Total hip replacement (THR) is a major orthopaedic procedure performed for advanced osteoarthritis, avascular necrosis, inflammatory arthropathy, fracture sequelae and other causes of end-stage hip disease. The operation involves extensive manipulation of bone and soft tissue and is accompanied by a substantial perioperative stress response and postoperative analgesic requirement. Spinal or combined spinal–epidural anaesthesia is widely used because it provides reliable lower-limb anaesthesia while avoiding some of the physiological consequences of general anaesthesia. However, the duration and quality of neuraxial block may be insufficient for lengthy procedures or prolonged postoperative analgesia, making adjuvant drugs an important component of contemporary practice.[1,2] Fentanyl is a highly lipophilic μ-opioid receptor agonist that can enhance the analgesic effect of local anaesthetics and provide rapid onset. Its limitations include nausea, vomiting, pruritus, respiratory depression at clinically relevant systemic exposures and a relatively short analgesic duration. Dexmedetomidine is a highly selective α2-adrenergic agonist with sedative, analgesic and sympatholytic properties. By reducing norepinephrine release and modulating nociceptive transmission, it can prolong sensory and motor blockade and extend the pain-free period. A systematic review and meta-analysis of randomized trials found that dexmedetomidine, compared with fentanyl, significantly prolonged stable sensory block, sensory and motor block duration and the pain-free period, with lower pruritus.[1] The haemodynamic effects of dexmedetomidine are clinically important. Central α2-receptor activation reduces sympathetic outflow and can lower heart rate and arterial pressure. This may be desirable during surgical stimulation, but excessive bradycardia or hypotension can occur, especially with higher loading doses, hypovolaemia or limited autonomic reserve. Early clinical studies demonstrated prolongation of spinal block with low-dose dexmedetomidine while maintaining acceptable haemodynamic stability.[3,4] Comparative randomized studies have subsequently reported longer block duration and analgesia with dexmedetomidine than fentanyl in lower-limb surgery, although the incidence of bradycardia and the precise haemodynamic profile vary with dose and route.[5–7] Intravenous dexmedetomidine administered during spinal anaesthesia is also of interest because it may prolong neuraxial blockade without requiring intrathecal administration of the α2 agonist. In lower-limb arthroplasty, intravenous dexmedetomidine has been shown to reduce opioid requirements and provide useful sedation and analgesic sparing.[8] More recent perioperative literature continues to examine dexmedetomidine within enhanced recovery pathways, where the goals include early mobilization, opioid minimization, predictable recovery and reduction of postoperative adverse effects. Recent evidence from peripheral nerve-block practice also supports the analgesic potential of dexmedetomidine while illustrating the importance of route and comparator. A 2025 randomized controlled trial by Agarwal et al. compared dexamethasone and dexmedetomidine as adjuvants to ropivacaine in ultrasound-guided saphenous nerve block for anterior cruciate ligament reconstruction (n=76). Early postoperative pain scores were similar, but pain scores at 12 and 24 hours were significantly lower with dexmedetomidine; time to rescue analgesia and total rescue analgesic consumption were not significantly different, while mild bradycardia and hypotension were observed in the dexmedetomidine group. These findings are relevant to the present study because they support a prolonged analgesic effect of dexmedetomidine across regional-anaesthesia techniques, while also demonstrating that the magnitude of benefit and haemodynamic profile depend on the block technique, comparator drug and dosing regimen.[16] THR represents a clinically relevant setting in which these effects may be amplified. The procedure is painful, often prolonged, and frequently performed in older adults with cardiovascular comorbidity. A spinal adjuvant that prolongs anaesthesia and reduces postoperative pain could facilitate smoother recovery and rehabilitation, but a drug that causes marked bradycardia or hypotension may increase monitoring and intervention requirements. The optimal choice therefore requires consideration of both efficacy and trade-offs. Evidence from other neuraxial opioid-delivery strategies also highlights the importance of route, drug-delivery method and duration of postoperative analgesia. Bharadwaj et al. (2024) conducted a randomized controlled study of 60 patients undergoing lumbar spinal fixation surgery and compared 5 mg epidural morphine delivered on absorbable Gelfoam with direct epidural instillation of 5 mg morphine. The Gelfoam group had lower postoperative VAS scores, a markedly longer time to first rescue analgesia (36.46±8.99 versus 9±2.08 hours; P<0.0001), and lower 48-hour rescue diclofenac consumption (144.23±56.97 versus 275±35.96 mg; P<0.0001), with similar respiratory rate, oxygen saturation, sedation, nausea and pruritus. Although this study used morphine rather than dexmedetomidine and involved lumbar spinal fixation rather than total hip replacement, it provides relevant evidence that the method of neuraxial drug delivery can materially influence the duration and quality of postoperative analgesia.[17] The present study was designed to compare intravenous dexmedetomidine and fentanyl in patients undergoing elective THR under combined spinal–epidural anaesthesia. The primary focus was haemodynamic stability and duration of spinal anaesthesia, with secondary assessment of time to first rescue analgesia, postoperative pain, sedation, adverse effects, blood loss, fluid requirement, patient satisfaction, orientation time and ICU stay. The study aimed to define whether the prolonged analgesic profile of dexmedetomidine translated into clinically meaningful postoperative benefits while remaining acceptably safe.

Study design and participants This was a prospective randomized comparative study performed over 18 months after institutional ethical approval. Adults aged 40–70 years with ASA physical status I or II, scheduled for elective THR under combined spinal–epidural anaesthesia and willing to provide written consent were eligible. Exclusion criteria included age outside the specified range, ASA III–IV, refusal, contraindications to CSE such as coagulopathy or infection at the injection site, and known allergy to dexmedetomidine or fentanyl. Sample size and randomization The thesis reports a total sample of 72 participants, with 36 in each group. Patients were screened from the orthopaedic surgical roster and allocated using a computer-generated random sequence after eligibility and consent. Anaesthetic intervention Patients were kept nil by mouth for six hours and preloaded with Ringer’s lactate. CSE anaesthesia was administered using 3–4 mL of 0.5% hyperbaric bupivacaine. Fifteen minutes after spinal anaesthesia, the designated intravenous study drug was started. Group A received fentanyl 2 µg/kg as a loading dose followed by 0.5 µg/kg/h; Group B received dexmedetomidine 1 µg/kg over 10 minutes followed by 0.5 µg/kg/h. The infusions continued perioperatively. Outcomes Primary outcomes were intraoperative heart rate and MAP, duration of spinal anaesthesia and postoperative pain measured by VAS. Secondary outcomes included sedation using the Ramsay scale, adverse events including bradycardia, hypotension, nausea/vomiting, shivering and desaturation, rescue analgesia, blood loss, fluid requirements, patient satisfaction, time to full orientation and ICU stay. Statistical analysis Continuous variables were expressed as mean±SD and compared using the unpaired t test or Mann–Whitney U test as appropriate. Categorical variables were assessed with chi-square or Fisher exact tests. A p value <0.05 was considered statistically significant. The analysis was performed using SPSS version 20.0.

Baseline characteristics The groups were comparable. Mean age was 58.4±6.2 years in the fentanyl group and 57.6±5.8 years in the dexmedetomidine group (p=0.72). Male participants accounted for 61.1% and 55.5%, respectively (p=0.62). Mean body weight was 66.8±7.4 versus 67.2±6.9 kg (p=0.81), and ASA I status was present in 50.0% versus 47.2% (p=0.82). Baseline HR was 84.2±7.1 versus 83.7±6.9 bpm (p=0.78), MAP 93.6±6.5 versus 92.9±7.2 mmHg (p=0.69), and SpO2 98.4±0.8% versus 98.6±0.7% (p=0.44). Intraoperative haemodynamics After spinal anaesthesia, the dexmedetomidine group had substantially lower HR at all measured time points. At 30 minutes, HR was 51.2±2.8 versus 87.6±6.4 bpm; at 60 minutes, 50.8±2.6 versus 88.9±7.2; at 120 minutes, 51.5±2.4 versus 90.5±6.8; and at the end of surgery, 52.1±2.5 versus 92.4±7.1 bpm (all p<0.001). MAP followed the same pattern, with dexmedetomidine values 88.5±6.2, 87.1±5.7, 86.3±6.1 and 85.6±6.0 mmHg compared with 96.1±5.9, 95.8±6.1, 96.7±6.5 and 97.2±6.8 mmHg with fentanyl (all p<0.001). Duration of spinal anaesthesia and rescue analgesia Spinal anaesthesia lasted 198±15 minutes with dexmedetomidine compared with 165±12 minutes with fentanyl (p<0.001), an absolute difference of 33 minutes. The first rescue analgesic was required after 8.2±1.1 hours versus 4.6±0.8 hours (p<0.001), indicating an approximately 78% longer analgesia-free interval with dexmedetomidine. Postoperative pain Pain scores were consistently lower in the dexmedetomidine group. At six hours VAS was 2.8±0.6 versus 4.2±0.7, at 12 hours 3.5±0.8 versus 5.3±0.9, and at 24 hours 3.9±0.7 versus 5.9±1.0, with p<0.001 at every time point. The magnitude of reduction was approximately 1.4, 1.8 and 2.0 VAS points, respectively. Sedation and adverse effects Ramsay sedation scores were higher with fentanyl immediately after surgery (3.5±0.6 versus 2.1±0.5) and at six hours (2.9±0.5 versus 1.8±0.4), both p<0.001. Bradycardia occurred in 38.9% of dexmedetomidine patients versus 8.3% of fentanyl patients (p=0.002). Hypotension occurred in 22.2% versus 16.7% (p=0.54). Nausea/vomiting occurred in 8.3% versus 25.0% (p=0.04). Shivering was 5.5% versus 19.4% (p=0.07), and desaturation 2.7% versus 11.1% (p=0.16). Blood loss, fluid requirement and patient-centred recovery Blood loss was similar (498±75 mL with dexmedetomidine versus 512±88 mL with fentanyl; p=0.46), as were IV fluids (2090±200 versus 2150±220 mL; p=0.33). Patient satisfaction was higher with dexmedetomidine (8.1±1.0 versus 6.5±1.2; p<0.001). Time to full orientation was shorter (12.3±2.1 versus 15.6±2.5 minutes; p<0.01), and ICU stay was shorter (16.5±2.8 versus 19.2±3.1 hours; p<0.01). Table 1. Baseline characteristics Variable Fentanyl (n=36) Dexmedetomidine (n=36) p value Age, years; mean±SD 58.4±6.2 57.6±5.8 0.72 Male, n (%) 22 (61.1) 20 (55.5) 0.62 Weight, kg; mean±SD 66.8±7.4 67.2±6.9 0.81 ASA I, n (%) 18 (50.0) 17 (47.2) 0.82 Baseline HR, bpm 84.2±7.1 83.7±6.9 0.78 Baseline MAP, mmHg 93.6±6.5 92.9±7.2 0.69 Baseline SpO2, % 98.4±0.8 98.6±0.7 0.44 Table 2. Intraoperative haemodynamics Time point Fentanyl HR Dexmedetomidine HR Fentanyl MAP Dexmedetomidine MAP p 30 min 87.6±6.4 51.2±2.8 96.1±5.9 88.5±6.2 <0.001 60 min 88.9±7.2 50.8±2.6 95.8±6.1 87.1±5.7 <0.001 120 min 90.5±6.8 51.5±2.4 96.7±6.5 86.3±6.1 <0.001 End surgery 92.4±7.1 52.1±2.5 97.2±6.8 85.6±6.0 <0.001 Table 3. Block and analgesia outcomes Outcome Fentanyl Dexmedetomidine P Spinal anaesthesia duration, min 165±12 198±15 <0.001 First rescue analgesia, h 4.6±0.8 8.2±1.1 <0.001 VAS at 6 h 4.2±0.7 2.8±0.6 <0.001 VAS at 12 h 5.3±0.9 3.5±0.8 <0.001 VAS at 24 h 5.9±1.0 3.9±0.7 <0.001 Table 4. Adverse effects and recovery Outcome Fentanyl Dexmedetomidine P Bradycardia 3 (8.3%) 14 (38.9%) 0.002 Hypotension 6 (16.7%) 8 (22.2%) 0.54 Nausea/vomiting 9 (25.0%) 3 (8.3%) 0.04 Shivering 7 (19.4%) 2 (5.5%) 0.07 Desaturation 4 (11.1%) 1 (2.7%) 0.16 Ramsay score, immediate postop 3.5±0.6 2.1±0.5 <0.001 Orientation time, min 15.6±2.5 12.3±2.1 <0.01 ICU stay, h 19.2±3.1 16.5±2.8 <0.01 Satisfaction VAS 6.5±1.2 8.1±1.0 <0.001

Principal findings The present study shows that intravenous dexmedetomidine produced a distinct perioperative profile compared with fentanyl in THR under CSE anaesthesia. Baseline characteristics and haemodynamics were well matched, but after neuraxial block the dexmedetomidine group maintained lower HR and MAP, had a longer duration of spinal anaesthesia, a substantially delayed need for rescue analgesia, lower postoperative pain scores and higher satisfaction. These benefits were accompanied by a predictable increase in bradycardia. Fentanyl, in contrast, was associated with more nausea/vomiting and deeper postoperative sedation. Haemodynamic interpretation The lower HR and MAP observed with dexmedetomidine are consistent with its central α2-adrenergic sympatholytic action. Activation of α2 receptors in the locus coeruleus reduces norepinephrine release and sympathetic outflow, producing a controlled reduction in cardiovascular activity. Kanazi et al. demonstrated that low-dose intrathecal dexmedetomidine prolongs sensory and motor blockade without major haemodynamic instability, while Mahendru et al. found prolonged block with dexmedetomidine compared with fentanyl in lower-limb surgery. [3,5] The present study differs in route because the study drug was administered intravenously, but the physiological direction is similar. The clinical value of lower HR and MAP should not be interpreted as 'better' without qualification. Excessive bradycardia or hypotension can compromise perfusion, particularly in elderly patients or those with limited cardiovascular reserve. In this study, the incidence of bradycardia was 38.9%, substantially higher than with fentanyl. Therefore, the main practical lesson is that dexmedetomidine offers controlled sympatholysis only when appropriate monitoring, fluid management and readiness to treat clinically significant bradycardia are available. The absence of a significant difference in hypotension suggests that the observed lower MAP was generally tolerated in this selected ASA I–II cohort. Prolongation of spinal anaesthesia Dexmedetomidine prolonged the duration of spinal anaesthesia by 33 minutes. This is clinically relevant in THR, where surgical stimulation can continue for several hours and early regression of block may expose patients to substantial pain. The systematic review by Sun et al. synthesized nine randomized trials involving 639 patients and found significant prolongation of stable sensory block, sensory and motor block and pain-free period with dexmedetomidine compared with fentanyl.[1] The direction and magnitude of the present result are therefore consistent with broader evidence. The mechanisms are likely multifactorial. Dexmedetomidine can act on spinal α2 receptors, reducing nociceptive neurotransmission and enhancing the effect of local anaesthetics. Presynaptic inhibition of norepinephrine release and postsynaptic hyperpolarization reduce neuronal excitability. Local vasoconstrictive effects may also decrease systemic uptake of local anaesthetic and contribute to prolonged residence within the neuraxial compartment. Fentanyl, while effective through μ-opioid receptors and highly lipophilic, generally provides shorter extension of neuraxial block. Kanazi and Mahendru demonstrated the ability of dexmedetomidine to prolong motor and sensory regression, while Nayagam et al. found both dexmedetomidine and fentanyl useful as intrathecal adjuvants but with different block and analgesic profiles.[3,5,7] Postoperative analgesia and VAS The nearly four-hour difference in time to first rescue analgesia is one of the most clinically important findings. Dexmedetomidine patients remained pain-free for 8.2 hours on average compared with 4.6 hours with fentanyl. This was accompanied by lower VAS scores at 6, 12 and 24 hours. The pattern suggests that dexmedetomidine did not merely prolong the sensory block; it provided sustained analgesic benefit during the early postoperative period when pain can interfere with mobilization and physiotherapy. These results align with the meta-analysis by Sun et al., which found a longer pain-free period with dexmedetomidine than fentanyl.[1] Randomized studies have also reported longer analgesic duration and reduced rescue requirements with dexmedetomidine.[5,7] For THR, this may have particular relevance because modern recovery pathways emphasize early mobilization and avoidance of excessive systemic opioids. Better pain control can facilitate physiotherapy, improve patient experience and potentially reduce opioid-related adverse effects. The findings of the present THR study are also consistent with a 2025 randomized controlled trial by Agarwal et al., which evaluated dexmedetomidine versus dexamethasone as adjuvants to ropivacaine for ultrasound-guided saphenous nerve block during ACL reconstruction. In that study of 76 patients, early postoperative pain scores did not differ significantly, whereas pain at 12 and 24 hours was significantly lower in the dexmedetomidine group. However, the time to first and second rescue analgesia and total analgesic consumption were comparable between groups. Mild bradycardia and hypotension were reported with dexmedetomidine, whereas the overall haemodynamic and sedation profiles were similar. The published study therefore provides complementary evidence that dexmedetomidine may improve later postoperative analgesia, but that this benefit does not necessarily translate into lower rescue-analgesic use in every peripheral nerve-block setting. The difference between those findings and the present study—where the rescue-free interval was substantially prolonged—may reflect differences in surgical procedure, neuraxial versus peripheral block technique, comparator agent, dosing regimen and postoperative analgesic protocols.[16] Another relevant randomized study by Bharadwaj et al. evaluated epidural morphine delivery after lumbar spinal fixation surgery. In 60 patients, morphine-soaked Gelfoam was compared with direct epidural morphine instillation. The Gelfoam technique was associated with lower VAS scores at most postoperative assessments, a substantially longer interval before first rescue analgesia (36.46±8.99 versus 9±2.08 hours), and lower 48-hour diclofenac consumption (144.23±56.97 versus 275±35.96 mg), while respiratory rate, SpO2, sedation, nausea and pruritus were comparable between groups.[17] These findings complement the present study from a different pharmacological perspective: whereas the current investigation evaluates intravenous dexmedetomidine as an adjuvant to CSE anaesthesia, Bharadwaj et al. examined the influence of epidural morphine delivery technique. Both studies emphasize that prolonged postoperative analgesia depends not only on the analgesic agent itself but also on its route, delivery characteristics and surgical context. Direct comparison of effect sizes should nevertheless be avoided because the drugs, doses, procedures, patient populations and rescue analgesic protocols were different. Sedation and recovery An interesting finding was the higher postoperative Ramsay sedation score in the fentanyl group. Dexmedetomidine is commonly described as a sedative that can produce cooperative, arousable sedation, whereas fentanyl may cause opioid-related somnolence when repeated systemic doses are required. In the present cohort, the shorter spinal analgesia and higher pain burden in the fentanyl arm may have prompted greater use of supplemental analgesic or sedative medication, contributing to deeper sedation. The faster orientation time with dexmedetomidine supports the clinical relevance of this difference. The literature is not uniform regarding sedation. Some trials of neuraxial dexmedetomidine report greater sedation in the dexmedetomidine arm, particularly when relatively high doses are used.[3,5] Therefore, the present finding should not be interpreted as an intrinsic guarantee that intravenous dexmedetomidine always causes less sedation than fentanyl. Rather, it likely reflects the dosing protocol, duration of surgery and the interaction between analgesic efficacy and supplemental medication use in this particular study. Adverse effects The adverse-effect pattern demonstrates the expected pharmacological trade-off. Bradycardia was significantly more frequent with dexmedetomidine, whereas nausea/vomiting was significantly more common with fentanyl. Shivering and desaturation also numerically favoured dexmedetomidine, although these differences were not statistically significant. The meta-analysis by Sun et al. found reduced pruritus with dexmedetomidine but did not demonstrate consistent differences in bradycardia, hypotension, nausea, vomiting, shivering or respiratory depression across all included studies.[1] Differences between the meta-analysis and the present study may reflect route, dose, surgical population and sample size. Blood loss and fluid requirements Blood loss and IV fluid requirements did not differ significantly. This finding is clinically useful because it suggests that the lower HR and MAP produced by dexmedetomidine did not result in measurable impairment of surgical haemostasis or increased fluid replacement in this cohort. However, the study was not powered specifically to evaluate bleeding or transfusion outcomes, and these observations should therefore be considered supportive rather than definitive. Patient satisfaction and ICU stay Patient satisfaction was substantially higher with dexmedetomidine. Satisfaction is a composite outcome influenced by pain, nausea, sedation, anxiety, recovery and perceived quality of care. The combination of longer block duration, delayed rescue analgesia, lower VAS scores and less nausea/vomiting provides a plausible explanation for the observed eight-point versus six-and-a-half-point satisfaction difference. ICU stay was also shorter by approximately 2.7 hours. This may reflect smoother recovery and fewer symptoms rather than a direct pharmacological effect on ICU requirements. The result is nevertheless relevant to resource utilization, particularly in high-volume arthroplasty services. Dose, route and interpretation The route of dexmedetomidine administration is central to interpretation of this study. Much of the published comparison literature evaluates intrathecal dexmedetomidine at fixed doses of approximately 3–5 µg, whereas the present thesis methodology describes intravenous dexmedetomidine as a weight-based loading dose followed by a maintenance infusion. Intravenous administration produces systemic sympatholysis and sedation in addition to analgesic synergy with spinal anaesthesia. Consequently, the findings should not be generalized directly to intrathecal dexmedetomidine regimens. The explicit reporting of route and dose is essential for reproducibility and for comparing the study with future trials.[1,3,5] Clinical balance between analgesia and bradycardia The study illustrates an important perioperative trade-off. Dexmedetomidine produced lower HR and MAP and a substantially longer pain-free interval, but bradycardia occurred in nearly two-fifths of patients. This does not automatically indicate clinical harm because the thesis does not report serious sequelae, but it demonstrates that the drug's beneficial sympatholytic effect has a predictable physiological cost. In practice, the decision should depend on baseline heart rate, conduction status, intravascular volume, concomitant β-blockers or other negative chronotropes, and the anticipated duration of surgery. A lower loading dose or slower titration may be preferable in patients at increased risk of bradycardia. Enhanced recovery perspective Modern THR pathways emphasize early mobilization, multimodal analgesia and minimization of opioid exposure. The present study's longer rescue-free interval and lower VAS scores are therefore clinically relevant beyond statistical significance. A patient who experiences less pain during the first postoperative day may participate more effectively in physiotherapy and may require fewer systemic opioids. The shorter orientation time and ICU stay observed with dexmedetomidine further suggest a potentially smoother recovery trajectory. These outcomes should, however, be validated using standardized ERAS endpoints such as time to first mobilization, opioid consumption in morphine equivalents, functional walking distance and length of hospital stay. Clinical implications The findings support considering intravenous dexmedetomidine as an opioid-sparing adjuvant for selected THR patients undergoing CSE anaesthesia. The ideal candidate is likely to be an adult without severe conduction disease or profound baseline bradycardia, in whom prolonged analgesia and haemodynamic attenuation are desirable. The protocol should include continuous ECG and blood-pressure monitoring, adequate intravascular volume assessment and immediate availability of atropine or another appropriate intervention for clinically significant bradycardia. The dose should be individualized rather than assumed to be universally optimal. The present study also supports the concept of integrating adjuvant selection with enhanced recovery principles. Longer analgesia without excessive opioid exposure can support early mobilization, while lower postoperative nausea/vomiting may improve oral intake and physiotherapy participation. However, a balance must be maintained because excessive sympatholysis can itself impair recovery if clinically significant bradycardia or hypotension occurs. Strengths and limitations The principal strengths are prospective randomization, equal group size, a relatively homogeneous THR population, systematic serial haemodynamic assessment, repeated postoperative pain measurements and inclusion of patient-centred and resource-related outcomes. The limitations include the modest single-centre sample, restriction to ASA I–II patients aged 40–70 years, exclusion of patients with major cardiac disease and reliance on the thesis-reported statistical analysis rather than patient-level data. The study also reports a specific intravenous dosing regimen that should be reproduced cautiously because the dose is relatively substantial. External validity to very elderly patients, obese patients, severe cardiovascular disease, revision arthroplasty or different perioperative pathways remains uncertain. An additional methodological issue deserves transparency: the thesis literature-review sections discuss fixed 5 µg dexmedetomidine and 25 µg fentanyl regimens used in previous studies, while the methodology specifies weight-based intravenous loading and maintenance infusions.

In adults aged 40–70 years with ASA I–II status undergoing elective total hip replacement under combined spinal–epidural anaesthesia, intravenous dexmedetomidine produced longer spinal anaesthesia, delayed rescue analgesia, lower postoperative pain scores, lighter postoperative sedation, faster orientation, greater satisfaction and shorter ICU stay than fentanyl. The principal trade-off was a significantly higher incidence of bradycardia, while fentanyl produced more nausea/vomiting. Dexmedetomidine therefore appears to be an effective opioid-sparing adjuvant in appropriately monitored patients, but dosing should be individualized and larger multicentre studies are required to confirm safety and determine the optimal regimen.

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