Diagnosis and management in Pitt-Hopkins syndrome: First international consensus statement.

Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder characterized by intellectual disability, specific facial features, and marked autonomic nervous system dysfunction, especially with disturbances of regulating respiration and intestinal mobility. It is caused by variants in the transcription factor TCF4. Heterogeneity in the clinical and molecular diagnostic criteria and care practices has prompted a group of international experts to establish guidelines for diagnostics and care. For issues, for which there was limited information available in international literature, we collaborated with national support groups and the participants of a syndrome specific international conference to obtain further information. Here, we discuss the resultant consensus, including the clinical definition of PTHS and a molecular diagnostic pathway. Recommendations for managing particular health problems such as dysregulated respiration are provided. We emphasize the need for integration of care for physical and behavioral issues. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimization of diagnostics and care.

Restoring heat stress-associated reduction in middle cerebral artery velocity does not reduce fatigue in the heat.

Heat-induced hyperventilation may reduce PaCO2 and thereby cerebral perfusion and oxygenation and in turn exercise performance. To test this hypothesis, eight volunteers completed three incremental exercise tests to exhaustion: (a) 18 °C ambient temperature (CON); (b) 38 °C (HEAT); and (c) 38 °C with addition of CO2 to inspiration to prevent the hyperventilation-induced reduction in PaCO2 (HEAT + CO2 ). In HEAT and HEAT + CO2 , rectal temperature was elevated prior to the exercise tests by means of hot water submersion and was higher (P < 0.05) than in CON. Compared with CON, ventilation was elevated (P < 0.01), and hence, PaCO2 reduced in HEAT. This caused a reduction (P < 0.05) in mean cerebral artery velocity (MCAvmean ) from 68.6 ± 15.5 to 53.9 ± 10.0 cm/s, which was completely restored in HEAT + CO2 (68.8 ± 5.8 cm/s). Cerebral oxygenation followed a similar pattern. V ˙ O 2   m a x was 4.6 ± 0.1 L/min in CON and decreased (P < 0.05) to 4.1 ± 0.2 L/min in HEAT and remained reduced in HEAT + CO2 (4.1 ± 0.2 L/min). Despite normalization of MCAvmean and cerebral oxygenation in HEAT + CO2 , this did not improve exercise performance, and thus, the reduced MCAvmean in HEAT does not seem to limit exercise performance.

Efficient extra- and intracellular alkalinization improves cardiovascular functions in severe lactic acidosis induced by hemorrhagic shock.

BACKGROUND: Lactic acidosis is associated with cardiovascular failure. Buffering with sodium bicarbonate is proposed in severe lactic acidosis. Bicarbonate induces carbon dioxide generation and hypocalcemia, both cardiovascular depressant factors. The authors thus investigated the cardiovascular and metabolic effects of an adapted sodium bicarbonate therapy, including prevention of carbon dioxide increase with hyperventilation and ionized calcium decrease with calcium administration. METHODS: Lactic acidosis was induced by hemorrhagic shock. Twenty animals were randomized into five groups: (1) standard resuscitation with blood retransfusion and norepinephrine (2) adapted sodium bicarbonate therapy (3) nonadapted sodium bicarbonate therapy (4) standard resuscitation plus calcium administration (5) hyperventilation. Evaluation was focused in vivo on extracellular pH, on intracellular pH estimated by P nuclear magnetic resonance and on myocardial contractility by conductance catheter. Aortic rings and mesenteric arteries were isolated and mounted in a myograph, after which arterial contractility was measured. RESULTS: All animals in the hyperventilation group died prematurely and were not included in the statistical analysis. When compared with sham rats, shock induced extracellular (median, 7.13; interquartile range, [0.10] vs. 7.30 [0.01]; P = 0.0007) and intracellular acidosis (7.26 [0.18] vs. 7.05 [0.13]; P = 0.0001), hyperlactatemia (7.30 [0.01] vs. 7.13 [0.10]; P = 0.0008), depressed myocardial elastance (2.87 [1.31] vs. 0.5 [0.53] mmHg/µl; P = 0.0001), and vascular hyporesponsiveness to vasoconstrictors. Compared with nonadapted therapy, adapted bicarbonate therapy normalized extracellular pH (7.03 [0.12] vs. 7.36 [0.04]; P < 0.05), increased intracellular pH to supraphysiological values, improved myocardial elastance (1.68 [0.41] vs. 0.72 [0.44] mmHg/µl; P < 0.05), and improved aortic and mesenteric vasoreactivity. CONCLUSIONS: A therapeutic strategy based on alkalinization with sodium bicarbonate along with hyperventilation and calcium administration increases pH and improves cardiovascular function.

Medical emergency management among Iranian dentists.

AIMS: More than 18,000 patients need medical emergencies management in dental offices in Iran annually. The present study investigates medical emergencies management among Iranian dentists. MATERIALS AND METHODS: From the list of the cell phone numbers of the dentists practicing in the city of Tehran, 210 dentists were selected randomly. A self-administered questionnaire was used as the data collection instrument. The questionnaire requested information on personal and professional characteristics of the dentists, as well as their knowledge and self-reported practice in the field of medical emergency management, and availability of required drugs and equipments to manage medical emergencies in their offices. RESULTS: Totally, 177 dentists (84%) completed the questionnaire. Less than 60% of the participants were knowledgeable about characteristics of hypoglycemic patient, chest pain with cardiac origin, and true cardiopulmonary resuscitation (CPR) practice. Regarding practice, less than one quarter of the respondents acquired acceptable scores. In regression models, higher practice scores were significantly associated with higher knowledge scores (p < 0.001). CONCLUSION: The results call for a need to further education on the subject for dentists. Continuing education and changing dental curriculum in the various forms seems to be useful in enhancement of the self-reported knowledge and practice of dentists. CLINICAL SIGNIFICANCE: To successful control of medical emergencies in the dental office, dentists must be prepared to recognize and manage a variety of such conditions. In addition to dentist's knowledge and skill, availability of necessary equipments and trained staff is also of critical importance.

Breathing exercises for dysfunctional breathing/hyperventilation syndrome in children.

BACKGROUND: Dysfunctional breathing is described as chronic or recurrent changes in breathing pattern causing respiratory and non-respiratory symptoms. It is an umbrella term that encompasses hyperventilation syndrome and vocal cord dysfunction. Dysfunctional breathing affects 10% of the general population. Symptoms include dyspnoea, chest tightness, sighing and chest pain which arise secondary to alterations in respiratory pattern and rate. Little is known about dysfunctional breathing in children. Preliminary data suggest 5.3% or more of children with asthma have dysfunctional breathing and that, unlike in adults, it is associated with poorer asthma control. It is not known what proportion of the general paediatric population is affected. Breathing training is recommended as a first-line treatment for adults with dysfunctional breathing (with or without asthma) but no similar recommendations are available for the management of children. As such, breathing retraining is adapted from adult regimens based on the age and ability of the child. OBJECTIVES: To determine whether breathing retraining in children with dysfunctional breathing has beneficial effects as measured by quality of life indices.To determine whether there are any adverse effects of breathing retraining in young people with dysfunctional breathing. SEARCH METHODS: We identified trials for consideration using both electronic and manual search strategies. We searched CENTRAL, MEDLINE and EMBASE. We searched the National Research Register (NRR) Archive, Health Services Research Projects in Progress (HSRProj), Current Controlled Trials register (incorporating the metaRegister of Controlled Trials and the International Standard Randomised Controlled Trial Number (ISRCTN) to identify research in progress and unpublished research. The latest search was undertaken in October 2013. SELECTION CRITERIA: We planned to include randomised, quasi-randomised or cluster-randomised controlled trials. We excluded observational studies, case studies and studies utilising a cross-over design. The cross-over design was considered inappropriate due to the purported long-lasting effects of breathing retraining. Children up to the age of 18 years with a clinical diagnosis of dysfunctional breathing were eligible for inclusion. We planned to include children with a primary diagnosis of asthma with the intention of undertaking a subgroup analysis. Children with symptoms secondary to cardiac or metabolic disease were excluded.We considered any type of breathing retraining exercise for inclusion in this review, such as breathing control, diaphragmatic breathing, yoga breathing, Buteyko breathing, biofeedback-guided breathing modification and yawn/sigh suppression. We considered programmes where exercises were either supervised (by parents or a health professional, or both) or unsupervised. We also considered relaxation techniques and acute episode management as long as it was clear that breathing exercises were a component of the intervention.Any intervention without breathing exercises or where breathing exercises were not key to the intervention were excluded. DATA COLLECTION AND ANALYSIS: We planned that two authors (NJB and MJ) would extract data independently using a standardised form. Any discrepancies would be resolved by consensus. Where agreement could not be reached a third review author (MLE) would have considered the paper. MAIN RESULTS: We identified 264 potential trials and reviews from the search. Following removal of duplicates, we screened 224 papers based on title and abstract. We retrieved six full-text papers and further evaluated them but they did not meet the inclusion criteria. There were, therefore, no studies suitable for inclusion in this review. AUTHORS' CONCLUSIONS: The results of this systematic review cannot inform clinical practice as no suitable trials were identified for inclusion. Therefore, it is currently unknown whether these interventions offer any added value in this patient group or whether specific types of breathing exercise demonstrate superiority over others. Given that breathing exercises are frequently used to treat dysfunctional breathing/hyperventilation syndrome, there is an urgent need for well-designed clinical trials in this area. Future trials should conform to the CONSORT statement for standards of reporting and use validated outcome measures. Trial reports should also ensure full disclosure of data for all important clinical outcomes.

Breathing exercises for dysfunctional breathing/hyperventilation syndrome in adults.

BACKGROUND: Dysfunctional breathing/hyperventilation syndrome (DB/HVS) is a respiratory disorder, psychologically or physiologically based, involving breathing too deeply and/or too rapidly (hyperventilation) or erratic breathing interspersed with breath-holding or sighing (DB). DB/HVS can result in significant patient morbidity and an array of symptoms including breathlessness, chest tightness, dizziness, tremor and paraesthesia. DB/HVS has an estimated prevalence of 9.5% in the general adult population, however, there is little consensus regarding the most effective management of this patient group. OBJECTIVES: (1) To determine whether breathing exercises in patients with DB/HVS have beneficial effects as measured by quality of life indices (2) To determine whether there are any adverse effects of breathing exercises in patients with DB/HVS SEARCH METHODS: We identified trials for consideration using both electronic and manual search strategies. We searched CENTRAL, MEDLINE, EMBASE, and four other databases. The latest search was in February 2013. SELECTION CRITERIA: We planned to include randomised, quasi-randomised or cluster randomised controlled trials (RCTs) in which breathing exercises, or a combined intervention including breathing exercises as a key component, were compared with either no treatment or another therapy that did not include breathing exercises in patients with DB/HVS. Observational studies, case studies and studies utilising a cross-over design were not eligible for inclusion.We considered any type of breathing exercise for inclusion in this review, such as breathing control, diaphragmatic breathing, yoga breathing, Buteyko breathing, biofeedback-guided breathing modification, yawn/sigh suppression. Programs where exercises were either supervised or unsupervised were eligible as were relaxation techniques and acute-episode management, as long as it was clear that breathing exercises were a key component of the intervention.We excluded any intervention without breathing exercises or where breathing exercises were not key to the intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently checked search results for eligible studies, assessed all studies that appeared to meet the selection criteria and extracted data. We used standard procedures recommended by The Cochrane Collaboration. MAIN RESULTS: We included a single RCT assessed at unclear risk of bias, which compared relaxation therapy (n = 15) versus relaxation therapy and breathing exercises (n = 15) and a no therapy control group (n = 15).Quality of life was not an outcome measure in this RCT, and no numerical data or statistical analysis were presented in this paper. A significant reduction in the frequency and severity of hyperventilation attacks in the breathing exercise group compared with the control group was reported. In addition, a significant difference in frequency and severity of hyperventilation attacks between the breathing and relaxation group was reported. However, no information could be extracted from the paper regarding the size of the treatment effects. AUTHORS' CONCLUSIONS: The results of this systematic review are unable to inform clinical practice, based on the inclusion of only one small, poorly reported RCT. There is no credible evidence regarding the effectiveness of breathing exercises for the clinical symptoms of DB/HVS. It is currently unknown whether these interventions offer any added value in this patient group or whether specific types of breathing exercise demonstrate superiority over others. Given that breathing exercises are frequently used to treat DB/HVS, there is an urgent need for further well designed clinical trials in this area. Future trials should conform to the CONSORT statement for standards of reporting and use appropriate, validated outcome measures. Trial reports should also ensure full disclosure of data for all important clinical outcomes.

Transcranial, Non-Invasive Evaluation of Potential Misery Perfusion During Hyperventilation Therapy of Traumatic Brain Injury Patients.

Hyperventilation (HV) therapy uses vasoconstriction to reduce intracranial pressure (ICP) by reducing cerebral blood volume. However, as HV also lowers cerebral blood flow (CBF), it may provoke misery perfusion (MP), in which the decrease in CBF is coupled with increased oxygen extraction fraction (OEF). MP may rapidly lead to the exhaustion of brain energy metabolites, making the brain vulnerable to ischemia. MP is difficult to detect at the bedside, which is where transcranial hybrid, near-infrared spectroscopies are promising because they non-invasively measure OEF and CBF. We have tested this technology during HV (∼30 min) with bilateral, frontal lobe monitoring to assess MP in 27 sessions in 18 patients with traumatic brain injury. In this study, HV did not lead to MP at a group level (p > 0.05). However, a statistical approach yielded 89 events with a high probability of MP in 19 sessions. We have characterized each statistically significant event in detail and its possible relationship to clinical and radiological status (decompressive craniectomy and presence of a cerebral lesion), without detecting any statistically significant difference (p > 0.05). However, MP detection stresses the need for personalized, real-time assessment in future clinical trials with HV, in order to provide an optimal evaluation of the risk-benefit balance of HV. Our study provides pilot data demonstrating that bedside transcranial hybrid near-infrared spectroscopies could be utilized to assess potential MP.

[Device diagnosis and combined treatment of hyperventilation syndrome].

Hyperventilation syndrome is a separate disease and a symptom of other psychosomatic diseases. A variant of device diagnosis of the disease is proposed--integral rheoplethysmography by M. I. Tischenko and cardiointervalography by R. M. Baevsky. Hyper- and asthenic courses of the disease are described, the pathological psychoemotional pattern is recognized. The proposed treatment combines physiohemotherapy (laser treatment) and pharmacotherapy.

[Hyperventilation syndrome]. / Syndrome d'hyperventilation.

Hyperventilation syndrome is a disorder affecting children and adults, mostly women. It is frequently associated with anxiety disorders, and greatly affects quality of life. Diagnosis, which unfortunately is most often established late, is a diagnosis of elimination. It rests on a wide range of non-specific signs, on Nijmegën's clinical scale as well as on a hyperventilation provocative test. In most cases, specialized therapeutic interventions allow for an adequate control of ventilation and symptom relief.

Habituation or Normalization? Experiential and Respiratory Recovery From Voluntary Hyperventilation in Treated Versus Untreated Patients With Panic Disorder.

Psychophysiological theories postulate respiratory dysregulation as a mechanism contributing to panic disorder (PD). Additionally, symptomatic and respiratory recovery from voluntary hyperventilation (HVT-recovery) have been shown to lag in PD and it is unclear if HVT-recovery normalizes with treatment. Thirty-seven panic disorder patients were randomized to hypoventilation therapy (TX, n = 20) or waitlist control (WL, n = 17) (Meuret et al., 2008). In a secondary analysis, their HVT-recovery was analyzed at pre- and post-TX/WL, compared to 29 healthy controls (HC). HVT included three phases: 5-min baseline, 3-min hyperventilation, and 8-min recovery. HVT-elicited symptom severity and anxiety were rated following each phase, and end-tidal PCO2 and respiratory rate (RR) were recorded throughout. Treatment, compared to WL, was highly effective in reducing PD pathology (d=2.21, Meuret et al., 2008). At pre-TX/WL, PD demonstrated delayed HVT-recovery PCO2 and higher RR. Treated patients demonstrated normalization of HVT-recovery for PCO2 and RR; however, improvements of HVT-recovery for symptom severity and anxiety did not differ between TX and WL. Results replicate pretreatment HVT respiratory recovery abnormalities in PD and further demonstrate normalization, comparable to HC, following successful treatment. The results provide support for respiratory dysregulation as a feature of PD and demonstrate the utility of HVT respiratory recovery as treatment outcome measure for respiration-based PD therapy.

Comparative analysis between available challenge tests in the hyperventilation syndrome.

BACKGROUND: The hyperventilation syndrome (HVS) is characterized by somatic/ psychological symptoms due to sustained hypocapnia and respiratory alkalosis without any organic disease. OBJECTIVE: The purpose of this study was to compare ventilatory parameters and symptoms reproducibility during the hyperventilation provocation test (HVPT) and cardiopulmonary exercise test (CPET) as diagnostic tools in patients with HVS, and to identify the most frequent etiologies of the HVS by a systematic assessment. METHODS: After exclusion of organic causes, 59 patients with HVS according to Nijmegen's questionnaire (NQ) score ≥23 with associated hypocapnia (PaCO2/PETCO2<35 mm Hg) were studied. RESULTS: The most frequent comorbidities of HVS were anxiety and asthma (respectively 95% and 73% of patients). All patients described ≥3 symptoms of NQ during the HVPT vs 14% of patients during the CPET (p<0.01). For similar maximal ventilation (61 L/min during HVPT vs 60 L/min during CPET), the median level of PETCO2 decreased from 30 mmHg at baseline to 15 mmHg during hyperventilation and increased from 31 mmHg at baseline to 34 mmHg at peak exercise (all p<0.01). No significant difference for the ventilatory parameters was found between patients with HVS (n = 16) and patients with HVS + asthma (n = 43). CONCLUSIONS: In term of symptoms reproducibility, HVPT is a better diagnostic tool than CPET for HVS. An important proportion of patients with HVS has an atypical asthma previously misdiagnosed. The exercise-induced hyperventilation did not induce abnormal reduction in PETCO2, suggesting that the exercise could be a therapeutic tool in HVS.

Acute exacerbation of asthma complicated by hyperventilation in emergency department.

Acute asthmatic attack is an important emergency medical condition. The author hereby reports a case in the emergency department of an acute exacerbation of asthma, complicated by hyperventilation. In this case, the patient had underlying needle phobia, which suddenly occurred during the salbutamol injection. Nevertheless, both physical and psychological approaches led to the successful control of the condition. This report addresses a situation, which, although rare, should not be overlooked.

Breathlessness and dysfunctional breathing in patients with postural orthostatic tachycardia syndrome (POTS): The impact of a physiotherapy intervention.

Postural orthostatic tachycardia syndrome (POTS) is a chronic, multifactorial syndrome with complex symptoms of orthostatic intolerance. Breathlessness is a prevalent symptom, however little is known about the aetiology. Anecdotal evidence suggests that breathless POTS patients commonly demonstrate dysfunctional breathing/hyperventilation syndrome (DB/HVS). There are, however, no published data regarding DB/HVS in POTS, and whether physiotherapy/breathing retraining may improve patients' breathing pattern and symptoms. The aim of this study was to explore the potential impact of a physiotherapy intervention involving education and breathing control on DB/HVS in POTS. A retrospective observational cohort study of all patients with POTS referred to respiratory physiotherapy for treatment of DB/HVS over a 20-month period was undertaken. 100 patients (99 female, mean (standard deviation) age 31 (12) years) with a clinical diagnosis of DB/HV were referred, of which data was available for 66 patients pre - post intervention. Significant improvements in Nijmegen score, respiratory rate and breath hold time (seconds) were observed following treatment. These data provide a testable hypothesis that breathing retraining may provide breathless POTS patients with some symptomatic relief, thus improving their health-related quality of life. The intervention can be easily protocolised to ensure treatment fidelity. Our preliminary findings provide a platform for a subsequent randomised controlled trial of breathing retraining in POTS.

Medical emergencies in dental practice: 2. Management of specific medical emergencies.

UNLABELLED: In the second of two papers on the diagnosis and management of medical emergencies, the measures needed to manage specific medical emergencies are discussed. Each emergency requires a correct diagnosis for effective and safe management. Signs and symptoms are highlighted at the beginning of each section describing patient management. The basis of management in contemporary dental practice avoids the intravenous route of drug administration, where drugs are required. CLINICAL RELEVANCE: All dental practitioners require a knowledge of the management of specific medical emergencies.

Medical emergencies in dental practice.

Serious medical emergencies are fortunately a rare occurrence in the dental practice environment; however, if an emergency situation is encountered a delay in treatment may result in potentially avoidable consequences. The risk of mortality or serious morbidity can be reduced by ensuring that basic emergency equipment and medications are in place, and that the dental team is appropriately trained in basic life support measures. This article aims to provide an overview of the basic emergency medications and equipment that should be present in dental practices, and to discuss specific responses to some of the more common adverse medical events that can present while providing dental treatment.

[Reflex cough: etiology, clinical features, diagnosis, and treatment].

Etiologic factors responsible for the development of reflex coughing are described. A highly efficacious and safe method is proposed for the management of this condition of psychogenic origin associated with hyperventilation by intradermal novocaine blockade of the laryngeal Head's zones in conjunction with preventive treatment of coughing attacks.