Systolic Blood Pressure and Survival to Very Old Age: Results From the Women's Health Initiative.

BACKGROUND: The relationship between systolic blood pressure (SBP) and longevity is not fully understood. We aimed to determine which SBP levels in women ≥65 years of age with or without blood pressure medication were associated with the highest probability of surviving to 90 years of age. METHODS: The study population consisted of 16 570 participants enrolled in the Women's Health Initiative who were eligible to survive to 90 years of age by February 28, 2020, without a history of cardiovascular disease, diabetes, or cancer. Blood pressure was measured at baseline (1993 through 1998) and then annually through 2005. The outcome was defined as survival to 90 years of age with follow-up. Absolute probabilities of surviving to 90 years of age were estimated for all combinations of SBP and age using generalized additive logistic regression modeling. The SBP that maximized survival was estimated for each age, and a 95% CI was generated. RESULTS: During a median follow-up of 19.8 years, 9723 of 16 570 women (59%) survived to 90 years of age. Women with an SBP between 110 and 130 mm Hg at attained ages of 65, 70, 75, and 80 years had a 38% (95% CI, 34%-48%), 54% (52%-56%), 66% (64%-67%), or 75% (73%-78%) absolute probability to survive to 90 years of age, respectively. The probability of surviving to 90 years of age was lower for greater SBP levels. Women at the attained age of 80 years with 0%, 20%, 40%, 60%, 80%, or 100% time in therapeutic range (defined as an SBP between 110 and 130 mm Hg) had a 66% (64%-69%), 68% (67%-70%), 71% (69%-72%), 73% (71%-74%), 75% (72%-77%), or 77% (74%-79%) absolute survival probability to 90 years of age. CONCLUSIONS: For women >65 years of age with low cardiovascular disease and other chronic disease risk, an SBP level <130 mm Hg was found to be associated with longevity. These findings reinforce current guidelines targeting an SBP target <130 mm Hg in older women.

Systolic Blood Pressure and Survival to Very Old Age. Results from the Women's Health Initiative.

Background: The association between systolic blood pressure (SBP) and longevity is not fully understood. We aimed to determine survival probabilities to age 90 for various SBP levels among women aged ≥ 65 years with or without BP medication. Methods: We analyzed blood pressure data from participants in the Women's Health Initiative (n=16,570) who were aged 65 or older and without history of cardiovascular disease, diabetes or cancer. Blood pressure was measured at baseline (1993-1998) and then annually through 2005. The outcome was defined as survival to age 90 with follow-up until February 28, 2020. Results: During a follow-up of 18 years, 9,723 (59%) of 16,570 women survived to age 90. The SBP associated with the highest probability of survival was about 120mmHg regardless of age. Compared to an SBP between 110 and 130 mmHg, women with uncontrolled SBP had a lower survival probability across all age groups and with or without BP medication. A 65-year-old women on BP medication with an interpolated SBP between 110 and 130 mmHg in 80% of the first 5 years of follow-up had a 31% (95% confidence interval, 24%, 38%) absolute survival probability. For those with 20% time in range, the probability was 21% (95% confidence interval, 16%, 26%). Conclusions: An SBP level below 130 mmHg was found to be associated with longevity among older women. The longer SBP was controlled at a level between 110 and 130 mmHg, the higher the survival probability to age 90. Preventing age-related rises in SBP and increasing the time with controlled BP levels constitute important measures for achieving longevity.

Relationship Between Risks for Obstructive Sleep Apnea, Resistant Hypertension, and Aldosterone Among African American Adults in the Jackson Heart Study.

BACKGROUND: African Americans have a higher prevalence of resistant hypertension compared with Caucasians. Racial differences in obstructive sleep apnea (OSA) and increased aldosterone level may explain the racial disparity in resistant hypertension prevalence. Therefore, the purpose of this study is to investigate if aldosterone level and hypertension status differ by risks for OSA (e.g., obesity, loud snoring, and daytime sleepiness) and how aldosterone level varies with hypertension severity and control among African Americans. METHODS: A cross-sectional analysis was performed using baseline data on 5,052 African American adults in the Jackson Heart Study to investigate the relationships of interest using multivariable linear and multinomial logistic regression models adjusted for potential confounders. Risks for OSA were defined by a "risk score" consisting of the number of risks for OSA. RESULTS: Of the 5,052 participants, 623 had no risks for OSA. Body mass index was the highest among those with a risk score of 6. About 39% of the sample had no hypertension, 29% had controlled hypertension, 26% had uncontrolled hypertension, and 6% had resistant hypertension. Higher odds of having uncontrolled hypertension or resistant hypertension were present in those with a higher risk score compared with those without risks for OSA. Log-aldosterone level increased with each additional risk for OSA (P-trend <0.05). Similarly, log-aldosterone also increased with more severe hypertension (P-trend <0.001). The highest aldosterone level was found in those with resistant hypertension that was inadequately controlled with medications. CONCLUSIONS: Risks for OSA were positively associated with resistant hypertension and higher aldosterone level in African American adults.

A 31-Year-Old Pregnant Woman With Asthma, Presenting With Worsening Dyspnea, Wheeze, and Hoarseness.

CASE PRESENTATION: A 31-year-old woman (gravida 3 and para 1-0-1-1 at 20 weeks gestation) was admitted to the hospital for a presumed acute asthma exacerbation. She had a history of severe persistent asthma since childhood. She described her symptoms as progressively worsening since the beginning of her pregnancy. In addition to her dyspnea and wheeze, both of which occurred at rest and with exertion, she complained of worsening hoarseness and mild dysphagia of solid foods over the week before admission. Her primary care provider treated her with a combined corticosteroid and long-acting beta-agonist inhaler, albuterol inhaler and nebulizer, azithromycin, and two courses of prednisone without improvement. Her allergist performed a handheld spirometry 2 months before admission that was repeated 3 weeks later in the office. She had a social history of alcohol dependence but had been sober for 9 months. She was a former one-pack-per-day smoker but quit 20 weeks before admission and used marijuana occasionally. She had no known occupational or inhalation exposures.

Nocturia in Women With Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is underdiagnosed in women compared with men. Women have a tendency to underreport or present with atypical symptoms such as behavior changes, insomnia, fatigue, and depression. Nocturia, waking up from sleep 2 times or more to void, has been shown to be associated with OSA, but it is not an included symptom in commonly used screening questionnaires in primary provider offices. About 50% of patients with OSA have nocturia, and treatment of OSA improves it. Recognition of nocturia as a relevant symptom of OSA is important for primary providers to provide timely referral for the diagnosis of OSA.

The Utility of Diaphragm Ultrasound in Reducing Time to Extubation.

PURPOSE: Prediction of optimal timing for extubation of mechanically ventilated patients is challenging. Ultrasound measures of diaphragm thickness or diaphragm dome excursion have been used to aid in predicting extubation success or failure. The aim of this study was to determine if incorporating results of diaphragm ultrasound into usual ICU care would shorten the time to extubation. METHODS: We performed a prospective, randomized, controlled study at three Brown University teaching hospitals. Included subjects underwent block randomization to either usual care (Control) or usual care enhanced with ultrasound measurements of the diaphragm (Intervention). The primary outcome was the time to extubation after ultrasound, and the secondary outcome was the total days on the ventilator. Only intensivists in the Intervention group would have the ultrasound information on the likelihood of successful extubation available to incorporate with traditional clinical and physiologic measures to determine the timing of extubation. RESULTS: A total of 32 subjects were studied; 15 were randomized into the Control group and 17 into the Intervention group. The time from ultrasound to extubation was significantly reduced in the Intervention group compared to the Control group in patients with a ∆tdi% ≥ 30% (4.8 ± 8.4 vs 35.0 ± 41.0 h, p = 0.04). The time from ultrasound to extubation was shorter in subjects with a normally functioning diaphragm (∆tdi% ≥ 30%) compared to those with diaphragm dysfunction (∆tdi% < 30%) (23.2 ± 35.2 vs 57.3 ± 52.0 h p = 0.046). When combining the Intervention and Control groups, a value of ∆tdi% ≥ 30% for extubation success at 24 h provided a sensitivity, specificity, PPV and NPV of 90.9%, 86.7%, 90.9%, and 86.7%, respectively. CONCLUSIONS: Diaphragm ultrasound evaluation of ∆tdi% aids in reducing time to extubation.

Prospective association of obstructive sleep apnea risk factors with heart failure and its subtypes in postmenopausal women: The Women's Health Initiative.

STUDY OBJECTIVES: The relationship between obstructive sleep apnea (OSA) and heart failure (HF) incidence in postmenopausal women has been understudied, given the limited representation of women in heart failure studies. We investigated the relationship between OSA risk factors and HF and its subtypes in postmenopausal women. METHODS: We performed a prospective analysis on the adjudicated HF outcomes in the Women's Health Initiative from enrollment (1993-1998) to September 30, 2016. HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) were defined as adjudicated acute HF hospitalization with EF ≥ 45% or < 45%, respectively. We employed Cox regression to examine the association between OSA risk factors and symptoms (individually and using a summary risk score) and time to first hospitalized HF. RESULTS: Of 42,362 women, 2,205 (5.21%) developed all HF, 1,162 (2.74%) women developed HFpEF, and 679 (1.60%) developed HFrEF. Individual OSA risk factors and symptoms, including obesity (hazard ratio = 1.33, 95% confidence interval [CI] 1.20-1.48), snoring (hazard ratio = 1.30, 95% CI 1.16-1.46), and hypertension (HR = 1.45, 95% CI 1.35-1.56), were positively associated with risk of HF and HFpEF, but only hypertension was associated with HFrEF. When examined as a summary risk score compared with those with none of the OSA risk factors, presence of each additional factor was significantly associated with increased risk of hospitalized HF in a dose-response fashion for HFpEF (P trend < .001), but not HFrEF (P trend = .26). CONCLUSIONS: OSA risk factors and symptoms were associated with HFpEF, but not HFrEF, among postmenopausal women and are largely dependent on body mass index, snoring, and hypertension.

End-expiratory lung volume decreases during REM sleep despite continuous positive airway pressure.

PURPOSE: Patients with obstructive sleep apnea (OSA) may experience apneas and hypopneas primarily during stage R (REM) sleep when end-expiratory lung volume (EELV) reaches its nadir. The purpose of this study was to determine if REM-related reductions in EELV persist in the presence of continuous positive airway pressure (CPAP) prescribed during non-stage REM (NREM) sleep. METHODS: We prospectively recruited 17 subjects referred to the sleep laboratory for CPAP titration. CPAP was titrated per AASM protocol to control respiratory events. The change in EELV was measured using magnetometry. RESULTS: Of the 17 subjects, 12 (71%) had moderate to severe OSA. Despite the application of CPAP, there was a significant reduction in EELV between NREM and REM sleep (- 105.9 ± 92.2 to - 325.0 ± 113.1 mL, respectively, p < 0.01). The change in EELV between non-stage R (NREM) and REM significantly correlated with overall apnea-hypopnea index (AHI) (r = 0.5, p = 0.04), the number of respiratory arousals during REM (r = 0.5, p = 0.04), and prescribed level of CPAP (r = 0.7, p < 0.01). CONCLUSION: REM-related reductions in EELV are associated with worsening sleep disordered breathing and occur despite the presence of CPAP.

Comparison of Endoscopic Ultrasound Biopsy Needles for Endoscopic Ultrasound-Guided Liver Biopsy.

BACKGROUND/AIMS: To compare the performance of latest commercially available endoscopic ultrasound biopsy needles. METHODS: Six latest commercially available needles were tested on a freshly harvested bovine liver; the tested needles included three 19 G, one 20 G, and two 22 G needles. Five biopsies were performed per needle with 10 mL of wet suction. The primary outcome was the number of complete portal tracts (CPTs) per needle aspirate. The secondary outcomes were the mean specimen length and mean fragment length. Analysis of variance and Tukey's test were applied. RESULTS: All 19 G needles and the 20 G needle yielded similar mean CPTs and were superior to the SharkCore 22 G needle (p<0.001 adjusted for multiplicity). There was no statistically significant difference in total specimen length among the three 19 G needles and the 20 G needle tested. The two 22 G needles performed similarly with respect to the number of CPTs, mean fragment length, and mean specimen length (adjusted p=0.07, p=0.59, and p=0.10, respectively). CONCLUSION: The specimen adequacy was similar among the 3 latest commercially available 19 G needles. The endoscopist may choose a larger-bore needle based on availability without concerns of specimen adequacy. Further studies are needed to assess the ease of needle use in various anatomical locations and to confirm the optimal needle design.

Anastomotic Biliary Stricture Development after Liver Transplantation in the Setting of Retained Prophylactic Intraductal Pediatric Feeding Tube: Case and Review.

The biliary anastomosis remains a common site of postoperative complications in liver transplantation (LT). Biliary complications have indeed been termed the "Achilles' heel" of LT, and while their prevention, diagnosis, and treatment have continued to evolve over the last two decades, various challenges and uncertainties persist. Here we present the case of a 33-year-old man who, 10 years after undergoing LT for idiopathic recurrent intrahepatic cholestasis, was noted to have developed pruritus and abnormalities in serum liver biochemistries during routine post-liver transplant follow-up. Abdominal ultrasound revealed a linear, 1.5 mm hyperechoic filling defect in the common bile duct; magnetic resonance cholangiopancreatography demonstrated a curvilinear filling defect at the level of the choledochocholedochostomy, corresponding to the ultrasound finding, as well as an anastomotic biliary stricture (ABS). On endoscopic retrograde cholangiography (ERC), a black tubular stricture with overlying sludge was encountered and extracted from the common bile duct, consistent with a retained 5 Fr pediatric feeding tube originally placed at the time of LT. The patient experienced symptomatic and biochemical relief and successfully underwent serial ERCs with balloon dilatation and maximal biliary stenting for ABS management. With this case, we emphasize the importance of ensuring spontaneous passage or removal of intraductal prostheses placed prophylactically at the time of LT in order to minimize the risk of chronic biliary inflammation and associated sequelae, including cholangitis and ABS formation. We also provide herein a brief review of the use of prophylactic internal transanastomotic prostheses, including biliary tubes and stents, during LT.

Metabolic Myopathies and the Respiratory System.

Metabolic myopathies are a heterogeneous group of disorders characterized by inherited defects of enzymatic pathways involved in muscle cellular energetics and adenosine triphosphate synthesis. Skeletal and respiratory muscles are most affected. There are multiple mechanisms of disease. The age of onset and prognosis vary. Metabolic myopathies cause exercise intolerance, myalgia, and increase in muscle breakdown products during exercise. Some affect smooth muscle like the diaphragm and cause respiratory failure. The pathophysiology is complex and the evidence in literature to guide diagnosis and management is sparse. Treatment is limited. This review discusses the pathophysiology and diagnostic evaluation of these disorders.

Prospective Association of Physical Activity and Heart Failure Hospitalizations Among Black Adults With Normal Ejection Fraction: The Jackson Heart Study.

BACKGROUND: Given high rates of obesity, hypertension, and diabetes mellitus, black persons are at risk to develop heart failure. The association of moderate to vigorous physical activity (MVPA) and heart failure in black adults is underresearched. The purpose of this study was to explore whether greater MVPA was associated with lower risk of heart failure hospitalizations (HFHs) among black adults with normal ejection fractions. METHODS AND RESULTS: We performed a prospective analysis of 4066 black adults who participated in the Jackson Heart Study and who had physical activity measured, had normal ejection fraction on 2-dimensional echocardiograms, and were followed for 7 years for incident HFH. We used Cox proportional regression analyses adjusted for age, sex, body mass index, smoking status, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, coronary heart disease, atrial fibrillation, and chronic kidney disease and examined effect modification by sex and body mass index. Of the eligible population, 1925 participants, according to the duration of MVPA, had poor health (0 minutes/week), 1332 had intermediate health (1-149 minutes/week), and 809 had ideal health (≥150 minutes/week). There were 168 incident HFHs. MVPA for intermediate and ideal health was associated with decreasing risk of incident HFH (hazard ratio: 0.70 [95% confidence interval, 49-1.00] and 0.35 [95% confidence interval, 0.19-0.64], respectively; Ptrend=0.003). The full model revealed hazard ratios of 0.74 [95% confidence interval, 0.52-1.07] and 0.41 [95% confidence interval, 0.22-0.74], respectively. There was no effect modification between MVPA and body mass index or sex on incident HFH. CONCLUSIONS: A dose-response relationship between increasing levels of MVPA and protection from incident HFH was found in black men and women with normal ejection fractions.

Change in End-Expiratory Lung Volume During Sleep in Patients at Risk for Obstructive Sleep Apnea.

STUDY OBJECTIVES: As lung volume decreases radial traction on the upper airway is reduced, making it more collapsible. The purpose of this study was to measure change in end-expiratory lung volume (EELV) following sleep onset and to evaluate the relationship between change in EELV and sleep-disordered breathing. METHODS: Twenty subjects underwent overnight polysomnography, of whom 14 (70%) had obstructive sleep apnea (OSA). Change in EELV was measured throughout the night using magnetometry. Sleep was staged and respiratory events scored using American Academy of Sleep Medicine criteria. An additional 10 subjects had change in EELV measured simultaneously by magnetometer and spirometer while awake. RESULTS: In the subjects studied while awake, change in EELV calculated from magnetometer data correlated very strongly (r = 0.89, P < .001) with that obtained by spirometry. In the 20 subjects who underwent polysomnography, there was a decline in EELV for sleep stages N1, N2, N3, and R (REM sleep); 17.9 ± 121.0 mL (mean ± standard deviation), 228.5 ± 151.8 mL, 198.1 ± 122.1 mL, and 316.7 ± 131.9 mL, respectively. Mean EELV reduction during stage R sleep doubled that noted during non-stage R sleep (316.7 ± 131.9 mL versus 150.9 ± 89.7 mL, respectively) (P < .001). The difference in EELV between non-stage R and stage R sleep inversely correlated with mean oxygen saturation (r = -0.56, P = .06). EELV reduction in individuals with moderate and severe OSA was greater than in those with mild SDB but did not reach statistical significance. CONCLUSIONS: Magnetometry provides a precise, unobtrusive, and continuous means to study lung volume changes during sleep. EELV declines from sleep onset, reaching its nadir during stage R sleep. The reduction in EELV in stage R sleep was associated with lower mean oxygen saturation but was not associated with greater sleep-disordered breathing.

The Maximal Expiratory-to-Inspiratory Pressure Ratio and Supine Vital Capacity as Screening Tests for Diaphragm Dysfunction.

PURPOSE: The change in vital capacity from the seated to supine position (∆VC-supine) is used to screen for diaphragm dysfunction (DD), but some individuals are unable to tolerate the supine position. Since expiratory muscle function is often preserved in patients with isolated DD and inspiratory strength is reduced, the purpose of this study was to examine if the ratio of maximal expiratory pressure to maximal inspiratory pressure (MEP/MIP) may provide an alternative to ∆VC-supine when screening patients for DD. METHODS: We performed a cross-sectional analysis on 76 patients referred for evaluation of unexplained dyspnea and possible DD. MEP and MIP were measured in the seated position as well as the percent change in VC from the seated to supine position (∆VC-supine %). The presence of unilateral diaphragm paralysis (UDP), bilateral diaphragm paralysis (BDP), or normal diaphragm function (N) was confirmed by ultrasound. RESULTS: Of the 76 patients, 23 had N, 40 had UDP, and 13 had BDP. MEP/MIP was significantly greater for UDP compared to N (2.1(1.2-5.7) and 1.5(0.7-2.2), respectively) (median and interquartile range) and for BDP compared to UDP (4.3(2.3-7.5) and 2.1(1.2-5.7), respectively) (p < 0.001). The area (AUC) under the receiver-operating characteristic curve for MEP/MIP between N and UDP was 0.84 (95% confidence interval (CI) 0.74-0.94) and between UDP and BDP was 0.90 (95% CI 0.80-0.99). MEP/MIP had a strong monotonic relationship with ∆VC-supine % (Spearman's ρ = 0.68, p < 0.001). CONCLUSIONS: The MEP/MIP ratio provides a method with comparable sensitivity and specificity to ∆VC-supine % that can be used to screen patients with suspected isolated phrenic neuropathy and alleviates the need for measuring supine pulmonary function.

Association of obstructive sleep apnea risk factors with nocturnal enuresis in postmenopausal women.

OBJECTIVE: The prevalence of obstructive sleep apnea (OSA) in women increases significantly after menopause. However, identifying at-risk women is difficult because they tend to underreport symptoms and their complaints may differ from those traditionally associated with OSA. We investigated whether OSA risk factors are associated with the presence of a "nontraditional" complaint, such as nocturnal enuresis, in postmenopausal women. METHODS: A cross-sectional study of postmenopausal women aged 50 to 79 years who participated in the Women's Health Initiative Observational Study and clinical trials (1993-2005) at 40 clinical centers in the United States was performed. Multiple variable logistic regression analysis was used to determine the association of OSA risk factors with nocturnal enuresis. RESULTS: A cohort of 2,789 women (1.7%) reported having nocturnal enuresis. Obesity (odds ratio [OR], 2.29; 95% CI, 2.00-2.62), snoring (OR, 2.01; 95% CI, 1.74-2.32), poor sleep quality (OR, 1.70; 95% CI, 1.52-1.91), sleep fragmentation (OR, 2.44; 95% CI, 2.14-2.79), daytime sleepiness (OR, 1.50; 95% CI, 1.33-1.68), and hypertension (OR, 1.13; 95% CI, 1.01-1.26) were associated with nocturnal enuresis. Each additional OSA risk factor in a predefined OSA score significantly increased the odds of having nocturnal enuresis in a dose-response fashion (OR of 1.38, 2.00, 2.80, 3.87, 5.10, and 7.02 for scores of 1-6, respectively) compared with no risk factors. CONCLUSIONS: OSA risk factors are associated with nocturnal enuresis in postmenopausal women. Mechanisms relating nocturnal enuresis to OSA may include apnea-associated changes in intrathoracic pressure, leading to increased urine output. Questioning at-risk postmenopausal women presenting with nocturnal enuresis about other OSA risk factors should be considered.

Acute obstructive suppurative pancreatic ductitis in an asymptomatic patient.

Acute obstructive suppurative pancreatic ductitis (AOSPD), defined as suppuration from the pancreatic duct without associated pseudocyst, abscess, or necrosis, is a rare complication of chronic pancreatitis. We present the first case of AOSPD in an asymptomatic patient with a polymicrobial infection and review the literature on this rare clinical entity.

Physiology in Medicine: physiological basis of diaphragmatic dysfunction with abdominal hernias-implications for therapy.

An incisional hernia is a common complication after abdominal surgery. Complaints of dyspnea in this population may be attributed to cardiopulmonary dysfunction or deconditioning. Large abdominal incisional hernias, however, may cause diaphragm dysfunction and result in dyspnea, which is more pronounced when standing (platypnea). The use of an abdominal binder may alleviate platypnea in this population. We discuss the link between diaphragm dysfunction and the lack of abdominal wall integrity and how abdominal wall support partially restores diaphragm function.

Methacholine-induced airway hyper-reactivity phenotypes.

OBJECTIVE: The incorporation of airways conductance/resistance is a rare feature in clinical methacholine challenge test (MCT) protocols, and the majority of pulmonary laboratories rely solely on the spirometric parameters. The importance and interpretation of an MCT demonstrating a significant decline in specific airway conductance specific airway conductance (sGaw), but not forced expiratory volume in one second (FEV(1)), remains undefined. This study sought to elucidate the clinical and physiologic phenotypes of individuals with a ≥40% sGaw decline but <20% FEV(1) change. METHODS: All subjects completed the Asthma Quality of Life Questionnaire (AQLQ), followed by standard MCT, with measurements of sGaw and an additional independent measurement of resistance and reactance by impulse oscillation system (IOS) before and after MCT. RESULTS: Of 201 subjects, 47(23.4%) were in Group 1 (FEV(1) declined by ≥20%), 45(22.4%) were in Group 2 (non-significant FEV(1) drop, sGaw declined ≥40%), and 109(54.2%) were in Group 3 (no significant decline in FEV(1)/sGaw). There was a nearly identical change in all oscillometric parameters and sGaw for Groups 1 and 2 versus Group 3. There were no differences between Groups 1 and 2 in any AQLQ category, and Groups 1 and 2 were statistically different from Group 3. CONCLUSIONS: Our prospective study suggests that patients with a significant sGaw decline alone during MCT are a clinically and physiologically important hyper-reactivity phenotype--whose hyper-reactivity independently was confirmed to be nearly identical to those with an FEV(1) decline. By failing to assess airways conductance/resistance, asthma may be inappropriately "ruled out" in ∼20% of the patients referred for MCT. Based on this, standardized incorporation of body plethysmography and/or IOS to MCT protocols should be considered.