term-born individuals (age = 21±2yrs.; gestational age = 29±3wk.; birth weight = 1160±273 g) underwent two 8 -h hypoxic/altitude exposures in a cross-over manner: 1) Normobaric hypoxic exposure (NH; FIO2 = 0.142±0.001; PIO2 = 90.6±0.9 mmHg) 2) Hypobaric hypoxic exposure (HH; terrestrial high-altitude 3840 m; PIO2 = 90.2±0.5 mmHg). Interstitial lung water was assessed via quantification of B-Lines (using lung ultrasound) before (normoxia) and after 4-h and 8-h of respective exposures. At each time point, B-Lines were quantified before (Pre) and immediately after (Post) a 6-min moderate-intensity exercise. The baseline B-lines count were comparable between both conditions (P = 0.191). A higher B-lines count was noted at Pre-H4 in HH versus NH (P = 0.0420). At Post-H8 B-lines score was significantly higher in HH (4.6 ± 1.6) than in NH (3.1 ± 1.4; P = 0.0073). Furthermore, at this time point, a significantly higher number of individuals with B-line scores ≥5 was observed in HH (n = 7) than in NH (n = 3; P = 0.0420). These findings suggest that short moderate-intensity exercise provokes a significant increase in the interstitial lung water accumulation after 8 h of exposure to terrestrial but not simulated altitude (≈3840 m) in prematurely born adults. Further work is needed to elucidate the exact mechanisms of (moderate-intensity) exercise-induced interstitial lung water accumulation in this population and directly compare the obtained data to full-term born adults.

Hepatitis C coinfection and extrahepatic cancer incidence among people living with HIV.

OBJECTIVES: We assessed the incidence of extrahepatic cancer among people with HIV/HCV coinfection and the potential impact of direct-acting antivirals (DAAs) on extrahepatic cancer risk among people with HIV/HCV coinfection. DESIGN: Our study cohort included adults who initiated HIV care at a CNICS site in the US during 1995-2017, excluding those with previous cancer and without HCV testing. METHODS: We used Cox regression to estimate hazard ratios for extrahepatic cancer incidence among patients with HIV/HCV coinfection compared with those with HIV monoinfection. Standardized morbidity ratio (SMR) weights were used to create a 'pseudopopulation' in which all patients were treated with antiretroviral therapy (ART), and to compare extrahepatic cancer incidence among patients with untreated HIV/HCV coinfection with the incidence that would have been observed if they had been successfully treated for HCV. RESULTS: Of 18 422 adults, 1775 (10%) had HCV RNA and 10 899 (59%) were on ART at baseline. Incidence rates of any extrahepatic cancer among patients with HIV/HCV coinfection and HIV monoinfection were 1027 and 771 per 100 000 person-years, respectively. In SMR-weighted analyses, the risk of any extrahepatic cancer among patients with untreated HCV coinfection at baseline was similar to the risk if they had been successfully treated for HCV. Patients with untreated HCV coinfection at baseline had higher incidence of kidney, lung and inflammation-related cancers than if their HCV had been successfully treated, but these associations were not statistically significant. CONCLUSIONS: We did not find evidence that treating HCV coinfection with DAAs would reduce the incidence of extrahepatic cancers among people with HIV receiving ART.

Can Machine Learning Help Identify Patients at Risk for Recurrent Sexually Transmitted Infections?

BACKGROUND: A substantial fraction of sexually transmitted infections (STIs) occur in patients who have previously been treated for an STI. We assessed whether routine electronic health record (EHR) data can predict which patients presenting with an incident STI are at greatest risk for additional STIs in the next 1 to 2 years. METHODS: We used structured EHR data on patients 15 years or older who acquired an incident STI diagnosis in 2008 to 2015 in eastern Massachusetts. We applied machine learning algorithms to model risk of acquiring ≥1 or ≥2 additional STIs diagnoses within 365 or 730 days after the initial diagnosis using more than 180 different EHR variables. We performed sensitivity analysis incorporating state health department surveillance data to assess whether improving the accuracy of identifying STI cases improved algorithm performance. RESULTS: We identified 8723 incident episodes of laboratory-confirmed gonorrhea, chlamydia, or syphilis. Bayesian Additive Regression Trees, the best-performing algorithm of any single method, had a cross-validated area under the receiver operating curve of 0.75. Receiver operating curves for this algorithm showed a poor balance between sensitivity and positive predictive value (PPV). A predictive probability threshold with a sensitivity of 91.5% had a corresponding PPV of 3.9%. A higher threshold with a PPV of 29.5% had a sensitivity of 11.7%. Attempting to improve the classification of patients with and without repeat STIs diagnoses by incorporating health department surveillance data had minimal impact on cross-validated area under the receiver operating curve. CONCLUSIONS: Machine algorithms using structured EHR data did not differentiate well between patients with and without repeat STIs diagnosis. Alternative strategies, able to account for sociobehavioral characteristics, could be explored.

Cardio-respiratory, oxidative stress and acute mountain sickness responses to normobaric and hypobaric hypoxia in prematurely born adults.

PURPOSE: We compared the effects of hypobaric and normobaric hypoxia on select cardio-respiratory responses, oxidative stress and acute mountain sickness (AMS) severity in prematurely born individuals, known to exhibit blunted hypoxic ventilatory response. METHODS: Sixteen prematurely born but otherwise healthy males underwent two 8-h hypoxic exposures under: (1) hypobaric hypoxic [HH; terrestrial altitude 3840 m; PiO2:90.2 (0.5) mmHg; BP: 478 (2) mmHg] and (2) normobaric hypoxic [NH; PiO2:90.6 (0.9) mmHg; FiO2:0.142 (0.001)] condition. Resting values of capillary oxyhemoglobin saturation (SpO2), heart rate (HR) and blood pressure were measured before and every 2 h during the exposures. Ventilatory responses and middle cerebral artery blood flow velocity (MCAv) were assessed at rest and during submaximal cycling before and at 4 and 8 h. Plasmatic levels of selected oxidative stress and antioxidant markers and AMS symptoms were also determined at these time points. RESULTS: HH resulted in significantly lower resting (P = 0.010) and exercise (P = 0.004) SpO2 as compared to NH with no significant differences in the ventilatory parameters, HR or blood pressure. No significant differences between conditions were found in resting or exercising MCAv and measured oxidative stress markers. Significantly lower values of ferric-reducing antioxidant power (P = 0.037) were observed during HH as opposed to NH. AMS severity was higher at 8 h compared to baseline (P = 0.002) with no significant differences between conditions. CONCLUSION: These data suggest that, in prematurely born adults, 8-h exposure to hypobaric, as opposed to normobaric hypoxia, provokes greater reductions in systemic oxygenation and antioxidant capacity. Further studies investigating prolonged hypobaric exposures in this population are warranted. REGISTRATION: NCT02780908 (ClinicalTrials.gov).

Mitochondrial oxygen affinity increases after sprint interval training and is related to the improvement in peak oxygen uptake.

AIMS: The body responds to exercise training by profound adaptations throughout the cardiorespiratory and muscular systems, which may result in improvements in maximal oxygen consumption (VO2 peak) and mitochondrial capacity. By convenience, mitochondrial respiration is often measured at supra-physiological oxygen levels, an approach that ignores any potential regulatory role of mitochondrial affinity for oxygen (p50mito ) at physiological oxygen levels. METHODS: In this study, we examined the p50mito of mitochondria isolated from the Vastus lateralis and Triceps brachii in 12 healthy volunteers before and after a training intervention with seven sessions of sprint interval training using both leg cycling and arm cranking. The changes in p50mito were compared to changes in whole-body VO2 peak. RESULTS: We here show that p50mito is similar in isolated mitochondria from the Vastus (40 ± 3.8 Pa) compared to Triceps (39 ± 3.3) but decreases (mitochondrial oxygen affinity increases) after seven sessions of sprint interval training (to 26 ± 2.2 Pa in Vastus and 22 ± 2.7 Pa in Triceps, both P < .01). The change in VO2 peak modelled from changes in p50mito was correlated to actual measured changes in VO2 peak (R2  = .41, P = .002). CONCLUSION: Together with mitochondrial respiratory capacity, p50mito is a critical factor when measuring mitochondrial function, it can decrease with sprint interval training and should be considered in the integrative analysis of the oxygen cascade from lung to mitochondria.

Insights for Blood Flow Restriction and Hypoxia in Leg Versus Arm Submaximal Exercise

PURPOSE: To assess tissue oxygenation, along with metabolic and physiological responses during blood flow restriction (BFR, bilateral vascular occlusion) and systemic hypoxia conditions during submaximal leg- versus arm-cycling exercise. METHODS: In both legs and arms, 4 randomized sessions were performed (normoxia 400 m, fraction of inspired oxygen [FIO2] 20.9% and normobaric hypoxia 3800 m, FIO2 13.1% [0.1%]; combined with BFR at 0% and 45% of resting pulse elimination pressure). During each session, a single 6-minute steady-state submaximal exercise was performed to measure physiological changes and oxygenation (near-infrared spectroscopy) of the muscle tissue in both the vastus lateralis (legs) and biceps brachii (arms). RESULTS: Total hemoglobin concentration ([tHb]) was 65% higher (P < .001) in arms versus legs, suggesting that arms had a greater blood perfusion capacity than legs. Furthermore, there were greater changes in tissue blood volume [tHb] during BFR compared with control conditions (P = .017, F = 5.45). The arms elicited 7% lower tissue saturation (P < .001) and were thus more sensitive to the hypoxia-induced reduction in oxygen supply than legs, no matter the condition. This indicates that legs and arms may elicit different regulatory hemodynamic mechanisms (ie, greater blood flow in arms) for limiting the decreased oxygen delivery during exercise with altered arterial oxygen content. CONCLUSIONS: The combination of BFR and/or hypoxia led to increased [tHb] in both limbs likely due to greater vascular resistance; further, arms were more responsive than legs. This possibly influences the maintenance of oxygen delivery and enhances perfusion pressure, suggesting greater vascular reactivity in arms than in legs.

Relationship between cardiorespiratory phase coherence during hypoxia and genetic polymorphism in humans.

KEY POINTS: High altitude-induced hypoxia in humans evokes a pattern of breathing known as periodic breathing (PB), in which the regular oscillations corresponding to rhythmic expiration and inspiration are modulated by slow periodic oscillations. The phase coherence between instantaneous heart rate and respiration is shown to increase significantly at the frequency of periodic breathing during acute and sustained normobaric and hypobaric hypoxia. It is also shown that polymorphism in specific genes, NOTCH4 and CAT, is significantly correlated with this coherence, and thus with the incidence of PB. Differences in phase shifts between blood flow signals and respiratory and PB oscillations clearly demonstrate contrasting origins of the mechanisms underlying normal respiration and PB. These novel findings provide a better understanding of both the genetic and the physiological mechanisms responsible for respiratory control during hypoxia at altitude, by linking genetic factors with cardiovascular dynamics, as evaluated by phase coherence. ABSTRACT: Periodic breathing (PB) occurs in most humans at high altitudes and is characterised by low-frequency periodic alternation between hyperventilation and apnoea. In hypoxia-induced PB the dynamics and coherence between heart rate and respiration and their relationship to underlying genetic factors is still poorly understood. The aim of this study was to investigate, through novel usage of time-frequency analysis methods, the dynamics of hypoxia-induced PB in healthy individuals genotyped for a selection of antioxidative and neurodevelopmental genes. Breathing, ECG and microvascular blood flow were simultaneously monitored for 30 min in 22 healthy males. The same measurements were repeated under normoxic and hypoxic (normobaric (NH) and hypobaric (HH)) conditions, at real and simulated altitudes of up to 3800 m. Wavelet phase coherence and phase difference around the frequency of breathing (approximately 0.3 Hz) and around the frequency of PB (approximately 0.06 Hz) were evaluated. Subjects were genotyped for common functional polymorphisms in antioxidative and neurodevelopmental genes. During hypoxia, PB resulted in increased cardiorespiratory coherence at the PB frequency. This coherence was significantly higher in subjects with NOTCH4 polymorphism, and significantly lower in those with CAT polymorphism (HH only). Study of the phase shifts clearly indicates that the physiological mechanism of PB is different from that of the normal respiratory cycle. The results illustrate the power of time-evolving oscillatory analysis content in obtaining important insight into high altitude physiology. In particular, it provides further evidence for a genetic predisposition to PB and may partly explain the heterogeneity in the hypoxic response.

More Screening or More Disease? Gonorrhea Testing and Positivity Patterns Among Men in 3 Large Clinical Practices in Massachusetts, 2010-2017.

BACKGROUND: Gonorrhea diagnosis rates in the United States increased by 75% during 2009-2017, predominantly in men. It is unclear whether the increase among men is being driven by more screening, an increase in the prevalence of disease, or both. We sought to evaluate changes in gonorrhea testing patterns and positivity among men in Massachusetts. METHODS: The analysis included men (aged ≥15 years) who received care during 2010-2017 in 3 clinical practice groups. We calculated annual percentages of men with ≥1 gonorrhea test and men with ≥1 positive result, among men tested. Log-binomial regression models were used to examine trends in these outcomes. We adjusted for clinical and demographic characteristics that may influence the predilection to test and probability of gonorrhea disease. RESULTS: On average, 306 348 men had clinical encounters each year. There was a significant increase in men with ≥1 gonorrhea test from 2010 (3.1%) to 2017 (6.4%; adjusted annual risk ratio, 1.12; 95% confidence interval, 1.12-1.13). There was a significant, albeit lesser, increase in the percentage of tested men with ≥1 positive result (1.0% in 2010 to 1.5% in 2017; adjusted annual risk ratio, 1.07; 95% confidence interval, 1.04-1.09). CONCLUSIONS: We estimated significant increases in the annual percentages of men with ≥1 gonorrhea test and men with ≥1 positive gonorrhea test result between 2010 and 2017. These results suggest that observed increases in gonorrhea rates could be explained by both increases in screening and the prevalence of gonorrhea.

On the Use of the Repeated-Sprint Training in Hypoxia in Tennis.

PURPOSE: To examine physiological and technical responses to repeated-sprint training in normobaric hypoxia at ∼3,000 m (RSH, n = 11) or in normoxia (RSN, n = 11) compared to a control group (CON, n = 8) in well-trained tennis players. Participants were 28.8 ± 5.9 years old without any previous experience of training in hypoxia. METHODS: In addition to maintaining their usual training (CON), both RSH and RSN groups completed five tennis specific repeated-shuttle sprint sessions (4 × 5 × âˆ¼8 s maximal sprints with ∼22 s passive recovery and ∼5 min rest between sets) over 12 days. Before (Pre), the week after (Post-1) and 3 weeks after Post-1 (Post-2), physical/technical performance during Test to Exhaustion Specific to Tennis (TEST), repeated-sprint ability (RSA) (8 × âˆ¼20 m shuttle runs-departing every 20 s) and heart rate variability (HRV) were assessed. RESULTS: From Pre to Post-1 and Post-2, RSH improved TEST time to exhaustion (+18.2 and +17.3%; both P < 0.001), while the "onset of blood lactate accumulation" at 4 mmol L-1 occurred at later stages (+24.4 and +19.8%, both P < 0.01). At the same time points, ball accuracy at 100% V̇O2m ax increased in RSH only (+38.2%, P = 0.003 and +40.9%, P = 0.007). Markers of TEST performance did not change for both RSN and CON. Compared to Pre, RSA total time increased significantly at Post-1 and Post-2 (-1.9 and -2.5%, P < 0.05) in RSH only and this was accompanied by larger absolute Δ total hemoglobin (+82.5 and +137%, both P < 0.001). HRV did not change either supine or standing positions. CONCLUSION: Five repeated sprint training sessions in hypoxia using tennis specific shuttle runs improve physiological and technical responses to TEST, RSA, and accompanying muscle perfusion responses in well-trained tennis players.