It had been reported that up to 37% of the adult male population smokes cigarettes in Qatar. The Global Youth Tobacco Survey also stated that 13.4% of male school students aged 13 to 15 years in Qatar smoke cigarettes. Smoking cessation is key to reducing smoking-related diseases and deaths. Healthcare providers are in an ideal position to encourage smoking cessation. Pharmacists are the most accessible healthcare providers and are uniquely situated to initiate behavior change among patients. Many studies have shown that pharmacists can be successful in helping patients quit smoking. Studies demonstrating the effectiveness of pharmacist-delivered smoking cessation programs are lacking in Qatar. This proposal aims to test the effect of a structured smoking cessation program delivered by trained ambulatory pharmacists in Qatar.A prospective, randomized, controlled trial is conducted at eight ambulatory pharmacies in Qatar. Participants are randomly assigned to receive an at least four-session face-to-face structured patient-specific smoking cessation program conducted by the pharmacist or 5 to 10 min of unstructured brief smoking cessation advice (emulating current practice) given by the pharmacist. Both groups are offered nicotine replacement therapy if feasible. The primary outcome of smoking cessation will be confirmed by an exhaled carbon monoxide test at 12 months. Secondary outcomes constitute quality-of-life adjustment as well as cost analysis of program resources consumed, including per case and patient outcome.If proven to be effective, this smoking cessation program will be considered as a model that Qatar and the region can apply to decrease the smoking burden.NCT02123329.Clinical Trials  The leading preventable cause of ill health today is cigarette smoking . It is aIn Qatar, tobacco use is a major public health problem that, in addition to the associated morbidity and mortality, constitutes a huge burden on healthcare services. To control tobacco use, Qatar has adopted the international approaches recommended by the World Health Organization (WHO) and regional plan of Arab countries in the Gulf. These approaches are based on three strategies: (1) imposing legislative tobacco control measures, for example, banning smoking in enclosed public places and prohibiting selling cigarettes, tobacco or its derivatives to anyone less than 18 years old, (2) providing smoking cessation services for free in two hospital-based smoking cessation clinics and (3) implementing antismoking public awareness activities . DespiteAlso important, in addition to the numerous knowledge gaps identified above in relation to Qatar, there are also no data on how cost beneficial the running of smoking cessation programs like the currently proposed one is, added to a lacking data on the associated resource implications in the pharmacy setting from the Qatari perspective.This proposal describes a study that is currently being implemented in eight public and private ambulatory clinic pharmacies in Qatar. Our hypothesis is that a patient-specific structured smoking cessation program delivered by smoking cessation-trained ambulatory pharmacists would be significantly more effective in helping smokers stop smoking and achieving long-term smoking abstinence than brief unstructured pharmacist-delivered advice.We also hypothesize that quitting smoking would lead to significant improvement in health-related quality of life.Primary: To test the effect of a face-to-face structured patient-specific smoking cessation program delivered by trained ambulatory pharmacists on smoking cessation rates in QatarSecondary: To assess the change in health-related quality of life in quitters vs. non-quittersSecondary: To explore the resource utilization of implementing the smoking cessation program as delivered by the ambulatory pharmacists in Qatar. This is a cost analysis of the overall cost of running the proposed patient-specific cessation program, including cost-effectiveness analyses.The study objectives are:The study is a prospective randomized controlled trial comparing the effectiveness of a face-to-face structured patient-specific smoking cessation program conducted by trained ambulatory pharmacists versus brief unstructured pharmacist-delivered advice on smoking cessation rates.The study is implemented in eight public and private ambulatory pharmacies in the State of Qatar. These pharmacies are located within large ambulatory clinics that serve a large proportion of the Qatar population. To prevent cross contamination with the study, none of these clinics has established smoking cessation programs. Each study pharmacy is staffed by at least three pharmacists. Two pharmacists from each pharmacy are invited to participate in the study. The study is taking place in a semiprivate area in the pharmacy. This area is secluded enough to ensure adequate patient confidentiality.Prior to starting the study, each study site pharmacist was sent a copy of the study methodology along with a written literature review on smoking cessation and asked to study the material.Two to three weeks after receipt of the material, the study pharmacist attended a 2-day (8 h/day) smoking cessation training workshop that was organized by the Hamad Medical Corporation (HMC) smoking cessation clinic team and Qatar University (QU) College of Pharmacy.The training team consisted of Dr. Ahmed al Mulla , Dr. Maguy El Hajj , Dr. Nadir Kheir (Associate Professor and CPPD coordinator at QU College of Pharmacy) and Dr. Mohamad Haniki Nik Mohamed [Deputy Dean (Academic Affairs) in Kulliyyahof Pharmacy at the International Islamic University Malaysia (IIUM)]. Dr. Haniki is considered an international authority in the area of substance abuse, including cigarette smoking.The HMC smoking cessation clinic is one of the smoking cessation facilities in Qatar. The clinic is run by highly qualified smoking cessation consultants and has a smoking cessation success rate of 40%. In addition to offering smoking cessation treatment, this clinic contributes to community education on the dangers of smoking among the citizens and residents of Qatar and provides smoking-related lectures and seminars for all age groups in the state .The general objective of this workshop is to provide the study pharmacists with enough smoking cessation knowledge and the necessary skills and tools to assess and treat smokers. A smoking cessation training manual that was developed by the study training team is extensively used in the workshop. This manual is also used as an on-site resource by the study pharmacists in their smoking cessation program.The workshop covered the following: smoking epidemiology and risks, benefits of quitting, a transtheoretical model for behavior change as applied to smoking cessation, the necessary elements for documentation in the patient smoking cessation profile, behavioral modification techniques, classification of smokers according to their stage of change , nicotine replacement therapy , patient counseling techniques, development of a personalized action plan, use of the exhaled carbon monoxide test, detailed instructions on the program methodology and other needed elements.In addition, the pharmacists’ training workshop included training the pharmacists on how to follow the study protocol exactly. The study team walked the pharmacists through the study protocol including how to randomly allocate participants to the intervention and control groups, how to deliver the intervention and how to deal with control patients.During the training workshops, emphasis was also placed on the importance of behavioral and lifestyle modifications. Pharmacists were instructed to encourage smokers who are anticipating quitting to identify the situations that may increase their risk of smoking such as having smokers within the household or at the workplace as well as getting into stressful situations. After identifying these situations, the pharmacists were provided with information they could give to smokers about strategies to improve coping including lifestyle changes to decrease stress and improve QoL, removing visual cues for smoking and staying away from these situations that normally make patients want to smoke . In addiParticipant counseling and interviewing techniques were also part of the training workshops. To enhance learning, the pharmacists applied these techniques using patient role-plays in small groups. Topics that were reviewed included counseling skills, verbal and nonverbal communication skills including use of empathy and active listening, use of open-ended and priming questions, verification of patient understanding, overcoming of communication barriers, communication with difficult patients, communication with patients not interested in discussing smoking cessation and use of strategies to improve medication adherence.Documentation was an important element of the workshop. The pharmacists were trained to document the patient’s smoking, medical and medication history, basic demographic characteristics, staging, assessment, education, counseling, follow-up and the personalized action plan to quit smoking. In addition, they were instructed on how to fill in the Fagerstrom test for nicotine dependence (FTND). The FTND is a six-item questionnaire designed to assist the healthcare professional in determining a patient’s degree of nicotine dependence . This quThe study pharmacists were trained to recognize many opportunities for the promotion of the smoking cessation program as possible. For example, when dispensing prescriptions, the study pharmacists were encouraged to ask patients about smoking and to tell them about the smoking cessation program. In addition, study site pharmacists displayed posters and leaflets in their pharmacy describing the smoking cessation program. Furthermore, the general practitioners and dentists practicing in the study ambulatory clinics were sent letters inviting them to refer their patients who are interested in quitting to the study pharmacies.Interested smokers meet with the study pharmacists. The study pharmacists use a scripted questionnaire to screen smokers in order to assess their eligibility for the study. Eligible participants are patients aged 18 years and older who currently smoke one or more cigarettes daily for 7 days, are motivated to quit, i.e., in the preparation stage of the stage-of-change model, able to communicate in Arabic or English, and are willing to and capable of attending the scheduled sessions at the study pharmacies. The motivation to quit is determined by the pharmacist using the transtheoretical model of behavior change . SmokersExclusion criteria are (1) use of other nicotine or tobacco products and (2) current use or use in the last 30 days of smoking cessation aids or medications, (3) planning to leave Qatar in the next 12 months, (4) presence of any major medical condition that would prevent use of the nicotine replacement therapy including hypersensitivity to the products, history of or recent myocardial infarction, life-threatening arrhythmias, severe or worsening angina, uncontrolled hypertension and temporomandibular joint disease (in case of nicotine gum), (5) pregnancy and (6) psychiatric illness or another debilitating condition that would interfere with participation in the study.Following the completion of the screening procedure, the study pharmacist gives the eligible participant pertinent background information on the program, explaining what his or her participation would involve , and his or her right to confidentiality. In order to enroll in the study, the interested participant is asked to sign an approved consent form. Once the consent form is signed, the pharmacist collects the participant’s contact information and sets an appointment with him or her at a date and time that is suitable for both of them.One to two days before his or her scheduled appointment, the study pharmacist contacts the enrolled participant to remind him or her about the appointment. At this initial appointment, which takes around 30 min, the study pharmacist first collects the participant’s sociodemographic characteristics, current medical problems and medications, smoking history  and vital signs . In addition, the pharmacist assesses the smoker’s level of nicotine dependence using the Fagerstrom Test for Nicotine Dependence and measures his or her baseline exhaled carbon monoxide (CO) level using the exhaled CO test. Furthermore, the pharmacist administers the smoking cessation quality-of-life (SCQOL) questionnaires. After baseline data collection, the smoker is randomly assigned to either the intervention group or the control group. Randomization is already anonymously preset by the study statistician for each study pharmacist. According to the participant number and the preset list, the participant will be randomized to the intervention or control group. A new appointment is set with the participants assigned to the intervention group. Participants assigned to the control group receive brief unstructured smoking cessation advice as outlined below. Participants in both groups do not pay for their participation.Participants assigned to the treatment group participate in a face-to-face four-session program at the pharmacy delivered by the study pharmacist at 2-4-week intervals over 8 weeks. The sessions are set at a date and time that are convenient for both the pharmacist and participant.The first session is time-intensive, taking around 30 min. In this session, the study pharmacist facilitates the participant’s preparation to quit. The participant selects a quit date within the next 2-4 weeks. Based on the transtheoretical model of change, this would give him or her time to get prepared to enter the action stage on the quit date.The pharmacist discusses the benefits of smoking cessation with the participant and provides him or her with tailored behavioral and lifestyle strategies. These strategies take into consideration the participant behaviors, values and beliefs. For example, if the smoker states that the hardest time would be at work when others are taking breaks to smoke, the pharmacist may suggest ways to spend the time during breaks. As outlined under the training section, the pharmacist also provides the participant with information about what to expect during the quit attempt with suggestions to cope with the early days of quitting. In addition, the pharmacist encourages the participant to seek family support during the attempt.To prevent nicotine withdrawal symptoms, the participant is also offered, without cost, nicotine replacement therapy (NRT) as a patch or lozenge depending on his or her previous experience, preference and adverse effect profile. Other NRT dosage forms, e.g., an inhaler, nasal spray and sublingual tablets, are not available in Qatar. The gum is usually not tolerated by patients. The participant is not offered the other smoking cessation aids, including bupropion and varenicline, as they require a prescription in order to be dispensed in Qatar. Before dispensing the NRT, the study pharmacist ensures that the participant does not have any contraindications to nicotine therapy and is not taking any medication that would interact with NRT. The NRT is started on the participant’s intended quit date. Patient counseling about NRT is provided to each participant regarding the dosage, administration, scheduling, duration of therapy, adverse effects, interactions and proper disposal.Participants who take the nicotine patch start at 21 mg if they smoke ten cigarettes or more per day. Otherwise, they receive a 14-mg patch. Both patches are continued for 6 weeks before being tapered. The 21-mg patch is decreased to 14 mg, continued for 2 weeks and decreased to 7 mg for a final 2 weeks. Patients who start with the 14-mg patch are tapered to 7 mg for a final 2 weeks . ParticiA personalized action plan is created by the pharmacist to document the participant’s quit date, nicotine replacement therapy dosage schedule and counseling, suggested behavioral and lifestyle strategies, and date/time of the next appointment. This plan is signed by both the participant and pharmacist.The first follow-up session is scheduled 1 week after of the participant’s quit day and takes around 20 min. In this session, the pharmacist determines the participant’s smoking status, measures his or her blood pressure/pulse/exhaled CO level, and assesses the NRT tolerability. If the patient succeeds in quitting, the pharmacist provides reinforcement and addresses problems associated with quitting such as managing withdrawal symptoms, coping with cravings, relieving stress, and managing fear of weight gain and of change in relationships with other smoking friends or relatives. If the participant fails to quit smoking, the pharmacist carefully reviews the participant’s experience during the attempt to quit and works through the identified problems. If the participant does not tolerate the NRT side effects , the pharmacist asks the participant to stop the NRT and refers him or her to the HMC smoking cessation clinic for further smoking cessation support. This participant is no longer enrolled in the study.The second follow-up session is scheduled 2 weeks after the first follow-up session. The third follow-up session is set at 4 weeks after the second follow-up session. These sessions take no more than 10 or 15 min each. In these sessions the pharmacist assesses the participant’s smoking status, blood pressure/heart rate/exhaled CO level and NRT tolerability and provides NRT refills. In addition, he or she focuses on maintenance of smoking abstinence with cognitive-behavioral strategies to prevent relapse. The pharmacist documents any action taken by him/her at each follow-up session. After the third follow-up session, all participants are instructed to call or visit the pharmacy for questions or to receive additional support as needed. For more information on participant flow during the study, see Figure Participants in the control group receive 5-10 min of unstructured brief smoking cessation counseling by the pharmacist (emulating current practice). In addition, they are provided with educational materials about smoking cessation and are offered nicotine replacement therapy (NRT). Before dispensing the NRT, the study pharmacist ensures that the participant does not have any contraindications to nicotine therapy and is not taking any medication that would interact with NRT. The choice of the NRT dosage form (patch or lozenge) depends on the participant’s previous experience, preference and adverse effect profile. The NRT dosage schedule and duration of therapy are similar to those in the intervention group. Control participants are not asked to attend any follow-up sessions.The education materials address the following topics: the adverse effects of smoking, benefits of smoking cessation, the methods of quitting, setting the quit date, coping with nicotine withdrawal symptoms, getting emotional and social support, and monitoring the blood pressure and pulse when using NRT and avoiding relapse.The study team invests a good deal of time orienting the study pharmacists on their role and training them on how to deal with the control and intervention groups. Part of that orientation is on how ‘not’ to provide any intervention to the control subset of smokers.Study pharmacists were provided with assistance in setting up the study pharmacies and given some time to familiarize themselves with the study protocol prior to commencement of the study. Then each pharmacist was asked to pilot the study in the presence of the study team. Piloting occurred by screening/recruiting around four patients in each site and by implementing the study protocol. Feedback was provided as required to the study pharmacists on the quality of patient counseling, patient education and documentation. Very minor adjustments or refinements were made to the study protocol and study tools including the patient consent form, Fagerstrom test for nicotine dependence (FTND) and smoking cessation quality-of-life (SCQOL) questionnaire as needed.At all stages of the study implementation, the study pharmacists are closely supervised by the study team. Supervision is through several mechanisms including meetings, communication and site visits.Regular meetings are invaluable for high-quality supervision. Meetings are used to guide the project toward its objectives through team involvement. Bi- or triweekly meetings involving all the team members including the study pharmacists are held. In these meetings, study harmacists summarize their activities during the previous 2-3 weeks, and the study team offers them constructive feedback, acknowledges their input and suggests new directions to them. In addition, ad-hoc meetings are conducted between the study pharmacists and the study team where necessary to address any irregular issues that might arise.The study team members are in direct touch with each other and with the study pharmacists through electronic communication such as emails.To maintain quality control in the smoking cessation study pharmacies, the study team visits each study pharmacy at least once every 2 to 3 weeks to monitor data collection, check protocol adherence, ensure the consistency of program delivery, address any queries that the study pharmacists might have in implementing the study, review patients’ folders for appropriate documentation, provide any on-site support required and provide individual pharmacists with feedback on their performance.Orient study pharmacists to the study’s objectives and methodology and to their role in the studyMonitor and follow-up the progress of the studyTackle any issues or concerns that might arise with the study pharmacists while the study is executedShare study updatesMotivate and support the study pharmacistsEnsure adherence to the study protocol in the different study sitesEnsure standardization of study implementation in the different study sitesSupervision is crucial to:A comparative overview of the cost of resource utilization  will be undertaken for the study arms in this study.This pharmacoeconomic analysis will be based on extrapolating data on resources from the randomized controlled trial; these data will be collected prospectively. Prospective data collection enhances the accuracy and robustness of data and limits bias.The economic analysis is performed from a social perspective. Direct medical costs will be evaluated to the best available, including in relation to NRT, CO monitoring tests and salaries. Direct nonmedical costs will also be evaluated and will include participants’ travel costs to pharmacies  and the paperwork and forms. The indirect costs will be accounted for as well, in relation to lost productivity (if any), whether for participants or any unpaid caregivers that participants utilize. Important is that any protocol-driven costs  will be excluded from the analysis.The monetary value of resources will be collected from internal sources at the Qatari clinics. It is worth noting that costs involved in this study will be based on wholesale prices, as paid by clinics.All calculated costs will be in Qatari Riyal, adjusted for the financial year 2015-2016, utilizing the Qatari Health Consumer Price Index as appropriate, and no discounts will be applied given the short timeframe of the analysis.The economic evaluation will be undertaken via decision analytic modeling, where a decision tree will be structured to follow the different options and consequences in the management pathways. For each of the participants, the proposed model may include five possible treatment outcomes depending on whether participants quit smoking, and if they do, after what duration. Smokers will be initially assigned to one of two pathways depending on whether they quit smoking at enrollment. Smokers who do not quit at enrollment will be further followed until assigned to one of two pathways, depending on whether the smoker quits smoking after 3 months or not. If not, smokers will be followed up until further assigned to one of two pathways, based on whether they quit smoking after 6 months or not. Those who do not quit by then will be followed up until assigned to one of two pathways depending on whether they quit at 12 months of follow-up or not, which will be the end of follow-up in any case. Smokers who quit at enrollment or after 3, 6 or 12 months will each be followed up separately until the end of the study. Based on this, in addition to data on resources consumed and their monetary values, the model will generate a weighted average cost for patient cessation and quality-of-life adjustment. As per the general decision analysis principles, this will be calculated as the sum-product of the costs of the management outcomes and the respective probabilities.The costs of managing the single episode of smoking cessation will be compared among different management options and against budgeted costs of clinics/government institutions.The goal of sensitivity analysis is to indicate the robustness of the evaluation conclusion against any potential variations in the model inputs. Deterministic and probabilistic sensitivity tests will be produced by modifications on the base case values of several key variables, in relevance to costs and probabilities, to evaluate the robustness of the study economic outcome. Base case values will be substituted by the highest and lowest values within a reasonable range of values. Where a substitution changes the study economic conclusion, more values within the range will replace the base case value. This will be repeated until the exact variable value that changes the study outcome is identified. Reporting this as part of the study results not only indicates the robustness of results, but also boosts the generalizability of them when being interpreted by decision makers in other settings, with different model inputs, e.g., different resource prices.Uncertainty analysis, by means of Monte Carlo simulation, will be performed via the @Risk-5.0® analysis tool  to investigate the likelihood (probability) of a therapy’s economic advantage. Monte Carlo is a method whereby simulated input values, chosen randomly across a range of probability distributions of a model input, are added into the model. The model is run for each simulated input, resulting in a range of outputs characterizing the output uncertainty. Based on this, a distribution of “cost savings” will be generated, indicating the probability of one management option to have an economic advantage over another.The study protocol and all associated measures, consent forms and recruitment procedures obtained ethical approval by Qatar University (QU) and Hamad Medical Corp. (HMC) institutional review boards (QU-IRB 76/11 and HMC 11113/11). All the participants’ folders are stored in a password-protected database on the site laptop. Only the study pharmacist can access these folders. In addition, all data are retained in a password-protected database maintained along with all related study documentation in a locked cabinet at QU College of Pharmacy.The study research assistants will call the study participants in the intervention and control groups to complete the assessment. To avoid any bias in data collection, the research assistants will be blinded to the participant group allocation.Self-reported 7-day point prevalence abstinence, defined as having smoked no cigarettes for the previous 7 days at 3, 6 and 12 monthsSelf-reported 30-day point prevalence abstinence defined as having smoked no cigarettes in the last 30 days at 3, 6 and 12 monthsSelf-reported continuous abstinence defined as having smoked no cigarettes since quit day at 3, 6 and 12 monthsSmoking abstinence as objectively verified by the CO exhaled test at 12 monthsMean change in health-related quality-of-life score from baseline at 3, 6 and 12 months for quitters vs. non-quittersOverall costs of interventions as studied, including those of utilization for individual recourses consumedAverage and incremental cost-effectiveness ratio of the study smoking cessation interventionThey will measure the following outcome variables at 3, 6 and 12 months after the start of the study :To objectively determine long-term abstinence, at 12 months, participants who will self-report not smoking for the previous 7 days will be invited to come to their study clinic to measure their exhaled CO level. The clinic nurse who is responsible for measuring the exhaled CO level will be blinded to the study participant group. Participants will be considered abstinent if they register less than 6 ppm on the test. Interpretation of the CO test results will be made carefully taking into consideration time since last smoke, time of the day the test is done and other factors.Exhaled carbon monoxide is a well-known indicator of cigarette smoking. But because of its short half-life (5-6 h), it only indicates very recent smoking exposure or abstinence. On the other hand, as a result of its relatively long half-life, cotinine can detect nicotine exposure for up to 1 week. However, the use of any NRT formulation can trigger a false-positive urinary cotinine test. Therefore, as it is not expensive and is noninvasive, and it gives the results in a timely manner, the exhaled carbon monoxide test is commonly used in most smoking cessation clinical trials .t-test  for numerical variables.The CONSORT guidelines will be followed when analyzing the study data. Demographics and other variables related to smoking and quality of life will be summarized using frequency distributions  and means with standard deviations (for numeric variables) and will be compared between the two study arms using the chi-squared test  for categorical variables and the independent The main outcome will be continuous abstinence at 12 months as self-reported and verified by the CO test. The percentages of participants achieving the main outcome will be computed and compared between the two groups using the chi-squared test. Moreover, the difference in the proportions of continuous abstinence at 12 months between the two study arms  will be computed along with the number needed to treat. Multiple logistic regression will be used to obtain the odds ratio of the main outcome between the two study arms adjusting for any imbalances in demographics or other baseline smoking-related variables. Moreover, mixed effects logistic regression, with pharmacy-level random effect, will be considered to adjust for the possible pharmacy effect if it existed. The intent-to-treat principal will be used in the analysis whereby participants who will be lost to follow-up will be classified as smokers and included in the main analysis. This includes those who were removed from the study because they could not tolerate NRT side effects. A sensitivity analysis following that of Borelli, Hogan et al. will be done where the outcome has three possible categories: abstinence, no abstinence and dropout . The sugTo assess the participants’ health-related quality of life, SCQOL  ratings for each question will be translated into scores. A total health-related quality of life score and a domain-specific score will be calculated at baseline, 3 months, 6 months and 12 months for each participant in the intervention and control groups. The change in the total and domain-specific quality-of-life score from baseline will be calculated for each participant at 3, 6 and 12 months and analyzed using linear mixed models, which will include the quitting (quitters and non-quitters) factor and time factor  and their interaction.There is no interim analysis planned for this trial. Statistical analyses will be conducted using the Statistical Package of Social Sciences (IBM-SPSS®), version 21. In all analyses, the level of significance will be set at 5%.For a priori sample size calculation, we assumed a 7-day point prevalence abstinence at 12 months of 3% for the control group and 15% for the intervention group based on the results of one of the previous studies that assessed the effect of a pharmacist-run smoking cessation program [This study is the first randomized controlled trial conducted within Qatar and the Middle East (ME) to test the effect of a pharmacist-delivered smoking cessation program on smoking cessation rates. Furthermore, it is the first study in Qatar to assess the change in health-related quality of life after quitting smoking.Having the economic analysis component in this study is also of unique significance. To our knowledge, there are no economic studies that have evaluated the economics of a smoking cessation program in Qatar or the region. This component is important as in settings where resources are scarce, proving that an intervention brings a good return to the investment can be as important as proving the intervention effective.Indeed, in consideration of limited resources and tight departmental budgets, the additional spending associated with any of the study options should be examined. This will be performed through determining the management option that yields benefits that are associated with most health costs savings. For example, the structured program in this study is expected to have a favorable comparative effect profile. But if the value that is associated with these advantages is not high enough, having the structured program in settings may not be the priority practice to implement. Here, the current study provides a great opportunity for such analysis, seeing that randomized controlled trials are the ideal source of data  to be used in the construction of economic analyses.This study will be of significance to Qatar, the ME and to some extent the world. It will advance knowledge about the role that the ambulatory pharmacists in Qatar and possibly in the ME can play in smoking cessation. It will show to what extent these pharmacists would be effective in helping smokers quit smoking. This would be important for Qatar and the ME given the high number of cigarette smokers in these countries . This stPatient recruitment is currently ongoing.


To decrease child mortality due to common but life-threatening illnesses, community health workers (CHWs) are trained to assess, classify and treat sick children. For pneumonia, CHWs are trained to count the respiratory rate of a child with cough and/or difficulty breathing, and determine whether the child has fast breathing or not based on how the child’s breath count relates to age-specific respiratory rate cut-off points. International organizations training CHWs to classify fast breathing realized that many of them faced challenges counting and determining how the respiratory rate relates to age-specific cut-off points. Counting beads were designed to overcome these challenges. This article presents findings from different studies on the utility of these beads, in conjunction with a timer, as a tool to improve classification of fast breathing. Studies conducted by the International Rescue Committee and Save the Children among illiterate CHWs assessed the effectiveness of counting beads to improve both counting and classifying respiratory rate against age-specific cut-off points. These studies found that the use of counting beads enabled and improved the assessment and classification of fast breathing. However, a Malaria Consortium study found that the use of counting beads decreased the accuracy of counting breaths among literate CHWs. Qualitative findings from these studies and two additional studies by UNICEF suggest that the design of the beads is crucial: beads should move comfortably, and a separate bead string, with colour coding, is required for the age groups with different cut-off thresholds—eliminating more complicated calculations. Further research, using standardized protocols and gold standard comparisons, is needed to understand the accuracy of beads in comparison to other tools used for classifying pneumonia, which CHWs benefit most from each different tool (i.e. disaggregating data by levels of literacy and numeracy) and what the impact is on improving appropriate treatment for pneumonia.  The use of age-specific and colour-coded beads enables community health workers (CHWs) to track rather than mentally count the child’s respiratory rate and eliminates the need to remember the age-specific fast breathing cut-offs for pneumonia classification.Well-designed age-specific and colour-coded counting beads, when used in conjunction with an accurate timing device, have the potential to improve correct classification of fast breathing by CHWs with limited numeracy and literacy in low-resource settings.Further research is required to demonstrate the relationship between well-designed age-specific and colour-coded beads and health outcomes, particularly when data are disaggregated by key characteristics of CHWs (e.g. by levels of literacy and numeracy) and severity of illness.Because of the overall complexity of diagnosis, the still staggering mortality, lack of diagnostic aids and the growing problem of antibiotic resistance for pneumonia, there is an urgent need for more robust data on tools for pneumonia diagnosis. Pneumonia is the leading cause of childhood mortality, accounting for 17% of global deaths of children under five . Timely There are two steps in detecting whether a child has fast breathing: (1) a CHW needs to visually count a child’s breath for 1 min and (2) the CHW has to determine how the child’s breath count relates to age-specific respiratory cut-off points . InternaWatches and timers have been used as timing aids to facilitate 1-min RR counting. The potential of the use of counting devices, such as beads, is unknown due to lack of information regarding their effectiveness and utility. However, several organizations  have conducted small-scale studies among CHWs with differing levels of literacy and numeracy, using counting beads, which contribute to the knowledge base.In this review, we compile the current evidence base of the effectiveness of counting beads to assess and classify breathing rates to guide pneumonia diagnosis. These findings are essential to further guide integrated Community Case Management (iCCM) programming aiming to decrease pneumonia deaths in young children.The findings presented are based on studies conducted by IRC, Save the Children, Malaria Consortium and UNICEF to improve iCCM programming in South Sudan, Uganda and Ghana. All CHWs in these studies were trained in iCCM using the World Health Organization (WHO) and UNICEF IMCI ‘Caring for Newborns and Children in the Community’ protocol. CHWs are named differently in various countries, e.g. in South Sudan they are called community-based distributors; however, in this article, we refer them as CHWs.What is known regarding primarily illiterate CHWs’ ability to assess and classify fast breathing without the use of counting beads?Does the use of beads improve the ability of CHWs, particularly those with limited or no literacy and numeracy, to correctly classify fast breathing ?Does the use of beads improve the ability of literate CHWs to correctly assess the breath count?What are CHWs’ perceptions of these tools, and does this differ by literacy level?We compiled all research findings on the use of counting beads within these programmes. Although most findings presented are part of larger research initiatives, in this review we focused on the following questions:A brief description of the studies is provided below and a summary of the key methodological elements of the different studies can be found in As part of a larger assessment evaluating the quality of care provided by CHWs, IRC compared the CHWs’ ability to assess fast breathing using the ARI timer alone vs using the timer and beads. The geographical areas (payams) were selected on the basis of their geographical accessibility to the evaluation team and recent start-up of the programme.First, CHWs were asked to describe the cut-off points for fast breathing for the two age groups (2–11 and 12–59 months) and to count the child’s RR using the ARI timer. A trained clinician who was part of the evaluation team counted simultaneously with the CHW. The RR from the clinician was written down and the CHW was asked to say his/her count. Afterwards, CHWs were given the right counting bead string for the age of the child being assessed and were shown how to move their fingers along the beads and to stop when the timer beeped. Then CHWs were asked to repeat the assessment with the same child using the timer and the beads. The clinician used the counting beads simultaneously with, but out of sight of, the CHW. The beads were counted back and recorded for both the CHW and the trained clinician. Microsoft Excel was used to analyse the data.The use of beads by CHWs with limited numeracy was part of an operational research lead by Save the Children. The research was conducted to assess the effectiveness of simulation-based training of CHWs using video technology.During the training, CHWs were shown video clips of cases with danger signs  and the interactions between CHWs and caretakers. The video also showed the assessment, classification, treatment and advice on home care. CHWs were given one set (two strings) of beads to count and classify the breath count along with the ARI timer acting as a stop watch. CHWs were taken to a hospital outpatient department for post-training skills assessment, where they assessed sick children (40 out of the 69 cases had a history of cough). Each CHW managed  two to three sick children aged 2–59 months. Each CHW also completed a knowledge questionnaire. As these particular CHWs were illiterate, one clinician trained in IMCI observed the CHWs’ management of sick children and recorded the assessment, classification and treatment findings on a study form. A senior evaluator who was also an IMCI trainer independently assessed the children at the same time and recorded his findings on a similar form. The RR was measured for all 69 children by the CHWs and the evaluator. To assess fast breathing the CHW had to choose the correct bead string for the age group. The observer marked the case as having fast breathing if the CHW reached the red beads (fast breathing for 2- to 11-month and 12- to 59-month age groups) within the minute. The evaluator used the ARI timer to count child breaths and noted the actual breath count in the form. The data were entered in CSPro and imported and analysed in Microsoft Excel.Malaria Consortium assessed whether there was a difference in accuracy in counting RR among CHWs using (1) the ARI timer alone vs (2) using the timer and beads and (3) using a mobile phone application, where the centre button on the phone was pressed for every breath observed, and which beeped after 1 min, after which the count was displayed. The sub-county was selected on the basis of its geographical location and mixture of CHWs with different age, sex and literacy levels [varying from being able to read and write well in any of the local languages (78%) to fairly well (22%)].First, each CHW received a detailed explanation of how to count the RR, while simultaneously using the ARI timer, the same timer with beads as well as the mobile phone application. The CHWs then had the opportunity to practise three different methods of counting RR on videos of children with different breath counts. After familiarizing themselves with the three methods, each CHW was observed counting using the three options, respectively, on children with different breath counts. The video case scenarios were displayed on laptop screens, enabling one CHW to assess a child at a time. The final RR was recorded for the three tools as follows: (1) when using the timer alone, the CHW was asked for the final RR count, (2) when using both the timer and beads, the beads were counted back by a research assistant who provided the final RR count and (3) for the mobile phone application, the result was read from the screen. The breathing rate of the children in the video was known and was used as the gold standard. STATA 12 was used to analyse the data. The research only assessed the impact on counting the RR and did not assess the impact of these devices on classifying the breath count against the age-specific cut-off points.Along with their quantitative research efforts, IRC and Malaria Consortium assessed CHWs’ perceptions about the beads, focusing on their opinions and proposed improvements. Data were collected through interviews. Malaria Consortium also assessed CHWs’ perceptions about how the use of counting beads helped them communicate the test results to caregivers.Other qualitative research was initiated by UNICEF, as part of a broader effort to identify CHWs’ unmet needs regarding tools to support the assessment and classification of RRs. In Uganda the focus of the research was on CHWs’ experiences assessing RR using the ARI timer and their ideas regarding tools that might be useful to help improve their assessment and the classification of RRs. The CHWs were not familiar with the use of beads. Building on these findings, a subsequent study was conducted in Northern Ghana, where the CHWs had been trained to use both the ARI timer and beads. The main objective of this study was to help UNICEF improve the design of diagnostic aids based on the challenges CHWs indicated they face while assessing, classifying and identifying treatment needs for children under 5 with rapid breathing.Non–age-specific counting beads: These counting beads are designed to help the CHW keep track of the amount of breaths taken. The CHW counts moves bead for each breath. When 1 min has passed the CHW counts back the beads to determine the RR. Because of the colour coding of the number of beads (e.g. every set of 10), the CHW can count back the beads per colour: e.g. 1 colour = 10 breaths, 2 colours = 20 breaths, etc. On the basis of the RR, the CHW compares the result against the IMCI guideline, correctly remembering the age-specific cut-off rate.Age-specific beads with colour coding: These counting beads support the CHW not only with counting but also with interpreting the RR against the IMCI guidelines. These beads remove the need to count by the CHWs to assess pneumonia  because they consist of a set of two strands or rows of beads that are colour-coded to match the thresholds for the two different age groups. Depending on the age of the child, the CHW selects the matching bead strand and moves the beads for 1 min. Once the minute has passed, the CHW can identify whether the child has pneumonia, depending on the colour of the bead she/he is holding between his/her fingers.The IRC assessed what the key challenges were for primarily illiterate CHWs while classifying fast breathing. Findings indicated that 46% (21/46) of CHWs in Uganda were not able to apply the age-specific cut-off points and 33% (15/46) made an incorrect count using the ARI timer. In South Sudan, 59% (19/32) of CHWs were not able to apply the age-specific cut-off points and 72% (23/32) of CHWs made an incorrect count using the ARI timer.P = 0.002) when they used the beads together with the timer. Findings were similar in Uganda, where the ability to classify fast breathing increased from 37% (17/46), using only the timer, to 73% (24/33) , using both tools. Combining the data from both countries, the ability to classify fast breathing increased from 27% (21/78) to 68% (44/65) , see In South Sudan 13% (4 out of 32) of the CHWs were able to classify fast breathing using only the ARI timer, whereas this number increased to 63% (20/32) (Odds Ratio (OR) OR = 11.7, Save the Children’s research did not have a component of assessing a sick child without the use of beads, as they identified that CHWs had limited numeracy, and were not able to count beyond 10. A total of 69 sick children were assessed by the 27 CHWs. Using the ‘age-specified and colour-coded’ beads and ARI timer, the CHWs classified 25 cases as suffering from fast breathing. The senior evaluator who only used the ARI timer classified 23 as fast breathers. Of the 25 CHW-classified fast-breathing cases, 15 (60%) matched with the evaluator-classified fast-breathing cases.CHWs were also administered a knowledge questionnaire that included questions on the use of beads appropriate for age. All 27 CHWs picked the beads appropriate for the two age groups. With respect to classifying a child as having fast breathing, 26 out of 27 picked the right colour (red) for the 2- to 11-month group and 27 out of 27 for the 12- to 59-month age group.P < 0.001). There was no significant difference between the ARI timer and mobile phone application , implying that CHWs have a similar capacity to correctly count RR using either of the assessment methods (i.e. counting themselves vs pressing a button for every breath observed).In Uganda, Malaria Consortium assessed whether the use of tools, including counting beads, improved the ability of literate CHWs to count RR. CHWs were 5.6 times more likely to count (not classify) RR correctly (i.e. ±2 breaths) using the timer alone compared with when it is combined with beads , whereas for the mobile phone application and counting beads, the difference between the rates observed and the true rate was significantly different from 0 . Using the same test, the median difference observed between the ARI timer and mobile phone application was not significantly different (P = 0.179), whereas the difference was significantly different between the ARI timer and the counting beads (P < 0.001) as well as between the mobile phone timer and the counting beads and timer (P = 0.001).Overall, the median difference between the ‘true rate’ and the rate observed with the three methods was −1 (interquartile range(IQR) −5 to 2) for the UNICEF timer, −1 (IQR −7 to 2) for the mobile phone application and −5 (−12 to 2) for the ARI timer with beads. Using the sign test for non-parametric data on matched pairs, the differences in rates observed using the ARI timer compared with the true rate was not significantly different from 0 , it was demonstrated that all three methods performed much better on the slower breathing rates (i.e. 40 breaths/min) than the fast rates (i.e. 65 and 66 breaths/min). All three methods tended to overestimate the rate in the slow-breathing scenario, whereas they underestimated the rate in the fast-breathing scenarios.The colour-coded beads designed by IRC in Uganda match the colour of the locally available amoxicillin packages for specific age groups, and according to (mainly illiterate) CHWs, this helped them to identify the correct string needed for the child, eliminating the need to recall the cut-off points for the different age groups. Regarding the use of counting beads, CHWs interviewed by IRC were most likely to say that: (1) the use of beads eliminated the need to count or worry about forgetting the number or making mistakes while counting; (2) it was easy to move hands along the beads; (3) it was easy to know when to give the treatment and (4) it was easy to explain to the mother that her child did not need medicine. The need for more training and practice regarding the use of beads in combination with the ARI timer was mentioned by CHWs in South Sudan and Uganda.What I have liked about this method is that I don’t have to count the beads as I move them, counting usually comes last and this gives me more concentration on observing the child and moving the beads.The method was acknowledged as one that could give a quick picture of the diagnosis by identifying the colour of the bead where the hand has stopped after the alarm has gone off (i.e. whether white or red/green bead), the next steps could follow later:From what I have learnt today, the combination of both the timer and beads is very helpful because it helps me to immediately know whether the child has fast breathing by looking at the colour of beads where I have stopped and then, I count the beads to confirm what I have seen, after which I write in my book.The use of the beads also made it easier to communicate the results to the caretaker, as the colours visually flagged if the child had a high breath rate (indicating pneumonia) or not.In the study amongst literate CHWs by Malaria Consortium in Uganda, CHWs expressed their support for alternative methods to count the RR other than the timer which they were familiar with. Using the beads, in addition to the timer, was perceived as being advantageous because each breath was being represented by movement of a bead and then counting of the beads could be done afterwards, thus giving more accurate results.For me, I find this method very challenging because I have to observe three things at the same time: I have to look at the child, start the timer and also move the beads at the same time, which is a bit tasking. That is why you have seen that I have been forgetting to put on the timer as I move the beads.However, the beads were also perceived by some as disadvantageous because combining the timer and beads was considered to be more tasking, with a slow bead movement process and therefore reduced accuracy. During observations, it was noted that CHWs often found it difficult to start moving the beads immediately after starting the timer.Related to the design, CHWs often mentioned that the space between individual beads can affect the outcome of the count. The space between the beads should be small, as the bigger the distance was between the beads, the more difficult it was to move them. The CHWs also suggested that the beads should be light and unattractive in order not to be mistaken for accessories and have a strong string, which would not break easily.I would have preferred the beads because each time I count, I hold a bead so I will be able to know how many beads I left behind in case I forget where I was when countingGreen is OK. Red is for danger.Data from the assessment in Uganda by UNICEF, where mainly illiterate CHWs only used the ARI timer, revealed that CHWs would find it useful to have a device that supports them with the classification of fast breathing and that would help them communicate the findings to the caregivers. When the CHWs in Uganda were shown counting beads they mentioned that beads might be confused with a toy; however, it would help them with the assessment and the classification of fast breathing.The main concern among mainly illiterate CHWs regarding the use of non–age-specific beads used in the Northern region of Ghana was that these beads still required counting and remembering the cut-off rate. The beads also have ‘separator bead’, which the CHWs thought creates confusion because ‘we move the beads without looking at them’. Nevertheless, the use of prayer beads in the region is common; CHWs are used to counting with beads and are at ease with this. However, the CHWs reported that this similarity could reduce the acceptance by caretakers as the beads are perceived as a tool for prayer and not as a healthcare-related tool.This one has only two colours and the colours easily tell if the child has pneumonia or not. I think that this one will be more convenient to use than the current one we have.When shown the ‘age-specific and colour-coded’ beads used by IRC and Save the Children, the CHWs and their supervisors in Ghana showed a strong preference to this design as it eliminated the need to count and remember the cut-off rate.This review of studies on the utility of counting beads as a tool to improve classification of fast breathing in children with cough and/or difficulty breathing to guide pneumonia diagnosis shows that the introduction of ‘age-specific and colour-coded’ counting beads, in addition to an accurate timer, can help CHWs with limited numeracy and literacy to more accurately assess fast breathing. Although CHWs also expressed concerns on the task intensity of the method, in general, it was acceptable and applicable across different settings.There are several limitations associated with the studies included in this review. First, the studies used several research approaches, methods (including gold standards) and research questions. Moreover, programmatic settings as well as the levels of literacy and numeracy of the CHWs differed. Second, the case scenarios by the various organizations assessed children in different settings , which resulted in different breathings patterns, e.g. the children assessed at home were unlikely to have fast breathing, although a few of them happened to have it. This review suggests that these factors influence the utility of beads.Data from IRC, Save the Children and anecdotal evidence from PSI and IRC suggest that ‘age-specific and colour-coded’ beads enable and improve accuracy in the classification of fast breathing by CHWs with limited literacy and numeracy. However, if literacy and numeracy is not an issue, findings from Malaria Consortium show that the use of beads complicates the assessment, as it resulted in more inaccurate counts (i.e. CHWs were 5.6 times less likely to count correctly using the beads and timer). A reason for the breathing count inaccuracy by literate CHWs was that some perceived the use of beads as more task intensive. Although for CHWs with limited literacy and numeracy (e.g. those not able to count beyond 10), the use of beads enabled them to track the breathing rates as well as classifying the count against the age-specific cut-off points, which would not be possible without these beads.It was also found that the rate of breathing influences the accuracy of the RR count. The research conducted by Malaria Consortium shows that, regardless of the tool CHWs used, they tended to overestimate the rate in the slow-breathing scenario, whereas they underestimated the rate in the fast-breathing scenarios.Regarding the use of counting beads, these data show that it is premature to conclude to which degree the beads, in addition to a timer, would improve the ability of trained CHWs to correctly classify fast breathing. A more conclusive assessment is needed amongst sick children, disaggregating data by intensity of training and supervision, levels of literacy, numeracy and comparing the final breath count to a gold standard.Previously conducted studies on pneumonia diagnosis by CHWs indicate that even if CHWs are good in counting, they still often make mistakes in classifying the breath count (Concurrent to the need of more evidence regarding the utility of beads, there is a need for more research assessing the effectiveness of other devices, such as automated RR counters.Given the overall paucity of data, this review of recent studies provides insights on a range of issues to consider when implementing counting beads in iCCM programmes. This emerging evidence suggests that the introduction of well-designed ‘age-specific and colour-coded’ beads in addition to an accurate timer can help CHWs who have difficulty counting breaths and remembering age-specific cut-off rates to more accurately assess and classify fast breathing. It also has the potential to improve communication with the child’s caretakers—particularly regarding appropriate treatment options. However, more research is needed on these and other devices to decrease the inaccuracy in pneumonia diagnosis.


Patients in ICUs frequently require tracheostomy for long-term ventilator support, and the percutaneous dilatational tracheostomy (PDT) method is preferred over surgical tracheostomy. The use of ultrasound (US) imaging to guide ICU procedures and interventions has recently emerged as a simple and noninvasive tool. The current evidence regarding the applications of US in PDT is encouraging; however, the exact role of US-guided dilatational tracheostomy (US-PDT) remains poorly defined. In this review, we describe the best available evidence concerning the safety and efficacy of US-PDT and briefly delineate the general principles of US image generation for the airway and of US-PDT procedures. The remarkable progress in the field of imaging has revolutionised the approach to critically ill patients. Advances in medical technology have made ultrasound (US) imaging less costly, easier to use, more precise, and sufficiently portable to be truly hand-carried. In ICUs, ultrasound scanning (USS) is frequently used to guide vascular access and procedures and for pleural and cardiac imaging. The use of USS in percutaneous dilatational tracheostomy (PDT) has the potential to improve the efficacy and reduce the complications of this common ICU procedure.PDT is commonly performed at the bedside in the ICU . With anBronchoscope guidance during PDT is used by many institutions as an additional safety adjunct , 10. It We performed a literature review to examine the efficacy and safety of US before or during PDT or both. MEDLINE, PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for trials reporting on the safety and efficacy of US or bronchoscope guidance before and during PDT. The terms used were ‘safety efficacy’, ‘ultrasound’, ‘tracheostomy’, and ‘tracheotomy’.Prospective trials that reported procedural safety or efficacy data for both the intervention group (US-PDT) and a control group of standard or bronchoscope-guided PDT cases were included. Case reports, review articles, letters to the editor, and surveys were excluded.The following sections summarise the role of USS use before, during, and after PDT.The difficulties encountered in locating anatomical landmarks, such as the crico-thyroid membrane, and difficulties with tracheal puncture when the tracheal anatomy is not readily palpable are well documented . ConsequUS-PDT can be used to measure the distance from the skin to the trachea, thus allowing the selection of an appropriately sized tracheostomy tube  .Another advantage of pre-procedure USS of the neck is that it allows the identification of vulnerable structures, such as blood vessels and the thyroid gland, in the neck prior to PDT. Moreover, real-time USS performed during the procedure plays a major role in revealing potentially aberrant vessels, which allows needles and dilators to be guided away from at-risk structures, thus avoiding immediate vascular complications . SeveralP < 0.05).The routine use of USS also enables the clear visualisation of the tracheal rings, which is necessary for the appropriate positioning of the tracheal puncture and correct midline placement –30. ChacP < 0.05) [Earlier studies of models have shown that, in subjects with simulated unidentifiable anterior neck airway anatomy and tracheal deviation, the use of USS improved the speed and success of cannula placement and reduced the number of attempts required. Sustić  reported < 0.05) . It is w < 0.05) –39.Real-time US guidance makes it possible to follow the needle path during tracheal puncture and to determine the final position of the tracheostomy tube , 41. HowKollig and colleagues  reportedNo studies have yet compared bronchoscope-guided PDT alone with US-guided PDT. Such a comparison is mandatory if we are to improve the PDT technique, minimise patient risks, and eliminate financial burdens.The use of portable US to detect pneumothorax has long been studied . RecentlOnly a few prospective randomised controlled trials (RCTs) have compared the safety and efficacy of US-PDT with the traditional landmark-guided technique (with or without bronchoscopy). The remainder of the available studies are all small and largely observational in nature. Table Because of the lack of strong supporting evidence, US-PDT is not yet practiced routinely. The small number of available studies suggests that US-PDT is safe and offers a potential benefit over the traditional landmark-guided procedure, particularly in selected patient groups, such as obese patients. Therefore, we decided to describe the procedure in detail (supported by images) to encourage critical care physicians to consider the great safety potential associated with the use of US-PDT and to plan for conducting a large RCT comparing US-PDT with bronchoscope-guided PDT.Transducer selection is important when evaluating the anatomy of the airway. Higher-frequency linear probes (7.5 MHz) provide better resolution of superficial structures. Therefore, they are the most suitable type of probe for imaging superficial airway structures (within 2 to 3 cm from the skin). In contrast, the curved low-frequency (5 MHz) transducer is best used for obtaining sagittal and parasagittal views of structures in the submandibular and supraglottic regions . These pHyperechoic structures (such as fat and bone) give a strong echo and thus appear white . Fluid cBefore proceeding to the PDT, the pre-tracheal area should be examined for the tracheal midline, the tracheal cartilage level, the anterior jugular veins (their diameter and location relative to the midline), and the thyroid isthmus or midline vessel. Aberrant vascular structures crossing the midline can also be observed and should be noted. In evaluating vascular structures, it is important to ensure that the structures are not compressed by excessive pressure from the probe. If in doubt, further evaluation using colour Doppler can be performed . Such prIdeally, the space between the first and second or the second and third tracheal rings should be selected for the insertion of the tracheostomy tube. According to sonographic criteria, the point of tracheal puncture should be below the first tracheal ring but above the fifth tracheal ring, with no vascular structures in the path of the needle. The precise inter-tracheal ring space is considered less important than the passage below the first and above the fifth tracheal rings .Avoiding the thyroid isthmus is often not possible and is not believed to be necessary . HoweverIn morbidly obese patients or patients with anatomical deformities resulting from pathology or injuries, palpation is almost always difficult or even impossible , 19, 59.For morbidly obese patients, US should first be used with the head in the neutral position to estimate the thickness of the soft tissue between the skin and the trachea to determine the length of the tracheostomy tube. The mode of imaging should then be adjusted while the trachea is in the centre of the screen to maximise the resolution and depth of imaging.After induction and positioning, the endotracheal tube should be withdrawn under direct laryngoscopic visualisation until the cuff is positioned immediately inferior to the vocal cords using a standard laryngoscope. Some operators have pulled the endotracheal tube back under US guidance until the cuff is at the level of the thyroid cartilage .With a linear array probe in a sterile sheath, it is possible to obtain transverse/axial real-time images of the upper airway, starting from the hyoid bone down to the thyroid gland and its isthmus. The viewed airway should always be in the centre of the screen. On axial imaging, the airway in the neck should be apparent at the midline and should show mixed hyper-echogenicity. The hyoid bone is a key landmark that separates the upper airway into the suprahyoid and infrahyoid regions Fig. . The invBy sliding the probe caudally, the clinician can identify the cricoid cartilage within the anterior wall of the larynx caudal to the cricothyroid membrane by its relatively large acoustic shadow (seen as a hump on the transverse view; Fig. Transverse/axial real-time imaging of the trachea allows continuous visualisation of the tracheal midline. Deviation of the guide wire too far from the midline can occur and can cause paratracheal tissue damage during the subsequent dilatation. Placing the transducer transverse to the tracheal cartilage and first obtaining a short-axis US image allow the identification of the tracheal midline, thereby helping to avoid this problem. However, on this view, it can be difficult to identify the correct space between the tracheal rings and to differentiate cartilage from air. We therefore recommend obtaining the details of the midline of the neck on the transverse/axial view, determining the absence of aberrant structures, and then moving the probe 90 degrees to obtain a longitudinal view with the cricoid cartilage and the first tracheal ring in the centre of the US screen. On this view, the space between the first and second or second and third tracheal cartilage at the midline of the trachea can be identified Fig. . This apThis so-called in-plane approach can sometimes be difficult in patients with short necks because of a lack of physical space. In such cases, a perpendicular angle of puncture is preferred, despite the increased risk of injury to the posterior wall of the trachea. In this approach, the transverse probe is positioned immediately above the level of the planned puncture. With slight caudal angulation of the probe, good visualisation and direction of the needle tip toward the tracheal midline should be possible. The needle is introduced perpendicularly to the skin, and the path is determined by the distinct acoustic shadow ahead of the needle, followed by the displacement of tissue layers observed with needle passage. The indentation of the anterior tracheal wall by the needle can sometimes be observed on these US images. This technique has been described by Chacko and colleagues .As soon as a loss of resistance is felt or air or fluid is aspirated into the attached syringe, the US probe is set aside, and the syringe is disconnected. A guide wire from a pre-assembled tracheostomy kit is then inserted through the needle into the trachea as a guide for further tracheostomy. Finally, a bronchoscope is used to determine whether injury to the posterior wall of the trachea has occurred.As US technology continues to evolve, its scope is becoming limited only by operator expertise and not by the capabilities of the bedside unit. USS of the upper airway can provide a great deal of anatomical information that would not be evident with clinical examination alone. With the development of better probes, high-resolution imaging, real-time pictures, and clinical experience, USS has become a potential first-line noninvasive airway assessment tool in intensive care practice. However, until prospective RCTs are conducted to evaluate the safety and efficacy of US-PDT compared with the traditional landmark-guided technique, the best available evidence highly recommends the use of USS prior to, during, and after PDT to improve the safety of the procedure.


Auditory hypersensitivities are a common feature of autism spectrum disorder (ASD). In the present study, the effectiveness of a novel intervention, the listening project protocol (LPP), was evaluated in two trials conducted with children diagnosed with ASD. LPP was developed to reduce auditory hypersensitivities. LPP is based on a theoretical “neural exercise” model that uses computer altered acoustic stimulation to recruit the neural regulation of middle ear muscles. Features of the intervention stimuli were informed by basic research in speech and hearing sciences that has identified the specific acoustic frequencies necessary to understand speech, which must pass through middle ear structures before being processed by other components of the auditory system. LPP was hypothesized to reduce auditory hypersensitivities by increasing the neural tone to the middle ear muscles to functionally dampen competing sounds in frequencies lower than human speech. The trials demonstrated that LPP, when contrasted to control conditions, selectively reduced auditory hypersensitivities. These findings are consistent with the polyvagal theory, which emphasizes the role of the middle ear muscles in social communication. Frequently accompanying a diagnosis of autism spectrum disorder (ASD) are speech and language delays, difficulties in extracting human voice from background sounds, auditory hypersensitivities, and a general compromise in social communication skills –8. In coSeveral mechanisms have been proposed as contributing to frequently reported deficits in auditory processing including damage or dysfunction to peripheral structures , neural pathways , and central structures  . A rBorg and Counter  describeSound enters the outer ear and travels through the external auditory canal to the eardrum where it is transduced by the structures of the middle ear , which connects the eardrum with the cochlea. The rigidity of the ossicular chain determines the stiffness of the eardrum. The middle ear muscles, via cranial nerves, regulate the position of the ossicles and stiffen or loosen the eardrum. When the eardrum is “tightened” higher frequencies are absorbed and transmitted to the inner ear and the energy of lower frequencies is attenuated  before being encoded by the inner ear (cochlea) and transmitted via the auditory nerve  to the cortex. Complementing the ascending pathways are descending pathways that regulate the middle ear muscles, which functionally determine the energy  of specific frequencies that reach the inner ear. The features describing the transformation of sound intensity from outer to inner ear defines the middle ear transfer function. If the acoustic information in the frequency band associated with speech is distorted by an atypical middle ear transfer function, the information being coded by the inner ear and subsequently being transmitted to the cortex will not contain sufficient information to enable accurate detection of speech sounds. In addition, there are descending pathways that regulate the hair cells in the cochlea to “fine tune” auditory perception, which is especially important in the development of language skills. If the acoustic information related to human speech that reaches the cortex via ascending pathways is distorted, then the descending pathways to the cochlea may also be atypical and will further distort the individual’s ability to process speech and to produce language.As proposed by Borg and Counter , atypicaThe listening project protocol (LPP) is a theoretical departure from the disciplines frequently involved in the treatment of auditory processing disorders, which emphasize the role of central structures in the processing of speech  the transfer function of the middle ear serves as an anti-masking mechanism to dampen low frequency sounds and to facilitate extraction of human voice from background sounds , (b) acoLPP applies computer altered vocal music  designed to exaggerate the features of human prosody and hypothetically to exercise the neural regulation of the middle ear muscles. By modulating the frequency band associated with human vocalizations, it was hypothesized that the ascending pathways would be providing dynamically changing information that would feedback on the descending pathways regulating the middle ear muscles. Metaphorically, the procedure could be conceptualized as a “treadmill” exercise for the middle ear muscles during which the demands to “listen” and process the acoustic features of the intervention stimuli were dynamically changing. To test the primary hypothesis that the filtered music condition would reduce hearing sensitivities in children with ASD, two trials were conducted. Trial I contrasted a filtered music group to a headphones only group and Trial II contrasted a filtered music group to an unfiltered music group.The intervention consisted of five daily sessions of approximately 45 min during which the participant passively listened to the acoustic stimulation through headphones in a quiet room, while researchers provided social support to insure that the participants remained calm. The frequency bands were temporally modulated within each session and, independent of amplitude, the band of frequencies that were modulated progressively increased across the five sessions. Theoretically, the changing frequency bands were presented to increase the neural regulation of middle ear structures to dampen the perception of background low frequency sounds and to potentiate the extraction of human voice. Although middle ear muscle regulation could not be assessed, the Borg and Counter  model prClinicalTrials.gov), since enrollment was initiated before January 1, 2001 and data collection was completed before December 26, 2007.Potential participants contacted the laboratory for initial inclusion screening. Participants were informed about the research project by clinicians, parents who previously participated in our research program, and via professional presentations and/or newsletters. Individuals with a suspected diagnosis of ASD, who did not have a history of seizures, were scheduled for a diagnostic assessment that consisted of the autism diagnostic interview-revised (ADI-R) . The ADIParents of 178 children contacted the laboratory to participate in the research. Based on the ADI-R criteria, 146 children met the full criteria of autism. Of the children, who did not meet full criteria, 29 exceeded the ADI-R cut off on at least the qualitative impairments in reciprocal social interaction and/or communication scales. Three children, who did not meet the cut off on either the qualitative impairments in reciprocal social interaction and/or communication scales, were excluded from participating in the research.Based on presentation at the laboratory the first 73 children were assigned to Trial I. In Trial I, data from nine children (two in the filtered music and seven in the headphone only groups) were lost due to technical problems. In Trial I, questionnaire data were scored for 36 children in the filtered music group and 28 children in the headphones only group. Following the completion of Trial I, 102 children, who had not participated in Trial I, were enrolled in Trial II. In Trial II, due to scheduling difficulties, families of six children withdrew before participating in the trial and one family withdrew after the second day of the intervention. In Trial II, data from one child who was diagnosed with Fragile X were excluded from the data analyses. In addition, data from 12 children in the filtered music group were lost due to parents not returning the questionnaires, or returning the questionnaires late, or health issues. Data are not available for documenting the specific causes for lack of compliance. Questionnaire data in Trial II were available from 50 participants in the filtered music group and 32 participants in the unfiltered music group. Descriptive statistics of demographic features of the subjects from Trial I and Trial II with questionnaire data are reported in Table Trial I and Trial II included 86 participants in the filtered music condition, 32 participants in the unfiltered music condition, and 28 participants in the headphones only condition  or the control condition within each trial . Circumaural headphones were used, since they provide excellent sound quality, are comfortable to wear, and have excellent external noise rejection. The features of the headphone in combination with low intensity auditory stimuli precluded the parents from detecting whether their child was receiving the filtered music condition or a control condition. Based on our interactions with parents, it appeared that parents were not informed about the group assignment of their children. After the completion of the follow-up assessment sessions, the children in the unfiltered and the headphones only conditions were given the opportunity to receive the filtered music. Since knowing group assignment might bias parental perceptions of the child’s behavior, data from the children, who received the filtered music after participating in either the headphones only or unfiltered music conditions, were not included in the data analyses.One week following the intervention, parent reports were obtained for all participants in both trials. None of the children who participated in Trial I participated in Trial II. In addition to the parent questionnaire, semi-structured play-based behavioral assessment sessions were conducted with the children and videotaped before and after the intervention.Each condition  consisted of approximately 45 min sessions conducted during five-consecutive days. During the intervention, regardless of group assignment, each child wore headphones in the same laboratory environment. The same vocal music selections were used for both the filtered music and the unfiltered music conditions. In the filtered music condition, the vocal music was computer processed based on a proprietary algorithm developed to remove low and high frequencies and to modulate the width of the frequency band associated with human voice. The intervention stimuli were stored on compact discs and played via high quality compact disc player (Marantz CC-4000) to high quality over the ear headphones (Beyerdynamic DT831). Maximum loudness was calibrated at a peak of 75 dBC before the intervention started. During the headphones only condition, no auditory stimulation was provided through the headphones, although the context was identical to the filtered music and unfiltered music conditions. The low volume of the intervention stimuli and the use of over the ear headphones insured that the intervention stimuli could not be distinguished from the ambient background sounds in the test room by the parents.The sessions were conducted in a research room with toys . During the intervention, the children were able to freely play with the toys. One experimenter stayed in the room during the intervention to assist the child with the headphones when needed. Parents were also allowed to be in the room with their child. The experimenter and the parents were instructed to be quiet and to interact with the child only to maintain and to support a calm behavioral state. Due to the nature of the study , the experimenter who conducted the intervention session was not always blind to the child’s group assignment. In Trial I, since the headphones only group received headphones without sound, the experimenter was frequently aware of the child’s group assignment. However, since only the experimenter adjusted the headphones, the parents remained blind. In Trial II, since acoustic stimulation was being presented to both groups, the experimenter and the parent were unaware of the child’s group assignment. Accordingly, to avoid the possibility of rating bias, the experimenter who conducted the intervention sessions did not participate in the play-based assessments during which sharing behaviors were coded.Following the intervention and the play-based assessments, parents were given a structured questionnaire developed in our laboratory, targeting specific categories of their child’s developmental and behavioral problems including auditory hypersensitivities. The parents of children in all groups were instructed to complete and to return the questionnaire to the laboratory in a week. The questionnaire focused on whether the child had difficulties in a specific behavioral area and whether there were any changes in this area following participation in the research. For each behavioral category, parents were required to document changes, if any, following the intervention by providing specific examples of observed new behaviors. The structured questionnaire focused on the behavioral domains listed in Table Each of the 10 items representing the behavioral domains described in Table Prior to and following their participation in the intervention project, all children participated in a 10-min semi-structured play-based observational assessment of social engagement skills with the social interaction coding scale (SICS) . The SICThe frequency of sharing behaviors was coded from videotapes by trained coders. Coders obtained reliability with each other on training tapes before using the scale for research . Each tape was coded by two trained coders independently and compared for agreement. At least one of the coders was not aware of the participant’s group assignment when coding. Consensus was used to establish the final code. If raters disagreed on the same item, the code of the unbiased coder was recorded. If coders were uncertain about the final code, the opinion of the third trained coder was requested and the code that received the consensus of at least two coders was recorded. If all three coders disagreed on the final code, the behavior was not coded.2 analyses were used to evaluate group differences within each trial on each of the behavioral domains. Since both analysis strategies identified the same group differences within each trial, only the analyses of variance are presented. A Bonferroni correction adjusted significance levels for multiple comparisons.Analyses of variance and non-parametric χConfirming the effectiveness of the randomization procedures, there were no group differences in the representation of the behavioral problems reported via the parental questionnaire within each trial or across trials  = 6.46, p = 0.017; spontaneous speech, F = 5.61, p = 0.022; listening, F = 8.25, p = 0.006; and behavioral organization, F = 5.39, p = 0.027. The percent of the participants improving, who had a problem within each domain, is presented in Table F = 7.76, p = 0.007.To evaluate the effectiveness of the filtered music treatment, group differences were evaluated with analyses of variance for each of the 10 behavioral dimensions included in the questionnaire. As illustrated in Figure F = 4.53, p = 0.040, and emotional control, F = 5.84, p = 0.019. The percent of the participants improving, who had a problem within each domain, is presented in Table Since the relative benefits observed during Trial I could be attributed to listening to music, independent of the computer modulation of the acoustic features, Trial II was conducted contrasting the filtered music condition to the same music in an unfiltered form. The unfiltered music condition was similar to the “structured listening” condition described by Bettison . As illuAnalyses of variance confirmed the similarity between the filtered music condition in Trial I and Trial II. The percent of participants improving on each domain was similar for the filtered music groups within Trial I and Trial II (see Table n = 61) were coded. The subsample was partitioned into three groups: children who had no hearing sensitivity at the start of the study (n = 34), children who showed improvements on hearing sensitivity following the intervention (n = 14), and children who had no improvements on hearing sensitivity following the intervention (n = 13). A repeated measures analysis of variance identified a significant group × condition interaction, F  = 4.88, p < 0.011. Consistent with the parental reports, only the subgroup of children with improvement on hearing sensitivity increased the amount of sharing behavior during the 10-min semi-structured play-based protocol. Descriptive statistics are reported in Table Post hoc Bonferroni adjustment confirmed that only children who were reported to improve on hearing sensitivity increased the amount of sharing behavior during the 10-min semi-structured play-based protocol following the 5-day program relative to the initial assessment (p < 0.005).Video data from a random subsample of children in the filtered music condition  selectively reduced auditory hypersensitivities. Trial I contrasted filtered music with a headphones only condition. The results of Trial I led to a more stringent Trial II in which filtered music was contrasted with an unfiltered music condition. In both trials, the LPP selectively reduced auditory hypersensitivities. In addition, within the filtered music groups the children with auditory hypersensitivities who improved following LPP significantly increased their spontaneous sharing behaviors. These findings, consistent with the polyvagal theory, support the hypothetical basis for designing the LPP as a neural exercise of pathways involved in regulating behavioral state, listening, looking, and other social engagement behaviors such as spontaneous sharing.The current findings are consistent with a previous study , evaluatSince LPP delivers computer altered acoustic stimuli through headphones, it shares some of the features of auditory intervention therapies . However, although LPP is a “sound therapy,” it is not a traditional clinically available AIT  andThere are several problems related to the evaluation of traditional auditory intervention therapies. First, since the interventions have evolved from clinical observations and insights, the neurophysiological theory underlying the interventions is often not well developed or tested. Second, research has been frequently structured to ask questions of efficacy instead of developing protocols to test theoretically relevant components of the treatment in order to understand the mechanisms and to refine the methodology. Third, since auditory interventions are applied within a clinical setting, several experimental design parameters are difficult to control including (1) a constant protocol, (2) limiting concurrent treatments including medication, (3) randomization of participants into conditions, and (4) the selection of outcome variables that are theoretically relevant to the intervention model. Perhaps the greatest limiting factor is the broad range of domains that auditory interventions are proposed to improve without a description of a causal link through which the intervention would result in functional changes in behavior. Due, in part, to the above limitations, the literature documenting an efficacy for the clinically available forms of AIT has been difficult to interpret.Some studies evaluating the effectiveness of the AIT report improvements , 43 and Gilmor  conducteThe data from the current study need to be cautiously interpreted for the reasons outlined below.The major findings were dependent on the subjective reports of parents.Some of the hypotheses tested were dependent on the small sizes of critical subgroups .The participants were receiving other treatments during the intervention and assessment period. Several participants were receiving daily interventions using behavioral approaches and other therapies, which may have enhanced or dampened the effects of the LPP.Frequent contact of parents with therapists might bias parental reports and compromise the validity of the parents as objective informants. These factors could obfuscate the real effects of the intervention and inaccurately identify changes. Alternatively, features that might have improved could have been neglected. Possibly the hearing sensitivity domain on the parent questionnaire is less vulnerable to clinician–parent bias. Based on our experience, the therapists and parents appear to be less interested in this dimension, although it was the focal point of our study.Improvements were observed in the groups not receiving the filtered music. Approximately 40% of the parents of children not receiving the filtered music reported improvements on at least one behavioral feature. These positive reactions might be due to non-specific features of the protocol, such as a relaxed intervention environment fostering social engagement and spontaneous play, as well as a positive “expectation” bias and the effects of familiarity with staff and context as the child progressed through the five laboratory sessions. However, the groups receiving filtered music diverged from the control groups when parents reported improvements in hearing sensitivity.Standardized assessments of cognitive function and developmental landmarks were not evaluated. The lack of this information precluded confirmation of matching on these variables, although, based on the sample size, random assignment should have led to a reasonable expectation of matched samples. The randomization of participants, with regard to the evaluated parameters, was effective and there were no group differences in their representation. Standardized assessments of cognitive function and development would provide data to investigate two questions: (1) Are auditory hypersensitivities related to cognitive function and developmental landmarks? (2) Is the effectiveness of the LPP related to individual differences in cognitive function?Our participants were young and on the severe end of the autism spectrum and the findings may not generalize to older or less severe ASD.The studies precluded an opportunity to confirm the specific neural pathways responsible for the observed behavioral improvements. The methods employed could not confirm whether auditory hypersensitivity was due to a compromise in functional neural regulation of the middle ear muscles  and remediated through an exercise model.The studies did not provide information necessary to distinguish among alternative pathways leading to or remediating auditory hypersensitivities, such as the potential influence of the intervention on damaged neural pathways , on damaged peripheral structures , or central structures involved in processing the acoustic signal or in cortical representation.The hypothesized link between the middle ear transfer function and auditory hypersensitivities could be limited. Hypersensitivities, especially to high frequency sounds, might be due, not to the neural regulation of the middle ear muscles, but to the olivary cochlear reflexes. Tests of inner ear function and the degree of auditory hypersensitivity to high frequency sounds need to be evaluated to rule out this possibility.The general improvements in behavior observed following a reduction in hearing sensitivity might not be related to the proposed integrative social engagement system. Rather, the enhanced behavior might be naturally occurring when the sounds are no longer painful and distracting.A measure of the hypothesized intervening mechanism, the middle ear transfer function, has been missing from the formal experiments evaluating effectiveness of LPP. At the time the participants were tested, no commercial clinical or research device was available to monitor the middle ear transfer function. Without a sensitive measure of the middle ear transfer function, the only method to demonstrate efficacy was to quantify physiology, auditory processing, and measures of behavior and to infer that the LPP normalized an atypical middle ear transfer function. Recently we have developed a middle ear sound absorption system (MESAS) to measure the middle ear transfer function . MESAS pBy providing an objective measure of the middle ear transfer function, future research with MESAS will enable a selective test of the efficacy of LPP in normalizing the middle ear transfer function. If confirmed, LPP could be applied to individuals with atypical middle ear function including rehabilitation following otitis media. In addition, MESAS will enable future research to evaluate the behavioral and psychological consequences of an atypical middle ear transfer function, provide data to validate a quantitatively scaled measure of auditory hypersensitivities independent of subjective reports, and contribute to the improvement of interventions  that may function as efficient neural exercises to normalize the middle ear transfer function.Stephen W. Porges was involved in all aspects of the research, including conception, design of the intervention stimuli, design of the protocol, analysis, interpretation, and writing the manuscript. Olga V. Bazhenova and Elgiz Bal were involved in the design, acquisition, and preliminary analyses and drafts. Nancy Carlson and Yevgeniya Sorokin were involved in acquisition of the data. Keri J. Heilman was involved in data acquisition, data analyses, and contributing to the final drafts. Edwin H. Cook was involved in developing the final draft and in interpreting the data. Gregory F. Lewis was involved in the development of the stimuli, developing the Middle Ear Sound Absorption System (MESAS), and in collecting and interpreting the preliminary data with MESAS.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Interaural Level Difference (ILD) provides an important cue for the location of a sound source in the azimuthal plane. Typically, ILD decoding in the brainstem is modeled as a subtraction of spike rates, with inhibitory inputs from one ear subtracted from the excitatory inputs from the other -3. The iRecent experimental evidence suggests that inhibitory input for ILD doesn’t provide subtraction, but instead provides a gain adjustment . In addiThe auditory periphery was modeled as a gammatone filterbank which provided inputs directly to a leaky integrate-and-fire model representing the cells of the cochlear nucleus. These cells are known to lock to the envelope of the sound stimulus, and this behavior was recreated by low-pass filtering of the gammatone filterbank inputs to the cells, and use of a dynamic spike threshold mechanism . The ILD