Comparison of 3 Days Amoxicillin Versus 5 Days Co-Trimoxazole for Treatment of Fast-breathing Pneumonia by Community Health Workers in Children Aged 2-59 Months in Pakistan: A Cluster-randomized Trial.

BACKGROUND: Globally, most deaths due to childhood pneumonia occur at the community level. Some countries are still using oral co-trimoxazole, despite a World Health Organization recommendation of oral amoxicillin for the treatment of fast-breathing pneumonia in children at the community level. METHODS: We conducted an unblinded, cluster-randomized, controlled-equivalency trial in Haripur District, Pakistan. Children 2-59 months of age with fast-breathing pneumonia were treated with oral amoxicillin suspension (50 mg/kg/day) for 3 days in 14 intervention clusters and oral co-trimoxazole suspension (8 mg trimethoprim/kg and 40 mg sulfamethoxazole/kg/day) for 5 days in 14 control clusters by lady health workers (LHW). The primary outcome was treatment failure by day 4 for intervention clusters and by day 6 for control clusters. The analysis was per protocol. RESULTS: Out of the 15 749 cases enrolled in the study, 9153 cases in intervention and 6509 cases in control clusters were included in the analysis. Treatment failure rates were 3.6% (326) in intervention clusters and 9.1% (592) in control clusters. After adjusting for clustering, the risk of treatment failure was lower in intervention clusters (risk difference [RD] -5.5%, 95% confidence interval [CI] -7.4--3.7%) than in control clusters. Children with incomplete adherence had a small increase in treatment failure versus those with complete adherence (RD 2.9%, 95% CI 1.6-4.1%). No deaths or serious adverse events occurred. CONCLUSIONS: A 3-day course of oral amoxicillin, administered by LHWs, is an effective and safe treatment for fast-breathing pneumonia in children 2-59 months of age. A shorter course of amoxicillin improves adherence to therapy, is low in cost, and puts less pressure on antimicrobial resistance. CLINICAL TRIALS REGISTRATION: ISRCTN10618300.

Resveratrol improves efficacy of oral amoxicillin against childhood fast breathing pneumonia in a randomized placebo-controlled double blind clinical trial.

Childhood pneumonia has been considered as a major cause of child morbidity and mortality worldwide. We aimed to investigate the effect of resveratral in synergizing with oral amoxicillin to improve the treatment outcome of oral amoxicillin administration against childhood fast breathing pneumonia. 647 children diagnosed fast breathing pneumonia were recruited and randomized to receive oral amoxicillin plus either resveratrol (AX + RV) or placebo (AX + placebo). The primary outcome was defined as treatment failure up to day 3, while the secondary outcome was defined as treatment failure at day 6 and 12 upon follow up. Incidences of treatment failure up to day 3 was significantly lower in the AX + RV group than the AX + placebo group. From day 6-12, the incidences of treatment failure were increased in both treatment groups. However, treatment failure cases were still much lower in the AX + RV group on both revisits. No serious adverse reaction to treatment drugs were found in either of the two groups. Resveratrol improves efficacy of oral amoxicillin against childhood fast breathing pneumonia, supporting the clincial potential of reseveratrol as a potent adjuvent of oral amoxicillin in the treatment of childhood pneumonia with no adverse effects.

Cerebrovascular Hemodynamics During the Practice of Bhramari Pranayama, Kapalbhati and Bahir-Kumbhaka: An Exploratory Study.

Various pranayama techniques are known to produce different physiological effects. We evaluated the effect of three-different pranayama techniques on cerebrovascular hemodynamics. Eighteen healthy volunteers with the mean ± standard deviation age of 23.78 ± 2.96 years were performed three-different pranayama techniques: (1) Bhramari, (2) Kapalbhati and (3) Bahir-Kumbhaka in three-different orders. Continuous transcranial Doppler (TCD) monitoring was performed before, during and after the pranayama techniques. TCD parameters such as peak systolic velocity, end diastolic velocity (EDV), mean flow velocity (MFV) and pulsatility index (PI) of right middle cerebral artery were recorded. Practice of Kapalbhati showed significant reductions in EDV and MFV with significant increase in PI while, Bahir-Kumbhaka showed significant increase in EDV and MFV with significant reduction in PI. However, no such significant changes were observed in Bhramari pranayama. Various types of pranayama techniques produce different cerebrovascular hemodynamic changes in healthy volunteers.

Probiotic Lactobacillus casei Shirota improves efficacy of amoxicillin-sulbactam against childhood fast breathing pneumonia in a randomized placebo-controlled double blind clinical study.

The aim of the present study was to investigate the efficacy of oral administration of probiotic Lactobacillus casei Shirota and amoxicillin-sulbactam in treating childhood fast breathing pneumonia. 518 children diagnosed of fast breathing pneumonia were enrolled and randomly assigned to be administered either amoxicillin-sulbactam + Lactobacillus casei Shirota or amoxicillin-sulbactam + placebo. Primary outcome was defined as treatment failure before day 3, and secondary outcome was defined as treatment failure during follow-ups on day 6 and 12. Serum levels of tumor necrosis factor-α and interferon-γ were also examined at the end of day 3. Treatment failure rate before day 3 was significantly reduced in amoxicillin-sulbactam + Lactobacillus casei Shirota group compared to amoxicillin-sulbactam + placebo group. Serum levels of tumor necrosis factor-α and interferon-γ were both significantly reduced in amoxicillin-sulbactam + placebo group on day 3. On day 6 and 12, although treatment failure rates were higher than on day 3 in both groups, it was still significantly reduced in amoxicillin-sulbactam + Lactobacillus casei Shirota group. No severe adverse effects were observed in either treatment group. In conclusion, Probiotic Lactobacillus casei Shirota, in combination with amoxicillin-sulbactam, is more effective in treating childhood fast breathing pneumonia, which supports the potential clinical application of Lactobacillus casei Shirota as a safe supplement to amoxicillin-sulbactam therapy against childhood fast breathing pneumonia.

Ambulatory Treatment of Fast Breathing in Young Infants Aged <60 Days: A Double-Blind, Randomized, Placebo-Controlled Equivalence Trial in Low-Income Settlements of Karachi.

(See the Editorial Commentary by Jehan and Qazi on pages 190-1) BACKGROUND: Integrated Management of Childhood Illness recommends that young infants with isolated fast breathing be referred to a hospital for antibiotic treatment, which is often impractical in resource-limited settings. Additionally, antibiotics may be unnecessary for physiologic tachypnea in otherwise well newborns. We tested the hypothesis that ambulatory treatment with oral amoxicillin for 7 days was equivalent (similarity margin of 3%) to placebo in young infants with isolated fast breathing in primary care settings where hospital referral is often unfeasible. METHODS: This randomized equivalence trial was conducted in 4 primary health centers of Karachi, Pakistan. Infants presenting with isolated fast breathing and oxygen saturation ≥90% were randomly assigned to receive either oral amoxicillin or placebo twice daily for 7 days. Enrolled infants were followed on days 1-8, 11, and 14. The primary outcome was treatment failure by day 8, analyzed per protocol. The trial was stopped by the data safety monitoring board due to higher treatment failure rate and the occurrence of 2 deaths in the placebo arm in an interim analysis. RESULTS: Four hundred twenty-three infants fulfilled per protocol criteria in the amoxicillin arm and 426 in the placebo arm. Twelve infants (2.8%) had treatment failure in the amoxicillin arm and 25 (5.9%) in the placebo arm (risk difference, 3.1; P value .04). Two infants in the placebo arm died, whereas no deaths occurred in the amoxicillin arm. Other adverse outcomes, as well as the proportions of relapse, were evenly distributed across both study arms. CONCLUSIONS: This trial failed to show equivalence of placebo to amoxicillin in the management of isolated fast breathing without hypoxemia or other clinical signs of illness in term young infants. CLINICAL TRIALS REGISTRATION: NCT01533818.

Sports Performance and Breathing Rate: What Is the Connection? A Narrative Review on Breathing Strategies.

Breathing is a natural and necessary process for humans. At the same time, the respiratory pace and frequency can vary so much, depending on the status of the subject. Specifically, in sports, breathing can have the effect of limiting performance from a physiological point of view, or, on the other hand, breathing can regulate the psychological status of the athletes. Therefore, the aim of this narrative review is to focus on the literature about the physiological and psychological aspects of breathing pace in sports performance, merging these two aspects because they are usually considered split, in order to create a new integrated vision of breathing and sports performance. Voluntary breathing can be divided into a slow or fast pace (VSB and VFB, respectively), and their effects on both the physiological and psychological parameters are very different. VSB can benefit athletes in a variety of ways, not just physically but mentally as well. It can help improve cardiovascular fitness, reduce stress and anxiety, and improve overall health and well-being, allowing athletes to maintain focus and concentration during training and competition. VFB is normal during physical training and competition, but away from training, if it is not voluntary, it can cause feelings of anxiety, panic, dizziness, and lightheadedness and trigger a stress response in the body, affecting the athlete's quality of life. In summary, the role of breathing in the performance of athletes should be considered, although no definitive data are available. The connection between breathing and sports performance is still unclear, but athletes can obtain benefits in focus and concentration using slow breathing strategies.

Acute effect of breathing exercises on muscle tension and executive function under psychological stress.

Introduction: Intensive and long-lasting office work is a common cause of muscular and mental disorders due to workplace stressors. Mindful and slow breathing exercises decrease psychological stress and improve mental health, whereas fast breathing increases neuronal excitability. This study aimed to explore the influence of 5 min of mindful breathing (MINDFUL), slow breathing (SLOW), fast breathing (FAST), and listening to music (MUSIC) on muscle tension and executive function during an intensive psychological task. Methods: Forty-eight participants (24 men and 24 women) were enrolled. Muscle tension was recorded using surface electromyography, and executive function was assessed using the Stroop Color and Word Test (Stroop Test). The respiration rate (RR), oxygen saturation (SpO2), end-tidal carbon dioxide (EtCO2), and the subjects' preferred method were also recorded. During the experiment, participants performed a one-time baseline test (watching a neutral video for 5 min) and then completed 5 min of MUSIC, MINDFUL, SLOW, and FAST in a random sequence. The Stroop Test was performed after each intervention, including the baseline test, and was followed by a 5 min rest before performing the next intervention. Results: None of the methods significantly influenced muscular activity and performance of the Stroop Test in both men and women, based on the average 5 min values. However, at the fifth minute, men's accuracy rate in the Stroop Test was significantly higher after SLOW than after MUSIC and FAST, and the reaction time after the SLOW was the shortest. SpO2 was significantly higher during SLOW than during MUSIC, and RR was relatively lower after SLOW than after MUSIC. Most men preferred SLOW, and most women preferred MUSIC, whereas FAST was the most unfavorable method for both men and women. Conclusion: Brief breathing exercises did not substantially affect muscle tension under psychological stress. SLOW demonstrated greater potential for sustaining executive function in men, possibly via its superior respiration efficiency on SpO2 and inhibition of RR.

Rib fracture: Different radiographic projections.

BACKGROUND: Rib fracture is the most common thoracic injury. It is thought to be present in 10% of all traumatic injuries and in almost 40% of patients who sustained severe non-penetrating trauma. There are 12 pairs of ribs. This study reviews various methods of acquisition and reconstruction of radiographic images of traumatic rib fractures in order to determine the optimal views and to simplify rib fracture diagnostics. MATERIAL/METHODS: Eight different plain radiography pictures of ribs were performed with the patient in an erect position. The following projections were obtained in sequence: oblique at 45° or 30° angle on inspiration, oblique at 45° or 30° angle on expiration as well as 45° and 39° projections during slow and fast breathing. All radiographic examinations were performed using a Philips three-phase scanner installed at the Al- Razi Hospital in Jenin, Palestine. RESULTS: The results demonstrate that the 45° antero-posterior oblique projection performed on expiration is recommended for diagnostics and interpretation of traumatic rib fractures. CONCLUSIONS: Conclusion emerging from this study are such that for a 45° oblique view on expiration is recommended for radiographic imaging of patients with clinical signs of fracture, e.g. evaluation of lower rib fractures, while 45° oblique view during fast breathing is recommended for suspected upper rib fractures.

Malawian children with fast-breathing pneumonia with and without comorbidities.

BACKGROUND: Due to high risk of mortality, children with comorbidities are typically excluded from trials evaluating pneumonia treatment. Understanding heterogeneity of outcomes among children with pneumonia and comorbidities is critical to ensuring appropriate treatment. METHODS: We explored whether the percentage of children with fast-breathing pneumonia cured at Day 14 was lower among those with selected comorbidities enrolled in a prospective observational study than among those enrolled in a concurrent randomized controlled trial evaluating treatment with amoxicillin in Lilongwe, Malawi. RESULTS: Among 79 children with fast-breathing pneumonia in the prospective observational cohort, 57 (72.2%) had HIV infection/exposure, 20 (25.3%) had malaria, 2 (2.5%) had severe acute malnutrition, and 17 (21.5%) had anemia. Treatment failure rate was slightly (not significantly) lower in children with comorbidities (4.1%, 3/73) compared to those without comorbidities (4.5%, 25/552) similarly treated. There was no significant difference in clinical cure rates by Day 14 (95.8% with vs 96.7% without comorbidity). CONCLUSIONS: Children with fast-breathing pneumonia excluded from a concurrent clinical trial due to comorbidities did not fare worse. Children at higher risk whose caregivers seek care early and who receive appropriate risk assessment (e.g., pulse oximetry, hemoglobin, HIV/malaria testing) and treatment, can achieve clinical cure by Day 14. TRIAL REGISTRATION: ClinicalTrials.gov NCT02960919 ; registered November 8, 2016.

Performance of Automated Point-of-Care Respiratory Rate Counting versus Manual Counting in Children under Five Admitted with Severe Febrile Illness to Kisantu Hospital, DR Congo.

To improve the early recognition of danger signs in children with severe febrile illness in low resource settings, WHO promotes automated respiratory rate (RR) counting, but its performance is unknown in this population. Therefore, we prospectively evaluated the field performance of automated point-of-care plethysmography-based RR counting in hospitalized children with severe febrile illness (<5 years) in DR Congo. A trained research nurse simultaneously counted the RR manually (comparative method) and automatically with the Masimo Rad G pulse oximeter. Valid paired RR measurements were obtained in 202 (83.1%) children, among whom 43.1% (87/202) had fast breathing according to WHO criteria based on manual counting. Automated counting frequently underestimated the RR (median difference of -1 breath/minute; p2.5-p97.5 limits of agreement: -34-6), particularly at higher RR. This resulted in a failure to detect fast breathing in 24.1% (21/87) of fast breathing children (positive percent agreement: 75.9%), which was not explained by clinical characteristics (p > 0.05). Children without fast breathing were mostly correctly classified (negative percent agreement: 98.3%). In conclusion, in the present setting the automated RR counter performed insufficiently to facilitate the early recognition of danger signs in children with severe febrile illness, given wide limits of agreement and a too low positive percent agreement.

The Effects of Fast and Slow Yoga Breathing on Cerebral and Central Hemodynamics.

BACKGROUND: Yoga breathing has shown to impose significant cardiovascular and psychological health benefits. OBJECTIVE: The mechanism (s) responsible for these health benefits remain unclear. The aim of the present study was to assess the differences in cerebral and central hemodynamic responses following fast breathing (FB) and slow breathing (SB) protocols compared to breathing awareness (BA) as a control. METHODS: Twenty healthy participants (10 males and 10 females) volunteered to take part in the study. Participants were between ages 18-55 years (group mean: 24 ± 5 years), with a height of 168.7 ± 9.8 cm and a weight of 70.16 ± 10.9 kg. A familiarization trial including FB and SB protocols were performed by each participant at least 24 h before the testing day. The breathing protocols were designed to achieve 6 breath/min for SB and ~ 120 breaths/min for FB. RESULTS: FB resulted in an increase in both right prefrontal cortex (RPFC) and left prefrontal cortex (LPFC) hemoglobin difference (Hbdiff) (brain oxygenation) compared to BA (P < 0.05). FB resulted in an increased Hbdiff in LPFC compared to RPFC SB (P < 0.05). FB resulted in an increased Hbdiff in LPFC compared to SB (P < 0.05). CONCLUSION: FB may be an effective yoga breathing technique for eliciting cerebral brain oxygenation indicated by increased Hbdiff. These results may be applicable to both healthy and clinical populations.

Management of fast breathing pneumonia in young infants aged 7 to 59 days by community level health workers: protocol for a multi-centre cluster randomized controlled trial.

BACKGROUND: WHO does not recommend community-level health workers (CLHWs) using integrated community case management (iCCM) to treat 7-59 days old infants with fast breathing with oral amoxicillin, whereas World Health Organization (WHO) integrated management of childhood illness (IMCI) recommends it. We want to collect evidence to help harmonization of both protocols. METHODS: A cluster, randomized, open-label trial will be conducted in Africa and Asia (Ethiopia, Malawi, Bangladesh and India) using a common protocol with the same study design, inclusion criteria, intervention, comparison, and outcomes to contribute to the overall sample size. This trial will also identify hypoxaemia in young infants with fast breathing. CLHWs will assess infants for fast breathing, which will be confirmed by a study supervisor. Enrolled infants in the intervention clusters will be treated with oral amoxicillin, whereas in the control clusters they will be managed as per existing iCCM protocol. An independent outcome assessor will assess all enrolled infants on days 6 and 14 of enrolment for the study outcomes in both intervention and control clusters. Primary outcome will be clinical treatment failure by day 6. This trial will obtain approval from the WHO and site institutional ethics committees. CONCLUSIONS: If the research shows that CLHWs can effectively and safely treat fast breathing pneumonia in 7-59 days old young infants, it will increase access to pneumonia treatment substantially for infants living in communities with poor access to health facilities. Additionally, this evidence will contribute towards the review of the current iCCM protocol and its harmonization with IMCI protocol. TRIAL REGISTRATION: The trial is registered at AZNCTR International Trial Registry as ACTRN12617000857303.

Should fast breathing pneumonia cases be treated with antibiotics? The scientific rationale for revisiting management in Low and Middle income countries.

BACKGROUND: Pneumonia is the largest single contributor to child mortality and the problem is more acute in low and middle income countries. The World Health Organization (WHO) currently recommends oral antibiotic treatment for all children with fast breathing pneumonia without danger signs. It is, however, widely acknowledged that most such infections are viral and self-limiting and that the evidence for the guidance is weak. RATIONALE: Overuse of antibiotics exposes children to adverse events, increases cost for families, burdens already stretched health care resources and may contribute to development of antibiotic resistance. CONCLUSION: There is equipoise regarding utility of antibiotic in case of fast breathing pneumonia and no high quality trial evidence exists. This paper provides further information behind the rationale for conducting non-inferiority trials to test the hypothesis that antibiotics may not be necessary for children with fast breathing as the sole symptomatology.

Non-treatment of children with community health worker-diagnosed fast-breathing pneumonia in rural Malawi: exploratory subanalysis of a prospective cohort study.

BACKGROUND: Despite recent progress, pneumonia remains the largest infectious killer of children globally. This paper describes outcomes of not treating community-diagnosed fast-breathing pneumonia on patient recovery. METHODS: We conducted an exploratory subanalysis of an observational prospective cohort study in Malawi. We recruited children (2-59 months) diagnosed by community health workers with fast-breathing pneumonia using WHO integrated community case management (iCCM) guidelines. Children were followed at days 5 and 14 with a clinical assessment of recovery. We conducted bivariate and multivariable logistic regression for the association between treatment of fast-breathing pneumonia and recovery, adjusting for potential confounders. RESULTS: We followed up 847 children, of whom 78 (9%) had not been given antibiotics (non-treatment). Non-treatment cases had higher baseline rates of diarrhoea, non-severe hypoxaemia and fever. Non-recovery (persistence or worsening of symptoms) was 13% and 23% at day 5 in those who did receive and those who did not receive co-trimoxazole. Non-recovery, when defined as worsening of symptoms only, at day 5 was 7% in treatment and 10% in non-treatment cases. For both definitions, combined co-trimoxazole and lumefantrine-artemether (LA) treatment trended towards protection (adjusted OR (aOR) 0.28; 95% CI 0.12 to 0.68/aOR 0.29; 95% CI 0.08 to 1.01). CONCLUSION: We found that children who did not receive co-trimoxazole treatment had worse clinical outcomes; malaria co-diagnosis and treatment also play a significant role in non-recovery. Further research into non-treatment of fast-breathing pneumonia, using a pragmatic approach with consideration for malaria co-diagnosis and HIV status is needed to guide refinement of community treatment algorithms in this region.