Vol. 2 No. 9 (2026): A Major Step Forward in Specialized Care: A Milestone Marked by the First Liver Transplant at Thong Nhat Hospital

Osteoporotic fractures in older adults represent a highly complex clinical challenge, requiring systematic and multidisciplinary coordination among orthopedic surgery, geriatrics, and metabolic bone specialists. Clinical evidence indicates that immediately following an initial fragility fracture, the risk of sustaining subsequent fractures escalates dramatically, particularly within the critical window of the first 1 to 2 years. Despite these severe consequences, a vast majority of patients in current practice remain significantly under-evaluated and undertreated for their underlying osteoporosis. This comprehensive review aims to systematically update the core principles of surgical intervention for osteoporotic fractures, effective perioperative management protocols, and specifically highlight the strategic implementation of the Fracture Liaison Service (FLS) model. FLS has been clinically proven as an exceptionally effective, structured, and coordinated care model that optimizes the entire patient management pathway, significantly enhances long-term treatment adherence, actively prevents secondary fragility fractures, reduces associated mortality rates, and lowers overall healthcare costs. Widespread adoption and expansion of the FLS framework serve as an essential and vital solution to establishing a standardized system for continuous, comprehensive, and high-quality care for osteoporotic patients throughout Vietnam.

Alzheimer’s disease (AD) is becoming a global health burden, necessitating a shift in diagnostic models from traditional clinical criteria to biomarkers based on the ATN classification system. This review aims to synthesize scientific evidence regarding the role of amyloid positron emission tomography (PET) in the early diagnosis and management of AD. Amyloid-PET enables the quantification of amyloid-beta (Aβ) plaque deposition in the living brain — a biological process that begins 15-20 years before symptom onset. The article reviews the development from the first-generation compound ¹¹C-PiB to ¹⁸F-labeled radiotracers (Florbetapir, Flutemetamol, Florbetaben), which have made this technique feasible in routine clinical practice. Notably, amyloid-PET serves as an indispensable “gold standard” for patient selection and monitoring the plaque-clearing efficacy of novel immunotherapies such as Lecanemab and Donanemab. Finally, the paper discusses challenges in Vietnam and proposes a multimodal coordination model, utilizing blood-based biomarkers for screening followed by amyloid-PET for confirmation, to optimize costs and enhance diagnostic efficiency within the local context.

Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease. In patients with persistent hypertriglyceridemia or mixed dyslipidemia despite statin therapy, fenofibrate–statin combination therapy, including the fixed-dose combination (FDC) of fenofibrate/pravastatin 160/40 mg, may be considered to further improve control of non-LDL-C lipid parameters. This systematic review was conducted according to Cochrane guidance and the PRISMA 2020 checklist to evaluate the efficacy/effectiveness and safety of fenofibrate–statin combination therapy in dyslipidemia treatment. Literature was searched in PubMed and Ovid EMBASE up to July 2026; risk of bias was assessed using RoB 2 for randomized controlled trials and ROBINS-I for non-randomized studies. From 3,660 screened records and 203 full-text assessments, 10 studies (3 RCTs and 7 non-randomized studies) were included. FDC fenofibrate/pravastatin further reduced non-HDL-C by 12.9–16.3% and triglycerides by 22.6–31.6%, and increased dual lipid target attainment versus statin monotherapy, with effects sustained over 3 years in the POSE study. Large cohort studies reported that fenofibrate–statin combinations were associated with a 9.9–20.0% reduction in selected cardiovascular events and a 27.0–28.4% reduction in all-cause mortality among patients with type 2 diabetes. The combination was generally well tolerated, with no myopathy or rhabdomyolysis reported in RCTs, although some observational studies signaled increased risks of acute kidney injury, myositis, or liver injury requiring monitoring during treatment.

The heart failure club model is considered an appropriate approach for providing patient education and psychosocial support in settings with limited specialized healthcare personnel. This study was conducted with the following objectives: (1) to evaluate patients’ knowledge, self-care behaviors, psychosocial benefits, and satisfaction with the Heart Failure Club model; and (2) to investigate factors associated with regular participation of the club’s activities A cross-sectional descriptive study among patients attending the Heart Failure Club at the Cardiology Department, Thong Nhat Hospital. Eligible patients completed a staff-assisted, structured 20-item Yes/No questionnaire immediately after a club session. 154 patients were surveyed (87.7% female; mean age 66.4 ±8.4 years, range 22-83). Most patients reported better understanding of heart failure (96.8%), the importance of regular medication (98.7%), and a low-salt diet (98.7%); 83.8% understood warning signs of decompensation. Self-care behavior improved in most patients: correct medication-taking (97.4%), dietary adherence (97.4%), daily self-monitoring (94.8%), proactive follow-up (95.5%), self-care confidence (91.6%). Psychosocial benefit and satisfaction were high (97.4-100%). Full/consistent attendance was linked to higher knowledge/self-care/satisfaction scores (15.5/16 vs 13.8/16, p = 0.039); prior topic awareness and convenient timing were both strongly associated with attendance (p < 0.001; p = 0.004). Patients attending the Thong Nhat Hospital Heart Failure Club reported high knowledge, self-care, psychosocial benefit, and satisfaction. Consistent attendance was associated with greater perceived benefit; advance notice of topics and convenient scheduling are simple, feasible levers to further strengthen the programme.

Depression is common among older inpatients with heart failure and may present differently by sex. To describe demographic, comorbidity and geriatric characteristics, and to compare sex differences in components of the 15-item Geriatric Depression Scale (GDS-15) among hospitalised older patients with heart failure at Thong Nhat Hospital. A cross-sectional study of 137 inpatients aged ≥60 years with heart failure at the Department of Cardiology, Thong Nhat Hospital (64 men, 73 women). Categorical variables were presented as frequency and percentage; skewed continuous variables as median and interquartile range. Comparisons between men and women used chi-square/Fisher’s exact or Mann-Whitney tests; depression was defined as GDS-15 ≥5. Median BMI was 22 (IQR 21-24) kg/m². Hypertension, dyslipidaemia and diabetes were the most common comorbidities. IADL dependence occurred in 85.4%, frailty in 86.8%, and GDS-15 depression in 81.8%; median GDS-15 score was 6 (IQR 5-7). No statistically significant sex differences were found in comorbidities, ejection fraction, ADL/IADL dependence, frailty, depression, or any GDS-15 component. The six GDS-15 items with the highest “yes” rates by sex were memory complaints, feeling full of energy, and preferring to stay home. Depression screened by GDS-15 was highly prevalent; women had a numerically higher rate than men without reaching statistical significance. Routine GDS-15 depression screening should be integrated into nursing care regardless of sex.

Diabetes mellitus is increasingly prevalent among older adults, and glycemic control remains challenging. According to the 2025 American Diabetes Association (ADA) recommendations, HbA1c targets should be individualized based on frailty, functional and cognitive status, life expectancy, comorbidities, and vascular complications. This study aimed to determine the proportion of older patients achieving glycemic control targets and to examine the associations between geriatric factors and treatment effectiveness in patients with type 2 diabetes mellitus. A descriptive cross-sectional study was conducted from April to August 2025 at the Endocrinology Outpatient Clinic, Thong Nhat Hospital, Ho Chi Minh City. Among 185 patients, the median age was 68 years (64–75.5), and 45.4% achieved their HbA1c target. Multivariable logistic regression showed that frailty and high cardiovascular risk were independently associated with the likelihood of achieving the HbA1c target, with OR = 0.48 (95% CI: 0.25–0.92; p = 0.027) and OR = 0.57 (95% CI: 0.32–0.99; p = 0.047), respectively. Multimorbidity and polypharmacy were not significantly associated with achieving the HbA1c target. The proportion of patients achieving their HbA1c target remained limited. Frailty and high cardiovascular risk were independently associated with the likelihood of achieving treatment targets.

To determine the prevalence and analyze the associated factors of protein-energy wasting (PEW) syndrome in chronic kidney disease patients on maintenance hemodialysis. A cross-sectional descriptive study. Study location and duration: Department of Nephrology, Ninh Thuan General Hospital from June 2025 to June 2026. Study subjects: 166 patients (>18 years old) with end-stage renal disease undergoing stable maintenance hemodialysis. The prevalence of patients with PEW syndrome is 24.1%. The most common constituent criteria are prominent signs of anorexia (57.8%), decreased mid-arm circumference (36.7%), and decreased serum albumin (36.1%). Associated factor analysis shows that male gender is a protective factor against PEW (OR = 0.167; p = 0.001), meaning females have a higher risk of the disease. The hemoglobin concentration in the PEW group is lower than that of the non-PEW group (8.2 compared to 9.0 g/dL; p = 0.010). The prevalence of PEW syndrome in maintenance hemodialysis patients is 24.1%. Female gender and anemia are associated factors, which require early monitoring and nutritional intervention.

Esophageal varices (EV) are a serious complication of cirrhosis, with 15–25% mortality when bleeding occurs. Endoscopy is the diagnostic gold standard but is invasive and costly. This study evaluated the correlation between gallbladder wall thickness (GBWT) and EV severity and the predictive value of GBWT and the platelet count-to-GBWT ratio (PLT/GBWT). This cross-sectional study included 72 patients aged ≥18 years with cirrhosis at Thong Nhat Hospital from December 2023 to October 2024. GBWT was measured by ultrasonography and EV by upper gastrointestinal endoscopy. Spearman correlation, ROC analysis, and the Youden index were used. Mean age was 61.1 ± 12 years, and 70.8% were male. EV and high-risk EV were present in 73.6% and 70.8%, respectively. GBWT showed a moderate positive correlation with EV severity (r = 0.64; p < 0.001). The AUC for GBWT was 0.93 for EV (cutoff 5.12 mm; sensitivity 73.6%; specificity 100%) and 0.90 for high-risk EV (sensitivity 74.5%; specificity 95.2%). The corresponding AUCs for PLT/GBWT were 0.74 and 0.72. GBWT showed good predictive performance and higher AUCs than PLT/GBWT, suggesting potential utility for risk stratification and prioritization of endoscopy where advanced diagnostic resources are limited.

Electroacupuncture combined with auricular acupuncture is considered a potential adjunctive therapy alongside proton pump inhibitors (PPIs) in the treatment of gastroesophageal reflux disease (GERD). A controlled clinical intervention study was conducted in GERD patients with a GerdQ score ≥ 8, who were randomly allocated to an intervention group (electroacupuncture combined with auricular acupuncture plus Esomeprazole 40 mg/day) and a control group (Esomeprazole alone), with follow-up assessments at baseline (day 0), day 7, and day 14, to investigate baseline clinical characteristics and treatment efficacy using the GerdQ scale and the 4GerdQ score (the four positive-predictive questions within the GerdQ questionnaire). Sixty-one patients completed the study (30 in the control group, 31 in the intervention group), with comparable baseline characteristics between the two groups (p>0.05). At baseline, the median GerdQ score was 10.0 in both groups (p=0.447); the 4GerdQ score was 8.0 in both groups (p=0.175). After 14 days, the GerdQ score decreased significantly within each group (p<0.001), and the between-group difference at day 14 was also statistically significant (6.0 versus 7.0; p=0.011). Likewise, the 4GerdQ score in the intervention group was significantly lower than in the control group (4.0 versus 5.0; p=0.008), and the reduction from baseline was also significantly greater (p=0.040). Combined electroacupuncture and auricular acupuncture significantly improved both the overall GerdQ score and the 4GerdQ score compared with PPI monotherapy after 14 days of treatment.

Chronic obstructive pulmonary disease (COPD) is common among older adults, while respiratory infection and antimicrobial resistance complicate the management of exacerbations. This study aimed to describe bacterial isolates and antimicrobial resistance in patients with pneumonia during COPD exacerbations at the Department of Respiratory Medicine, Thong Nhat Hospital. A retrospective cross-sectional study included 271 patients admitted to the department from January to December 2025. Variables included age, sex, sputum culture results, bacterial species, and antimicrobial susceptibility. The median age was 73 years (interquartile range, 16), and 243 patients (89.7%) were male. Among 197 patients with sputum cultures, 63 (32.0%) had positive cultures, yielding 75 isolates. Gram-negative bacilli accounted for 66/75 isolates (88.0%); Klebsiella pneumoniae and Pseudomonas aeruginosa each accounted for 17 isolates (22.7%). Acinetobacter baumannii showed 66.7% (6/9) resistance to imipenem and meropenem; Klebsiella aerogenes showed 85.7% (6/7) resistance to piperacillin/tazobactam, cefepime, and ciprofloxacin, and 71.4% (5/7) resistance to meropenem. K. pneumoniae remained 90.9% susceptible to meropenem and 81.8% susceptible to imipenem but only 9.1% susceptible to ciprofloxacin. Gram-negative bacilli predominated among positive cultures. Antibiotic selection should be guided by local microbiological data and adjusted according to susceptibility results, particularly in older patients.

Intra-articular hyaluronic acid (HA) is used to treat knee osteoarthritis; however, data on medication utilization patterns and healthcare costs in Vietnam remain limited. This retrospective observational study analyzed electronic medical records, medication utilization data, and billing records of patients with knee osteoarthritis with and without recorded HA use at Thong Nhat Hospital during 2024–2025. Among 25,575 patients with an ICD-10 M17.x diagnosis, 894 (3.5%) were classified into the HA group and 24,681 into the non-HA group. Patients in the HA group were older on average (65.7 vs. 61.0 years) and more likely to be female (77.9% vs. 63.0%). Compared with the non-HA group, the HA group had lower proportions of visits involving NSAIDs (45.0% vs. 57.5%) and analgesics (24.5% vs. 31.7%), but a higher proportion involving symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) (29.5% vs. 26.3%). In the primary analysis restricted to patients with at least 30 days of available observation (n=25,365), the median annualized direct medical cost was VND 13.23 million per person-year [8.07–24.11] in the HA group and VND 1.86 million per person-year [0.88–3.79] in the non-HA group (p<0.001). After adjustment, annualized costs were higher in the HA group than in the non-HA group (adjusted cost ratio: 4.833; 95% CI: 4.019–5.874; p<0.001). These findings reflect differences in medication utilization patterns and costs between the two groups in routine hospital practice.

According to the Global Burden of Disease Study 2021, the burden of musculoskeletal disorders increased rapidly between 1990 and 2020, with the knee being one of the most commonly affected sites of osteoarthritis. The disease is characterized by symptoms such as pain and restricted mobility and is more prevalent among older adults and women. Treatment is often prolonged and requires a multimodal approach. Currently, traditional medicine combined with modern medicine is widely applied, with thread embedding acupuncture and therapeutic ultrasound being among the treatment modalities of interest for knee osteoarthritis. To evaluate the therapeutic effectiveness of thread embedding therapy combined with therapeutic ultrasound in patients with primary knee osteoarthritis. The study included 62 patients diagnosed with primary knee osteoarthritis who were treated at Phu Yen Hospital of Traditional Medicine using a combination of thread embedding therapy and therapeutic ultrasound. A clinical interventional study with a before-and-after treatment design and no control group was conducted. Patients aged ≥60 years accounted for the majority of the study population, and the proportion of female patients was higher than that of male patients. After 21 days of treatment, the mean VAS score decreased from 72.63 ± 5.90 mm to 20.71 ± 9.99 mm, while the median decreased from 72 mm to 21 mm. The mean reductions in the Lequesne index and knee joint range of motion were 8.61 ± 1.34 points and 30.16 ± 7.20°, respectively. The mean heel-to-buttock distance decreased from 25.95 ± 8.49 cm to 9.84 ± 5.72 cm, with the median decreasing from 25 cm to 10.0 cm (p < 0.001). The combination of thread embedding acupuncture and therapeutic ultrasound may improve pain and physical function; however, further controlled studies with longer follow-up periods are needed to evaluate its efficacy and safety.

To describe the clinical and paraclinical characteristics of patients undergoing grade II lumbar spondylolisthesis fusion at Thong Nhat Hospital, Ho Chi Minh City. This retrospective study reviewed 29 patients with grade II lumbar spondylolisthesis who underwent transforaminal lumbar interbody fusion (TLIF) between May 2020 and December 2023 at Thong Nhat Hospital. Data were analyzed using SPSS 25.0. The mean age was 53.66 ± 9.76 years, and the female-to-male ratio was 4.8:1. All patients presented with lower back pain, with 37.9% accompanied by unilateral radicular pain and 62.1% by bilateral radicular pain. The step-off sign was present in 86.2% of patients. Positive Lasègue test (< 70°) was observed in 68.9%. Slippage occurred at L4 in 58.6% (17 patients), L5 in 37.9% (11 patients), and L3 in 3.4% (1 patient). The causes included isthmic defects (62.1%) and degeneration (37.9%). Degenerative spondylolisthesis occurred predominantly at L4 (81.8%), whereas isthmic spondylolisthesis was more frequent at L5 (55.6%) (p = 0.028). The mean percentage of vertebral slippage on conventional X-ray was 31.29 ± 5.98%, with a mean slippage distance of 12.04 ± 2.28 mm and mean disc height of 6.72 ± 2.81 mm. There was a moderate inverse correlation between percentage of slippage and disc height (r = -0.432; p = 0.019). Spinal stenosis and foraminal stenosis on MRI were found in all patients (100%). Neuromuscular conduction abnormalities on electromyography were present in 55.2% of cases. Surgical patients with grade II lumbar spondylolisthesis prominently present with features of spinal stenosis and foraminal stenosis, along with a high prevalence of the step-off sign. Vertebral slippage percentage shows a moderate inverse correlation with disc space height.

Introduction: Supraclavicular brachial plexus block is commonly used for upper limb surgery but provides limited analgesia duration (<12 hours). This study aimed to evaluate the effect of intravenous dexamethasone on prolonging postoperative analgesia. Methods: A prospective descriptive study was conducted on 40 patients undergoing upper limb surgery at Thong Nhat Hospital (02–09/2025). Patients received a supraclavicular brachial plexus block with 20 ml of 0.5% ropivacaine under ultrasound guidance combined with intravenous dexamethasone 8 mg. Outcomes included duration of anesthesia and analgesia, block quality, VAS scores, opioid consumption, and adverse events. Results: The mean duration of anesthesia and analgesia was 1018.1±216.8 minutes. Good block quality was achieved in 92.5% of patients. VAS scores were low during the first 6 hours, increased at 24 hours, and stabilized by 48 hours. Mean opioid consumption was 115±24.7 mg. No complications related to the block or dexamethasone were observed. Conclusion: Intravenous dexamethasone combined with ropivacaine significantly prolongs postoperative analgesia, reduces opioid requirements, and is safe for clinical practice.

To evaluate the preliminary efficacy, opioid-sparing effect, and safety of ultrasound-guided adductor canal block (ACB) combined with genicular nerve block in total knee arthroplasty (TKA). A prospective case series of 21 primary TKA patients receiving preoperative 4-branch genicular block and postoperative single-injection ACB. Resting VAS (0–48h), cumulative 48-hour fentanyl consumption, complications, and satisfaction were recorded. Patients (95.2% female, mean age 66.1 ± 6.3) showed maximum pain relief at 6h (VAS 0.81 ± 0.60), followed by a rebound at 24h (3.24 ± 0.83; $p < 0.001$) which stabilized through 48h (3.14 ± 0.79). Mean 48-hour fentanyl consumption was 121 ± 34.6 mcg. No procedural complications occurred, and 95.2% of patients were satisfied/very satisfied. Combined ACB and genicular nerve block provides safe, effective early post-TKA analgesia (6–12h) and reduces opioid requirements. Proactive multimodal systemic analgesia is required to manage rebound pain at 12–24 hours.

According to the World Health Organization (WHO), the quality of life among cancer patients is significantly affected throughout the course of treatment and recovery, highlighting the need for a comprehensive care approach. This study aimed to describe the quality of life of cancer patients undergoing treatment at the Tay Nguyen Regional General Hospital, thereby providing evidence to propose appropriate interventions to improve patient care quality. A cross-sectional descriptive study was conducted cancer patients receiving treatment at the Oncology Department, Tay Nguyen Regional General Hospital. Quality of life was assessed through face-to-face interviews using the EORTC QLQ-C30 questionnaire. The mean score of global health status was 50.1 ± 22.9. The mean score of functional scale was 59.0 ± 16.5, while the mean score of symptom scale was 30.2 ± 10.2. Financial difficulties were reported at a high level, with a median of 66.7 (33.3–66.7). The quality of life of patients with cancer remains limited, particularly due to symptom burden and financial difficulties. These findings underscore the need for targeted interventions to improve the quality of life for cancer patients.

Background: Health education is an essential component of patient care, improving knowledge, self-care ability, and treatment adherence. This study aimed to describe health education consultation activities provided by nurses to inpatients at Thong Nhat Hospital in 2025 and analyze associated factors. Materials and methods: A descriptive analytical cross-sectional study was conducted from January to August 2025 among 500 inpatients (expanded from a minimum sample size n = 385, 23% non-response buffer) at clinical departments. Data were collected using a structured questionnaire with high internal consistency (Cronbach’s alpha = 0.89). Among 500 patients (male 63.2%, aged > 60 years 70.4%), 472 patients (94.4%) reported receiving health education from nurses. The 94.4% rate represents self-reported coverage rather than technical performance. All 15 health education topics exceeded 90.0% reception. Nurses were the primary information source (97.0%). The proportion of patients intending to return/refer reached 73.0% (365/500) as a supplementary indicator of brand loyalty. Multivariable analysis revealed 3 independent predictors: Comfort in communication with staff (aOR = 4.88; 95% CI: 2.15–11.08; p < 0.001), Convenient technology access (aOR = 2.45; 95% CI: 1.22–4.92; p = 0.012), and Absence of psychological stress (aOR = 2.54; 95% CI: 1.31–4.94; p = 0.006). Nurses’ health education consultation achieved high coverage. Strengthening communication skills, standardizing contents, and introducing supportive digital tools tailored for elderly inpatients are recommended.

After mechanical thrombectomy, hyperattenuating areas on non-contrast CT may represent intracranial hemorrhage, contrast extravasation, or both, and conventional CT may not reliably distinguish them. This article aims to describe the role of spectral/dual-energy CT in this setting at Thong Nhat Hospital. This article describes the principles and applications of virtual monoenergetic images (MonoE), virtual non-contrast (VNC) images, and iodine density maps generated on a Spectral CT 7500 system, illustrated by post-thrombectomy clinical cases from Thong Nhat Hospital. Iodine-containing lesions change more across MonoE energy levels, decrease or disappear on VNC images, and are visible on iodine density maps. Blood components tend to persist on VNC and show less energy-dependent attenuation change; mixed lesions require integrated assessment of multiple spectral reconstructions. Spectral CT improves early differentiation between intracranial hemorrhage and contrast extravasation, supporting post-procedural antithrombotic decisions and follow-up. Findings should be interpreted with the clinical context and follow-up imaging rather than a single universal iodine concentration threshold.

Living donor liver transplantation (LDLT) is a potentially curative treatment for hepatocellular carcinoma (HCC) in patients with decompensated cirrhosis, particularly in countries with limited availability of deceased-donor organs. We report the first LDLT performed at Thong Nhat Hospital, Ho Chi Minh City, Vietnam. A 50-year-old man had a solitary 4.8-cm HCC within the Milan criteria on a background of Child–Pugh class C cirrhosis (MELD score, 18) associated with hepatitis B and C virus coinfection. He also had type 2 diabetes mellitus. His healthy 29-year-old brother, who was ABO-compatible, served as the living donor, and a right-lobe graft was used. Clinical, biochemical, and imaging findings were followed from the preoperative period through postoperative day (POD) 16. The operation was completed in 8 hours. Serum lactate decreased substantially within the first 12 hours and normalized by POD 2. Aspartate aminotransferase peaked at 474 U/L on POD 2 and alanine aminotransferase at 626 U/L on POD 3, followed by a progressive decline. Between POD 7 and POD 10, a secondary increase in aminotransferases, gamma-glutamyl transferase, and direct bilirubin occurred. Doppler ultrasonography and computed tomography showed no vascular thrombosis or biliary dilatation. CT demonstrated mild hepatic artery anastomotic narrowing, while the available Doppler measurements did not suggest a clear hemodynamic impact; drain-fluid bilirubin did not suggest a bile leak. Biochemical indices improved after optimization of immunosuppressive therapy; however, liver biopsy was not performed to confirm rejection. By POD 16, prothrombin activity was 82% and the platelet count was 122 × 10⁹/L; the most recent serum albumin level was 42.7 g/L on POD 15. The donor recovered uneventfully and was discharged on POD 12. No vascular thrombosis, bile leak, severe infection, or biopsy-proven rejection was documented during the observation period. This case demonstrates the initial feasibility of establishing an LDLT program at Thong Nhat Hospital. Multidisciplinary preparation and technical collaboration with 108 Military Central Hospital were important contributors to the favorable early outcome. Longer follow-up and additional cases are required to establish the safety and effectiveness of the program.