Provision of smoking cessation support for patients following a diagnosis of cancer in Ireland.

There is growing evidence that smoking cessation (SC) improves outcomes following diagnosis of cancer. Notwithstanding adverse outcomes, a significant number of those diagnosed with cancer continue to smoke. Our objective was to document the SC services provided for patients with cancer by specialist adult cancer hospitals across Ireland, a country with a stated tobacco endgame goal. A cross-sectional survey based on recent national clinical guidelines was used to determine SC care delivery across eight adult cancer specialist hospitals, and one specialist radiotherapy centre. Qualtrics was used. The response rate was 88.9% with data reported from seven cancer hospitals and one specialist radiotherapy centre, all indicating they had some SC related provision (100%). Stop smoking medications were provided to cancer inpatients in two hospitals, at outpatients and attending day ward services in one hospital. Smokers with cancer were referred automatically to the SC service in two hospitals at diagnosis. While stop smoking medications were available 24 h a day in five hospitals, most did not stock all three (Nicotine Replacement Therapy, Bupropion, Varenicline). One hospital advised they had data on uptake of SC services for smokers with cancer but were unable to provide detail. There is considerable variation in SC information and services provided to cancer patients across adult cancer specialist centres in Ireland, reflecting the suboptimal practice of smoking cessation for patients with cancer found in the limited international audits. Such audits are essential to demonstrate service gaps and provide a baseline for service improvement.

Physician Health in the Times of COVID-19.

BACKGROUND AND OBJECTIVES: A virtual registry study evaluating real world evidence on physicians' use of prophylactic regimens for protection against SARS-CoV-2. This paper summarizes the interim results. METHODS: Asymptomatic physicians at risk of acquiring SARS-CoV-2 responded to online questions at baseline and 7 weeks post-baseline. Baseline data included demographics, prophylaxis regimen (including "no prophylaxis") and start date. Participants who provided complete week-7 data (information on type of health facility [COVID/Non-COVID], number of presumed/confirmed cases exposed to, PPE use, SARS-CoV-2 testing and symptoms, regimen adherence and intercurrent illness) comprised the Completer population. Limited data (regimen adherence, SARS-CoV-2 testing) was collected for participants who failed to provide complete week7 data. Those providing limited/complete information comprised the Evaluable population. RESULTS: Of 369 enrolled participants, 182 (mean age 42±11.05 years) comprised the Evaluable population. They showed a male preponderance (67.6%). Practitioners from Maharashtra (59.9%) and specialties of Pediatrics, Internal Medicine, Anesthesiology and Critical Care (63.2%) accounted for the majority. ICMR's HCQ prophylaxis regimen was initiated by 125 (68.7%) participants with 31 (17%) initiating 'No prophylaxis'. The highest adherence was for the ICMRregimen (87.2%). In the Completer population comprising 150 participants, 87 were exposed to presumed (81) and/or confirmed cases (60). Most exposures to confirmed cases (49, 81.7%) were high-risk. PPE use was generally high (75-100%). Most participants (94.7%) did not report an AE. The proportions with an AE was similar with ICMR regimen (5.9%) and no prophylaxis (6.5%). INTERPRETATION AND CONCLUSIONS: Physicians in India preferred ICMR's HCQ regimen. The regimen appears to be safe and associated with a high level of adherence.

Granular Activated Carbon Adsorption of Carcinogenic Volatile Organic Compounds at Low Influent Concentrations.

The effectiveness of granular activated carbon (GAC) for carcinogenic volatile organic compounds (cVOCs) has not been evaluated in the low- to sub- microgram per liter range. Rapid small scale column tests (RSSCTs) were employed to determine the GAC performance at empty bed contact times (EBCTs) of 7.5 and 15 minutes for 13 cVOCs at a target influent concentration of 5 µg/L in a typical groundwater matrix. Breakthrough was assessed for vinyl chloride, dichloromethane, 1,1-dichloroethane, 1,2-dichloroethane, 1,2-dichloropropane, carbon tetrachloride, 1,3-butadiene, 1,1,1,2-tetrachloroethane, 1,2,3-trichloropropane, trichloroethylene and tetrachloroethylene. The throughput to breakthrough was found to be linearly correlated to capacities calculated with single-solute equilibrium isotherm parameters. Modest decreases, 9 to 13% on average, in throughput to 50% and 75% breakthrough were found when the EBCT was increased from 7.5 to 15 minutes. The carbon use rate (CUR), when scaled to simulate full-scale adsorption, indicated that GAC would be a viable technology for seven of the VOCs evaluated, with a CUR threshold less than 0.2 lbs/1000 gal. It may be possible to use 1,1 DCA and 1,2 DCA as surrogates for assessing chemicals near the feasibility limit.

Randomized Prospective Comparative Study of Adductor Canal Block vs Periarticular Infiltration on Early Functional Outcome After Unilateral Total Knee Arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is associated with significant postoperative pain. Effective pain relief is essential for early postoperative rehabilitation. Periarticular infiltration (PAI) and adductor canal block (ACB) have become popular modes of pain management after TKA. Our aim is to compare their efficacy and impact on early functional outcome in patients undergoing TKA. METHODS: A single-blinded randomized controlled trial, 100 patients undergoing unilateral primary TKA for symptomatic osteoarthritis were allocated to either of the 2 groups (50 in each arm): postoperative ultrasound-guided single shot of ACB (group A) or intraoperative PAI (group B). All patients underwent TKA without patella resurfacing under spinal anesthesia. Preoperative workup, surgical technique, and postoperative management were standardized for all the patients. Patients were assessed for pain using visual analogue scale at 6, 12, and 24 hours after surgery; hemoglobin level preoperatively and postoperatively on day 1 to calculate blood loss; hospital stay; tourniquet time; operative time; and postoperative complications by an independent observer blinded to the group allocation. RESULTS: Patients were matched for age, gender, American Society of Anesthesiologists grade, and deformity. Visual analogue scale (scale 0-10) between PAI and ACB at 6, 12, and 24 hours were significantly different (P < .05) with higher scores seen in patients with ACB at all time points. Tourniquet time and operative time were significantly longer in the PAI than ACB. No significant difference in hospital stay was observed. No complications occurred during the study. CONCLUSION: PAI achieves better pain control as compared to ACB in patients undergoing unilateral TKA.

Is a cross-ß-sheet structure of low molecular weight peptides necessary for the formation of fibrils and peptide hydrogels?

Short peptides have emerged as versatile building blocks for supramolecular structures and hydrogels. In particular, the presence of aromatic amino acid residues and/or aromatic end groups is generally considered to be a prerequisite for initiating aggregation of short peptides into nanotubes or cross ß-sheet type fibrils. However, the cationic GAG tripeptide surprisingly violates these rules. Specifically, in water/ethanol mixtures, GAG peptides aggregate into very long crystalline fibrils at temperatures below 35 °C where they eventually form a spanning network structure and, thus, a hydrogel. Two gel phases are formed in this network, and they differ substantially in chirality and thickness of the underlying fibrils, their rheological parameters, and the kinetics of oligomerization, fibrilization, and gel formation. The spectroscopic data strongly suggests that the observed fibrils do not exhibit canonical cross ß-sheet structures and are indicative of a yet unknown secondary conformation. To complement our unusual experimental observations in this perspective article, we performed large-scale DFT calculations to probe the geometry and spectroscopic properties of these GAG oligomers. Most importantly, our experimental and computational results yield rather unconventional structures that are not reminiscent of classical cross-ß-sheet structures, and we give two extremely likely candidates for oligomer structures that are consistent with experimental amide I' profiles in IR and vibrational circular dichroism (VCD) spectra of the two gel phases.

Real-Time Quantum Dynamics of Long-Range Electronic Excitation Transfer in Plasmonic Nanoantennas.

Using large-scale, real-time, quantum dynamics calculations, we present a detailed analysis of electronic excitation transfer (EET) mechanisms in a multiparticle plasmonic nanoantenna system. Specifically, we utilize real-time, time-dependent, density functional tight binding (RT-TDDFTB) to provide a quantum-mechanical description (at an electronic/atomistic level of detail) for characterizing and analyzing these systems, without recourse to classical approximations. We also demonstrate highly long-range electronic couplings in these complex systems and find that the range of these couplings is more than twice the conventional cutoff limit considered by Förster resonance energy transfer (FRET)-based approaches. Furthermore, we attribute these unusually long-ranged electronic couplings to the coherent oscillations of conduction electrons in plasmonic nanoparticles. This long-range nature of plasmonic interactions has important ramifications for EET; in particular, we show that the commonly used "nearest-neighbor" FRET model is inadequate for accurately characterizing EET even in simple plasmonic antenna systems. These findings provide a real-time, quantum-mechanical perspective for understanding EET mechanisms and provide guidance in enhancing plasmonic properties in artificial light-harvesting systems.

Mycobacterial Cultures Contain Cell Size and Density Specific Sub-populations of Cells with Significant Differential Susceptibility to Antibiotics, Oxidative and Nitrite Stress.

The present study shows the existence of two specific sub-populations of Mycobacterium smegmatis and Mycobacterium tuberculosis cells differing in size and density, in the mid-log phase (MLP) cultures, with significant differential susceptibility to antibiotic, oxidative, and nitrite stress. One of these sub-populations (~10% of the total population), contained short-sized cells (SCs) generated through highly-deviated asymmetric cell division (ACD) of normal/long-sized mother cells and symmetric cell divisions (SCD) of short-sized mother cells. The other sub-population (~90% of the total population) contained normal/long-sized cells (NCs). The SCs were acid-fast stainable and heat-susceptible, and contained high density of membrane vesicles (MVs, known to be lipid-rich) on their surface, while the NCs possessed negligible density of MVs on the surface, as revealed by scanning and transmission electron microscopy. Percoll density gradient fractionation of MLP cultures showed the SCs-enriched fraction (SCF) at lower density (probably indicating lipid-richness) and the NCs-enriched fraction (NCF) at higher density of percoll fractions. While live cell imaging showed that the SCs and the NCs could grow and divide to form colony on agarose pads, the SCF, and NCF cells could independently regenerate MLP populations in liquid and solid media, indicating their full genomic content and population regeneration potential. CFU based assays showed the SCF cells to be significantly more susceptible than NCF cells to a range of concentrations of rifampicin and isoniazid (antibiotic stress), H2O2 (oxidative stress),and acidified NaNO2 (nitrite stress). Live cell imaging showed significantly higher susceptibility of the SCs of SC-NC sister daughter cell pairs, formed from highly-deviated ACD of normal/long-sized mother cells, to rifampicin and H2O2, as compared to the sister daughter NCs, irrespective of their comparable growth rates. The SC-SC sister daughter cell pairs, formed from the SCDs of short-sized mother cells and having comparable growth rates, always showed comparable stress-susceptibility. These observations and the presence of M. tuberculosis SCs and NCs in pulmonary tuberculosis patients' sputum earlier reported by us imply a physiological role for the SCs and the NCs under the stress conditions. The plausible reasons for the higher stress susceptibility of SCs and lower stress susceptibility of NCs are discussed.

Unusual Bandgap Oscillations in Template-Directed π-Conjugated Porphyrin Nanotubes.

Using large-scale DFT calculations (up to 1476 atoms and 18 432 orbitals), we present the first detailed analysis on the unusual electronic properties of recently synthesized porphyrin nanotubes. We surprisingly observe extremely large oscillations in the bandgap of these nanostructures as a function of size, in contradiction to typical quantum confinement effects (i.e., the bandgap increases with size in several of these nanotubes). In particular, we find that these intriguing electronic oscillations arise from a size-dependent alternation of aromatic/nonaromatic characteristics in these porphyrin nanotubes. Our analyses of band structures and orbital diagrams indicate that the electronic transitions in these nanostructures are direct-bandgap, optically active "bright" states that can be readily observed in photoelectron spectroscopic experiments. Most importantly due to their unusual bandgap oscillations, we find that both type I and type II donor-acceptor p-n heterojunctions are possible in these template-directed, "bottom-up synthesized" porphyrin nanotubes-a unique property that is not present in conventional carbon nanotubes.

Polarizabilities of π-Conjugated Chains Revisited: Improved Results from Broken-Symmetry Range-Separated DFT and New CCSD(T) Benchmarks.

We present a detailed analysis of nonempirically tuned range-separated functionals, with both short- and long-range exchange, for calculating the static linear polarizability and second hyperpolarizabilities of various polydiacetylene (PDA) and polybutatriene (PBT) oligomers. Contrary to previous work on these systems, we find that the inclusion of some amount of short-range exchange does improve the accuracy of the computed polarizabilities and second hyperpolarizabilities. Most importantly, in contrast to prior studies on these oligomers, we find that the lowest-energy electronic states for PBT are not closed-shell singlets, and enhanced accuracy with range-separated DFT can be obtained by allowing the system to relax to a lower-energy broken-symmetry solution. Both the computed polarizabilities and second hyperpolarizabilities for PBT are significantly improved with these broken-symmetry solutions when compared to previously published and current benchmarks. In addition to these new analyses, we provide new large-scale CCSD(T) and explicitly correlated CCSD(T)-F12 benchmarks for the PDA and PBT systems, which comprise the most complete and accurate calculations of linear polarizabilities and second hyperpolarizabilities on these systems to date. These new CCSD(T) and CCSD(T)-F12 benchmarks confirm our DFT results and emphasize the importance of broken-symmetry effects when calculating polarizabilities and hyperpolarizabilties of π-conjugated chains.

Connecting Active-Site Loop Conformations and Catalysis in Triosephosphate Isomerase: Insights from a Rare Variation at Residue†96 in the Plasmodial Enzyme.

Despite extensive research into triosephosphate isomerases (TIMs), there exists a gap in understanding of the remarkable conjunction between catalytic loop-6 (residues 166-176) movement and the conformational flip of Glu165 (catalytic base) upon substrate binding that primes the active site for efficient catalysis. The overwhelming occurrence of serine at position 96 (98% of the 6277 unique TIM sequences), spatially proximal to E165 and the loop-6 residues, raises questions about its role in catalysis. Notably, Plasmodium falciparum TIM has an extremely rare residue--phenylalanine--at this position whereas, curiously, the mutant F96S was catalytically defective. We have obtained insights into the influence of residue 96 on the loop-6 conformational flip and E165 positioning by combining kinetic and structural studies on the PfTIM F96 mutants F96Y, F96A, F96S/S73A, and F96S/L167V with sequence conservation analysis and comparative analysis of the available apo and holo structures of the enzyme from diverse organisms.

Sultam-Based Hetero[5]helicene: Synthesis, Structure, and Crystallization-Induced Emission Enhancement.

A deep-blue-emitting sultam-based hetero[5]helicene was synthesized in four steps, and its crystal structure and physical properties were characterized. The helicene displays more than two-fold crystallization-induced emission enhancement as well as atypical blue-shifting of its solid-state emission relative to the solution phase. This rapid synthesis of an unusual sulfonamide-based helicene fluorophore is expected to generate new molecular design options that will help address the ongoing challenges associated with designing pure-blue emitters for organic optoelectronic and sensing applications.

Breaking Badly: DFT-D2 Gives Sizeable Errors for Tensile Strengths in Palladium-Hydride Solids.

Dispersion interactions play a crucial role in noncovalently bound molecular systems, and recent studies have shown that dispersion effects are also critical for accurately describing covalently bound solids. While most studies on bulk solids have solely focused on equilibrium properties (lattice constants, bulk moduli, and cohesive energies), there has been little work on assessing the importance of dispersion effects for solid-state properties far from equilibrium. In this work, we present a detailed analysis of both equilibrium and highly nonequilibrium properties (tensile strengths leading to fracture) of various palladium-hydride systems using representative DFT methods within the LDA, GGA, DFT-D2, DFT-D3, and nonlocal vdw-DFT families. Among the various DFT methods, we surprisingly find that the empirically constructed DFT-D2 functional gives extremely anomalous and qualitatively incorrect results for tensile strengths in palladium-hydride bulk solids. We present a detailed analysis of these effects and discuss the ramifications of using these methods for predicting solid-state properties far from equilibrium. Most importantly, we suggest caution in using DFT-D2 (or other coarse-grained parametrizations obtained from DFT-D2) for computing material properties under large stress/strain loads or for evaluating solid-state properties under extreme structural conditions.

Assessing backbone solvation effects in the conformational propensities of amino acid residues in unfolded peptides.

Conformational ensembles of individual amino acid residues within model GxG peptides (x representing different amino acid residues) are dominated by a mixture of polyproline II (pPII) and ß-strand like conformations. We recently discovered rather substantial differences between the enthalpic and entropic contributions to this equilibrium for different amino acid residues. Isoleucine and valine exceed all other amino acid residues in terms of their rather large enthalpic stabilization and entropic destabilization of polyproline II. In order to shed light on these underlying physical mechanisms, we performed high-level DFT calculations to explore the energetics of four representative GxG peptides where x = alanine (A), leucine (L), valine (V), and isoleucine (I) in explicit water (10 H2O molecules with a polarizable continuum water model) and in vacuo. We found that the large energetic contributions to the stabilization of pPII result, to a major extent, from peptide-water, water-water interactions, and changes of the solvent self-energy. Differences between the peptide-solvent interaction energies of hydration in pPII and ß-strand peptides are particularly important for the pPII ⇌ ß equilibria of the more aliphatic peptides GIG and GLG. Furthermore, we performed a vibrational analysis of the four peptides in both conformations and discovered a rather substantial mixing between water motions and peptide vibrations below 700 cm(-1). We found that the respective vibrational entropies are substantially different for the considered conformations, and their contributions to the Gibbs/Helmholtz energy stabilize ß-strand conformations. Taken together, our results underscore the notion of the solvent being the predominant determinant of peptide (and protein) conformations in the unfolded state.

Antimicrobial resistance pattern in Escherichia coli causing urinary tract infection among inpatients.

BACKGROUND & OBJECTIVES: Recent studies suggest an increasing antimicrobial resistance among Escherichia coli causing urinary tract infection (UTI). We undertook this study to know the resistance pattern of E. coli causing UTI in patients admitted to a tertiary care hospital in north India, and to know the treatment given and response of the patients. METHODS: The details of E. coli grown from urine samples and their antibiotic sensitivity pattern were collected from the laboratory registers and the patient details were collected from the case records. The urine samples received were processed using standard methods and antibiotic susceptibility was done by Kirby-Bauer disk diffusion test. RESULTS: Of the total 311 E. coli isolates, 119 (38.2%) were isolated from in-patients, which were considered for the study. Of these 119 E. coli isolates, 91 (76.51%) were multi drug resistant (MDR). The isolates showed high levels of resistance to ampicillin (88.4%), amoxicillin-clavulanic acid (74.4%), norfloxacin (74.2%), cefuroxime (72.2%), ceftriaxone (71.4%) and co-trimoxazole (64.2%). The isolates were sensitive to amikacin (82.6%), piperacillin-tazobactum (78.2%), nitrofurantoin (82.1%) and imipenem (98.9%). Ceftriaxone was most commonly used for empirical therapy for UTI among inpatients in our hospital. Of the 93 cases of UTI due to MDR E. coli, 73 improved on treatment and 12 worsened, which were referred to higher centres. INTERPRETATION & CONCLUSIONS: Our study showed that 76.5 per cent of E. coli isolates from urine samples of inpatients were MDR. Diabetes, chronic renal disease and catherization were some of the risk factors associated. The high rate of resistance could be because only inpatients were included and the increased usage of cephalosporins in our hospital for empirical therapy.

The posology of oseltamivir in infants with influenza infection using a population pharmacokinetic approach.

Infants are at increased risk for morbidity and mortality due to influenza. Until recently, few data were available with which to optimize oseltamivir dosing in this high-risk population. Here, data for 133 infants were pooled from two prospective pharmacokinetic/pharmacodynamic safety studies to develop a population pharmacokinetic model. A three-compartment model with allometric scaling of all clearance and volume parameters described the disposition of oseltamivir and its carboxylate metabolite (OC). Weight dependence, OC clearance, and volume of distribution increased linearly with age. Analyses showed no association between OC exposure and viral clearance, the development of resistance (phenotypic/genotypic), normalization of body temperature, or safety endpoints. Pharmacokinetic bridging showed that a 3 mg/kg dose yielded acceptable OC exposure and good tolerability while minimizing the risk of underexposure and resistance/treatment failure. These pharmacological analyses formed the basis of the US Food and Drug Administration's recent approval of oseltamivir treatment for infants with influenza aged as young as 2 weeks.

Determinants of incident hyperglycemia 6 years after delivery in young rural Indian mothers: the Pune Maternal Nutrition Study (PMNS).

OBJECTIVE: To study determinants of incident hyperglycemia in rural Indian mothers 6 years after delivery. RESEARCH DESIGN AND METHODS: The Pune Maternal Nutrition Study collected information in six villages near Pune on prepregnant characteristics and nutrition, physical activity, and glucose tolerance during pregnancy. An oral glucose tolerance test (OGTT) was repeated 6 years after delivery. RESULTS: A total of 597 mothers had an OGTT at 28 weeks' gestation; 3 had gestational diabetes (by World Health Organization 1999 criteria). Six years later, 42 of 509 originally normal glucose-tolerant mothers were hyperglycemic (8 diabetic, 20 with impaired glucose tolerance, and 14 with impaired fasting glucose). The hyperglycemic women had shorter legs and thicker skinfolds before pregnancy (P < 0.01, both), were less active and more hyperglycemic (2-h plasma glucose 4.8 vs. 4.4 mmol/l, P < 0.001) during pregnancy, and gained more weight during follow-up (6.0 vs. 2.7 kg, P < 0.001). Multivariate analysis revealed that total leukocyte count and blood pressure during pregnancy were additional independent predictors of 2-h glucose concentration at follow-up. CONCLUSIONS: Our results suggest that compromised linear growth, adiposity, inflammation, and less physical activity predispose to hyperglycemia in young rural Indian women. International cut points of diabetes risk factors are largely irrelevant in these women.

A mechano-electro-acoustical model for the cochlea: response to acoustic stimuli.

A linear, physiologically based, three-dimensional finite element model of the cochlea is developed. The model integrates the electrical, acoustic, and mechanical elements of the cochlea. In particular, the model includes interactions between structures in the organ of Corti (OoC), piezoelectric relations for outer hair cell (OHC) motility, hair bundle (HB) conductance that changes with HB deflection, current flow in the cross section and along the different scalae, and the feed-forward effect. The parameters in the model are based on guinea-pig data as far as possible. The model is vetted using a variety of experimental data on basilar membrane motion and data on voltages and currents in the OoC. Model predictions compare well, qualitatively and quantitatively, with experimental data on basilar membrane frequency response, impulse response, frequency glides, and scala tympani voltage. The close match of the model predictions with experimental data demonstrates the validity of the model for simulating cochlear response to acoustic input and for testing hypotheses of cochlear function. Analysis of the model and its results indicates that OHC somatic motility is capable of powering active amplification in the cochlea. At the same time, the model supports a possible synergistic role for HB motility in cochlear amplification.

A study of thyrotropin-releasing hormone for the treatment of spinal muscular atrophy: a preliminary report.

OBJECTIVE: To determine whether thyrotropin-releasing hormone (TRH) can increase muscle strength in children with spinal muscular atrophy types 2 and 3. DESIGN: A randomized, double-blinded, controlled, 5-wk drug trial of six subjects and three controls. Subjects and controls ranged from 4 to 8 yr of age and were randomly assigned to treatment and placebo groups in a ratio of 2:1. TRH (protirelin) or placebo was delivered intravenously through percutaneous intravenous catheters at a dose of 0.1 mg/kg (in 50 ml of normal saline) for a total of 29 days. Patients were evaluated using electromyography and handheld dynamometry of the deltoids, biceps, triceps, wrist extensors, hip flexors, quadriceps, hamstrings, and grip strength before and immediately after 5 wk of treatment. A unidirectional t test was used to compare mean values. RESULTS: Dynamometry improved significantly only for the six treated subjects (P < 0.02). Peroneal nerve conduction velocities were significantly faster in the treatment group (paired t test, P = 0.036). The parents of the treated children also provided anecdotal evidence of improvements in function. Improvements lasted 6-12 mo. CONCLUSIONS: TRH may be a useful treatment for spinal muscular atrophy. A larger, crossover design group comparison study is warranted.

Spinal muscular atrophy type 1: A noninvasive respiratory management approach.

STUDY OBJECTIVE: To determine whether spinal muscular atrophy (SMA) type 1 can be managed without tracheostomy and to compare extubation outcomes using a respiratory muscle aid protocol vs conventional management. DESIGN: A retrospective cohort study. METHODS: Eleven SMA type 1 children were studied during episodes of respiratory failure. Nine children required multiple intubations. Along with standard treatments, these children received manually and mechanically assisted coughing to reverse airway mucus-associated decreases in oxyhemoglobin saturation. Extubation was not attempted until, most importantly, there was no oxygen requirement to maintain oxyhemoglobin saturation greater than 94%. After extubation, all patients received nasal ventilation with positive end-expiratory pressure. Successful extubation was defined by no need to reintubate during the current hospitalization. RESULTS: Two children have survived for 37 and 66 months and have never been intubated despite requiring 24-h nasal ventilation since 5 and 7 months of age, respectively. One other child underwent tracheostomy for persistent left lung collapse and inadequate home care, another for need for frequent readmission and intubation, and one child was lost to follow-up 3 months after successful extubation. The other six children have been managed at home for 15 to 59 (mean 30.4) months using nocturnal nasal ventilation after an episode of respiratory failure. The nine children were successfully extubated by our protocol 23 of 28 times. The same children managed conventionally were successfully extubated 2 of 20 times when not using this protocol (p < 0.001 by the two-tailed Fisher's Exact t Test). CONCLUSION: Although intercurrent chest colds may necessitate periods of hospitalization and intubation, tracheostomy can be avoided throughout early childhood for some children with SMA type 1.