Domiciliary non-invasive ventilation post lung transplantation.

BACKGROUND AND OBJECTIVE: The benefits of domiciliary non-invasive ventilation (NIV) post lung transplantation (LTx) have not previously been described. This was a single-centre retrospective audit of patients requiring domiciliary NIV post-LTx. Our aim was to describe indications for NIV and outcomes in chronic lung allograft dysfunction (CLAD) and diaphragmatic palsy. METHODS: All patients requiring domiciliary NIV post-LTx between 2010 and June 2016 were assessed. NIV indications, respiratory function and patient outcomes were collected. RESULTS: Out of 488 LTx recipients, 20 patients were identified as requiring NIV over the 6.5-year study period. The most common indications for NIV were CLAD and diaphragmatic palsy. Hypercapnia improved significantly with NIV. Patient outcomes were poor with nine (45%) patients dying, four (20%) undergoing redo-LTx, four (20%) continuing domiciliary NIV and only three (15%) patients weaned off NIV. CONCLUSION: This is the first case series to describe the use of domiciliary NIV post-LTx. Patients commenced on NIV post-LTx had severely impaired lung function and severe hypercapnia. Patients with diaphragmatic palsy often recovered. The mortality rate was high in chronic allograft dysfunction.

Models of care for non-invasive ventilation in the Acute COPD Comparison of three Tertiary hospitals (ACT3) study.

BACKGROUND AND OBJECTIVE: Non-invasive ventilation (NIV) improves clinical outcomes in hypercapnic acute exacerbations of COPD (AECOPD), but the optimal model of care remains unknown. METHODS: We conducted a prospective observational non-inferiority study comparing three models of NIV care: general ward (Ward) (1:4 nurse to patient ratio, thrice weekly consultant ward round), a high dependency unit (HDU) (1:2 ratio, twice daily ward round) and an intensive care unit (ICU) (1:1 ratio, twice daily ward round) model in three similar teaching tertiary hospitals. Changes in arterial blood gases (ABG) and clinical outcomes were compared and corrected for differences in AECOPD severity (Blood urea > 9 mmol/L, Altered mental status (Glasgow coma scale (GCS) < 14), Pulse > 109 bpm, age > 65 (BAP-65)) and co-morbidities. An economic analysis was also undertaken. RESULTS: There was no significant difference in age (70 ± 10 years), forced expiratory volume in 1 s (FEV1 ) (0.84 ± 0.35 L), initial pH (7.29 ± 0.08), partial pressure of CO2 in arterial blood (PaCO2 ) (72 ± 22 mm Hg) or BAP-65 scores (2.9 ± 1.01) across the three models. The Ward achieved an increase in pH (0.12 ± 0.07) and a decrease in PaCO2 (12 ± 18 mm Hg) that was equivalent to HDU and ICU. However, the Ward treated more patients (38 vs 28 vs 15, P < 0.001), for a longer duration in the first 24 h (12.3 ± 4.8 vs 7.9 ± 4.1 vs 8.4 ± 5.3 h, P < 0.05) and was more cost-effective per treatment day ($AUD 1231 ± 382 vs 1745 ± 2673 vs 2386 ± 1120, P < 0.05) than HDU and ICU. ICU had a longer hospital stay (9 ± 11 vs 7 ± 7 vs 13 ± 28 days, P < 0.002) compared with the Ward and HDU. There was no significant difference in intubation rate or survival. CONCLUSION: In acute hypercapnic Chronic obstructive pulmonary disease (COPD) patients, the Ward model of NIV care achieved equivalent clinical outcomes, whilst being more cost-effective than HDU or ICU models.

Antagonists of human CCR5 receptor containing 4-(pyrazolyl)piperidine side chains. Part 3: SAR studies on the benzylpyrazole segment.

Extensive SAR studies in our benzylpyrazole series of CCR5 antagonists have shown that both lipophilic and hydrophilic substituents on the phenyl of the benzyl group increase antiviral potency. However, improvements in pharmacokinetic profiles were generally only observed with more lipophilic substitutions. 4-Biphenyl (51) performed the best in this regard. Highly lipophilic substituents impart undesirable ion channel activity to these CCR5 antagonists. Alkoxy substituents provide a good balance of antiviral activity, pharmacokinetic parameters, and selectivity. Compounds 42b and 42d, containing a 3,4-dimethoxy substituent, are considered the most promising improvements over parent compounds 9. They demonstrate improved antiviral activity while retaining good pharmacokinetic profile and selectivity.