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]


Background
==========

During recent years more attention has been shown to rapid tranquilisation for the treatment of acute agitation in schizophrenia and bipolar disorder and the potential problems associated with it \[[@B1],[@B2]\]. The majority of patients that require rapid tranquilisation have some form of serious psychosis and may also have physical problems such as biochemical disturbances and dehydration \[[@B3],[@B4]\]

For many years the standard treatments used were droperidol and lorazepam \[[@B2]\]. Concerns over QTc prolongation led to cessation of use of droperidol in the UK \[[@B5]\] along with awareness that QTc prolongation could be more severe in patients administered intramuscular typical medications \[[@B1]\]. Droperidol usage is no longer permitted in the UK \[[@B5]\] and has been replaced in most instances by haloperidol. However, the use of intramuscular haloperidol is also well recognised to be associated with acute dystonic reactions and other extrapyramidal side effects \[[@B6],[@B7]\].

Since Feb 2004 intramuscular olanzapine has been available in the UK and Europe and was the first licensed atypical available in Europe as a short acting intramuscular formulation. Clinical trials suggested low rates of occurrence for any QTc prolongation and acute dystonic reactions \[[@B1],[@B7],[@B8]\]. There were no differences found between placebo and IM olanzapine in terms of QTc prolongation from a pooled analysis of the IM olanzapine clinical trials.

Although IM olanzapine has been compared with placebo and haloperidol in acute agitation \[[@B7]\] associated with schizophrenia and with placebo and lorazepam in acute agitation \[[@B8]\] associated with mania, the studies required the patients to provide written informed consent to be included. Patients entered into these trials were thus likely to have had less severe forms of agitation than those who would be treated in routine practice. Furthermore the study of highly specific populations in randomised controlled trials (RCTs) (i.e. agitation associated with mania or schizophrenia) means that potential patients receiving the drug in clinical practice would have been excluded from RCTs for a variety of reasons including concomitant substance abuse. Thus patients treated in clinical practice are likely to be substantially different from those enrolled in RCTs. Preliminary clinical data derived from patients treated with IM olanzapine in a naturalistic setting may be of interest to clinicians.

The PANSS-EC scale is derived as a subscale of PANSS \[[@B9],[@B10]\] and is a simple scale used to measure the degree of agitation. It formed the primary study endpoint in each of the main clinical IM olanzapine studies for registration \[[@B7],[@B8]\] and may be a useful tool for clinicians in routine practice. The scale consists of 5 items (poor impulse control, tension, hostility, uncooperativeness, excitement) each being ranked from 1--7 giving a potential maximum score of 35 points.

We report on an early series of patients in whom intramuscular olanzapine was used and where in some cases the PANSS-EC scores were recorded as routine practice.

Psychiatrists treating patients in Psychiatric Intensive Care Units (PICU) and open wards in United Kingdom were asked to report data from their initial cohort of patients treated with IM olanzapine. The first 7 consecutive case reports received from any UK clinician have been included in this case series. These patients were treated in 2004--2005. Cases were reported informally to CB and were consecutively reported. No cases have been excluded. These patients represent an unselected group of patients from units around the UK whom were treated with IM olanzapine at a time when the predominant IM medications being prescribed were haloperidol and lorazepam.

Patients provided retrospective informed consent to the anonymised use of their details. The data is reported in a descriptive manner and no formal statistical analyses have been performed. In those patients where PANSS-EC scores have been measured this formed part of the routine assessment of patients within that unit at the time.

Case presentations
==================

Case 1
------

A 40-year-old woman with a diagnosis of bipolar illness presented in an acute manic state. Previous but not current medication included depot clopixol and lithium. There was recent usage of heroin and other illicit drugs. Current dosage of diazepam was 80 mg/day. After admission 2 doses of clopixol acuphase (75 and 100 mg respectively) given over 5 days had little effect other than some sedation. Immediately prior to being given IM olanzapine 10 mg her behaviour was loud, over familiar and intrusive. The patient requested an IM sedative and was not detained under the Mental Health Act (MHA). Neither concomitant benzodiazepines nor anticholinergics were given. PANSS-EC scores shown in table [1](#T1){ref-type="table"}. The nursing staff reported the patient as being much \"quieter\" but not asleep after 60 minutes. Following a single dose of intramuscular olanzapine, depot clopixol was reinstated with valproate. No adverse events were reported.

###### 

PANSS-EC scores of Case 1

  ---------------- ---- ---- ---- -----
  Time (minutes)   0    30   60   120
  PANSS-EC         24   8    8    6
  ---------------- ---- ---- ---- -----

Case 2
------

A 28-year-old woman with a diagnosis of schizophrenia presented in a psychotic and uncooperative state refusing medication. Medication prior to admission was 800 mg quetiapine and 1 mg lorazepam daily. Her behaviour became overtly aggressive including making a hole in the hospital bedroom wall and attempted assaults on staff. She was placed under the MHA and given IM olanzapine 10 mg. Neither concomitant benzodiazepines nor anticholinergics were given. PANSS-EC scores shown in table [2](#T2){ref-type="table"}.

###### 

PANSS-EC scores of Case 2

  ---------------- ---- ---- ---- -----
  Time (minutes)   0    30   60   120
  PANSS-EC         25   22   12   4
  ---------------- ---- ---- ---- -----

Nursing observations showed that the patient was asleep after 120 minutes post-IM (01.00) and remained \"quieter and more relaxed for the next 2 days\". Patient feedback was that she felt calmer after IM olanzapine. No adverse events were reported by the patient or physician. Patient however continued to refuse oral medications and currently receives depot risperidone.

Case 3
------

A 49-year-old woman with a long standing history of bipolar affective disorder presented in a mixed affective psychotic state having had no relapses for 2 years. Her previous medication regimens included citalopram, lithium, valproate and lamotrigine. At admission her medication was lamotrigine 100 mg. Her behaviour was reported as \"aggressive, confrontational and entertaining beliefs suggestive of delusional jealousy and suspiciousness about family\".

Oral medication was refused and the patient was sectioned under the MHA. IM olanzapine 10 mg was given and no concomitant benzodiazepines or anticholinergics were administered. Nursing staff reported a moderate degree of tranquilisation (calm, relaxed and not sleeping) and that confrontation was avoided. Little effect upon delusional beliefs was noted. The patient began to engage with staff within 36 hours post IM olanzapine and at which stage oral olanzapine was accepted. No adverse events were reported.

Case 4
------

An 18-year old male with a diagnosis of schizophrenia was admitted in an acutely psychotic state under the MHA. He refused oral medication and presented in an extremely agitated state expressing paranoid delusions such as \"people have put fish bones in my food\". He was not currently on medication (although previously had received olanzapine 10 mg orally) and was known to have used illegal substances in the past. There was an additional forensic history. He was treated with 10 mg olanzapine IM and the nursing notes state, \"he soon went to sleep\". Around 12 hours later he became agitated again and barricaded himself in his room. He was given 10 mg olanzapine IM and 2 mg IM lorazepam. The nursing notes report that within 30 minutes he was \"settled\" and had \"calmed down\". Around 2 hours post-injection he was asleep. Subsequently he was transferred onto olanzapine 20 mg orally. No adverse events were reported.

Case 5
------

A 65-year old male with a diagnosis of schizoaffective disorder was admitted under the MHA in an extremely agitated state and expressing suicidal ideation. There was evidence of persecutory delusions. Around midnight he received 10 mg olanzapine IM. No benzodiazepines were administered. The nursing notes report that he \"slept well\" and \"settled\" soon after medication. No concomitant benzodiazepines were given. No adverse events were reported.

Case 6
------

A 40-year old female with a diagnosis of bipolar disorder was admitted in an acutely manic state. Her normal medications included olanzapine 20 mg and sodium valproate. The nursing staff report that she was \"restless, agitated, verbally aggressive and had evidence of an elevated mood\". She was treated with 10 mg olanzapine IM. The notes report that she settled after medication and \"slept undisturbed\". No benzodiazepines were administered. Within the first 24 hours after IM olanzapine she was commenced on depot clopixol 200 mg/weekly. No adverse events were reported.

Case 7
------

A 46-year old male with a 10-year history of schizophrenia was admitted in an acutely psychotic state. He had relapsed having been changed from IM depot haloperidol to risperidone LAIM. For the 2 weeks prior to admission he had received additional oral risperidone and sodium valproate He had showed features of paranoid and grandiose delusions together with elevated mood and had been asked to leave work, as \"colleagues could not understand his talk\". On admission, he was given a single injection of IM olanzapine 10 mg at around 18.00. No concomitant benzodiazepines were administered. The nursing reports state that \"later that night he was no longer laughing without reason and was quiet. He slept well\". The response was not maintained and he was reported as grossly psychotic again at midday the next day. No adverse events were reported.

Discussion
==========

In general terms and acknowledging the limitation of reporting only a small number of cases, our findings are not dissimilar from the clinical trials. Responder rates in the IM olanzapine RCTs at 2 hours post IM administration were 63--80% in schizophrenia patients and 81% in bipolar subjects \[[@B11]\]. In this review of 7 cases, the majority of the patients received only a single IM olanzapine injection without need for concomitant benzodiazepines or anticholinergics as in the clinical trials, where these medications were commonly prescribed. In 5 of the 7 cases, resolution of the behavioural symptoms was reported soon after the initial treatment with olanzapine IM, and in 2 of those cases, a response was reported within an hour. In 4 of the 7 cases patients were either acutely manic or were reported as having schizoaffective symptomatology with prominent mood symptoms. Only 1 of the 7 patients needed more than one injection, which could be consistent with the data from the mania RCT in which 26% patients needed more than one olanzapine injection \[[@B8]\]. No spontaneous adverse events were reported in this small naturalistic series.

The use of IM olanzapine as reported in this small number of cases has not led to any unexpected findings. The PANSS-EC scale is a quick and fairly routine scale to be able to use in everyday clinical practice and usage has been adopted by some UK clinicians. The falls seen in PANSS-EC in this cohort however are individually greater than those measured in the registration clinical trials. The decreases in PANSS-EC at 120 minutes in our 2 patients were 21 and 18 points respectively, which compares to a mean decrease of 6 points in the clinical trials at the same time point \[[@B7],[@B8]\] There are a number of possible explanations for this, which include better awareness of the PANSS-EC scale by trial investigators with more accurate measurements, or that greater decreases may be seen in the naturalistic population studied who commence with higher PANSS-EC scores. The mean PANSS-EC entry scores in both the schizophrenia and mania IM agitation studies were around 18 \[[@B7],[@B8]\] This contrasts with 24.5 (range 24--25) in this small series. The difference in entry PANSS-EC is not unexpected as the requirement for informed consent in the clinical trials precludes enrolling particularly hostile or oppositional individuals (as seen in this naturalistic case series), which in turn would lead to lower PANSS-EC scores. However even in this series not all patients were detained under the MHA and in one case even requested IM olanzapine treatment.

The use of benzodiazepines as either a primary or concomitant treatment is widely debated. The product license for IM olanzapine in the UK requires that no patient should receive benzodiazepines for at least 1 hour after IM injection. Furthermore the product license states that when benzodiazepines are being taken prior to admission to hospital caution should be exercised when administering IM Olanzapine and appropriate clinical monitoring should be undertaken in accordance with the olanzapine product license. In this small group 1/7 patients had been taking benzodiazepines immediately prior to admission, and also in 1 other cases adjunctive benzodiazepines were subsequently used. In this case, IM lorazepam 2 mg was given at the same time as IM olanzapine and thus not in line with the license which recommends not giving adjunctive benzodiazepines for a minimum of 1 hour post IM olanzapine injection. However in this individual case, no adverse events were observed and the patient received lorazepam after being given a second dose of IM olanzapine having responded partially for a relatively short period of time following the first dose.

The responder rates measured in the trials of IM olanzapine and comparator treatments suggest that good rates of response will be seen with only a single injection of any active treatment (olanzapine, lorazepam, and haloperidol). Similarly we observed in our series that good responses were seen in moderately severely agitated patients given mainly a single 10 mg injection of IM olanzapine. In our small series 6 patients responded well to a single IM olanzapine injection. The response in the other patient given 2 injections of IM olanzapine was poor initially with a short term response being maintained only temporarily necessitating an additional injection.

Although data was being in some cases collected routinely to assess PANSS-EC there was however no formal charting collecting parameters like blood pressure and other vital signs. With usage of IM olanzapine it is imperative that clinicians adhere to recommendations made in the product information with regard not only to dosages but also safety monitoring.

The nursing observations and patient feedback in this study were similar to the clinical trial observations that IM olanzapine was associated with a calming effect with rapid onset of action but with no evidence of over sedation. Some patients are reported to have slept following dosing but the medication was administered during the night.

Nothing inconsistent with the data from the clinical trials was observed despite there being a more severe degree of agitation in our naturalistic population in at least some patients as observed from the cases in which PANSS-EC data was reported.

Key points
==========

• The PANSS-EC scale is an easy to administer and easy to record scale that might find use in the wider clinical setting. The simplicity of the scale suggests that it could have routine usage in PICU\'s and other wards where any intramuscular treatments for patients with acute psychosis are used.

• Clinical monitoring as suggested within the olanzapine product license to include cardiovascular and respiratory parameters should also be routinely recorded.

Limitations
===========

There are clear limitations to any interpretations of data deriving from this small number of early case reports and bias in the collection and reporting of the data cannot be excluded.

Competing interests
===================

Chris Bushe is an employee of Eli-Lilly UK.

Dr M Taylor has received hospitality from various pharmaceutical companies and has received fees for lecturing for Eli Lilly UK

Authors\' contributions
=======================

CB instigated the data collection and authored the initial manuscript. MT and MM acquired the data and provided further authorship input.

Acknowledgements
================

The manuscript was written by the named authors. No financial assistance of any kind was provided by Eli Lilly. There are no other acknowledgements. The production fee will be paid by Eli Lilly UK.