Autotitrating versus standard noninvasive ventilation: a randomised crossover trial.

The aim of the present study was to compare the efficacy of automatic titration of noninvasive ventilation (NIV) with conventional NIV in stable neuromuscular and chest wall disorder patients established on long-term ventilatory support. In total, 20 neuromuscular and chest wall disease patients with nocturnal hypoventilation treated with long-term NIV completed a randomised crossover trial comparing two noninvasive pressure support ventilators: a standard bilevel ventilator (VPAP III) and a novel autotitrating bilevel ventilator (AutoVPAP). Baseline physiological measurements, overnight polysomnography and Holter monitoring were repeated at the end of each 1-month treatment period. Nocturnal oxygenation was comparable between the autotitrating device and standard ventilator, as were sleep efficiency, arousals and heart rate variability. However, there was a small significant increase in mean overnight transcutaneous carbon dioxide tension (median (interquartile range) 7.2 (6.7-7.7) versus 6.7 (6.1-7.0) kPa) and a decrease in percentage stage 1 sleep (mean+/-sd 16+/-9 versus 19+/-10%) on autotitrating NIV compared with conventional NIV. Autotitrating noninvasive ventilation using AutoVPAP produced comparable control of nocturnal oxygenation to standard nonivasive ventilation, without compromising sleep quality in stable neuromuscular and chest wall disease patients requiring long-term ventilatory support for nocturnal hypoventilation.

Risk of Adverse Reactions to Oral Antibiotics Prescribed by Dentists.

Dentists prescribe a large portion of all oral antibiotics, and these are associated with a risk of adverse drug reactions (ADRs). The aim of this study was to quantify the risk of ADRs associated with oral antibiotics commonly prescribed by dentists. NHS Digital Prescribing data and Yellow Card Drug Analysis data for 2010 to 2017 were abstracted to quantify dental antibiotic prescribing in England, and the rate and types of ADRs associated with them. During the period of study, the mean number of actively practicing dentists in England was 23,624. Amoxicillin accounted for 64.8% of dental antibiotic prescribing and had the lowest reported rate of fatal ADRs (0.1/million prescriptions) and overall ADRs (21.5/million prescriptions). Indeed, amoxicillin was respectively 6 and 3 times less likely to cause an ADR than the other penicillins, penicillin V and amoxicillin + clavulanic acid, and appears to be very safe in patients with no history of penicillin allergy. In contrast, clindamycin, which is often used in patients with penicillin allergy, had the highest rate of fatal (2.9/million prescriptions) and overall (337.3/million prescriptions) ADRs, with Clostridiodes (formerly Clostridium) difficile infections pivotal to its ADR profile. Other amoxicillin alternatives, clarithromycin and metronidazole, while significantly worse than amoxicillin, were 3 and nearly 5 times less likely to cause an ADR than clindamycin. Ranked from least to most likely to cause an ADR, antibiotics most commonly prescribed were as follows: amoxicillin < cephalosporins < erythromycin < tetracyclines < azithromycin < metronidazole < amoxicillin + clavulanic acid < clarithromycin < penicillin V < clindamycin. This study confirmed the high level of safety associated with use of amoxicillin by dentists and the significantly worse rates of fatal and nonfatal ADRs associated with other penicillins and alternatives to amoxicillin for those who are penicillin allergic. In particular, clindamycin had the highest rate of fatal and nonfatal ADRs of any of the antibiotics commonly prescribed by dentists.

A high prevalence of sleep disordered breathing in men with mild symptomatic chronic heart failure due to left ventricular systolic dysfunction.

BACKGROUND: Sleep disordered breathing (SDB) is common in severe chronic heart failure (CHF) and is associated with increased morbidity and mortality. The prevalence of SDB in mild symptomatic CHF is unknown. AIM: The aim of this study was to determine the prevalence and characteristics of SDB in male patients with NYHA class II symptoms of CHF. METHODS AND RESULTS: 55 male patients with mild symptomatic CHF underwent assessment of quality of life, echocardiography, cardiopulmonary exercise, chemoreflex testing and polysomnography. 53% of the patients had SDB. 38% had central sleep apnoea (CSA) and 15% had obstructive sleep apnoea. SDB patients had steeper VE/VCO(2) slope [median (inter-quartile range) 31.1 (28-37) vs. 28.1 (27-30) respectively; p=0.04], enhanced chemoreflexes to carbon dioxide during wakefulness [mean+/-sd: 2.4+/-1.6 vs. 1.5+/-0.7 %VE Max/mmHg CO(2) respectively; p=0.03], and significantly higher levels of brain natriuretic peptide and endothelin-1 compared to patients without SDB. No differences in left ventricular ejection fraction, percent predicted peak oxygen uptake, or symptoms of SDB were observed. CONCLUSIONS: A high prevalence of SDB was found in men with mild symptomatic CHF. Patients with SDB could not be differentiated by symptoms or by routine cardiac assessment making clinical diagnosis of SDB in CHF difficult.

A novel technique for nonvolitional assessment of quadriceps muscle endurance in humans.

Assessment of quadriceps endurance is of interest to investigators studying human disease. We hypothesized that repetitive magnetic stimulation (rMS) of the intramuscular branches of the femoral nerve could be used to induce and quantify quadriceps endurance. To test this hypothesis, we used a novel stimulating coil to compare the quadriceps endurance properties in eight normal humans and, to confirm that the technique could be used in clinical practice, in eight patients with advanced chronic obstructive pulmonary disease (COPD). To validate the method, we compared in vivo contractile properties of the quadriceps muscle with the fiber-type composition and oxidative enzyme capacity. We used a Magstim Rapid(2) magnetic nerve stimulator with the coil wrapped around the quadriceps. Stimuli were given at 30 Hz, a duty cycle of 0.4 (2 s on, 3 s off), and for 50 trains. Force generation and the surface electromyogram were measured throughout. Quadriceps twitch force, elicited by supramaximal magnetic stimulation of the femoral nerve, was measured before and after the protocol. Quadriceps muscle biopsies were analyzed for oxidative (citrate synthase, CS) and glycolytic (phosphofructokinase, PFK) enzyme activity and myosin heavy chain isoform protein expression. The time for force to fall to 70% of baseline (T(70)) was shorter in the COPD group than the control group: 55.6 +/- 26.0 vs. 121 +/- 38.7 s (P = 0.0014). Considering patients and controls together, positive correlations were observed between T(70) and the proportion of type I fibers (r = 0.68, P = 0.004) and CS-to-PFK ratio (CS/PFK) (r = 0.67, P = 0.005). We conclude that quadriceps endurance assessed using rMS is feasible in clinical studies.

Right hemi-diaphragm paralysis following cardiac radiofrequency ablation.

Diaphragm paralysis may occur after traumatic phrenic nerve injury. Here we report three patients in whom right hemi-diaphragmatic paralysis developed after cardiac radiofrequency ablation. We hypothesise that local focused thermal energy at the time of the ablation may have caused direct neuronal damage by axonal coagulation necrosis. The prognosis for this type of injury may be reasonably good; two of the three patients fully recovered diaphragm function by 1 year.

Guidelines on prophylaxis to prevent infective endocarditis.

Infective endocarditis is a devastating disease with high morbidity and mortality. The link to oral bacteria has been known for many decades and has caused ongoing concern for dentists, patients and cardiologists. Since 2008, the UK has been out of step with the rest of the world where antibiotic prophylaxis is recommended for high-risk patients undergoing invasive dental procedures. Recent evidence that identified an increase in endocarditis incidence prompted a guideline review by NICE and the European Society for Cardiology--which produces guidance for the whole of Europe. Despite reviewing the same evidence they reached completely opposing conclusions. The resulting conflict of opinions and guidance is confusing and poses difficulties for dentists, cardiologists and their patients. Recent changes in the law on consent, however, may provide a patient-centred and pragmatic solution to these problems. This Opinion piece examines the evidence and opposing guidance on antibiotic prophylaxis in the context of the recent changes in the law on consent and provides a framework for how patients at risk of endocarditis might be managed in practice.

A change in the NICE guidelines on antibiotic prophylaxis.

Since 2008, NICE clinical guidelines have stated: 'Antibiotic prophylaxis against infective endocarditis is not recommended for people undergoing dental procedures'. This put UK guidance at odds with guidance in the rest of the world, where antibiotic prophylaxis is recommended for patients at high-risk of infective endocarditis undergoing invasive dental procedures. Many dentists also felt this wording prohibited the use of antibiotic prophylaxis, regardless of the wishes of the patient or their personal risk of infective endocarditis and made it difficult for them to use their clinical judgment to deliver individualised care in the best interests of their patients. NICE have now changed this guidance to 'Antibiotic prophylaxis against infective endocarditis is not recommended routinely for people undergoing dental procedures.' This article examines the implications of this small but important change.

Adoptive transfer of diabetes in BB rats induced by CD4 T lymphocytes.

Unseparated splenocytes (SPCs) or purified SPC subsets from diabetes-prone BB (BBdp) or diabetic BB (BBd) rats were activated in vitro with either phorbol myristate acetate (PMA) and ionomycin (I) or concanavalin A (ConA). Such activated SPCs were then injected intravenously into 30-day-old BBdp rats, and their capacity to induce adoptive transfer (AT) of diabetes was studied. The proliferative response in vitro of BBd unseparated SPCs or purified W3/13+ SPCs (i.e., T lymphocytes + large granular lymphocytes) to PMA + I far exceeded that of ConA, resulting in mean stimulation indices of 68 and 112 (PMA + I) and 1.9 and 30 (ConA). The incidence of AT was similar when equal numbers of unseparated SPCs from the same BBd donor were injected after activation by either PMA + I + interleukin 2 (PII) or ConA (57 vs. 50%, respectively); however, injection of PII-activated and macrophage-depleted W3/13+ SPCs from BBd animals resulted in a significantly higher incidence of AT (90%, P less than 0.05). As few as 0.5 x 10(6) PII-activated W3/13+ SPCs were sufficient to induce AT. Sixteen percent of recipients developed diabetes after injection of activated W3/13+ cells from 40-day-old BBdp donors. To determine which W3/13+ cells might mediate such transfer, purified and PII-preactivated CD4 T lymphocytes from BBd rats were injected, and they succeeded in AT in 44% of the recipients. Preactivated BBd B lymphocytes were unable to induce AT. Although a possible role for large granular lymphocytes cannot be excluded, the results demonstrate that in the BB rat, the beta-cell destruction can be induced by CD4 T lymphocytes.

Effects of single and repeated blood withdrawals on circulating mononuclear cells in BB rats. Failure to prevent diabetes despite acute changes in counts.

Repeated large-volume blood withdrawals started at a young age previously appeared to correct lymphopenia and prevent diabetes in Ottawa diabetes-prone BB (BBdp) rats. Therefore, we sought an early effect 24 h after withdrawal of 25% of estimated blood volume and then reexamined the long-term effects in BBdp rats. The reexamination was prompted by the occurrence of variable numbers of BBdp rats positive for RT6.1 (a T-lymphocyte differentiation alloantigen) whose presence appears to "protect" against diabetes development (identified as BBp rats). Four groups were studied: non-diabetes-prone (BBn), RT6.1- BBdp, RT6.1+ BBp, and acutely diabetic BB (BBd) rats. An acute increase in the number of peripheral blood mononuclear cells and many subsets occurred in BBd and BBp rats. Despite these acute effects, a long-term effect of repeated blood withdrawal was not found in circulating cell counts or prevention of diabetes in BBdp rats. Thus, the previous finding was probably attributable to the presence of BBp rats. The long-term study demonstrated that RT6.1 expression in BBn rats increased from low levels at 15 days, peaked at 50 days, and decreased thereafter, an important finding in interpreting RT6.1 status at different ages. Furthermore, in contrast with other subsets, MARK-1+ B lymphocytes and OX42+ monocytes/macrophages decreased markedly in number at 120 and 150 days in BBn and BBp rats, whereas counts were higher and sustained in BBdp rats. The latter finding could be related to BBdp rats successfully resisting the autoaggressive process beyond the peak age of diabetes onset.

The reliability and validity of two HIV-specific health-related Quality-of-Life measures: a preliminary analysis.

OBJECTIVE: To evaluate the reliability and validity of two HIV-specific Quality-of-Life (QoL) questionnaires in a UK sample. METHOD: Subjects were 99 HIV-seropositive gay men (23 were asymptomatic, 41 were asymptomatic, 35 had AIDS). QoL was measured using two HIV-specific QoL questionnaires. MEASURES: An adaptation of the Medical Outcomes Study questionnaire and a self-completion version of the Health-Related Quality-of-Life Questions. Affect was measured using the Hospital Anxiety and Depression (HAD) Scale. Disease measures included Centers for Disease Control and Prevention (CDC) stage, and CD4 and CD8 cell count. RESULTS: Both QoL instruments showed good internal reliability on all scales used. Many of the scales, particularly those related to physical health and functional performance, showed significant correlations with CD4 cell count and other measures of disease progression. Measures of physical health showed a deterioration in QoL as disease progressed from asymptomatic disease to AIDS. In contrast, most subscales purporting to measure psychological aspects of QoL did not correlate significantly with measures of disease progression, nor was there any difference between CDC stages. Subjects' global ratings of QoL were most strongly correlated with the HAD depression scale, although there were also significant correlations with most other QoL scales. CONCLUSION: This study provides further evidence for the reliability and validity of two HIV-specific QoL questionnaires in a wider range of disease stages than hitherto reported and raises issues relevant to the practical use of QoL scales in HIV disease.

Facet joint osteomyelitis in a patient on long-term hemodialysis.

Spinal osteomyelitis is a recognized complication in dialysis patients related to hematogenous spread of infection during bacteremia-septicemia. These episodes are often associated with sepsis due to temporary dialysis access. We describe the case of an unfortunate man whose osteomyelitis was located in the posterior facet joints. Such infection is rare and in the reviewed literature is usually associated with a more favorable outcome than described here.

NICE guidance on antibiotic prophylaxis to prevent infective endocarditis: a survey of clinicians' attitudes.

BACKGROUND: Since the introduction of the National Institute for Health and Clinical Excellence (NICE) guideline (CG064) in 2008 recommending cessation of antibiotic prophylaxis (AP) against infective endocarditis (IE), low level prescribing persists in the UK and is a potential reason why there has been no significant change in the general upward trend in cases of IE. AIM: To undertake a survey of dentists (Ds), cardiologists and cardiothoracic surgeons (C/CTSs) and infection specialists (ISs) to determine why this might be the case. DESIGN: Internet questionnaire-based survey. METHODS: A questionnaire was distributed by email to specialists via UK national societies. RESULTS: A total of 1168 responses were received. All the specialist groups are aware of the guideline (99%). Ds are broadly satisfied, whereas C/CTSs are not. Most Ds follow the NICE guidance (87%), whereas many C/CTSs (39%) do not; ISs adopt a middle course (56%). Even amongst Ds, a significant proportion believe that patients with a prosthetic heart valve (25%) or previous history of IE (38%) should receive AP. A total of 36% of Ds have prescribed AP since March 2008 and many have undertaken procedures where AP has been prescribed by someone else. The majority of respondents (65%) feel that more evidence is required, preferably in the form of a randomized controlled trial. CONCLUSION: Many patients perceived to be at high risk of IE are still receiving AP in conflict with current NICE guidance.

New evidence on hypoglycemic effect of quinolinic acid in diabetic rats.

In the present study, the effects of administrating 4 mM and 300 mg kg(-1) b.wt. of quinolinic acid were studied, in vitro and in vivo, respectively, to evaluate its inhibitory activity on phosphoenolpyruvate carboxykinase in diabetic rats. The results of in vitro studies have clearly indicated the inhibitory effect of quinolinic acid on enzyme activity. The hill plot showed the binding stoichiometry of quinolinic acid per enzyme to be 4:1. The in vivo studies showed that intra peritoneal injection of 300 mg kg(-1) b.wt. initiates reduction of blood glucose level in 1 h after injection, restoring the blood glucose to its normal level at 2 h post injection and keeping it constant for at least further 4 h. Based on present results we concluded that quinolinic acid and hence its precursor tryptophan having induced obvious hypoglycemic effects in normal and diabetic rats at high enough concentrations, they are worthy of further study and research for their hyperglycemic effect in other diabetic animal models.

Adaptive servo-ventilation and deadspace: effects on central sleep apnoea.

Central Sleep Apnoea (CSA) occurs commonly in heart failure. Adaptive servo-ventilation (ASV) and deadspace (DS) have been shown in research settings to reverse CSA. The likely mechanism for this is the increase of PaCO(2) above the apnoeic threshold. However the role of increasing FiCO(2) on arousability remains unclear. To compare the effects of ASV and DS on sleep and breathing, in particular effects on Arousal Index (ArI), ten male patients with heart failure and CSA were studied during three nights with polysomnography plus measurements of PetCO(2). The order of the interventions control (C), ASV and DS was randomized. ASV and DS caused similar reductions in apnoea-hypopnoea index [(C) 30.0 +/- 6.6, (ASV) 14.0 +/- 3.8, (DS) 15.9 +/- 4.7 e h(-1); both P < 0.05]. However, DS was associated with decreased total sleep time compared with C (P < 0.02) and increased spontaneous ArI compared to C and ASV (both P < 0.01). Only DS was associated with increased DeltaPetCO(2) from resting wakefulness to eupnic sleep [(C) 2.1 +/- 0.9, (ASV) 1.3 +/- 1.0, (DS) 5.6 +/- 0.5 mmHg; P = 0.01]. ASV and DS both stabilized ventilation however DS application also increased sleep fragmentation with negative impacts on sleep architecture. We speculate that this effect is likely to be mediated by increased PetCO(2) and respiratory effort associated with DS application.

Can heart rate variation rule out sleep-disordered breathing in heart failure?

In patients with obstructive sleep apnoea (OSA), the very low frequency power spectral density index (VLFI) derived from analysis of heart rate correlates with the severity of obstructive apnoeas. VLFI is also associated with Cheyne-Stokes respiration/central sleep apnoea (CSR/CSA) in congestive heart failure (CHF). The present authors have tested the hypothesis that per cent VLFI, derived from a standard Holter ECG recording, can be used to detect the presence of OSA and CSR/CSA in patients with mild-to-moderate CHF. In total, 60 CHF patients underwent polysomnography with monitoring of heart rate. Data from 33 patients were analysed for per cent VLFI. Of the 60 patients, 27 were excluded due to atrial fibrillation, extensive pacing or frequent ventricular extra systoles. Receiver operator characteristic curves were constructed to establish the per cent VLFI that would optimally identify the presence or absence of sleep-disordered breathing. Using an apnoea-hypopnoea index>20 events.h-1 and setting the per cent VLFI at 2.23% yielded a sensitivity of 85%, specificity of 65%, positive predictive value of 61% and a negative predictive value of 87%. The latter increased to 100% when using an apnoea-hypopnoea cut-off of 30 events.h-1. In conclusion, these results suggest that spectral analysis of heart rate may be useful as a "rule-out test" for sleep-disordered breathing in patients with mild-to-moderate congestive heart failure.