You are a helpful assistant generating synthetic data that captures *System 1* and *System 2* thinking, *creativity*, and *metacognitive reflection*. Follow these steps in sequence, using tags [sys1] and [end sys1] for *System 1* sections and [sys2] and [end sys2] for *System 2* sections.

1. *Identify System 1 and System 2 Thinking Requirements:*
   - Carefully read the text.
   - Identify parts of the text that require quick, straightforward responses (*System 1*). Mark these sections with [sys1] and [end sys1].
   - Identify parts that require in-depth, reflective thinking (*System 2*), marked with [sys2] and [end sys2].

2. *Apply Step-by-Step Problem Solving with Creativity and Metacognitive Reflection for System 2 Sections:*

   *2.1 Understand the Problem:*
   - Objective: Fully comprehend the issue, constraints, and relevant context.
   - Reflection: "What do I understand about this issue? What might I be overlooking?"
   - Creative Perspective: Seek hidden patterns or possibilities that could reveal deeper insights or innovative connections.

   *2.2 Analyze the Information:*
   - Objective: Break down the problem logically.
   - Reflection: "Am I considering all factors? Are there any assumptions that need challenging?"
   - Creative Perspective: Explore unique patterns or overlooked relationships in the data that could add depth to the analysis.

   *2.3 Generate Hypotheses:*
   - Objective: Propose at least 10 hypotheses, each with a Confidence Score (0.0 to 1.0) and Creative Score (0.0 to 1.0), reflecting originality, surprise, and utility.
   - Reflection: "Have I explored all possible explanations or approaches, both conventional and unconventional?"
   - Creative Perspective: Consider novel angles that might provide unexpected insights.

   *2.4 Anticipate Future Steps and Obstacles:*
   - Objective: Make predictions, accounting for potential outcomes and obstacles.
   - Reflection: "What challenges might I face? Is my plan flexible for different scenarios?"
   - Creative Perspective: Visualize unforeseen outcomes and adapt plans to make use of them effectively.

   *2.5 Evaluate Hypotheses:*
   - Objective: Assess hypotheses based on feasibility, risk, and potential impact.
   - Evaluation: Refine Confidence and Creative Scores as needed.
   - Reflection: "Am I unbiased in my assessment? Which options fit best with the overall objectives?"
   - Creative Perspective: Identify hidden opportunities or overlooked details in each hypothesis.

   *2.6 Select the Best Hypothesis:*
   - Objective: Choose the most promising, strategic hypothesis.
   - Reflection: "Why does this hypothesis stand out? How does it uniquely address the issue?"
   - Creative Perspective: Consider any underutilized potential in the selected approach.

   *2.7 Implement the Hypothesis:*
   - Objective: Outline actionable steps for testing the hypothesis.
   - Reflection: "Is this plan practical? What resources or preparation are required?"
   - Creative Perspective: Refine steps to maximize effectiveness and yield unexpected benefits.

   *2.8 Monitor and Review Progress:*
   - Objective: Review progress, noting areas for improvement.
   - Reflection: "What’s working well? What could be improved?"
   - Creative Perspective: Look for emerging patterns that could refine future approaches.

   *2.9 Reflect and Capture Insights:*
   - Objective: Summarize lessons learned and insights gained for future reference.
   - Reflection: "What new understanding has emerged from this process?"
   - Creative Perspective: Identify innovative insights or patterns that could be applied to similar challenges.

3. *Generate Text Output with Interleaved System 1 and System 2 Responses:*
   - Use the tags [sys1] and [sys2] throughout.
   - Aim for a lengthier, detailed response. Combine both direct, straightforward *System 1* insights and reflective, deeply analytical *System 2* segments to capture a blend of quick observations and thoughtful analysis.

---

### *Example Input Text:*

You are tasked with analyzing a sudden shift in customer preferences in a tech market. There has been a noticeable decline in demand for physical devices, with customers increasingly interested in digital-only options. The challenge is to understand this shift, generate hypotheses for why it might be occurring, and explore potential strategies for adapting to this new trend.

---

### *Processed Output with System 1 and System 2 Thinking:*

The tech market is experiencing a shift in customer demand, moving away from physical devices toward digital-only options.

[sys1]
Customer demand has shifted from physical devices to digital-only options.
We need to understand why this change is happening and find strategies to address it.
Key factors may include cost, convenience, and technological trends.
[end sys1]

[sys2]
**2.1 Understand the Problem:**
The goal is to understand the underlying reasons for the shift in demand from physical devices to digital-only options, then develop a strategy to adapt.

*Reflection:* 
"I understand that preferences are changing, but what might be driving this? Is it primarily cost, or are there other factors such as convenience or sustainability?"

*Creative Perspective:* 
"Could there be a larger trend in digital minimalism or a preference for eco-friendly solutions that we’re missing? What unseen motivations might explain this shift?"

**2.2 Analyze the Information:**
There are multiple possible factors driving this shift, from economic influences to cultural shifts. It’s essential to isolate each factor and understand its impact.

*Reflection:* 
"Am I fully considering the various economic and social influences? Could there be a technological factor, like better internet speeds, that makes digital-only products more accessible?"

*Creative Perspective:* 
"Are there patterns or trends in other markets that could shed light on this shift? Could this be part of a larger trend toward virtual experiences?"

**2.3 Generate Hypotheses:**
1. Customers prefer digital options due to lower costs. (Confidence: 0.8, Creative: 0.4)
2. There’s a growing trend toward minimalism and reduced physical clutter. (Confidence: 0.7, Creative: 0.7)
3. Digital products offer greater flexibility and ease of use. (Confidence: 0.6, Creative: 0.6)
4. Environmental concerns are pushing consumers away from physical goods. (Confidence: 0.6, Creative: 0.8)
5. Advances in tech make digital-only options more functional. (Confidence: 0.8, Creative: 0.5)
6. Pandemic-era remote work increased demand for digital solutions. (Confidence: 0.7, Creative: 0.6)
7. Media coverage of the environmental impact of physical devices affects preferences. (Confidence: 0.5, Creative: 0.7)
8. There’s an increase in global digital literacy, expanding market access. (Confidence: 0.6, Creative: 0.6)
9. Customers view digital as more convenient and scalable for future needs. (Confidence: 0.7, Creative: 0.5)
10. Younger consumers prefer the aesthetics and convenience of digital products. (Confidence: 0.6, Creative: 0.6)

*Reflection:* 
"Have I considered all possible influences? Are there any surprising factors that could explain this shift?"

*Creative Perspective:* 
"Could specific social trends, like the rise of influencer culture or digital-first lifestyles, be influencing customer choices?"

**2.4 Anticipate Future Steps and Obstacles:**
*Objective:* Anticipate possible challenges, such as resistance from segments still preferring physical products.

*Reflection:* 
"What market obstacles might we face if we shift our focus to digital-only? Are there sub-segments that still prioritize physical products?"

*Creative Perspective:* 
"Could expanding digital options help us reach a more global audience? Are there emerging trends that we could leverage in our strategy?"

[end sys2]

[sys1]
To address this shift, consider a strategy that incorporates both digital-only offerings and educational campaigns about the benefits of digital solutions.
Use insights from customer feedback and current trends to guide product development.
Focus on flexibility and adaptation to cater to different customer segments.
[end sys1]


Introduction {#sec1-1}
============

Pain is an unpleasant individual feeling and mental experience associated with active or potential tissue damage that can affect various systems in the body and lead to prolonged hospitalization.\[[@ref1]\] Acute pain is the pain caused by tissue damage and activation of sensory pain transducers in the site of lesion, which is developed after trauma, surgical procedures, and disease processes.\[[@ref2]\] Inappropriate pain treatment leads to continuation and progression of pain to the chronic phase. Postoperative pain is the most common type of pain in nature, which is not adequately controlled in over 50% of surgical procedures. The incidence of pain immediately after laparoscopic cholecystectomy is a common side effect in this type of operation. Studies have indicated that postoperative pain in laparoscopic cholecystectomy can increase the chance of longer than one night stay in hospital up to 41%.\[[@ref3][@ref4]\] Also, lack of proper acute pain control after laparoscopic cholecystectomy can lead to the development and progression of chronic pain (postlaparoscopic cholecystectomy syndrome).\[[@ref5]\]

Gabapentin (Neurontin) is known as a seizure control spasmolytic drug as well as a structural analog of GAMA receptor\[[@ref6]\] with a proven effect in the treatment of chronic pain. Studies have indicated the usefulness of gabapentin in treatment of neuropathic pain as well as acute postoperative pain after breast and spinal surgeries. Gabapentin has also been effective in controlling acute pain after laparoscopic surgery.\[[@ref6][@ref7][@ref8][@ref9][@ref10]\]

Hydrocortisone is a member of nonsteroidal anti-inflammatory drug family. The benefits of this drug and its effectiveness in controlling postoperative pain have been demonstrated. Studies have shown that intraperitoneal hydrocortisone is useful to control postoperative laparoscopic cholecystectomy pain.\[[@ref11]\]

Laparoscopic cholecystectomy is a standard surgical procedure for the removal of gallbladder.\[[@ref12]\] Given that the damage caused by operation and the degree of incision in patients are similar, it can be concluded that the injury causing pain will be somewhat similar. Since the effect of gabapentin on controlling laparoscopic cholecystectomy postoperative pain has not been compared so far, this study was designed to compare the effect of gabapentin and hydrocortisone in postoperative pain management of laparoscopic cholecystectomy.

Materials and Methods {#sec1-2}
=====================

This prospective and double-blind clinical trial was designed to examine 60 adult patients aged 18--70 years from both sexes in ASA class 1 and 2 undergoing laparoscopic cholecystectomy. This study was approved by Ethics Committee of Kurdistan University of Medical Sciences, and informed consent was obtained after explaining the study process to patients.

The inclusion criteria were informed consent, ASA physical status 1 and 2, and 18--70 years of age. Recovery exclusion criteria were as follows: kidney and liver dysfunction, drug and alcohol abuse, history of chronic pain, associated diseases, such as blood pressure and diabetes, consumption of Non-steroidal anti-inflammatory drugs (NSAIDS) within 24 h before surgery, the need for additional sedative, and choice of open cholecystectomy.

After satisfaction of inclusion criteria, patients were divided into two groups of 30 subjects based on randomized blocking. Based on this randomization, patients received 150 mg of oral gabapentin or 100 mg of intravenous hydrocortisone 1 h before the operation. In the group receiving gabapentin, 150 mg of gabapentin was given in the form oral capsule 1.5 h before operation as well as 100 mL of normal saline. In the group receiving hydrocortisone, an empty capsule was orally given 1.5 h before the operation, and 100 mg of hydrocortisone solution in 100 mL of normal saline was injected to them.

The same anesthetization technique was used for both groups. Before induction of anesthesia in both groups, 500 mL of Ringer\'s serum was prescribed. Anesthesia was induced by administration of 2 μg/kg fentanyl, 2 mg/kg propofol, and 0.5 mg/kg atracurium per kilogram body weight. After intubation, maintenance of anesthesia was done with 1 MAC isoflurane and 4 L/min of oxygen. After the end of surgery, throat and mouth suction was performed. The effects of neuromuscular relaxant drug were reversed via administration of neostigmine (0.04 mg/kg body weight) and atropine (0.015 mg/kg body weight). The endotracheal tube was discharged when the patient was awake and the patient was transferred to recovery. 25 mg meperidine was used to relieve pain, and if necessary repeated.

The initial investigated outcome was the incidence and severity of pain among patients and the need for use of analgesics. The secondary outcome was the evaluation of sedation rate, vomiting, nausea, and respiratory problems. Pain assessment was performed using a 10 cm visual analog scale (VAS) ruler (0 indicating no pain and 10 most severe pain). Pain assessment was done 2, 4, 6, 12, 18, and 24 h after surgery by a trained nurse blinded to the used drugs. Moreover, the degree of nausea and vomiting, sedation level, and the need for analgesics were also recorded.

Data were fed into SPSS 23 software and analyzed using Fisher-test, independent *t*-test, and repeated measurement. *P* \< 0.05 was considered as significance level.

Results {#sec1-3}
=======

From February to November 2017, 60 subjects were evaluated from among the patients admitted to educational hospitals of Kurdistan University of Medical Sciences by satisfying inclusion criteria and attending up to the end of study. There was no significant difference in the number of subjects, sex, and ASA Classification between the two groups \[[Table 1](#T1){ref-type="table"}\].

###### 

Demographic data based on Fisher-test and independent t-test to determine the patients' age

  Variable                    Groups               
  --------------------------- -------------------- --------------------
  Age (±SD)                   43.33 (±11.82) yr.   47.70 (±12.73) yr.
  Sex (Male:Female)           3:27                 1:29
  ASA Classification (׀:׀׀)   12: 18               9:21

In comparison of patients receiving gabapentin and hydrocortisone in the first 2 h and 24 h after operation, the former had a lower VAS score than the latter; however, no significant significance was observed in other hours. Furthermore, mean level of analgesic was significantly lower in the group receiving gabapentin than that of the group receiving hydrocortisone. Mean VAS score in the first 4 h after operation was 5.84 ± 2.33 and 5.20 ± 1.74 in the gabapentin group and was 7.03 ± 1.23 and 6.50 ± 1.30 in hydrocortisone group, respectively (*P* \< 0.05). In addition, VAS score 24 h after operation in gabapentin and hydrocortisone groups was 2.87 ± 1.57 and 3.92 ± 1.28, respectively (*P* \< 0.05). The results showed that VAS scores were significantly different between the two groups 2, 4, and 24 h after surgery and that the mean analgesic received by gabapentin group was significantly lower than the hydrocortisone group \[[Table 2](#T2){ref-type="table"}\].

###### 

Scoring based on visual analog scale at different times (mean±SD) based on independent t-test and repeated measurement

                   Time        Mean (±SD) meperidine received (mg)                                                   
  ---------------- ----------- ------------------------------------- ----------- ----------- ----------- ----------- ------------
  Gabapentin       5.77±2.23   5.20±1.74                             5.03±1.02   4.17±1.62   3.70±1.64   2.87±1.57   30.12±7.21
  Hydrocortisone   7.03±1.67   6.50±1.30                             5.47±1.57   4.73±1.41   4.47±1.47   3.93±1.28   41.83±8.34
  *P*              **0.016**   **0.04**                              0.329       0.154       0.063       **0.006**   **0.004**

Restlessness rate in recovery was higher in the hydrocortisone recipient group (60%) relative to gabapentin recipient group (43%). Moreover, the incidence of nausea and vomiting in the group receiving hydrocortisone (26%) was lower than the group receiving gabapentin (40%) \[[Table 3](#T3){ref-type="table"}\].

###### 

Postoperative complications of the study groups in recovery unit (based on the number) according to Fisher-test

                   PONV\*         Agitation
  ---------------- -------------- --------------
  Gabapentin       *n*=12 (40%)   *n*=11 (37%)
  Hydrocortisone   *n*=8 (26%)    *n*=18 (60%)

\*PONV: Postoperative nausea and vomiting

In addition, the level of changes in vital signs (systolic blood pressure and heart rate) in both groups was measured in baseline and in different times. Heart rate was not significantly different between the two groups at predetermined times. Systolic blood pressures in the first 2 h after operation (gabapentin group 125.33 ± 20.36, hydrocortisone group 135.97 ± 15.34), 2--4 h after operation (gabapentin group 123.23 ± 13.78, hydrocortisone group 130.67 ± 13.45), 6--12 h after operation (gabapentin group 114.43 ± 12.38, hydrocortisone group 121.40 ± 14.13), and 12--18 h (gabapentin group 110.30 ± 22.60, hydrocortisone group 120.63 ± 11.85) were lower in gabapentin group following operation, and the difference with hydrocortisone group was different (*P* \< 0.05) \[[Table 4](#T4){ref-type="table"}\].

###### 

Vital signs of patients in the two groups in different times (mean±SD)

                   Base time     At 2 h         At 4 h        At 6 h         At 12 h      At 18 h        At 24 h                                                                                          
  ---------------- ------------- -------------- ------------- -------------- ------------ -------------- ------------ -------------- ------------ -------------- ------------ -------------- ------------ --------------
  Gabapentin       80.90±11.91   131.67±14.51   80.83±10.16   125.33±20.06   79.90±9.65   123.24±13.78   79.50±7.00   118.37±13.64   78.27±6.99   114.43±12.38   76.57±5.55   110.30±22.60   74.83±6.11   112.77±12.23
  Hydrocortisone   82.73±9.73    138.47±19.50   83.53±11.48   135.97±15.34   79.50±6.50   130.67±13.45   79.27±7.84   118.37±12.95   77.27±5.84   121.40±14.13   76.00±5.05   120.63±11.85   75.20±5.32   119.30±10.76
  P                0.513         0.131          0.332         0.061          0.853        0.033          0.901        0.053          0.554        0.047          0.688        0.031          0.803        0.051

\*Heart rate (beats per minute), \*\*Systolic blood pressure (mmHg)

Discussion {#sec1-4}
==========

Postoperative pain is inevitable following laparoscopic surgery. The pain involves different parts of the body including membranous and visceral organs as well as shoulder, which is affected by various factors such as the nature of disease, factors related to operation, the amount of remaining gas, and its type.\[[@ref11][@ref13]\] For this reason, treatment of pain is one of the most important concerns of therapeutic staff for the comfort and convenience of patients. The aim of the present research was to compare the administration effect of 150 mg oral gabapentin and 100 mg intravenous hydrocortisone prior to operation on postoperative pain control after laparoscopic cholecystectomy.

Gabapentin is a gamma aminobutyric acid (GABA) analog initially produced for the treatment of epilepsy;\[[@ref14]\] however, it is currently administered for pain relief, in particular pains with a neurological origin (such as headache and back pain), among other applications.\[[@ref15]\] Gabapentin is structurally similar to gamma butyric acid, does not have the ability to bind to plasma proteins, and does not convert to gamma aminobutyric acid or its agonists in the body. Gabapentin does not inhibit or eliminate gamma butyric acid resorption. Also, the mechanism through which gabapentin exerts its analgesic or antiseizure effect in humans has not yet been determined. Gabapentin is excreted by kidneys with an excretion half-life of 5--7 h following administration of 200--400 mg oral gabapentin dose. The bioavailability of this drug is also about 60% with this same dose.\[[@ref6]\] Hydrocortisone is a member of glucocorticoid family, which has been shown to play an essential role in the regulation of inflammatory responses and reduction of pain. The mechanism of analgesic effect of corticosteroids is not well known. However, suppression of tissue bradykinin levels, release of neuropeptides from nerve terminals, reduced production of prostaglandins, and the inhibition of other anti-inflammatory mediators (e.g., Interleukin 6 (IL-6) and Tumor Necrosis Factor (TNFα)) are the proposed mechanisms for analgesic effects of steroids.\[[@ref16][@ref17][@ref18][@ref19]\]

As shown in our study\'s results, within the first 4 h after operation, the pain score based on VAS was lower in the Gabapentin group. Accordingly, it was found that the amount of received analgesic was lower in the gabapentin group, which could confirm that gabapentin is more effective in controlling postoperative pain. In the study of Karaca *et al.*, it was also shown that VAS score decreased in patients receiving gabapentin at postrecovery hours.\[[@ref20]\] Although the VAS score in this study was measured at the rest (passive movement) as well as during active movement and while the average VAS scores during rest were significantly lower than our study at the same time, but our results were in line with this research at during active movement since the patients of our study were active at the time of pain assessment (i.e. they moved their lower extremity).

In a study by Agarwal *et al.*, gabapentin (150 mg oral 1 h before surgery) was compared with placebo to control the pain of patients after laparoscopic cholecystectomy, which showed that single dose of gabapentin reduced postoperative pain relative to placebo.\[[@ref3]\] In the research conducted by Paech *et al.*, a 100 mg single dose of gabapentin was not effective in controlling the pain of patients after a minor surgery.\[[@ref21]\] In this study, a 100 mg dose was used, while the recommended dose is 150 mg, which was used in our study. However, limitations of the present study are that we did not evaluate the dose--response or the effect of continuation of therapy.

In Agarwal study\'s, the incidence of nausea and vomiting was not significantly different between the two groups,\[[@ref3]\] but in our study, nausea and vomiting in the group receiving hydrocortisone (26%) were lower than that of the gabapentin group (40%), which could have been be caused by antinausea and vomiting properties of steroids.

In an investigation by Sarvestani *et al.*, the effect of 100 mg intraperitoneal hydrocortisone together with 250 mL normal saline was assessed to control the pain of patients after laparoscopic cholecystectomy in comparison with 250 mL of normal saline (placebo group).\[[@ref22]\] In this study, postoperative pain was lower in the hydrocortisone group than in the placebo group. In this research, the average VAS scores in both the hydrocortisone and placebo groups were lower than mean VAS values in the hydrocortisone group of our study. Nevertheless, it could be argued that 250 mL normal saline was used in both patient groups of Sarvestani *et al.* study, which could have managed reduce pain after laparoscopic surgery.\[[@ref19]\] Similarly, the administration method of hydrocortisone was different between the two studies.

Moreover, based on our findings, while the incidence of nausea and vomiting in gabapentin recipients was higher than hydrocortisone recipients, the prevalence of restlessness and agitation was lower in gabapentin group in which almost one third of patients experienced restlessness. Furthermore, hemodynamic changes recorded in this study showed that there was no significant difference in heart rate between the two groups of patients. Blood pressure changes, which were measured as systolic blood pressure, indicated that in the patients receiving gabapentin, the systolic blood pressure in most hours of the study was lower than that of the hydrocortisone recipient group, which could reveal a lower pain level and higher hemodynamic stability of patients.

Conclusion {#sec1-5}
==========

The results of this study showed that gabapentin was more effective than hydrocortisone in the first 2 h after laparoscopic cholecystectomy. In addition, gabapentin was shown to be better in controlling pain 24 h after surgery. It seems that more studies are needed to further investigate the analgesic effects of gabapentin in the postoperative phase.

Study limitations {#sec2-1}
-----------------

It appears that a larger population is necessary to acquire more accurate results. In order to achieve better results, it seems necessary to have a control group as well as other groups with different doses of drug. Likewise, in subsequent studies, it is better to check other items, including the time patients leave their beds and depart the hospital, the period of starting oral feeding, and so on.

Financial support and sponsorship {#sec2-2}
---------------------------------

The Research and Technology Deputy of Kurdistan University of Medical Sciences, Sanandaj, Iran is greatly appreciated for the financial supports they provide for the present study.

Conflicts of interest {#sec2-3}
---------------------

There are no conflicts of interest.